Combination therapies using molecules binding to TCR

Abstract

Provides herein is method of treating a disease or condition in a subject, or a combination therapy using agents that bind to a T cell receptor alpha variable region (TCRαV) and / or a T cell receptor beta variable region (TCRβV).

Description

COMBINATION THERAPIES USING MOLECULES BINDING TO TCRRELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 498,671 filed on April 27, 2023, the entire contents of which are hereby incorporated by reference.BACKGROUND

[0002] Currently available molecules designed to redirect T cells to promote tumor cell lysis for cancer immunotherapy typically target the CD3 epsilon (CD3e) subunit of the T cell receptor (TCR). However, there are limitations to this approach. Previous studies have shown that, e.g., low doses of anti-CD3e monoclonal antibody (mAb) can cause T cell dysfunction and exert immunosuppressive effects. In addition, anti-CD3e mAbs bind to all T cells and thus activate a large number of T cells. Such non -physiological massive activation of T cells by these anti-CD3e mAbs can result in the production of proinflammatory cytokines such as IFN-gamma, IL- 1 -beta, IL-6, IL- 10 and TNF-alpha, causing a “cytokine storm” known as the cytokine release syndrome (CRS), which is also associated with neurotoxicity (NT). Thus, there is a need for improved T cell receptor-binding molecules that redirect T cells for cancer immunotherapy.SUMMARY

[0003] In an aspect, provided herein is, inter alia, a method of treating a disease or condition in a subject in need thereof comprising administering a first agent that comprises a first binder that binds to a first target molecule to the subject, and administering a second agent that comprises a second binder that binds to a second target molecule to the subject, thereby treating the disease or condition in the subject; wherein an administration of the first agent is followed by an administration of the second agent; wherein the first target molecule and the second target molecule are independently selected from the group consisting of a T cell receptor alpha variable region (TCRaV) and a T cell receptor beta variable region (TCR[3V); and wherein the first target molecule and the second target molecule are different.

[0004] In some embodiments, the first agent and the second agent are not concomitantly administered to the subject.

[0005] In some embodiments, administering the first agent comprises administering a therapeutically effective amount of the first agent to the subject.

[0006] In some embodiments, administering the second agent comprises administering a therapeutically effective amount of the second agent to the subject.

[0007] In some embodiments, the method is more effective to treat the disease or condition in the subject relative to a method in which the first agent is administered to the subject but not the second agent.

[0008] In some embodiments, the method is more effective to treat the disease or condition in the subject relative to a method in which the second agent is administered to the subject but not the first agent.

[0009] In some embodiments, the method is more effective to treat the disease or condition in the subject relative to a method in which the first agent is administered to the subject at a first administration and the first agent is administered to the subject subsequently at a second administration.

[0010] In some embodiments, the method is more effective to treat the disease or condition in the subject relative to a method in which the second agent is administered to the subject at a first administration and the second agent is administered to the subject subsequently at a second administration.

[0011] In some embodiments, the method is more effective to treat the disease or condition in the subject relative to a method in which the second agent is administered to the subject at a first administration and the first agent is administered to the subject subsequently at a second administration.

[0012] In some embodiments, the administration of the first agent comprises one or more doses.

[0013] In some embodiments, the administration of the first agent comprises two or more doses.

[0014] In some embodiments, the administration of the first agent comprises one dose per week.

[0015] In some embodiments, the administration of the first agent comprises two or more doses per week.

[0016] In some embodiments, the first agent is administered to the subject once every two weeks.

[0017] In some embodiments, the first agent is administered to the subject once every three weeks.

[0018] In some embodiments, the first agent is administered to the subject once every week for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

[0019] In some embodiments, the administration of the first agent comprises two or more doses per week for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

[0020] In some embodiments, the first agent is administered to the subject once every two weeks for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

[0021] In some embodiments, the first agent is administered to the subject once every three weeks for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

[0022] In some embodiments, the administration of the second agent comprises one or more doses.

[0023] In some embodiments, the administration of the second agent comprises two or more doses.

[0024] In some embodiments, the administration of the second agent comprises one dose per week.

[0025] In some embodiments, the administration of the second agent comprises two or more doses per week.

[0026] In some embodiments, the second agent is administered to the subject once every two weeks.

[0027] In some embodiments, the second agent is administered to the subject once every three weeks.

[0028] In some embodiments, the second agent is administered to the subject once every week for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

[0029] In some embodiments, the administration of the second agent comprises two or more doses per week for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

[0030] In some embodiments, the second agent is administered to the subject once every two weeks for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

[0031] In some embodiments, the second agent is administered to the subject once every three weeks for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

[0032] In some embodiments, the administration of the first agent and the administration of the second agent is separated by one week.

[0033] In some embodiments, the administration of the first agent and the administration of the second agent is separated by two or more weeks.

[0034] In some embodiments, the administration of the first agent and the administration of the second agent is separated by 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 12 months.

[0035] In some embodiments, the administration of the first agent and the second agent is repeated twice or more.

[0036] In some embodiments, the first agent and the second agent are administered to the subject according to a dosing regimen, wherein the dosing regimen comprises an administration of the first agent once every week for two weeks followed by an administration of the second agent once a week for two weeks, wherein the second agent is administered to the subject one week after the last administration of the first agent.

[0037] In some embodiments, the dosing regimen is repeated twice or more.

[0038] In some embodiments, the dosing regimen is repeated at the interval of one week.

[0039] In some embodiments, the dosing regimen is repeated at the interval of 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 12 months.

[0040] In some embodiments, the first agent and the second agent are administered to the subject in a same amount.

[0041] In some embodiments, the first agent and the second agent are administered to the subject in different amounts.

[0042] In some embodiments, the administration of the first agent comprises two or more doses, and each dose comprises a same amount of the first agent.

[0043] In some embodiments, the administration of the first agent comprises two or more doses, and each dose comprises different amounts of the first agent.

[0044] In some embodiments, the administration of the second agent comprises two or more doses, and each dose comprises a same amount of the second agent.

[0045] In some embodiments, the administration of the second agent comprises two or more doses, and each dose comprises different amounts of the second agent.

[0046] In some embodiments, the first agent is administered to the subject at a dose of from about 0.001 mg / kg to about 10 mg / kg.

[0047] In some embodiments, the second agent is administered to the subject at a dose of from about 0.001 mg / kg to about 10 mg / kg.

[0048] In some embodiments, the first agent is administered to the subject at a dose of about 0.3 mg / kg or about 1 mg / kg.

[0049] In some embodiments, the second agent is administered to the subject at a dose of about 0.3 mg / kg or about 1 mg / kg.

[0050] In some embodiments, the first target molecule is a first TCRJ3V, and the second target molecule is a second TCRJ3V, wherein the first TCRJ3V and the second TCRJ3V are different.

[0051] In some embodiments, the first target molecule is a first TCRaV, and the second target molecule is a second TCRaV, wherein the first TCRaV and the second TCRaV are different.

[0052] In some embodiments, the first target molecule is a TCRJ3V, and the second target molecule is a TCRaV.

[0053] In some embodiments, the first target molecule is a TCRaV, and the second target molecule is a TCR|3V.

[0054] In some embodiments, the first target molecule is human TCRJ3V6.

[0055] In some embodiments, the first target molecule is human TCRpVIO.

[0056] In some embodiments, the second target molecule is human TCRPV15.

[0057] In some embodiments, the second target molecule is human TCRPV27.

[0058] In some embodiments, the second target molecule is human TCRPV5.

[0059] In some embodiments, the first target molecule is human TCRPV6, and the second target molecule is human TCRPV5.

[0060] In some embodiments, the first target molecule is human TCRPV6, and the second target molecule is human TCRPV15.

[0061] In some embodiments, the first target molecule is human TCRPV6, and the second target molecule is human TCRPV27

[0062] In some embodiments, the first target molecule is human TCRpVIO, and the second target molecule is human TCRPV5.

[0063] In some embodiments, the first target molecule is human TCRpVIO, and the second target molecule is human TCRPV15.

[0064] In some embodiments, the first target molecule is human TCRpVIO, and the second target molecule is human TCRPV27.

[0065] In some embodiments, the first target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV19, human TRBV20, or human TRBV28.

[0066] In some embodiments, the first target molecule is human TRBV5-1, human TRBV6-5, human TRBV10-1, human TRBV10-2, human TRBV10-3, human TRBV7-2, human TRBV7-3, human TRBV19, human TRBV20-1, or human TRBV28.

[0067] In some embodiments, the first target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30.

[0068] In some embodiments, the first target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30.

[0069] In some embodiments, the second target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV15, human TRBV27, human TRBV19, human TRBV20, or human TRBV28.

[0070] In some embodiments, the second target molecule is human TRBV5-1, human TRBV6-5, human TRBV10-1, human TRBV10-2, human TRBV10-3, human TRBV7-2, human TRBV7-3, human TRBV15, human TRBV27, human TRBV19, human TRBV20-1, or human TRBV28.

[0071] In some embodiments, the second target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30.

[0072] In some embodiments, the second target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30.

[0073] In some embodiments, the first target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV19, human TRBV20, or human TRBV28, and the second target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV15, human TRBV27, human TRBV19, human TRBV20, or human TRBV28, wherein the first target molecule and the second target molecule are different.

[0074] In some embodiments, the first target molecule and the second target molecule are: human TRBV5 and human TRBV5, respectively; human TRBV5 and human TRBV6, respectively; human TRBV5 and human TRBV10, respectively; human TRBV5 and human TRBV7, respectively; human TRBV5 and human TRBV19, respectively; human TRBV5 and human TRBV20, respectively; human TRBV5 and human TRBV28, respectively; human TRBV6 and human TRBV5, respectively; human TRBV6 and human TRBV6, respectively; human TRBV6 and human TRBV10, respectively; human TRBV6 and human TRBV7, respectively; human TRBV6 and human TRBV15, respectively; human TRBV6 and human TRBV27, respectively; human TRBV6 and human TRBV19, respectively; human TRBV6 and human TRBV20, respectively; human TRBV6 and human TRBV28, respectively; human TRBV10 and human TRBV5, respectively; human TRBV10 and human TRBV10, respectively; human TRBV10 and human TRBV6, respectively; human TRBV10 and human TRBV7, respectively; human TRBV10 and human TRBV15, respectively; human TRBV10 and human TRBV27, respectively; human TRBV10 and human TRBV19, respectively; human TRBV10 and human TRBV20, respectively; human TRBV10 and human TRBV28, respectively; human TRBV7 and human TRBV5, respectively; human TRBV7 and human TRBV6, respectively; human TRBV7 and human TRBV10, respectively; human TRBV7 and human TRBV7, respectively; human TRBV7 and human TRBV19, respectively; human TRBV7 and human TRBV20, respectively; human TRBV7and human TRBV28, respectively; human TRBV19 and human TRBV5, respectively; human TRBV19 and human TRBV6, respectively; human TRBV19 and human TRBV10, respectively; human TRBV19 and human TRBV7, respectively; human TRBV19 and human TRBV19, respectively; human TRBV19 and human TRBV20, respectively; human TRBV19 and human TRBV28, respectively; human TRBV20 and human TRBV5, respectively; human TRBV20 and human TRBV6, respectively; human TRBV20 and human TRBV1O, respectively; human TRBV20 and human TRBV7, respectively; human TRBV20 and human TRBV19, respectively; human TRBV20 and human TRBV20, respectively; human TRBV20 and human TRBV28, respectively; human TRBV28 and human TRBV5, respectively; human TRBV28 and human TRBV6, respectively; human TRBV28 and human TRBV1O, respectively; human TRBV28 and human TRBV7, respectively; human TRBV28 and human TRBV19, respectively; human TRBV28 and human TRBV20, respectively; or human TRBV28 and human TRBV28, respectively.

[0075] In some embodiments, the first target molecule is human TRBV5-1, human TRBV6-5, human TRBV10-1, human TRBV10-2, human TRBV10-3, human TRBV7-2, human TRBV7-3, human TRBV19, human TRBV20-1, or human TRBV28, and the second target molecule is human TRBV5- 1, human TRBV6-5, human TRBV10-1, human TRBV10-2, human TRBV10-3, human TRBV7-2, human TRBV7-3, human TRBV15, human TRBV27, human TRBV19, human TRBV20-1, or human TRBV28, wherein the first target molecule and the second target molecule are different.

[0076] In some embodiments, the first target molecule and the second target molecule are: human TRBV5-1 and human TRBV6-5, respectively; human TRBV5-1 and human TRBV10-1, respectively; human TRBV5-1 and human TRBV10-2, respectively; human TRBV5-1 and human TRBV10-3, respectively; human TRBV5-1 and human TRBV7-2, respectively; human TRBV5-1 and human TRBV7-3, respectively; human TRBV5-1 and human TRBV19, respectively; human TRBV5- 1 and human TRBV20-1, respectively; human TRBV5-1 and human TRBV28, respectively; human TRBV6-5 and human TRBV5-1, respectively; human TRBV6-5 and human TRBV7-2, respectively; human TRBV6-5 and human TRBV7-3, respectively; human TRBV6-5 and human TRBV15, respectively; human TRBV6-5 and human TRBV27, respectively; human TRBV6-5 and human TRBV19, respectively; human TRBV6-5 and human TRBV20-1, respectively; human TRBV6-5 and human TRBV28, respectively; human TRBV10-1 and human TRBV5-1, respectively; human TRBV10-1 and human TRBV7-2, respectively; human TRBV10-1 and human TRBV7-3, respectively; human TRBV10-1 and human TRBV15, respectively; human TRBV10-1 and human TRBV27, respectively; human TRBV10-1 and human TRBV19, respectively; human TRBV10-1 and human TRBV20-1, respectively; human TRBV10-1 and human TRBV28, respectively; human TRBV10-2 and human TRBV5-1, respectively; human TRBV10-2 and human TRBV7-2, respectively; human TRBV10-2 and human TRBV7-3, respectively; human TRBV10-2 and human TRBV15, respectively; human TRBV10-2 and human TRBV27, respectively; human TRBV10-2 and human TRBV19, respectively; human TRBV10-2 and human TRBV20-1, respectively; human TRBV10-2 and human TRBV28, respectively; human TRBV10-3 and human TRBV5-1, respectively; human TRBV10-3 and human TRBV7-2, respectively; human TRBV10-3 and human TRBV7-3,respectively; human TRBV10-3 and human TRBV15, respectively; human TRBV10-3 and human TRBV27, respectively; human TRBV10-3 and human TRBV19, respectively; human TRBV10-3 and human TRBV20-1, respectively; human TRBV10-3 and human TRBV28, respectively; human TRBV7-2 and human TRBV5-1, respectively; human TRBV7-2 and human TRBV6-5, respectively; human TRBV7-2 and human TRBV10-1, respectively; human TRBV7-2 and human TRBV10-2, respectively; human TRBV7-2 and human TRBV10-3, respectively; human TRBV7-2 and human TRBV7-3, respectively; human TRBV7-2 and human TRBV19, respectively; human TRBV7-2 and human TRBV20-1, respectively; human TRBV7-2 and human TRBV28, respectively; human TRBV7-3 and human TRBV5-1, respectively; human TRBV7-3 and human TRBV6-5, respectively; human TRBV7-3 and human TRBV10-1, respectively; human TRBV7-3 and human TRBV10-2, respectively; human TRBV7-3 and human TRBV10-3, respectively; human TRBV7-3 and human TRBV7-2, respectively; human TRBV7-3 and human TRBV19, respectively; human TRBV7-3 and human TRBV20-1, respectively; human TRBV7-3 and human TRBV28, respectively; human TRBV19 and human TRBV5-1, respectively; human TRBV19 and human TRBV6-5, respectively; human TRBV19 and human TRBV10-1, respectively; human TRBV19 and human TRBV10-2, respectively; human TRBV19 and human TRBV10-3, respectively; human TRBV19 and human TRBV7-2, respectively; human TRBV19 and human TRBV7-3, respectively; human TRBV19 and human TRBV20-1, respectively; human TRBV19 and human TRBV28, respectively; human TRBV20-1 and human TRBV5-1, respectively; human TRBV20-1 and human TRBV6-5, respectively; human TRBV20-1 and human TRBV10-1, respectively; human TRBV20-1 and human TRBV10-2, respectively; human TRBV20-1 and human TRBV10-3, respectively; human TRBV20-1 and human TRBV7-2, respectively; human TRBV20-1 and human TRBV7-3, respectively; human TRBV20-1 and human TRBV19, respectively; human TRBV20-1 and human TRBV28, respectively; human TRBV28 and human TRBV5-1, respectively; human TRBV28 and human TRBV6-5, respectively; human TRBV28 and human TRBV10-1, respectively; human TRBV28 and human TRBV10-2, respectively; human TRBV28 and human TRBV10-3, respectively; human TRBV28 and human TRBV7-2, respectively; human TRBV28 and human TRBV7-3, respectively; human TRBV28 and human TRBV19, respectively; or human TRBV28 and human TRBV20-1, respectively.

[0077] In some embodiments, the first target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30, and the second target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30, wherein the first target molecule and the second target molecule are different.

[0078] In some embodiments, the first target molecule and the second target molecule are: human TRAV12 and human TRAV12, respectively; human TRAV12 and human TRAV13, respectively; human TRAV12 and human TRAV19, respectively; human TRAV12 and human TRAV21, respectively; human TRAV12 and human TRAV30, respectively; human TRAV13 and human TRAV12, respectively;human TRAV13 and human TRAV13, respectively; human TRAV13 and human TRAV19, respectively; human TRAV13 and human TRAV21, respectively; human TRAV13 and human TRAV30, respectively; human TRAV19 and human TRAV12, respectively; human TRAV19 and human TRAV13, respectively; human TRAV19 and human TRAV19, respectively; human TRAV19 and human TRAV21, respectively; human TRAV19 and human TRAV30, respectively; human TRAV21 and human TRAV12, respectively; human TRAV21 and human TRAV13, respectively; human TRAV21 and human TRAV19, respectively; human TRAV21 and human TRAV21, respectively; human TRAV21 and human TRAV30, respectively; human TRAV30 and human TRAV12, respectively; human TRAV30 and human TRAV13, respectively; human TRAV30 and human TRAV19, respectively; human TRAV30 and human TRAV21, respectively; or human TRAV30 and human TRAV30, respectively.

[0079] In some embodiments, the first target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30, and the second target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30, wherein the first target molecule and the second target molecule are different.

[0080] In some embodiments, the first target molecule and the second target molecule are: human TRAV12-2 and human TRAV13-1, respectively; human TRAV12-2 and human TRAV19, respectively; human TRAV12-2 and human TRAV21, respectively; human TRAV12-2 and human TRAV30, respectively; human TRAV13-1 and human TRAV12-2, respectively; human TRAV13-1 and human TRAV19, respectively; human TRAV13-1 and human TRAV21, respectively; human TRAV13-1 and human TRAV30, respectively; human TRAV19 and human TRAV12-2, respectively; human TRAV19 and human TRAV13-1, respectively; human TRAV19 and human TRAV21, respectively; human TRAV19 and human TRAV30, respectively; human TRAV21 and human TRAV12-2, respectively; human TRAV21 and human TRAV13-1, respectively; human TRAV21 and human TRAV19, respectively;human TRAV21 and human TRAV30, respectively; human TRAV30 and human TRAV12-2, respectively; human TRAV30 and human TRAV13-1, respectively; human TRAV30 and human TRAV19, respectively; or human TRAV30 and human TRAV21, respectively.

[0081] In some embodiments, the first target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV19, human TRBV20, or human TRBV28, and the second target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30.

[0082] In some embodiments, the first target molecule and the second target molecule are: human TRBV5 and human TRAV12, respectively; human TRBV5 and human TRAV13, respectively; human TRBV5 and human TRAV19, respectively; human TRBV5 and human TRAV21, respectively; human TRBV5 and human TRAV30, respectively; human TRBV6 and human TRAV12, respectively; human TRBV6 and human TRAV13, respectively; human TRBV6 and human TRAV19, respectively; human TRBV6 and human TRAV21, respectively; human TRBV6 and human TRAV30, respectively; human TRBV10 and human TRAV12, respectively; human TRBV10 and human TRAV13, respectively; human TRBV10 and human TRAV19, respectively; human TRBV10 and human TRAV21, respectively; human TRBV10 and human TRAV30, respectively; human TRBV7 and human TRAV12, respectively; human TRBV7 and human TRAV13, respectively; human TRBV7 and human TRAV19, respectively; human TRBV7 and human TRAV21, respectively; human TRBV7 and human TRAV30, respectively; human TRBV19 and human TRAV12, respectively; human TRBV19 and human TRAV13, respectively; human TRBV19 and human TRAV19, respectively; human TRBV19 and human TRAV21, respectively; human TRBV19 and human TRAV30, respectively; human TRBV20 and human TRAV12, respectively; human TRBV20 and human TRAV13, respectively; human TRBV20 and human TRAV19, respectively; human TRBV20 and human TRAV21, respectively; human TRBV20 and human TRAV30, respectively; human TRBV28 and human TRAV12, respectively; human TRBV28 and human TRAV13, respectively; human TRBV28 and human TRAV19, respectively; human TRBV28 and human TRAV21, respectively; or human TRBV28 and human TRAV30, respectively.

[0083] In some embodiments, the first target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV19, human TRBV20, or human TRBV28, and the second target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30.

[0084] In some embodiments, the first target molecule and the second target molecule are: human TRBV5 and human TRAV12-2, respectively; human TRBV5 and human TRAV13-1, respectively; human TRBV5 and human TRAV19, respectively; human TRBV5 and human TRAV21, respectively; human TRBV5 and human TRAV30, respectively; human TRBV6 and human TRAV12-2, respectively; human TRBV6 and human TRAV13-1, respectively; human TRBV6 and human TRAV19, respectively; human TRBV6 and human TRAV21, respectively; human TRBV6 andhuman TRAV30, respectively; human TRBV10 and human TRAV12-2, respectively; human TRBV1O and human TRAV13-1, respectively; human TRBV1O and human TRAV19, respectively; human TRBV1O and human TRAV21, respectively; human TRBV1O and human TRAV3O, respectively; human TRBV7 and human TRAV12-2, respectively; human TRBV7 and human TRAV13-1, respectively; human TRBV7 and human TRAV19, respectively; human TRBV7 and human TRAV21, respectively; human TRBV7 and human TRAV3O, respectively; human TRBV19 and human TRAV12-2, respectively; human TRBV19 and human TRAV13-1, respectively; human TRBV19 and human TRAV19, respectively; human TRBV19 and human TRAV21, respectively; human TRBV19 and human TRAV3O, respectively; human TRBV20 and human TRAV12-2, respectively; human TRBV20 and human TRAV13-1, respectively; human TRBV20 and human TRAV19, respectively; human TRBV20 and human TRAV21, respectively; human TRBV20 and human TRAV3O, respectively; human TRBV28 and human TRAV12-2, respectively; human TRBV28 and human TRAV13-1, respectively; human TRBV28 and human TRAV19, respectively; human TRBV28 and human TRAV21, respectively; or human TRBV28 and human TRAV30, respectively.

[0085] In some embodiments, the first target molecule is human TRBV5-1, human TRBV6-5, human TRBV10-1, human TRBV10-2, human TRBV10-3, human TRBV7-2, human TRBV7-3, human TRBV19, human TRBV20-1, or human TRBV28, and the second target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30.

[0086] In some embodiments, the first target molecule and the second target molecule are: human TRBV5-1 and human TRAV12, respectively; human TRBV5-1 and human TRAV13, respectively; human TRBV5-1 and human TRAV19, respectively; human TRBV5-1 and human TRAV21, respectively; human TRBV5-1 and human TRAV30, respectively; human TRBV6-5 and human TRAV12, respectively; human TRBV6-5 and human TRAV13, respectively; human TRBV6-5 and human TRAV19, respectively; human TRBV6-5 and human TRAV21, respectively; human TRBV6-5 and human TRAV30, respectively; human TRBV10-1 and human TRAV12, respectively; human TRBV10-1 and human TRAV13, respectively; human TRBV10-1 and human TRAV19, respectively; human TRBV10-1 and human TRAV21, respectively; human TRBV10-1 and human TRAV30, respectively; human TRBV10-2 and human TRAV12, respectively; human TRBV10-2 and human TRAV13, respectively; human TRBV10-2 and human TRAV19, respectively; human TRBV10-2 and human TRAV21, respectively; human TRBV10-2 and human TRAV30, respectively; human TRBV10-3 and human TRAV12, respectively; human TRBV10-3 and human TRAV13, respectively; human TRBV10-3 and human TRAV19, respectively; human TRBV10-3 and human TRAV21, respectively; human TRBV10-3 and human TRAV30, respectively; human TRBV7-2 and human TRAV12, respectively; human TRBV7-2 and human TRAV13, respectively; human TRBV7-2 and human TRAV19, respectively; human TRBV7-2 and human TRAV21, respectively; human TRBV7-2 and human TRAV30, respectively; human TRBV7-3 and human TRAV12, respectively; human TRBV7-3 and human TRAV13, respectively; human TRBV7-3 and human TRAV19, respectively; human TRBV7-3 and human TRAV21, respectively; human TRBV7-3 and humanTRAV30, respectively; human TRBV19 and human TRAV12, respectively; human TRBV19 and human TRAV13, respectively; human TRBV19 and human TRAV19, respectively; human TRBV19 and human TRAV21, respectively; human TRBV19 and human TRAV30, respectively; human TRBV20-1 and human TRAV12, respectively; human TRBV20-1 and human TRAV13, respectively; human TRBV20-1 and human TRAV19, respectively; human TRBV20-1 and human TRAV21, respectively; human TRBV20-1 and human TRAV30, respectively; human TRBV28 and human TRAV12, respectively; human TRBV28 and human TRAV13, respectively; human TRBV28 and human TRAV19, respectively; human TRBV28 and human TRAV21, respectively; or human TRBV28 and human TRAV30, respectively.

[0087] In some embodiments, the first target molecule is human TRBV5-1, human TRBV6-5, human TRBV10-1, human TRBV10-2, human TRBV10-3, human TRBV7-2, human TRBV7-3, human TRBV19, human TRBV20-1, or human TRBV28, and the second target molecule is human TRAV12- 2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30.

[0088] In some embodiments, the first target molecule and the second target molecule are: human TRBV5-1 and human TRAV12-2, respectively; human TRBV5-1 and human TRAV13-1, respectively; human TRBV5-1 and human TRAV19, respectively; human TRBV5-1 and human TRAV21, respectively; human TRBV5-1 and human TRAV30, respectively; human TRBV6-5 and human TRAV12-2, respectively; human TRBV6-5 and human TRAV13-1, respectively; human TRBV6-5 and human TRAV19, respectively; human TRBV6-5 and human TRAV21, respectively; human TRBV6-5 and human TRAV30, respectively; human TRBV10-1 and human TRAV12-2, respectively; human TRBV10-1 and human TRAV13-1, respectively; human TRBV10-1 and human TRAV19, respectively; human TRBV10-1 and human TRAV21, respectively; human TRBV10-1 and human TRAV30, respectively; human TRBV10-2 and human TRAV12-2, respectively; human TRBV10-2 and human TRAV13-1, respectively; human TRBV10-2 and human TRAV19, respectively; human TRBV10-2 and human TRAV21, respectively; human TRBV10-2 and human TRAV30, respectively; human TRBV10-3 and human TRAV12-2, respectively; human TRBV10-3 and human TRAV13-1, respectively; human TRBV10-3 and human TRAV19, respectively; human TRBV10-3 and human TRAV21, respectively; human TRBV10-3 and human TRAV30, respectively; human TRBV7-2 and human TRAV12-2, respectively; human TRBV7-2 and human TRAV13-1, respectively; human TRBV7-2 and human TRAV19, respectively; human TRBV7-2 and human TRAV21, respectively; human TRBV7-2 and human TRAV30, respectively; human TRBV7-3 and human TRAV12-2, respectively; human TRBV7-3 and human TRAV13-1, respectively; human TRBV7-3 and human TRAV19, respectively; human TRBV7-3 and human TRAV21, respectively; human TRBV7-3 and human TRAV30, respectively; human TRBV19 and human TRAV12-2, respectively; human TRBV19 and human TRAV13-1, respectively; human TRBV19 and human TRAV19, respectively; human TRBV19 and human TRAV21, respectively; human TRBV19 and human TRAV30, respectively; human TRBV20-1 and human TRAV12-2, respectively; human TRBV20-1 and human TRAV13-1, respectively; human TRBV20-1 and human TRAV19, respectively; human TRBV20-1 and human TRAV21, respectively; human TRBV20-1 and humanTRAV30, respectively; human TRBV28 and human TRAV12-2, respectively; human TRBV28 and human TRAV13-1, respectively; human TRBV28 and human TRAV19, respectively; human TRBV28 and human TRAV21, respectively; or human TRBV28 and human TRAV30, respectively.

[0089] In some embodiments, the first target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30, and the second target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV19, human TRBV20, or human TRBV28.

[0090] In some embodiments, the first target molecule and the second target molecule are: human TRAV12 and human TRBV5, respectively; human TRAV12 and human TRBV6, respectively; human TRAV12 and human TRBV10, respectively; human TRAV12 and human TRBV7, respectively; human TRAV12 and human TRBV19, respectively; human TRAV12 and human TRBV20, respectively; human TRAV12 and human TRBV28, respectively; human TRAV13 and human TRBV5, respectively; human TRAV13 and human TRBV6, respectively; human TRAV13 and human TRBV10, respectively; human TRAV13 and human TRBV7, respectively; human TRAV13 and human TRBV19, respectively; human TRAV13 and human TRBV20, respectively; human TRAV13 and human TRBV28, respectively; human TRAV19 and human TRBV5, respectively; human TRAV19 and human TRBV6, respectively; human TRAV19 and human TRBV10, respectively; human TRAV19 and human TRBV7, respectively; human TRAV19 and human TRBV19, respectively; human TRAV19 and human TRBV20, respectively; human TRAV19 and human TRBV28, respectively; human TRAV21 and human TRBV5, respectively; human TRAV21 and human TRBV6, respectively; human TRAV21 and human TRBV10, respectively; human TRAV21 and human TRBV7, respectively; human TRAV21 and human TRBV19, respectively; human TRAV21 and human TRBV20, respectively; human TRAV21 and human TRBV28, respectively; human TRAV30 and human TRBV5, respectively; human TRAV30 and human TRBV6, respectively; human TRAV30 and human TRBV10, respectively; human TRAV30 and human TRBV7, respectively; human TRAV30 and human TRBV19, respectively; human TRAV30 and human TRBV20, respectively; or human TRAV30 and human TRBV28, respectively.

[0091] In some embodiments, the first target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30, and the second target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV19, human TRBV20, or human TRBV28.

[0092] In some embodiments, the first target molecule and the second target molecule are: human TRAV12-2 and human TRBV5, respectively; human TRAV12-2 and human TRBV6, respectively; human TRAV12-2 and human TRBV10, respectively; human TRAV12-2 and human TRBV7, respectively; human TRAV12-2 and human TRBV19, respectively; human TRAV12-2 and human TRBV20, respectively; human TRAV12-2 and human TRBV28, respectively; human TRAV13-1 and human TRBV5, respectively; human TRAV13-1 and human TRBV6, respectively; human TRAV13-1 and human TRBV10, respectively; human TRAV13-1 and human TRBV7, respectively; human TRAV13-1 and human TRBV19, respectively; human TRAV13-1 and humanTRBV20, respectively; human TRAV13-1 and human TRBV28, respectively; human TRAV19 and human TRBV5, respectively; human TRAV19 and human TRBV6, respectively; human TRAV19 and human TRBV10, respectively; human TRAV19 and human TRBV7, respectively; human TRAV19 and human TRBV19, respectively; human TRAV19 and human TRBV20, respectively; human TRAV19 and human TRBV28, respectively; human TRAV21 and human TRBV5, respectively; human TRAV21 and human TRBV6, respectively; human TRAV21 and human TRBV1O, respectively; human TRAV21 and human TRBV7, respectively; human TRAV21 and human TRBV19, respectively; human TRAV21 and human TRBV20, respectively; human TRAV21 and human TRBV28, respectively; human TRAV3O and human TRBV5, respectively; human TRAV3O and human TRBV6, respectively; human TRAV3O and human TRBV1O, respectively; human TRAV3O and human TRBV7, respectively; human TRAV3O and human TRBV19, respectively; human TRAV3O and human TRBV20, respectively; or human TRAV30 and human TRBV28, respectively.

[0093] In some embodiments, the first target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30, and the second target molecule is human TRBV5-1, human TRBV6-5, human TRBV10-1, human TRBV10-2, human TRBV10-3, human TRBV7-2, human TRBV7-3, human TRBV19, human TRBV20-1, or human TRBV28.

[0094] In some embodiments, the first target molecule and the second target molecule are: human TRAV12 and human TRBV5-1, respectively; human TRAV12 and human TRBV6-5, respectively; human TRAV12 and human TRBV10-1, respectively; human TRAV12 and human TRBV10-2, respectively; human TRAV12 and human TRBV10-3, respectively; human TRAV12 and human TRBV7-2, respectively; human TRAV12 and human TRBV7-3, respectively; human TRAV12 and human TRBV19, respectively; human TRAV12 and human TRBV20-1, respectively; human TRAV12 and human TRBV28, respectively; human TRAV13 and human TRBV5-1, respectively; human TRAV13 and human TRBV6-5, respectively; human TRAV13 and human TRBV10-1, respectively; human TRAV13 and human TRBV10-2, respectively; human TRAV13 and human TRBV10-3, respectively; human TRAV13 and human TRBV7-2, respectively; human TRAV13 and human TRBV7-3, respectively; human TRAV13 and human TRBV19, respectively; human TRAV13 and human TRBV20-1, respectively; human TRAV13 and human TRBV28, respectively; human TRAV19 and human TRBV5-1, respectively; human TRAV19 and human TRBV6-5, respectively; human TRAV19 and human TRBV10-1, respectively; human TRAV19 and human TRBV10-2, respectively; human TRAV19 and human TRBV10-3, respectively; human TRAV19 and human TRBV7-2, respectively; human TRAV19 and human TRBV7-3, respectively; human TRAV19 and human TRBV19, respectively; human TRAV19 and human TRBV20-1, respectively; human TRAV19 and human TRBV28, respectively; human TRAV21 and human TRBV5-1, respectively; human TRAV21 and human TRBV6-5, respectively; human TRAV21 and human TRBV10-1, respectively; human TRAV21 and human TRBV10-2, respectively; human TRAV21 and human TRBV10-3, respectively; human TRAV21 and human TRBV7-2, respectively; human TRAV21 and human TRBV7-3, respectively; human TRAV21 and human TRBV19, respectively; human TRAV21and human TRBV20-1, respectively; human TRAV21 and human TRBV28, respectively; human TRAV30 and human TRBV5-1, respectively; human TRAV30 and human TRBV6-5, respectively; human TRAV30 and human TRBV10-1, respectively; human TRAV30 and human TRBV10-2, respectively; human TRAV30 and human TRBV10-3, respectively; human TRAV30 and human TRBV7-2, respectively; human TRAV30 and human TRBV7-3, respectively; human TRAV30 and human TRBV19, respectively; human TRAV30 and human TRBV20-1, respectively; or human TRAV30 and human TRBV28, respectively.

[0095] In some embodiments, the first target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30, and the second target molecule is human TRBV5-1, human TRBV6-5, human TRBV 10-1, human TRBV 10-2, human TRBV 10-3, human TRBV7-2, human TRBV7-3, human TRBV19, human TRBV20-1, or human TRBV28.

[0096] In some embodiments, the first target molecule and the second target molecule are: human TRAV12-2 and human TRBV5-1, respectively; human TRAV12-2 and human TRBV6-5, respectively; human TRAV12-2 and human TRBV10-1, respectively; human TRAV12-2 and human TRBV 10-2, respectively; human TRAV12-2 and human TRBV 10-3, respectively; human TRAV12-2 and human TRBV7-2, respectively; human TRAV12-2 and human TRBV7-3, respectively; human TRAV12-2 and human TRBV19, respectively; human TRAV12-2 and human TRBV20-1, respectively; human TRAV12-2 and human TRBV28, respectively; human TRAV13-1 and human TRBV5-1, respectively; human TRAV13-1 and human TRBV6-5, respectively; human TRAV13-1 and human TRBV10-1, respectively; human TRAV13-1 and human TRBV10-2, respectively; human TRAV13-1 and human TRBV10-3, respectively; human TRAV13-1 and human TRBV7-2, respectively; human TRAV13-1 and human TRBV7-3, respectively; human TRAV13-1 and human TRBV19, respectively; human TRAV13-1 and human TRBV20-1, respectively; human TRAV13-1 and human TRBV28, respectively; human TRAV19 and human TRBV5-1, respectively; human TRAV19 and human TRBV6-5, respectively; human TRAV19 and human TRBV 10-1, respectively; human TRAV19 and human TRBV10-2, respectively; human TRAV19 and human TRBV10-3, respectively; human TRAV19 and human TRBV7-2, respectively; human TRAV19 and human TRBV7-3, respectively; human TRAV19 and human TRBV19, respectively; human TRAV19 and human TRBV20-1, respectively; human TRAV19 and human TRBV28, respectively; human TRAV21 and human TRBV5-1, respectively; human TRAV21 and human TRBV6-5, respectively; human TRAV21 and human TRBV 10-1, respectively; human TRAV21 and human TRBV 10-2, respectively; human TRAV21 and human TRBV10-3, respectively; human TRAV21 and human TRBV7-2, respectively; human TRAV21 and human TRBV7-3, respectively; human TRAV21 and human TRBV 19, respectively; human TRAV21 and human TRBV20-1, respectively; human TRAV21 and human TRBV28, respectively; human TRAV30 and human TRBV5-1, respectively; human TRAV30 and human TRBV6-5, respectively; human TRAV30 and human TRBV10-1, respectively; human TRAV30 and human TRBV10-2, respectively; human TRAV30 and human TRBV10-3, respectively; human TRAV30 and human TRBV7-2, respectively; human TRAV30 andhuman TRBV7-3, respectively; human TRAV30 and human TRBV19, respectively; human TRAV30 and human TRBV20-1, respectively; or human TRAV30 and human TRBV28, respectively.

[0097] In some embodiments, the first target molecule is human TCRJ3V27, and the second target molecule is human TCRJ3V6.

[0098] In some embodiments, the first binder comprises a full antibody or antigen-binding fragment thereof, a bivalent antibody, bispecific antibody, or a biparatopic antibody.

[0099] In some embodiments, the second binder comprises a full antibody or antigen-binding fragment thereof, a bivalent antibody, bispecific antibody, or a biparatopic antibody.

[0100] In some embodiments, the antigen-binding fragment is a Fab, F(ab')2, Fv, a single chain Fv (scFv), a single domain antibody, a diabody, a single domain antibody, or a camelid antibody.

[0101] In some embodiments, the first binder comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 3 (HC CDR3) comprising the sequence of SEQ ID NO: 3343, SEQ ID NO: 3323, SEQ ID NO: 3353, SEQ ID NO: 1187, SEQ ID NO: 3373, SEQ ID NO: 3383, SEQ ID NO: 3393, SEQ ID NO: 3403, or SEQ ID NO: 3413.

[0102] In some embodiments, the first binder comprises a VH comprising a heavy chain complementarity determining region 1 (HC CDR1) comprising the sequence of SEQ ID NO: 3341, SEQ ID NO: 3321, SEQ ID NO: 3351, SEQ ID NO: 1190, SEQ ID NO: 3371, SEQ ID NO: 3381, SEQ ID NO: 3391, SEQ ID NO: 3401, SEQ ID NO: 3411, SEQ ID NO: 3421, or SEQ ID NO: 3702.

[0103] In some embodiments, the first binder comprises a VH comprising a heavy chain complementarity determining region 2 (HC CDR2) comprising the sequence of SEQ ID NO: 3342, SEQ ID NO: 3322, SEQ ID NO: 3352, SEQ ID NO: 1186, SEQ ID NO: 3372, SEQ ID NO: 3382, SEQ ID NO: 3392, SEQ ID NO: 3402, or SEQ ID NO: 3412.

[0104] In some embodiments, the first binder comprises a VH comprising:(i) a HC CDR1 comprising the sequence of SEQ ID NO: 3341, a HC CDR2 comprising the sequence of SEQ ID NO: 3342, and a HC CDR3 comprising the sequence of SEQ ID NO: 3343;(ii) a HC CDR1 comprising the sequence of SEQ ID NO: 3321, a HC CDR2 comprising the sequence of SEQ ID NO: 3322, and a HC CDR3 comprising the sequence of SEQ ID NO: 3323;(iii) a HC CDR1 comprising the sequence of SEQ ID NO: 3351, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, and a HC CDR3 comprising the sequence of SEQ ID NO: 3353;(iv) a HC CDR1 comprising the sequence of SEQ ID NO: 1190, a HC CDR2 comprising the sequence of SEQ ID NO: 1186, and a HC CDR3 comprising the sequence of SEQ ID NO: 1187;(v) a HC CDR1 comprising the sequence of SEQ ID NO: 3371, a HC CDR2 comprising the sequence of SEQ ID NO: 3372, and a HC CDR3 comprising the sequence of SEQ ID NO: 3373;(vi) a HC CDR1 comprising the sequence of SEQ ID NO: 3381, a HC CDR2 comprising the sequence of SEQ ID NO: 3382, and a HC CDR3 comprising the sequence of SEQ ID NO: 3383;(vii) a HC CDR1 comprising the sequence of SEQ ID NO: 3391, a HC CDR2 comprising the sequence of SEQ ID NO: 3392, and a HC CDR3 comprising the sequence of SEQ ID NO: 3393;(viii) a HC CDR1 comprising the sequence of SEQ ID NO: 3401, a HC CDR2 comprising the sequence of SEQ ID NO: 3402, and a HC CDR3 comprising the sequence of SEQ ID NO: 3403;(ix) a HC CDR1 comprising the sequence of SEQ ID NO: 3351, SEQ ID NO: 3421, or SEQ ID NO: 3702, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, and a HC CDR3 comprising the sequence of SEQ ID NO: 3353; or(x) a HC CDR1 comprising the sequence of SEQ ID NO: 3411, a HC CDR2 comprising the sequence of SEQ ID NO: 3412, and a HC CDR3 comprising the sequence of SEQ ID NO: 3413.

[0105] In some embodiments, the first binder comprises a light chain variable region (VL) comprising a light chain complementarity determining region 3 (LC CDR3) comprising the sequence of SEQ ID NO: 3346, SEQ ID NO: 3326, SEQ ID NO: 3356, SEQ ID NO: 1193, SEQ ID NO: 3376, SEQ ID NO: 3386, SEQ ID NO: 3396, SEQ ID NO: 3406, or SEQ ID NO: 3416.

[0106] In some embodiments, the first binder comprises a VL comprising a light chain complementarity determining region 1 (LC CDR1) comprising the sequence of SEQ ID NO: 3344, SEQ ID NO: 3324, SEQ ID NO: 3354, SEQ ID NO: 1191, SEQ ID NO: 3374, SEQ ID NO: 3384, SEQ ID NO: 3394, SEQ ID NO: 3404, or SEQ ID NO: 3414.

[0107] In some embodiments, the first binder comprises a VL comprising a light chain complementarity determining region 2 (LC CDR2) comprising the sequence of SEQ ID NO: 3345, SEQ ID NO: 3325, SEQ ID NO: 3355, SEQ ID NO: 1192, SEQ ID NO: 3375, SEQ ID NO: 3395, SEQ ID NO: 3405, SEQ ID NO: 3415, or SEQ ID NO: 3443.

[0108] In some embodiments, the first binder comprises a VL comprising:(i) a LC CDR1 comprising the sequence of SEQ ID NO: 3344, a LC CDR2 comprising the sequence of SEQ ID NO: 3345, and a LC CDR3 comprising the sequence of SEQ ID NO: 3346;(ii) a LC CDR1 comprising the sequence of SEQ ID NO: 3324, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3326;(iii) a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3355, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356;(iv) a LC CDR1 comprising the sequence of SEQ ID NO: 1191, a LC CDR2 comprising the sequence of SEQ ID NO: 1192, and a LC CDR3 comprising the sequence of SEQ ID NO: 1193;(v) a LC CDR1 comprising the sequence of SEQ ID NO: 3374, a LC CDR2 comprising the sequence of SEQ ID NO: 3375, and a LC CDR3 comprising the sequence of SEQ ID NO: 3376;(vi) a LC CDR1 comprising the sequence of SEQ ID NO: 3384, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3386;(vii) a LC CDR1 comprising the sequence of SEQ ID NO: 3394, a LC CDR2 comprising the sequence of SEQ ID NO: 3395, and a LC CDR3 comprising the sequence of SEQ ID NO: 3396;(viii) a LC CDR1 comprising the sequence of SEQ ID NO: 3404, a LC CDR2 comprising the sequence of SEQ ID NO: 3405, and a LC CDR3 comprising the sequence of SEQ ID NO: 3406;(ix) a LC CDR1 comprising the sequence of SEQ ID NO: 3414, a LC CDR2 comprising the sequence of SEQ ID NO: 3415, and a LC CDR3 comprising the sequence of SEQ ID NO: 3416; or(x) a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3443, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356.

[0109] In some embodiments, the first binder comprises:(i) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3341, a HC CDR2 comprising the sequence of SEQ ID NO: 3342, a HC CDR3 comprising the sequence of SEQ ID NO: 3343, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3344, a LC CDR2 comprising the sequence of SEQ ID NO: 3345, and a LC CDR3 comprising the sequence of SEQ ID NO: 3346;(ii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3321, a HC CDR2 comprising the sequence of SEQ ID NO: 3322, a HC CDR3 comprising the sequence of SEQ ID NO: 3323, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3324, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3326;(iii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3351, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, a HC CDR3 comprising the sequence of SEQ ID NO: 3353, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3355, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356;(iv) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 1190, a HC CDR2 comprising the sequence of SEQ ID NO: 1186, a HC CDR3 comprising the sequence of SEQ ID NO: 1187, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 1191, a LC CDR2 comprising the sequence of SEQ ID NO: 1192, and a LC CDR3 comprising the sequence of SEQ ID NO: 1193;(v) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3371, a HC CDR2 comprising the sequence of SEQ ID NO: 3372, a HC CDR3 comprising the sequence of SEQ ID NO: 3373, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3374, a LC CDR2 comprising the sequence of SEQ ID NO: 3375, and a LC CDR3 comprising the sequence of SEQ ID NO: 3376;(vi) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3381, a HC CDR2 comprising the sequence of SEQ ID NO: 3382, a HC CDR3 comprising the sequence of SEQ ID NO: 3383, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3384, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3386;(vii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3391, a HC CDR2 comprising the sequence of SEQ ID NO: 3392, a HC CDR3 comprising the sequence of SEQ ID NO: 3393, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3394, a LC CDR2 comprising the sequence of SEQ ID NO: 3395, and a LC CDR3 comprising the sequence of SEQ ID NO: 3396;(viii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3401, a HC CDR2 comprising the sequence of SEQ ID NO: 3402, a HC CDR3 comprising the sequence of SEQ ID NO: 3403, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3404, a LC CDR2comprising the sequence of SEQ ID NO: 3405, and a LC CDR3 comprising the sequence of SEQ ID NO: 3406;(ix) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3411, a HC CDR2 comprising the sequence of SEQ ID NO: 3412, a HC CDR3 comprising the sequence of SEQ ID NO: 3413, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3414, a LC CDR2 comprising the sequence of SEQ ID NO: 3415, and a LC CDR3 comprising the sequence of SEQ ID NO: 3416;(x) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3351, SEQ ID NO: 3421, or SEQ ID NO: 3702, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, a HC CDR3 comprising the sequence of SEQ ID NO: 3353, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3355, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356; or(xi) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3351, SEQ ID NO: 3421, or SEQ ID NO: 3702, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, a HC CDR3 comprising the sequence of SEQ ID NO: 3353, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3443, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356.

[0110] In some embodiments, the first binder comprises a VH comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO: 3445, SEQ ID NO: 3448, SEQ ID NO: 3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO: 3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO: 3465, and SEQ ID NO: 3470.[OHl] In some embodiments, the first binder comprises a VH comprising any one sequence selected from the group consisting of: SEQ ID NO: 3445, SEQ ID NO: 3448, SEQ ID NO: 3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO: 3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO:3465, and SEQ ID NO: 3470.

[0112] In some embodiments, the first binder comprises a VL comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO: 3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO: 3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO: 3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

[0113] In some embodiments, the first binder comprises a VL comprising any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO: 3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO: 3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO:3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

[0114] In some embodiments, the first binder comprises:(i) a VH comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO: 3445, SEQ ID NO: 3448, SEQ ID NO: 3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO: 3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO: 3465, and SEQ ID NO: 3470; and(ii) a VL comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO: 3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO: 3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO: 3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

[0115] In some embodiments, the first binder comprises:(i) a VH comprising any one sequence selected from the group consisting of: SEQ ID NO: 3445, SEQ ID NO: 3448, SEQ ID NO: 3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO: 3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO: 3465, and SEQ ID NO: 3470; and(ii) a VL comprising any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO: 3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO: 3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO: 3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

[0116] In some embodiments, the first binder comprises:(i) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3445, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3446;(ii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3448, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3449;(iii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3450, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3451;(iv) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1346, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1349;(v) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1196, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1195;(vi) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3455, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3456;(vii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3457, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3458;(viii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3463, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3464;(ix) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3465, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3466;(x) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3470, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3471;(xi) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1346, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3475; or(xii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1346, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3476.

[0117] In some embodiments, the first binder comprises:(i) a VH comprising the sequence of SEQ ID NO: 3445, and a VL comprising the sequence of SEQ ID NO: 3446;(ii) a VH comprising the sequence of SEQ ID NO: 3448, and a VL comprising the sequence of SEQ ID NO: 3449;(iii) a VH comprising the sequence of SEQ ID NO: 3450, and a VL comprising the sequence of SEQ ID NO: 3451;(iv) a VH comprising the sequence of SEQ ID NO: 1346, and a VL comprising the sequence of SEQ ID NO: 1349;(v) a VH comprising the sequence of SEQ ID NO: 1196, and a VL comprising the sequence of SEQ ID NO: 1195;(vi) a VH comprising the sequence of SEQ ID NO: 3455, and a VL comprising the sequence of SEQ ID NO: 3456;(vii) a VH comprising the sequence of SEQ ID NO: 3457, and a VL comprising the sequence of SEQ ID NO: 3458;(viii) a VH comprising the sequence of SEQ ID NO: 3463, and a VL comprising the sequence of SEQ ID NO: 3464;(ix) a VH comprising the sequence of SEQ ID NO: 3465, and a VL comprising the sequence of SEQ ID NO: 3466;(x) a VH comprising the sequence of SEQ ID NO: 3470, and a VL comprising the sequence of SEQ ID NO: 3471;(xi) a VH comprising the sequence of SEQ ID NO: 1346, and a VL comprising the sequence of SEQ ID NO: 3475; or(xii) a VH comprising the sequence of SEQ ID NO: 1346, and a VL comprising the sequence of SEQ ID NO: 3476.

[0118] In some embodiments, the second binder comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 3 (HC CDR3) comprising thesequence of SEQ ID NO: 3343, SEQ ID NO: 3323, SEQ ID NO: 3353, SEQ ID NO: 1187, SEQ ID NO: 3373, SEQ ID NO: 3383, SEQ ID NO: 3393, SEQ ID NO: 3403, or SEQ ID NO: 3413.

[0119] In some embodiments, the second binder comprises a VH comprising a heavy chain complementarity determining region 1 (HC CDR1) comprising the sequence of SEQ ID NO: 3341, SEQ ID NO: 3321, SEQ ID NO: 3351, SEQ ID NO: 1190, SEQ ID NO: 3371, SEQ ID NO: 3381, SEQ ID NO: 3391, SEQ ID NO: 3401, SEQ ID NO: 3411, SEQ ID NO: 3421, or SEQ ID NO: 3702.

[0120] In some embodiments, the second binder comprises a VH comprising a heavy chain complementarity determining region 2 (HC CDR2) comprising the sequence of SEQ ID NO: 3342, SEQ ID NO: 3322, SEQ ID NO: 3352, SEQ ID NO: 1186, SEQ ID NO: 3372, SEQ ID NO: 3382, SEQ ID NO: 3392, SEQ ID NO: 3402, or SEQ ID NO: 3412.

[0121] In some embodiments, the second binder comprises a VH comprising:(i) a HC CDR1 comprising the sequence of SEQ ID NO: 3341, a HC CDR2 comprising the sequence of SEQ ID NO: 3342, and a HC CDR3 comprising the sequence of SEQ ID NO: 3343;(ii) a HC CDR1 comprising the sequence of SEQ ID NO: 3321, a HC CDR2 comprising the sequence of SEQ ID NO: 3322, and a HC CDR3 comprising the sequence of SEQ ID NO: 3323;(iii) a HC CDR1 comprising the sequence of SEQ ID NO: 3351, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, and a HC CDR3 comprising the sequence of SEQ ID NO: 3353;(vi) a HC CDR1 comprising the sequence of SEQ ID NO: 1190, a HC CDR2 comprising the sequence of SEQ ID NO: 1186, and a HC CDR3 comprising the sequence of SEQ ID NO: 1187;(v) a HC CDR1 comprising the sequence of SEQ ID NO: 3371, a HC CDR2 comprising the sequence of SEQ ID NO: 3372, and a HC CDR3 comprising the sequence of SEQ ID NO: 3373;(vi) a HC CDR1 comprising the sequence of SEQ ID NO: 3381, a HC CDR2 comprising the sequence of SEQ ID NO: 3382, and a HC CDR3 comprising the sequence of SEQ ID NO: 3383;(vii) a HC CDR1 comprising the sequence of SEQ ID NO: 3391, a HC CDR2 comprising the sequence of SEQ ID NO: 3392, and a HC CDR3 comprising the sequence of SEQ ID NO: 3393;(viii) a HC CDR1 comprising the sequence of SEQ ID NO: 3401, a HC CDR2 comprising the sequence of SEQ ID NO: 3402, and a HC CDR3 comprising the sequence of SEQ ID NO: 3403;(ix) a HC CDR1 comprising the sequence of SEQ ID NO: 3351, SEQ ID NO: 3421, or SEQ ID NO: 3702, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, and a HC CDR3 comprising the sequence of SEQ ID NO: 3353; or(x) a HC CDR1 comprising the sequence of SEQ ID NO: 3411, a HC CDR2 comprising the sequence of SEQ ID NO: 3412, and a HC CDR3 comprising the sequence of SEQ ID NO: 3413.

[0122] In some embodiments, the second binder comprises a light chain variable region (VL) comprising a light chain complementarity determining region 3 (LC CDR3) comprising the sequence of SEQ ID NO: 3346, SEQ ID NO: 3326, SEQ ID NO: 3356, SEQ ID NO: 1193, SEQ ID NO: 3376, SEQ ID NO: 3386, SEQ ID NO: 3396, SEQ ID NO: 3406, or SEQ ID NO: 3416.

[0123] In some embodiments, the second binder comprises a VL comprising a light chain complementarity determining region 1 (LC CDR1) comprising the sequence of SEQ ID NO: 3344,SEQ ID NO: 3324, SEQ ID NO: 3354, SEQ ID NO: 1191, SEQ ID NO: 3374, SEQ ID NO: 3384, SEQ ID NO: 3394, SEQ ID NO: 3404, or SEQ ID NO: 3414.

[0124] In some embodiments, the second binder comprises a VL comprising a light chain complementarity determining region 2 (LC CDR2) comprising the sequence of SEQ ID NO: 3345, SEQ ID NO: 3325, SEQ ID NO: 3355, SEQ ID NO: 1192, SEQ ID NO: 3375, SEQ ID NO: 3395, SEQ ID NO: 3405, SEQ ID NO: 3415, or SEQ ID NO: 3443.

[0125] In some embodiments, the second binder comprises a VL comprising:(i) a LC CDR1 comprising the sequence of SEQ ID NO: 3344, a LC CDR2 comprising the sequence of SEQ ID NO: 3345, and a LC CDR3 comprising the sequence of SEQ ID NO: 3346;(ii) a LC CDR1 comprising the sequence of SEQ ID NO: 3324, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3326;(iii) a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3355, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356;(iv) a LC CDR1 comprising the sequence of SEQ ID NO: 1191, a LC CDR2 comprising the sequence of SEQ ID NO: 1192, and a LC CDR3 comprising the sequence of SEQ ID NO: 1193;(v) a LC CDR1 comprising the sequence of SEQ ID NO: 3374, a LC CDR2 comprising the sequence of SEQ ID NO: 3375, and a LC CDR3 comprising the sequence of SEQ ID NO: 3376;(vi) a LC CDR1 comprising the sequence of SEQ ID NO: 3384, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3386;(vii) a LC CDR1 comprising the sequence of SEQ ID NO: 3394, a LC CDR2 comprising the sequence of SEQ ID NO: 3395, and a LC CDR3 comprising the sequence of SEQ ID NO: 3396;(viii) a LC CDR1 comprising the sequence of SEQ ID NO: 3404, a LC CDR2 comprising the sequence of SEQ ID NO: 3405, and a LC CDR3 comprising the sequence of SEQ ID NO: 3406;(ix) a LC CDR1 comprising the sequence of SEQ ID NO: 3414, a LC CDR2 comprising the sequence of SEQ ID NO: 3415, and a LC CDR3 comprising the sequence of SEQ ID NO: 3416; or(x) a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3443, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356.

[0126] In some embodiments, the second binder comprises:(i) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3341, a HC CDR2 comprising the sequence of SEQ ID NO: 3342, a HC CDR3 comprising the sequence of SEQ ID NO: 3343, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3344, a LC CDR2 comprising the sequence of SEQ ID NO: 3345, and a LC CDR3 comprising the sequence of SEQ ID NO: 3346;(ii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3321, a HC CDR2 comprising the sequence of SEQ ID NO: 3322, a HC CDR3 comprising the sequence of SEQ ID NO: 3323, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3324, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3326;(iii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3351, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, a HC CDR3 comprising the sequence of SEQ ID NO: 3353, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3355, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356;(iv) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 1190, a HC CDR2 comprising the sequence of SEQ ID NO: 1186, a HC CDR3 comprising the sequence of SEQ ID NO: 1187, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 1191, a LC CDR2 comprising the sequence of SEQ ID NO: 1192, and a LC CDR3 comprising the sequence of SEQ ID NO: 1193;(v) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3371, a HC CDR2 comprising the sequence of SEQ ID NO: 3372, a HC CDR3 comprising the sequence of SEQ ID NO: 3373, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3374, a LC CDR2 comprising the sequence of SEQ ID NO: 3375, and a LC CDR3 comprising the sequence of SEQ ID NO: 3376;(vi) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3381, a HC CDR2 comprising the sequence of SEQ ID NO: 3382, a HC CDR3 comprising the sequence of SEQ ID NO: 3383, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3384, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3386;(vii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3391, a HC CDR2 comprising the sequence of SEQ ID NO: 3392, a HC CDR3 comprising the sequence of SEQ ID NO: 3393, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3394, a LC CDR2 comprising the sequence of SEQ ID NO: 3395, and a LC CDR3 comprising the sequence of SEQ ID NO: 3396;(viii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3401, a HC CDR2 comprising the sequence of SEQ ID NO: 3402, a HC CDR3 comprising the sequence of SEQ ID NO: 3403, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3404, a LC CDR2 comprising the sequence of SEQ ID NO: 3405, and a LC CDR3 comprising the sequence of SEQ ID NO: 3406;(ix) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3411, a HC CDR2 comprising the sequence of SEQ ID NO: 3412, a HC CDR3 comprising the sequence of SEQ ID NO: 3413, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3414, a LC CDR2 comprising the sequence of SEQ ID NO: 3415, and a LC CDR3 comprising the sequence of SEQ ID NO: 3416;(x) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3351, SEQ ID NO: 3421, or SEQ ID NO: 3702, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, a HC CDR3 comprising the sequence of SEQ ID NO: 3353, and a VL comprising a LC CDR1 comprising thesequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3355, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356; or(xi) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3351, SEQ ID NO: 3421, or SEQ ID NO: 3702, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, a HC CDR3 comprising the sequence of SEQ ID NO: 3353, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3443, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356.

[0127] In some embodiments, the second binder comprises a VH comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO:3445, SEQ ID NO: 3448, SEQ ID NO: 3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO:3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO: 3465, and SEQ ID NO: 3470.

[0128] In some embodiments, the second binder comprises a VH comprising any one sequence selected from the group consisting of: SEQ ID NO: 3445, SEQ ID NO: 3448, SEQ ID NO: 3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO: 3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO: 3465, and SEQ ID NO: 3470.

[0129] In some embodiments, the second binder comprises a VL comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO:3446, SEQ ID NO: 3449, SEQ ID NO: 3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO:3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO: 3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

[0130] In some embodiments, the second binder comprises a VL comprising any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO: 3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO: 3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO: 3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

[0131] In some embodiments, the second binder comprises:(i) a VH comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO: 3445, SEQ ID NO: 3448, SEQ ID NO: 3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO: 3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO:3465, and SEQ ID NO: 3470; and(ii) a VL comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO: 3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO: 3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO:3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

[0132] In some embodiments, the second binder comprises:(i) a VH comprising any one sequence selected from the group consisting of: SEQ ID NO: 3445, SEQ ID NO: 3448, SEQ ID NO: 3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO: 3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO: 3465, and SEQ ID NO: 3470; and(ii) a VL comprising any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO: 3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO: 3456, SEQ IDNO: 3458, SEQ ID NO: 3464, SEQ ID NO: 3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

[0133] In some embodiments, the second binder comprises:(i) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3445, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3446;(ii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3448, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3449;(iii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3450, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3451;(iv) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1346, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1349;(v) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1196, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1195;(vi) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3455, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3456;(vii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3457, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3458;(viii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3463, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3464;(ix) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3465, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3466;(x) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3470, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3471;(xi) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1346, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3475; or(xii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1346, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3476.

[0134] In some embodiments, the second binder comprises:(i) a VH comprising the sequence of SEQ ID NO: 3445, and a VL comprising the sequence of SEQ ID NO: 3446;(ii) a VH comprising the sequence of SEQ ID NO: 3448, and a VL comprising the sequence of SEQ ID NO: 3449;(iii) a VH comprising the sequence of SEQ ID NO: 3450, and a VL comprising the sequence of SEQ ID NO: 3451;(iv) a VH comprising the sequence of SEQ ID NO: 1346, and a VL comprising the sequence of SEQ ID NO: 1349;(v) a VH comprising the sequence of SEQ ID NO: 1196, and a VL comprising the sequence of SEQ ID NO: 1195;(vi) a VH comprising the sequence of SEQ ID NO: 3455, and a VL comprising the sequence of SEQ ID NO: 3456;(vii) a VH comprising the sequence of SEQ ID NO: 3457, and a VL comprising the sequence of SEQ ID NO: 3458;(viii) a VH comprising the sequence of SEQ ID NO: 3463, and a VL comprising the sequence of SEQ ID NO: 3464;(ix) a VH comprising the sequence of SEQ ID NO: 3465, and a VL comprising the sequence of SEQ ID NO: 3466;(x) a VH comprising the sequence of SEQ ID NO: 3470, and a VL comprising the sequence of SEQ ID NO: 3471;(xi) a VH comprising the sequence of SEQ ID NO: 1346, and a VL comprising the sequence of SEQ ID NO: 3475; or(xii) a VH comprising the sequence of SEQ ID NO: 1346, and a VL comprising the sequence of SEQ ID NO: 3476.

[0135] T In some embodiments, the first binder and the second binder bind to different TCRpV regions.

[0136] In some embodiments, the first binder and the second binder bind to different TCRpV s belonging to different subfamilies.

[0137] In some embodiments, the first binder and the second binder bind to different members of the same TCRpV subfamily.

[0138] In some embodiments, the first binder comprises one or more heavy chain constant regions selected from the group consisting of IgGl heavy chain constant region or fragment thereof, IgG2 heavy chain constant region or fragment thereof, IgG3 heavy chain constant region or fragment thereof, IgGAl heavy chain constant region or fragment thereof, IgGA2 heavy chain constant region or fragment thereof, IgG4 heavy chain constant region or fragment thereof, IgJ heavy chain constant region or fragment thereof, IgM heavy chain constant region or fragment thereof, IgD heavy chain constant region or fragment thereof, and IgE heavy chain constant region or fragment thereof.

[0139] In some embodiments, the first binder comprises a kappa light chain constant region or fragment thereof, a lambda light chain constant region or fragment thereof, or a combination thereof.

[0140] In some embodiments, the second binder comprises one or more heavy chain constant regions selected from the group consisting of IgGl heavy chain constant region or fragment thereof, IgG2 heavy chain constant region or fragment thereof, IgG3 heavy chain constant region or fragment thereof, IgGAl heavy chain constant region or fragment thereof, IgGA2 heavy chain constant region or fragment thereof, IgG4 heavy chain constant region or fragment thereof, IgJ heavy chain constant region or fragment thereof, IgM heavy chain constant region or fragment thereof, IgD heavy chain constant region or fragment thereof, and IgE heavy chain constant region or fragment thereof.

[0141] In some embodiments, the second binder comprises a kappa light chain constant region or fragment thereof, a lambda light chain constant region or fragment thereof, or a combination thereof.

[0142] In some embodiments, the first agent is a multifunctional molecule.

[0143] In some embodiments, the first agent is a multispecific molecule.

[0144] In some embodiments, the second agent is a multifunctional molecule.

[0145] In some embodiments, the second agent is a multispecific molecule.

[0146] In some embodiments, the first agent, the second agent, or a combination thereof comprises at least two non-contiguous polypeptide chains; wherein a first polypeptide chain of the at least two non-contiguous polypeptide chains comprises a first Fc region, and a second polypeptide chain of the at least two non-contiguous polypeptide chains comprises a second Fc region; and wherein the first Fc region and the second Fc region comprise an Fc interface with a knob-in-a hole.

[0147] In some embodiments, the first Fc region, the second Fc region, or a combination thereof comprises an Asn297Ala mutation, a Leu234Ala / Leu235Ala mutation, or a combination thereof.

[0148] In some embodiments, the first agent is a multispecific molecule that further comprises one or more of a tumor-targeting moiety, a cytokine molecule, a stromal modifying moiety, or an immune cell engager.

[0149] In some embodiments, the second agent is a multispecific molecule that further comprises one or more of a tumor-targeting moiety, a cytokine molecule, a stromal modifying moiety, or an immune cell engager.

[0150] In some embodiments, the first agent comprises the following con-figuration:A-, B-[dimerization module] -C, -D, wherein:(a) the dimerization module comprises a first immunoglobulin chain constant region and a second immunoglobulin chain constant region;(b) A and C are linked to the first immunoglobulin chain constant region; and B and D are linked to the second immunoglobulin chain constant region;(c) A, B, C, and D are independently (i) absent; (ii) the first binder; (iii) the tumor targeting moiety, (iv) the cytokine molecule; (v) stromal modifying moiety; or (vi) the immune cell engager; and wherein at least one, two, or three of A, B, C, and D comprises the first binder.

[0151] In some embodiments, the second agent comprises the following configuration:A-, B-[dimerization module] -C, -D, wherein:(a) the dimerization module comprises a first immunoglobulin chain constant region and a second immunoglobulin chain constant region;(b) A and C are linked to the first immunoglobulin chain constant region; and B and D are linked to the second immunoglobulin chain constant region;(c) A, B, C, and D are independently (i) absent; (ii) the second binder; (iii) the tumor targeting moiety, (iv) the cytokine molecule; (v) stromal modifying moiety; or (vi) the immune cell engager; and wherein at least one, two, or three of A, B, C, and D comprises the second binder.

[0152] In some embodiments, the first immunoglobulin chain constant region comprises the first fragment crystallizable region (Fc region) and the second first immunoglobulin chain constant region comprises the second fragment crystallizable region (Fc region).

[0153] In some embodiments, dimerization of the first Fc region and the second Fc region is enhanced by providing an Fc interface of the first Fc region and the second Fc region with one or more of a paired cavity-protuberance, an electrostatic interaction, or a strand-exchange, such that a greater ratio of heteromultimer to homomultimer forms relative to a non-engineered interface.

[0154] In some embodiments, the immune cell engager is selected from the group consisting of a T cell engager, an NK cell engager, a B cell engager, a dendritic cell engager, a macrophage cell engager, and any combination thereof.

[0155] In some embodiments, the cytokine molecule is selected from the group consisting of interleukin-2 (IL-2) or functional variant thereof, interleukin-7 (IL-7) or functional variant thereof, interleukin- 12 (IL-12) or functional variant thereof, interleukin- 15 (IL-15) or functional variant thereof, interleukin- 18 (IL- 18) or functional variant thereof, inter-leukin-21 (IL-21) or functional variant thereof, interferon gamma or functional variant thereof, and any combination thereof.

[0156] In some embodiments, the cytokine molecule comprises interleukin-2 (IL-2) or functional variant thereof.

[0157] In some embodiments, the interleukin-2 (IL-2) or functional variant thereof comprises the sequence of SEQ ID NO : 2270 or SEQ ID NO : 2191.

[0158] In some embodiments, the cytokine molecule comprises interleukin- 15 (IL-15) or functional variant thereof.

[0159] In some embodiments, the interleukin- 15 (IL-15) or functional variant thereof comprises the sequence of SEQ ID NO: 2170.

[0160] In some embodiments, the cytokine molecule further comprises an IL15Ralpha dimerizing domain covalently linked the interleukin- 15 (IL-15) or functional variant thereof.

[0161] In some embodiments, the IL15Ralpha dimerizing domain comprises an IL-15 receptor alpha sushi domain or functional variant thereof.

[0162] In some embodiments, the IL15Ralpha dimerizing domain comprises the sequence of SEQ ID NO: 3472.

[0163] In some embodiments, the interleukin- 15 (IL- 15) or functional variant thereof is covalently linked to the IL15Ralpha dimerizing domain via a linker.

[0164] In some embodiments, the interleukin- 15 (IL- 15) or functional variant thereof is covalently linked to the IL15Ralpha dimerizing domain via a linker comprising the sequence of SEQ ID NO: 3473.

[0165] In some embodiments, the cytokine molecule comprises the sequence of SEQ ID NO: 3474.

[0166] In some embodiments, the stromal modifying moiety is selected from the group consisting of a hyaluronidase, a collagenase, a chondroitinase, and a matrix metalloproteinase.

[0167] In some embodiments, the tumor-targeting moiety binds to a cancer antigen.

[0168] In some embodiments, wherein the tumor-targeting moiety binds to a cancer antigen.

[0169] In some embodiments, the cancer antigen is present on a hematological cancer, a solid tumor, a metastatic cancer, a soft tissue tumor, a metastatic lesion, or a combination thereof.

[0170] In some embodiments, the cancer antigen is a tumor antigen, a stromal antigen, or a hematological antigen.

[0171] In some embodiments, the cancer antigen is selected from the group consisting of BCMA, CD19, CD20, CD22, FcRH5, PDL1, CD47, ganglioside 2 (GD2), prostate stem cell antigen (PSCA), prostate specific membrane antigen (PMSA), prostate-specific antigen (PSA), carcinoembryonic antigen (CEA), Ron Kinase, c-Met, Immature laminin receptor, TAG-72, BING-4, Calcium-activated chloride channel 2, Cyclin-Bl, 9D7, Ep-CAM, EphA3, Her2 / neu, Telomerase, SAP-1, Survivin, NY- ESO-I / LAGE-1, PRAME, SSX-2, Melan-A / MART-1, Gpl00 / pmell7, Tyrosinase, MC1R, p-catenin, BRCA1 / 2, CDK4, CML66, Fibronectin, p53, Ras, TGF-B receptor, AFP, ETA, MAGE, CA-125, BAGE, GAGE, CDC27, a actinin-4, TRPl / gp75, TRP2, gangliosides, WT1, Epidermal growth factor receptor (EGFR), MART-2, MUC1, MUC2, MUM1, MUM2, MUM3, NA88-1, NPM, OA1, OGT, RCC, RU11, RU12, SAGE, TRG, TSTA, Folate receptor alpha, LI -CAM, CAIX, gpA33, GD3, GM2, VEGFR, Integrins, Carbohydrates, IGF1R, TRAILR1, TRAILR2, RANKL, FAP, TGF-beta, hyaluronic acid, collagen, tenascin C, and tenascin W.

[0172] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3445, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3446, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0173] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3448, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3449, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0174] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3450, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3451, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0175] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3450, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3454 or the sequence of SEQ ID NO: 3501 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3451, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0176] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3454 or the sequence of SEQ ID NO: 3501 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 1349, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0177] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1196, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 1195, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0178] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3455, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3456, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0179] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3457, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3459, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3460,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3462 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2191, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3458, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3461.

[0180] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3463, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3459, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3460,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3462 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2191, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3464, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3461.

[0181] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3465, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3467, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3468,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3469 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2191, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3466, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3461.

[0182] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3470, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3471, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0183] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-15 or functional variant thereof comprising the sequence of SEQ ID NO: 2170, wherein the IL-15 or functional variant thereof is covalently linked to an IL15Ralpha dimerizing domain comprising the sequence of the SEQ ID NO: 3472 via a linker comprising the sequence of SEQ ID NO: 3473, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 1349, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0184] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-15 or functional variant thereof comprising the sequence of SEQ ID NO: 2170, wherein the IL-15 or functional variant thereof is covalently linked to an IL15Ralpha dimerizing domain comprising the sequence of the SEQ ID NO: 3472 via a linker comprising the sequence of SEQ ID NO: 3473, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3475, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0185] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-15 or functional variant thereof comprising the sequence of SEQ ID NO: 2170, wherein the IL-15 or functional variant thereof is covalently linked to an IL15Ralpha dimerizing domain comprising the sequence of the SEQ ID NO: 3472 via a linker comprising the sequence of SEQ ID NO: 3473, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3476, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0186] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3445, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3446, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0187] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3448, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3449, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0188] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3450, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3451, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0189] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3450, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3454 or the sequence of SEQ ID NO: 3501 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3451, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0190] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3454 or the sequence of SEQ ID NO: 3501 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 1349, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0191] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1196, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 1195, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0192] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3455, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3456, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0193] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3457, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3459, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3460,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3462 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2191, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3458, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3461.

[0194] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3463, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3459, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3460,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3462 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2191, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3464, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3461.

[0195] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3465, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3467, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3468,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3469 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2191, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3466, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3461.

[0196] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3470, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3471, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0197] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-15 or functional variant thereof comprising the sequence of SEQ ID NO: 2170, wherein the IL-15 or functional variant thereof is covalently linked to an IL15Ralpha dimerizing domain comprising the sequence of the SEQ ID NO: 3472 via a linker comprising the sequence of SEQ ID NO: 3473, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 1349, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0198] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-15 or functional variant thereof comprising the sequence of SEQ ID NO: 2170, wherein the IL-15 or functional variant thereof is covalently linked to an IL15Ralpha dimerizing domain comprising the sequence of the SEQ ID NO: 3472 via a linker comprising the sequence of SEQ ID NO: 3473, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3475, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0199] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-15 or functional variant thereof comprising the sequence of SEQ ID NO: 2170, wherein the IL-15 or functional variant thereof is covalently linked to an IL15Ralpha dimerizing domain comprising the sequence of the SEQ ID NO: 3472 via a linker comprising the sequence of SEQ ID NO: 3473, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3476, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0200] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3338;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3339.

[0201] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3318;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3319.

[0202] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3328;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3329.

[0203] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3328;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3350 or the sequence of SEQ ID NO: 3500; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3329.

[0204] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3349.

[0205] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3358;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3359.

[0206] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3368;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3369.

[0207] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3378;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3380; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3379.

[0208] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3388;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3390; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3389.

[0209] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3398;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3400; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3399.

[0210] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3408;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3409.

[0211] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3349.

[0212] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3428.

[0213] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3437.

[0214] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3338;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3339.

[0215] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3318;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3319.

[0216] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3328;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3329.

[0217] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3328;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3350 or the sequence of SEQ ID NO: 3500; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3329.

[0218] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3349.

[0219] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3358;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3359.

[0220] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3368;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3369.

[0221] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3378;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3380; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3379.

[0222] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3388;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3390; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3389.

[0223] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3398;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3400; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3399.

[0224] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3408;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3409.

[0225] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3349.

[0226] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3428.

[0227] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3437.

[0228] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3338;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3339.

[0229] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3318;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3319.

[0230] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3328;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3329.

[0231] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3328;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3350 or the sequence of SEQ ID NO: 3500; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3329.

[0232] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3349.

[0233] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3358;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3359.

[0234] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3368;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3369.

[0235] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3378;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3380; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3379.

[0236] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3388;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3390; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3389.

[0237] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3398;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3400; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3399.

[0238] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3408;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3409.

[0239] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3349.

[0240] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3428.

[0241] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3437.

[0242] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3338;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3339.

[0243] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3318;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3319.

[0244] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3328;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3329.

[0245] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3328;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3350 or the sequence of SEQ ID NO: 3500; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3329.

[0246] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3349.

[0247] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3358;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3359.

[0248] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3368;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3369.

[0249] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3378;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3380; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3379.

[0250] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3388;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3390; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3389.

[0251] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3398;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3400; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3399.

[0252] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3408;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3409.

[0253] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3349.

[0254] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3428.

[0255] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3437.

[0256] In some embodiments, the disease or condition is cancer.

[0257] In some embodiments, the cancer is a solid tumor.

[0258] In some embodiments, the solid tumor is melanoma, pancreatic cancer, breast cancer, colorectal cancer, lung cancer, skin cancer, ovarian cancer, or liver cancer.

[0259] In some embodiments, the solid tumor is selected from the group consisting of high mutational burden (TMB-H), microsatellite instability / DNA mismatch repair (MSI-H / dMMR), virally associated tumor, metastatic triple -negative breast cancer (mTNBC), re-lapsed and refractory epithelial ovarian cancer, metastatic castration-resistant prostate cancer (mCRPC), K-Ras wild type CRC, K-Ras mutant CRC, and primary stage IV or recurrent non-small cell lung cancer (NSCLC).

[0260] In some embodiments, the virally associated tumor comprises Merkel cell carcinoma, cervical cancer, oropharyngeal cancer, anal cancer, penile cancer, vaginal cancer, or vulvar cancer.

[0261] In some embodiments, the cancer is a hematological cancer.

[0262] In some embodiments, the hematological cancer is a B-cell or T cell malignancy.

[0263] In some embodiments, the B-cell or T cell malignancy is Hodgkin’s lymphoma, NonHodgkin’s lymphoma, acute myeloid leukemia (AML), chronic myeloid leukemia, myelodysplastic syndrome, multiple myeloma, or acute lymphocytic leukemia.

[0264] In some embodiments, the Non-Hodgkin’s lymphoma is B cell lymphoma, diffuse large B cell lymphoma, follicular lymphoma, chronic lymphocytic leukemia, mantle cell lymphoma, marginal zone B-cell lymphoma, Burkitt lymphoma, lymphoplasmacytic lymphoma, or hairy cell leukemia.

[0265] In some embodiments, the administering comprises administering a first pharmaceutical composition comprising the first agent, and a second pharmaceutical com-position comprising the second agent, wherein the first pharmaceutical composition and the second pharmaceutical composition independently further comprises a pharmaceutically acceptable excipient, carrier or diluent.

[0266] In another aspect, provided herein is, inter alia, a combination therapy for treating a disease or condition in a subject in need thereof comprising administering a first agent that comprises a first binder that binds to a first target molecule to the subject, and administering a second agent that comprises a second binder that binds to a second target molecule to the subject, thereby treating the disease or condition in the subject; wherein an administration of the first agent is followed by an administration of the second agent; wherein the first target molecule and the second target molecule are independently selected from the group consisting of a T cell receptor alpha variable region (TCRaV) and a T cell receptor beta variable region (TCR[3V); and wherein the first target molecule and the second target molecule are different.

[0267] In some embodiments, the first agent and the second agent are not concomitantly administered to the subject.

[0268] In some embodiments, administering the first agent comprises administering a therapeutically effective amount of the first agent to the subject.

[0269] In some embodiments, administering the second agent comprises administering a therapeutically effective amount of the second agent to the subject.

[0270] In some embodiments, the combination therapy is more effective to treat the disease or condition in the subject relative to a method in which the first agent is administered to the subject but not the second agent.

[0271] In some embodiments, the combination therapy is more effective to treat the disease or condition in the subject relative to a method in which the second agent is administered to the subject but not the first agent.

[0272] In some embodiments, the combination therapy is more effective to treat the disease or condition in the subject relative to a method in which the first agent is administered to the subject at a first administration and the first agent is administered to the subject subsequently at a second administration.

[0273] In some embodiments, the combination therapy is more effective to treat the disease or condition in the subject relative to a method in which the second agent is administered to the subject at a first administration and the second agent is administered to the subject subsequently at a second administration.

[0274] In some embodiments, the combination therapy is more effective to treat the disease or condition in the subject relative to a method in which the second agent is administered to the subject at a first administration and the first agent is administered to the subject subsequently at a second administration.

[0275] In some embodiments, the administration of the first agent comprises one or more doses.

[0276] In some embodiments, the administration of the first agent comprises two or more doses.

[0277] In some embodiments, the administration of the first agent comprises one dose per week.

[0278] In some embodiments, the administration of the first agent comprises two or more doses per week.

[0279] In some embodiments, the first agent is administered to the subject once every two weeks.

[0280] In some embodiments, the first agent is administered to the subject once every three weeks.

[0281] In some embodiments, the first agent is administered to the subject once every week for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

[0282] In some embodiments, the administration of the first agent comprises two or more doses per week for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

[0283] In some embodiments, the first agent is administered to the subject once every two weeks for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

[0284] In some embodiments, the first agent is administered to the subject once every three weeks for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

[0285] In some embodiments, the administration of the second agent comprises one or more doses.

[0286] In some embodiments, the administration of the second agent comprises two or more doses.

[0287] In some embodiments, the administration of the second agent comprises one dose per week.

[0288] In some embodiments, the administration of the second agent comprises two or more doses per week.

[0289] In some embodiments, the second agent is administered to the subject once every two weeks.

[0290] In some embodiments, the second agent is administered to the subject once every three weeks.

[0291] In some embodiments, the second agent is administered to the subject once every week for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

[0292] In some embodiments, the administration of the second agent comprises two or more doses per week for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

[0293] In some embodiments, the second agent is administered to the subject once every two weeks for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

[0294] In some embodiments, the second agent is administered to the subject once every three weeks for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

[0295] In some embodiments, the administration of the first agent and the administration of the second agent is separated by one week.

[0296] In some embodiments, the administration of the first agent and the administration of the second agent is separated by two or more weeks.

[0297] In some embodiments, the administration of the first agent and the administration of the second agent is separated by 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 12 months.

[0298] In some embodiments, the administration of the first agent and the second agent is repeated twice or more.

[0299] In some embodiments, the first agent and the second agent are administered to the subject according to a dosing regimen, wherein the dosing regimen comprises an administration of the first agent once every week for two weeks followed by an administration of the second agent once a week for two weeks, wherein the second agent is administered to the subject one week after the last administration of the first agent.

[0300] In some embodiments, the dosing regimen is repeated twice or more.

[0301] In some embodiments, the dosing regimen is repeated at the interval of one week.

[0302] In some embodiments, the dosing regimen is repeated at the interval of 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 12 months.

[0303] In some embodiments, the first agent and the second agent are administered to the subject in a same amount.

[0304] In some embodiments, the first agent and the second agent are administered to the subject in different amounts.

[0305] In some embodiments, the administration of the first agent comprises two or more doses, and each dose comprises a same amount of the first agent.

[0306] In some embodiments, the administration of the first agent comprises two or more doses, and each dose comprises different amounts of the first agent.

[0307] In some embodiments, the administration of the second agent comprises two or more doses, and each dose comprises a same amount of the second agent.

[0308] In some embodiments, the administration of the second agent comprises two or more doses, and each dose comprises different amounts of the second agent.

[0309] In some embodiments, the first agent is administered to the subject at a dose of from about 0.001 mg / kg to about 10 mg / kg.

[0310] In some embodiments, the second agent is administered to the subject at a dose of from about 0.001 mg / kg to about 10 mg / kg.

[0311] In some embodiments, the first agent is administered to the subject at a dose of about 0.3 mg / kg or about 1 mg / kg.

[0312] In some embodiments, the second agent is administered to the subject at a dose of about 0.3 mg / kg or about 1 mg / kg.

[0313] In some embodiments, the first target molecule is a first TCRJ3V, and the second target molecule is a second TCRJ3V, wherein the first TCRJ3V and the second TCRJ3V are different.

[0314] In some embodiments, the first target molecule is a first TCRaV, and the second target molecule is a second TCRaV, wherein the first TCRaV and the second TCRaV are different.

[0315] In some embodiments, the first target molecule is a TCRJ3V, and the second target molecule is a TCRaV.

[0316] In some embodiments, the first target molecule is a TCRaV, and the second target molecule is a TCR|3V.

[0317] In some embodiments, the first target molecule is human TCRJ3V6.

[0318] In some embodiments, the first target molecule is human TCRpVIO.

[0319] In some embodiments, the second target molecule is human TCRPV15.

[0320] In some embodiments, the second target molecule is human TCRPV27.

[0321] In some embodiments, the second target molecule is human TCRPV5.

[0322] In some embodiments, the first target molecule is human TCRPV6, and the second target molecule is human TCRPV5.

[0323] In some embodiments, the first target molecule is human TCRPV6, and the second target molecule is human TCRPV15.

[0324] In some embodiments, the first target molecule is human TCRPV6, and the second target molecule is human TCRPV27.

[0325] In some embodiments, the first target molecule is human TCRpVIO, and the second target molecule is human TCRPV5.

[0326] In some embodiments, the first target molecule is human TCRpVIO, and the second target molecule is human TCRPV15.

[0327] In some embodiments, the first target molecule is human TCRJ3V10, and the second target molecule is human TCRJ3V27.

[0328] In some embodiments, the first target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV19, human TRBV20, or human TRBV28.

[0329] In some embodiments, the first target molecule is human TRBV5-1, human TRBV6-5, human TRBV10-1, human TRBV10-2, human TRBV10-3, human TRBV7-2, human TRBV7-3, human TRBV19, human TRBV20-1, or human TRBV28.

[0330] In some embodiments, the first target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30.

[0331] In some embodiments, the first target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30.

[0332] In some embodiments, the second target molecule is human TRBV5, human TRBV15, human TRBV27, human TRBV6, human TRBV10, human TRBV7, human TRBV19, human TRBV20, or human TRBV28.

[0333] In some embodiments, the second target molecule is human TRBV5-1, human TRBV6-5, human TRBV10-1, human TRBV10-2, human TRBV10-3, human TRBV7-2, human TRBV7-3, human TRBV15, human TRBV27, human TRBV19, human TRBV20-1, or human TRBV28.

[0334] In some embodiments, the second target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30.

[0335] In some embodiments, the second target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30.

[0336] In some embodiments, the first target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV19, human TRBV20, or human TRBV28, and the second target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV15, human TRBV27, human TRBV19, human TRBV20, or human TRBV28, wherein the first target molecule and the second target molecule are different.

[0337] In some embodiments, the first target molecule and the second target molecule are: human TRBV5 and human TRBV5, respectively; human TRBV5 and human TRBV6, respectively; human TRBV5 and human TRBV10, respectively; human TRBV5 and human TRBV7, respectively; human TRBV5 and human TRBV19, respectively; human TRBV5 and human TRBV20, respectively; human TRBV5 and human TRBV28, respectively; human TRBV6 and human TRBV5, respectively; human TRBV6 and human TRBV6, respectively; human TRBV6 and human TRBV10, respectively; human TRBV6 and human TRBV7, respectively; human TRBV6 and human TRBV15, respectively; human TRBV6 and human TRBV27, respectively; human TRBV6 and human TRBV19, respectively; human TRBV6 and human TRBV20, respectively; human TRBV6 and human TRBV28, respectively; human TRBV10 and human TRBV5, respectively; human TRBV10 and human TRBV6, respectively; human TRBV10 and human TRBV10, respectively; human TRBV10 and human TRBV7, respectively; human TRBV10 and human TRBV15, respectively; human TRBV10 and human TRBV27, respectively; human TRBV10 and human TRBV19, respectively; human TRBV10 andhuman TRBV20, respectively; human TRBV10 and human TRBV28, respectively; human TRBV7 and human TRBV5, respectively; human TRBV7 and human TRBV6, respectively; human TRBV7 and human TRBV1O, respectively; human TRBV7 and human TRBV7, respectively; human TRBV7 and human TRBV19, respectively; human TRBV7 and human TRBV20, respectively; human TRBV7 and human TRBV28, respectively; human TRBV19 and human TRBV5, respectively; human TRBV19 and human TRBV6, respectively; human TRBV19 and human TRBV1O, respectively; human TRBV19 and human TRBV7, respectively; human TRBV19 and human TRBV19, respectively; human TRBV19 and human TRBV20, respectively; human TRBV19 and human TRBV28, respectively; human TRBV20 and human TRBV5, respectively; human TRBV20 and human TRBV6, respectively; human TRBV20 and human TRBV1O, respectively; human TRBV20 and human TRBV7, respectively; human TRBV20 and human TRBV19, respectively; human TRBV20 and human TRBV20, respectively; human TRBV20 and human TRBV28, respectively; human TRBV28 and human TRBV5, respectively; human TRBV28 and human TRBV6, respectively; human TRBV28 and human TRBV1O, respectively; human TRBV28 and human TRBV7, respectively; human TRBV28 and human TRBV19, respectively; human TRBV28 and human TRBV20, respectively; or human TRBV28 and human TRBV28, respectively.

[0338] In some embodiments, the first target molecule is human TRBV5-1, human TRBV6-5, human TRBV10-1, human TRBV10-2, human TRBV10-3, human TRBV7-2, human TRBV7-3, human TRBV19, human TRBV20-1, or human TRBV28, and the second target molecule is human TRBV5- 1, human TRBV6-5, human TRBV10-1, human TRBV10-2, human TRBV10-3, human TRBV7-2, human TRBV7-3, human TRBV15, human TRBV27, human TRBV19, human TRBV20-1, or human TRBV28, wherein the first target molecule and the second target molecule are different.

[0339] In some embodiments, the first target molecule and the second target molecule are: Human TRBV5-1 and human TRBV6-5, respectively; human TRBV5-1 and human TRBV10-1, respectively; human TRBV5-1 and human TRBV10-2, respectively; human TRBV5-1 and human TRBV10-3, respectively; human TRBV5-1 and human TRBV7-2, respectively; human TRBV5-1 and human TRBV7-3, respectively; human TRBV5-1 and human TRBV19, respectively; human TRBV5- 1 and human TRBV20-1, respectively; human TRBV5-1 and human TRBV28, respectively; human TRBV6-5 and human TRBV5-1, respectively; human TRBV6-5 and human TRBV7-2, respectively; human TRBV6-5 and human TRBV7-3, respectively; human TRBV6-5 and human TRBV15, respectively; human TRBV6-5 and human TRBV27, respectively; human TRBV6-5 and human TRBV19, respectively; human TRBV6-5 and human TRBV20-1, respectively; human TRBV6-5 and human TRBV28, respectively; human TRBV10-1 and human TRBV5-1, respectively; human TRBV10-1 and human TRBV7-2, respectively; human TRBV10-1 and human TRBV7-3, respectively; human TRBV10-1 and human TRBV15, respectively; human TRBV10-1 and human TRBV27, respectively; human TRBV10-1 and human TRBV19, respectively; human TRBV10-1 and human TRBV20-1, respectively; human TRBV10-1 and human TRBV28, respectively; human TRBV10-2 and human TRBV5-1, respectively; human TRBV10-2 and human TRBV7-2, respectively; human TRBV10-2 and human TRBV7-3, respectively; human TRBV10-2 and humanTRBV15, respectively; human TRBV10-2 and human TRBV27, respectively; human TRBV10-2 and human TRBV19, respectively; human TRBV10-2 and human TRBV20-1, respectively; human TRBV10-2 and human TRBV28, respectively; human TRBV10-3 and human TRBV5-1, respectively; human TRBV10-3 and human TRBV7-2, respectively; human TRBV10-3 and human TRBV7-3, respectively; human TRBV10-3 and human TRBV15, respectively; human TRBV10-3 and human TRBV27, respectively; human TRBV10-3 and human TRBV19, respectively; human TRBV10-3 and human TRBV20-1, respectively; human TRBV10-3 and human TRBV28, respectively; human TRBV7-2 and human TRBV5-1, respectively; human TRBV7-2 and human TRBV6-5, respectively; human TRBV7-2 and human TRBV10-1, respectively; human TRBV7-2 and human TRBV10-2, respectively; human TRBV7-2 and human TRBV10-3, respectively; human TRBV7-2 and human TRBV7-3, respectively; human TRBV7-2 and human TRBV19, respectively; human TRBV7-2 and human TRBV20-1, respectively; human TRBV7-2 and human TRBV28, respectively; human TRBV7-3 and human TRBV5-1, respectively; human TRBV7-3 and human TRBV6-5, respectively; human TRBV7-3 and human TRBV10-1, respectively; human TRBV7-3 and human TRBV10-2, respectively; human TRBV7-3 and human TRBV10-3, respectively; human TRBV7-3 and human TRBV7-2, respectively; human TRBV7-3 and human TRBV19, respectively; human TRBV7-3 and human TRBV20-1, respectively; human TRBV7-3 and human TRBV28, respectively; human TRBV19 and human TRBV5-1, respectively; human TRBV19 and human TRBV6-5, respectively; human TRBV19 and human TRBV10-1, respectively; human TRBV19 and human TRBV10-2, respectively; human TRBV19 and human TRBV10-3, respectively; human TRBV19 and human TRBV7-2, respectively; human TRBV19 and human TRBV7-3, respectively; human TRBV19 and human TRBV20-1, respectively; human TRBV19 and human TRBV28, respectively; human TRBV20-1 and human TRBV5-1, respectively; human TRBV20-1 and human TRBV6-5, respectively; human TRBV20-1 and human TRBV10-1, respectively; human TRBV20-1 and human TRBV10-2, respectively; human TRBV20-1 and human TRBV10-3, respectively; human TRBV20-1 and human TRBV7-2, respectively; human TRBV20-1 and human TRBV7-3, respectively; human TRBV20-1 and human TRBV19, respectively; human TRBV20-1 and human TRBV28, respectively; human TRBV28 and human TRBV5-1, respectively; human TRBV28 and human TRBV6-5, respectively; human TRBV28 and human TRBV10-1, respectively; human TRBV28 and human TRBV10-2, respectively; human TRBV28 and human TRBV10-3, respectively; human TRBV28 and human TRBV7-2, respectively; human TRBV28 and human TRBV7-3, respectively; human TRBV28 and human TRBV19, respectively; or human TRBV28 and human TRBV20-1, respectively.

[0340] In some embodiments, the first target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30, and the second target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30, wherein the first target molecule and the second target molecule are different.

[0341] In some embodiments, the first target molecule and the second target molecule are: human TRAV12 and human TRAV12, respectively; human TRAV12 and human TRAV13, respectively;human TRAV12 and human TRAV19, respectively; human TRAV12 and human TRAV21, respectively; human TRAV12 and human TRAV30, respectively; human TRAV13 and human TRAV12, respectively; human TRAV13 and human TRAV13, respectively; human TRAV13 and human TRAV19, respectively; human TRAV13 and human TRAV21, respectively; human TRAV13 and human TRAV30, respectively; human TRAV19 and human TRAV12, respectively; human TRAV19 and human TRAV13, respectively; human TRAV19 and human TRAV19, respectively; human TRAV19 and human TRAV21, respectively; human TRAV19 and human TRAV30, respectively; human TRAV21 and human TRAV12, respectively; human TRAV21 and human TRAV13, respectively; human TRAV21 and human TRAV19, respectively; human TRAV21 and human TRAV21, respectively; human TRAV21 and human TRAV30, respectively; human TRAV30 and human TRAV12, respectively; human TRAV30 and human TRAV13, respectively; human TRAV30 and human TRAV19, respectively; human TRAV30 and human TRAV21, respectively; or human TRAV30 and human TRAV30, respectively.

[0342] In some embodiments, the first target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30, and the second target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30, wherein the first target molecule and the second target molecule are different.

[0343] In some embodiments, the first target molecule and the second target molecule are: human TRAV12-2 and human TRAV13-1, respectively; human TRAV12-2 and human TRAV19, respectively; human TRAV12-2 and human TRAV21, respectively; human TRAV12-2 and human TRAV30, respectively; human TRAV13-1 and human TRAV12-2, respectively; human TRAV13-1 and human TRAV19, respectively; human TRAV13-1 and human TRAV21, respectively; human TRAV13-1 and human TRAV30, respectively; human TRAV19 and human TRAV12-2, respectively; human TRAV19 and human TRAV13-1, respectively; human TRAV19 and human TRAV21, respectively;human TRAV19 and human TRAV30, respectively; human TRAV21 and human TRAV12-2, respectively; human TRAV21 and human TRAV13-1, respectively; human TRAV21 and human TRAV19, respectively; human TRAV21 and human TRAV30, respectively; human TRAV30 and human TRAV12-2, respectively; human TRAV30 and human TRAV13-1, respectively; human TRAV30 and human TRAV19, respectively; or human TRAV30 and human TRAV21, respectively.

[0344] In some embodiments, the first target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV19, human TRBV20, or human TRBV28, and the second target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30.

[0345] In some embodiments, the first target molecule and the second target molecule are: human TRBV5 and human TRAV12, respectively; human TRBV5 and human TRAV13, respectively; human TRBV5 and human TRAV19, respectively; human TRBV5 and human TRAV21, respectively; human TRBV5 and human TRAV30, respectively; human TRBV6 and human TRAV12, respectively; human TRBV6 and human TRAV13, respectively; human TRBV6 and human TRAV19, respectively; human TRBV6 and human TRAV21, respectively; human TRBV6 and human TRAV30, respectively; human TRBV10 and human TRAV12, respectively; human TRBV10 and human TRAV13, respectively; human TRBV10 and human TRAV19, respectively; human TRBV10 and human TRAV21, respectively; human TRBV10 and human TRAV30, respectively; human TRBV7 and human TRAV12, respectively; human TRBV7 and human TRAV13, respectively; human TRBV7 and human TRAV19, respectively; human TRBV7 and human TRAV21, respectively; human TRBV7 and human TRAV30, respectively; human TRBV19 and human TRAV12, respectively; human TRBV19 and human TRAV13, respectively; human TRBV19 and human TRAV19, respectively; human TRBV19 and human TRAV21, respectively; human TRBV19 and human TRAV30, respectively; human TRBV20 and human TRAV12, respectively; human TRBV20 and human TRAV13, respectively; human TRBV20 and human TRAV19, respectively; human TRBV20 and human TRAV21, respectively; human TRBV20 and human TRAV30, respectively; human TRBV28 and human TRAV12, respectively; human TRBV28 and human TRAV13, respectively; human TRBV28 and human TRAV19, respectively; human TRBV28 and human TRAV21, respectively; or human TRBV28 and human TRAV30, respectively.

[0346] In some embodiments, the first target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV19, human TRBV20, or human TRBV28, and the second target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30.

[0347] In some embodiments, the first target molecule and the second target molecule are:human TRBV5 and human TRAV12-2, respectively; human TRBV5 and human TRAV13-1, respectively; human TRBV5 and human TRAV19, respectively; human TRBV5 and human TRAV21, respectively; human TRBV5 and human TRAV30, respectively; human TRBV6 and human TRAV12-2, respectively; human TRBV6 and human TRAV13-1, respectively; human TRBV6 and human TRAV19, respectively; human TRBV6 and human TRAV21, respectively; human TRBV6 and human TRAV30, respectively; human TRBV10 and human TRAV12-2, respectively; human TRBV1O and human TRAV13-1, respectively; human TRBV1O and human TRAV19, respectively; human TRBV1O and human TRAV21, respectively; human TRBV1O and human TRAV3O, respectively; human TRBV7 and human TRAV12-2, respectively; human TRBV7 and human TRAV13-1, respectively; human TRBV7 and human TRAV19, respectively; human TRBV7 and human TRAV21, respectively; human TRBV7 and human TRAV3O, respectively; human TRBV19 and human TRAV12-2, respectively; human TRBV19 and human TRAV13-1, respectively; human TRBV19 and human TRAV19, respectively; human TRBV19 and human TRAV21, respectively; human TRBV19 and human TRAV3O, respectively; human TRBV20 and human TRAV12-2, respectively; human TRBV20 and human TRAV13-1, respectively; human TRBV20 and human TRAV19, respectively; human TRBV20 and human TRAV21, respectively; human TRBV20 and human TRAV3O, respectively; human TRBV28 and human TRAV12-2, respectively; human TRBV28 and human TRAV13-1, respectively; human TRBV28 and human TRAV19, respectively; human TRBV28 and human TRAV21, respectively; or human TRBV28 and human TRAV30, respectively.

[0348] In some embodiments, the first target molecule is human TRBV5-1, human TRBV6-5, human TRBV10-1, human TRBV10-2, human TRBV10-3, human TRBV7-2, human TRBV7-3, human TRBV19, human TRBV20-1, or human TRBV28, and the second target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30.

[0349] In some embodiments, the first target molecule and the second target molecule are: human TRBV5-1 and human TRAV12, respectively; human TRBV5-1 and human TRAV13, respectively; human TRBV5-1 and human TRAV19, respectively; human TRBV5-1 and human TRAV21, respectively; human TRBV5-1 and human TRAV30, respectively; human TRBV6-5 and human TRAV12, respectively; human TRBV6-5 and human TRAV13, respectively; human TRBV6-5 and human TRAV19, respectively; human TRBV6-5 and human TRAV21, respectively; human TRBV6-5 and human TRAV30, respectively; human TRBV10-1 and human TRAV12, respectively; human TRBV10-1 and human TRAV13, respectively; human TRBV10-1 and human TRAV19, respectively; human TRBV10-1 and human TRAV21, respectively; human TRBV10-1 and human TRAV30, respectively; human TRBV10-2 and human TRAV12, respectively; human TRBV10-2 and human TRAV13, respectively; human TRBV10-2 and human TRAV19, respectively; human TRBV10-2 and human TRAV21, respectively; human TRBV10-2 and human TRAV30, respectively; human TRBV10-3 and human TRAV12, respectively; human TRBV10-3 and human TRAV13, respectively; human TRBV10-3 and human TRAV19, respectively; human TRBV10-3 and human TRAV21, respectively; human TRBV10-3 and human TRAV30, respectively; human TRBV7-2 andhuman TRAV12, respectively; human TRBV7-2 and human TRAV13, respectively; human TRBV7-2 and human TRAV19, respectively; human TRBV7-2 and human TRAV21, respectively; human TRBV7-2 and human TRAV30, respectively; human TRBV7-3 and human TRAV12, respectively; human TRBV7-3 and human TRAV13, respectively; human TRBV7-3 and human TRAV19, respectively; human TRBV7-3 and human TRAV21, respectively; human TRBV7-3 and human TRAV30, respectively; human TRBV19 and human TRAV12, respectively; human TRBV19 and human TRAV13, respectively; human TRBV19 and human TRAV19, respectively; human TRBV19 and human TRAV21, respectively; human TRBV19 and human TRAV30, respectively; human TRBV20-1 and human TRAV12, respectively; human TRBV20-1 and human TRAV13, respectively; human TRBV20-1 and human TRAV19, respectively; human TRBV20-1 and human TRAV21, respectively; human TRBV20-1 and human TRAV30, respectively; human TRBV28 and human TRAV12, respectively; human TRBV28 and human TRAV13, respectively; human TRBV28 and human TRAV19, respectively; human TRBV28 and human TRAV21, respectively; or human TRBV28 and human TRAV30, respectively.

[0350] In some embodiments, the first target molecule is human TRBV5-1, human TRBV6-5, human TRBV10-1, human TRBV10-2, human TRBV10-3, human TRBV7-2, human TRBV7-3, human TRBV19, human TRBV20-1, or human TRBV28, and the second target molecule is human TRAV12- 2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30.

[0351] In some embodiments, the first target molecule and the second target molecule are: human TRBV5-1 and human TRAV12-2, respectively; human TRBV5-1 and human TRAV13-1, respectively; human TRBV5-1 and human TRAV19, respectively; human TRBV5-1 and human TRAV21, respectively; human TRBV5-1 and human TRAV30, respectively; human TRBV6-5 and human TRAV12-2, respectively; human TRBV6-5 and human TRAV13-1, respectively; human TRBV6-5 and human TRAV19, respectively; human TRBV6-5 and human TRAV21, respectively; human TRBV6-5 and human TRAV30, respectively; human TRBV10-1 and human TRAV12-2, respectively; human TRBV10-1 and human TRAV13-1, respectively; human TRBV10-1 and human TRAV19, respectively; human TRBV10-1 and human TRAV21, respectively; human TRBV10-1 and human TRAV30, respectively; human TRBV10-2 and human TRAV12-2, respectively; human TRBV10-2 and human TRAV13-1, respectively; human TRBV10-2 and human TRAV19, respectively; human TRBV10-2 and human TRAV21, respectively; human TRBV10-2 and human TRAV30, respectively; human TRBV10-3 and human TRAV12-2, respectively; human TRBV10-3 and human TRAV13-1, respectively; human TRBV10-3 and human TRAV19, respectively; human TRBV10-3 and human TRAV21, respectively; human TRBV10-3 and human TRAV30, respectively; human TRBV7-2 and human TRAV12-2, respectively; human TRBV7-2 and human TRAV13-1, respectively; human TRBV7-2 and human TRAV19, respectively; human TRBV7-2 and human TRAV21, respectively; human TRBV7-2 and human TRAV30, respectively; human TRBV7-3 and human TRAV12-2, respectively; human TRBV7-3 and human TRAV13-1, respectively; human TRBV7-3 and human TRAV19, respectively; human TRBV7-3 and human TRAV21, respectively; human TRBV7-3 and human TRAV30, respectively; human TRBV19 and human TRAV12-2,respectively; human TRBV19 and human TRAV13-1, respectively; human TRBV19 and human TRAV19, respectively; human TRBV19 and human TRAV21, respectively; human TRBV19 and human TRAV30, respectively; human TRBV20-1 and human TRAV12-2, respectively; human TRBV20-1 and human TRAV13-1, respectively; human TRBV20-1 and human TRAV19, respectively; human TRBV20-1 and human TRAV21, respectively; human TRBV20-1 and human TRAV30, respectively; human TRBV28 and human TRAV12-2, respectively; human TRBV28 and human TRAV13-1, respectively; human TRBV28 and human TRAV19, respectively; human TRBV28 and human TRAV21, respectively; or human TRBV28 and human TRAV30, respectively.

[0352] In some embodiments, the first target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30, and the second target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV19, human TRBV20, or human TRBV28.

[0353] In some embodiments, the first target molecule and the second target molecule are: human TRAV12 and human TRBV5, respectively; human TRAV12 and human TRBV6, respectively; human TRAV12 and human TRBV10, respectively; human TRAV12 and human TRBV7, respectively; human TRAV12 and human TRBV19, respectively; human TRAV12 and human TRBV20, respectively; human TRAV12 and human TRBV28, respectively; human TRAV13 and human TRBV5, respectively; human TRAV13 and human TRBV6, respectively; human TRAV13 and human TRBV10, respectively; human TRAV13 and human TRBV7, respectively; human TRAV13 and human TRBV19, respectively; human TRAV13 and human TRBV20, respectively; human TRAV13 and human TRBV28, respectively; human TRAV19 and human TRBV5, respectively; human TRAV19 and human TRBV6, respectively; human TRAV19 and human TRBV10, respectively; human TRAV19 and human TRBV7, respectively; human TRAV19 and human TRBV19, respectively; human TRAV19 and human TRBV20, respectively; human TRAV19 and human TRBV28, respectively; human TRAV21 and human TRBV5, respectively; human TRAV21 and human TRBV6, respectively; human TRAV21 and human TRBV10, respectively; human TRAV21 and human TRBV7, respectively; human TRAV21 and human TRBV19, respectively; human TRAV21 and human TRBV20, respectively; human TRAV21 and human TRBV28, respectively; human TRAV30 and human TRBV5, respectively; human TRAV30 and human TRBV6, respectively; human TRAV30 and human TRBV10, respectively; human TRAV30 and human TRBV7, respectively; human TRAV30 and human TRBV19, respectively; human TRAV30 and human TRBV20, respectively; or human TRAV30 and human TRBV28, respectively.

[0354] In some embodiments, the first target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30, and the second target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV19, human TRBV20, or human TRBV28.

[0355] In some embodiments, the first target molecule and the second target molecule are: human TRAV12-2 and human TRBV5, respectively; human TRAV12-2 and human TRBV6, respectively; human TRAV12-2 and human TRBV10, respectively; human TRAV12-2 and humanTRBV7, respectively; human TRAV12-2 and human TRBV19, respectively; human TRAV12-2 and human TRBV20, respectively; human TRAV12-2 and human TRBV28, respectively; human TRAV13-1 and human TRBV5, respectively; human TRAV13-1 and human TRBV6, respectively; human TRAV13-1 and human TRBV10, respectively; human TRAV13-1 and human TRBV7, respectively; human TRAV13-1 and human TRBV19, respectively; human TRAV13-1 and human TRBV20, respectively; human TRAV13-1 and human TRBV28, respectively; human TRAV19 and human TRBV5, respectively; human TRAV19 and human TRBV6, respectively; human TRAV19 and human TRBV1O, respectively; human TRAV19 and human TRBV7, respectively; human TRAV19 and human TRBV19, respectively; human TRAV19 and human TRBV20, respectively; human TRAV19 and human TRBV28, respectively; human TRAV21 and human TRBV5, respectively; human TRAV21 and human TRBV6, respectively; human TRAV21 and human TRBV1O, respectively; human TRAV21 and human TRBV7, respectively; human TRAV21 and human TRBV19, respectively; human TRAV21 and human TRBV20, respectively; human TRAV21 and human TRBV28, respectively; human TRAV3O and human TRBV5, respectively; human TRAV3O and human TRBV6, respectively; human TRAV3O and human TRBV1O, respectively; human TRAV3O and human TRBV7, respectively; human TRAV3O and human TRBV19, respectively; human TRAV3O and human TRBV20, respectively; or human TRAV30 and human TRBV28, respectively.

[0356] In some embodiments, the first target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30, and the second target molecule is human TRBV5-1, human TRBV6-5, human TRBV10-1, human TRBV10-2, human TRBV10-3, human TRBV7-2, human TRBV7-3, human TRBV19, human TRBV20-1, or human TRBV28.

[0357] In some embodiments, the first target molecule and the second target molecule are: human TRAV12 and human TRBV5-1, respectively; human TRAV12 and human TRBV6-5, respectively; human TRAV12 and human TRBV10-1, respectively; human TRAV12 and human TRBV10-2, respectively; human TRAV12 and human TRBV10-3, respectively; human TRAV12 and human TRBV7-2, respectively; human TRAV12 and human TRBV7-3, respectively; human TRAV12 and human TRBV19, respectively; human TRAV12 and human TRBV20-1, respectively; human TRAV12 and human TRBV28, respectively; human TRAV13 and human TRBV5-1, respectively; human TRAV13 and human TRBV6-5, respectively; human TRAV13 and human TRBV10-1, respectively; human TRAV13 and human TRBV10-2, respectively; human TRAV13 and human TRBV10-3, respectively; human TRAV13 and human TRBV7-2, respectively; human TRAV13 and human TRBV7-3, respectively; human TRAV13 and human TRBV19, respectively; human TRAV13 and human TRBV20-1, respectively; human TRAV13 and human TRBV28, respectively; human TRAV19 and human TRBV5-1, respectively; human TRAV19 and human TRBV6-5, respectively; human TRAV19 and human TRBV10-1, respectively; human TRAV19 and human TRBV10-2, respectively; human TRAV19 and human TRBV10-3, respectively; human TRAV19 and human TRBV7-2, respectively; human TRAV19 and human TRBV7-3, respectively; human TRAV19 and human TRBV19, respectively; human TRAV19 and human TRBV20-1, respectively; humanTRAV19 and human TRBV28, respectively; human TRAV21 and human TRBV5-1, respectively; human TRAV21 and human TRBV6-5, respectively; human TRAV21 and human TRBV10-1, respectively; human TRAV21 and human TRBV10-2, respectively; human TRAV21 and human TRBV10-3, respectively; human TRAV21 and human TRBV7-2, respectively; human TRAV21 and human TRBV7-3, respectively; human TRAV21 and human TRBV19, respectively; human TRAV21 and human TRBV20-1, respectively; human TRAV21 and human TRBV28, respectively; human TRAV30 and human TRBV5-1, respectively; human TRAV30 and human TRBV6-5, respectively; human TRAV30 and human TRBV10-1, respectively; human TRAV30 and human TRBV10-2, respectively; human TRAV30 and human TRBV10-3, respectively; human TRAV30 and human TRBV7-2, respectively; human TRAV30 and human TRBV7-3, respectively; human TRAV30 and human TRBV19, respectively; human TRAV30 and human TRBV20-1, respectively; or human TRAV30 and human TRBV28, respectively.

[0358] In some embodiments, the first target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30, and the second target molecule is human TRBV5-1, human TRBV6-5, human TRBV 10-1, human TRBV 10-2, human TRBV 10-3, human TRBV7-2, human TRBV7-3, human TRBV19, human TRBV20-1, or human TRBV28.

[0359] In some embodiments, the first target molecule and the second target molecule are: human TRAV12-2 and human TRBV5-1, respectively; human TRAV12-2 and human TRBV6-5, respectively; human TRAV12-2 and human TRBV10-1, respectively; human TRAV12-2 and human TRBV 10-2, respectively; human TRAV12-2 and human TRBV 10-3, respectively; human TRAV12-2 and human TRBV7-2, respectively; human TRAV12-2 and human TRBV7-3, respectively; human TRAV12-2 and human TRBV19, respectively; human TRAV12-2 and human TRBV20-1, respectively; human TRAV12-2 and human TRBV28, respectively; human TRAV13-1 and human TRBV5-1, respectively; human TRAV13-1 and human TRBV6-5, respectively; human TRAV13-1 and human TRBV10-1, respectively; human TRAV13-1 and human TRBV10-2, respectively; human TRAV13-1 and human TRBV10-3, respectively; human TRAV13-1 and human TRBV7-2, respectively; human TRAV13-1 and human TRBV7-3, respectively; human TRAV13-1 and human TRBV19, respectively; human TRAV13-1 and human TRBV20-1, respectively; human TRAV13-1 and human TRBV28, respectively; human TRAV19 and human TRBV5-1, respectively; human TRAV19 and human TRBV6-5, respectively; human TRAV19 and human TRBV 10-1, respectively; human TRAV19 and human TRBV10-2, respectively; human TRAV19 and human TRBV10-3, respectively; human TRAV19 and human TRBV7-2, respectively; human TRAV19 and human TRBV7-3, respectively; human TRAV19 and human TRBV19, respectively; human TRAV19 and human TRBV20-1, respectively; human TRAV19 and human TRBV28, respectively; human TRAV21 and human TRBV5-1, respectively; human TRAV21 and human TRBV6-5, respectively; human TRAV21 and human TRBV 10-1, respectively; human TRAV21 and human TRBV 10-2, respectively; human TRAV21 and human TRBV10-3, respectively; human TRAV21 and human TRBV7-2, respectively; human TRAV21 and human TRBV7-3, respectively; human TRAV21 and human TRBV 19, respectively; human TRAV21 and human TRBV20-1, respectively; humanTRAV21 and human TRBV28, respectively; human TRAV30 and human TRBV5-1, respectively; human TRAV30 and human TRBV6-5, respectively; human TRAV30 and human TRBV10-1, respectively; human TRAV30 and human TRBV10-2, respectively; human TRAV30 and human TRBV10-3, respectively; human TRAV30 and human TRBV7-2, respectively; human TRAV30 and human TRBV7-3, respectively; human TRAV30 and human TRBV19, respectively; human TRAV30 and human TRBV20-1, respectively; or human TRAV30 and human TRBV28, respectively.

[0360] In some embodiments, the first binder comprises a full antibody or antigen-binding fragment thereof, a bivalent antibody, bispecific antibody, or a biparatopic antibody.

[0361] In some embodiments, the second binder comprises a full antibody or antigen-binding fragment thereof, a bivalent antibody, bispecific antibody, or a biparatopic antibody.

[0362] In some embodiments, the antigen-binding fragment is a Fab, F(ab')2, Fv, a single chain Fv (scFv), a single domain antibody, a diabody (dAb), a single do-main antibody, or a camelid antibody.

[0363] In some embodiments, the first binder comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 3 (HC CDR3) comprising the sequence of SEQ ID NO: 3343, SEQ ID NO: 3323, SEQ ID NO: 3353, SEQ ID NO: 1187, SEQ ID NO: 3373, SEQ ID NO: 3383, SEQ ID NO: 3393, SEQ ID NO: 3403, or SEQ ID NO: 3413.

[0364] In some embodiments, the first binder comprises a VH comprising a heavy chain complementarity determining region 1 (HC CDR1) comprising the sequence of SEQ ID NO: 3341, SEQ ID NO: 3321, SEQ ID NO: 3351, SEQ ID NO: 1190, SEQ ID NO: 3371, SEQ ID NO: 3381, SEQ ID NO: 3391, SEQ ID NO: 3401, SEQ ID NO: 3411, SEQ ID NO: 3421, or SEQ ID NO: 3702.

[0365] In some embodiments, the first binder comprises a VH comprising a heavy chain complementarity determining region 2 (HC CDR2) comprising the sequence of SEQ ID NO: 3342, SEQ ID NO: 3322, SEQ ID NO: 3352, SEQ ID NO: 1186, SEQ ID NO: 3372, SEQ ID NO: 3382, SEQ ID NO: 3392, SEQ ID NO: 3402, or SEQ ID NO: 3412.

[0366] In some embodiments, the first binder comprises a VH comprising:(i) a HC CDR1 comprising the sequence of SEQ ID NO: 3341, a HC CDR2 comprising the sequence of SEQ ID NO: 3342, and a HC CDR3 comprising the sequence of SEQ ID NO: 3343;(ii) a HC CDR1 comprising the sequence of SEQ ID NO: 3321, a HC CDR2 comprising the sequence of SEQ ID NO: 3322, and a HC CDR3 comprising the sequence of SEQ ID NO: 3323;(iii) a HC CDR1 comprising the sequence of SEQ ID NO: 3351, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, and a HC CDR3 comprising the sequence of SEQ ID NO: 3353;(iv) a HC CDR1 comprising the sequence of SEQ ID NO: 1190, a HC CDR2 comprising the sequence of SEQ ID NO: 1186, and a HC CDR3 comprising the sequence of SEQ ID NO: 1187;(v) a HC CDR1 comprising the sequence of SEQ ID NO: 3371, a HC CDR2 comprising the sequence of SEQ ID NO: 3372, and a HC CDR3 comprising the sequence of SEQ ID NO: 3373;(vi) a HC CDR1 comprising the sequence of SEQ ID NO: 3381, a HC CDR2 comprising the sequence of SEQ ID NO: 3382, and a HC CDR3 comprising the sequence of SEQ ID NO: 3383;(vii) a HC CDR1 comprising the sequence of SEQ ID NO: 3391, a HC CDR2 comprising the sequence of SEQ ID NO: 3392, and a HC CDR3 comprising the sequence of SEQ ID NO: 3393;(viii) a HC CDR1 comprising the sequence of SEQ ID NO: 3401, a HC CDR2 comprising the sequence of SEQ ID NO: 3402, and a HC CDR3 comprising the sequence of SEQ ID NO: 3403;(ix) a HC CDR1 comprising the sequence of SEQ ID NO: 3351, SEQ ID NO: 3421, or SEQ ID NO: 3702, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, and a HC CDR3 comprising the sequence of SEQ ID NO: 3353; or(x) a HC CDR1 comprising the sequence of SEQ ID NO: 3411, a HC CDR2 comprising the sequence of SEQ ID NO: 3412, and a HC CDR3 comprising the sequence of SEQ ID NO: 3413.

[0367] In some embodiments, the first binder comprises a light chain variable region (VL) comprising a light chain complementarity determining region 3 (LC CDR3) comprising the sequence of SEQ ID NO: 3346, SEQ ID NO: 3326, SEQ ID NO: 3356, SEQ ID NO: 1193, SEQ ID NO: 3376, SEQ ID NO: 3386, SEQ ID NO: 3396, SEQ ID NO: 3406, or SEQ ID NO: 3416.

[0368] In some embodiments, the first binder comprises a VL comprising a light chain complementarity determining region 1 (LC CDR1) comprising the sequence of SEQ ID NO: 3344, SEQ ID NO: 3324, SEQ ID NO: 3354, SEQ ID NO: 1191, SEQ ID NO: 3374, SEQ ID NO: 3384, SEQ ID NO: 3394, SEQ ID NO: 3404, or SEQ ID NO: 3414.

[0369] In some embodiments, the first binder comprises a VL comprising a light chain complementarity determining region 2 (LC CDR2) comprising the sequence of SEQ ID NO: 3345, SEQ ID NO: 3325, SEQ ID NO: 3355, SEQ ID NO: 1192, SEQ ID NO: 3375, SEQ ID NO: 3395, SEQ ID NO: 3405, SEQ ID NO: 3415, or SEQ ID NO: 3443.

[0370] In some embodiments, the first binder comprises a VL comprising:(i) a LC CDR1 comprising the sequence of SEQ ID NO: 3344, a LC CDR2 comprising the sequence of SEQ ID NO: 3345, and a LC CDR3 comprising the sequence of SEQ ID NO: 3346;(ii) a LC CDR1 comprising the sequence of SEQ ID NO: 3324, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3326;(iii) a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3355, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356;(iv) a LC CDR1 comprising the sequence of SEQ ID NO: 1191, a LC CDR2 comprising the sequence of SEQ ID NO: 1192, and a LC CDR3 comprising the sequence of SEQ ID NO: 1193;(v) a LC CDR1 comprising the sequence of SEQ ID NO: 3374, a LC CDR2 comprising the sequence of SEQ ID NO: 3375, and a LC CDR3 comprising the sequence of SEQ ID NO: 3376;(vi) a LC CDR1 comprising the sequence of SEQ ID NO: 3384, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3386;(vii) a LC CDR1 comprising the sequence of SEQ ID NO: 3394, a LC CDR2 comprising the sequence of SEQ ID NO: 3395, and a LC CDR3 comprising the sequence of SEQ ID NO: 3396;(viii) a LC CDR1 comprising the sequence of SEQ ID NO: 3404, a LC CDR2 comprising the sequence of SEQ ID NO: 3405, and a LC CDR3 comprising the sequence of SEQ ID NO: 3406;(ix) a LC CDR1 comprising the sequence of SEQ ID NO: 3414, a LC CDR2 comprising the sequence of SEQ ID NO: 3415, and a LC CDR3 comprising the sequence of SEQ ID NO: 3416; or(x) a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3443, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356.

[0371] In some embodiments, the first binder comprises:(i) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3341, a HC CDR2 comprising the sequence of SEQ ID NO: 3342, a HC CDR3 comprising the sequence of SEQ ID NO: 3343, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3344, a LC CDR2 comprising the sequence of SEQ ID NO: 3345, and a LC CDR3 comprising the sequence of SEQ ID NO: 3346;(ii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3321, a HC CDR2 comprising the sequence of SEQ ID NO: 3322, a HC CDR3 comprising the sequence of SEQ ID NO: 3323, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3324, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3326;(iii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3351, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, a HC CDR3 comprising the sequence of SEQ ID NO: 3353, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3355, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356;(iv) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 1190, a HC CDR2 comprising the sequence of SEQ ID NO: 1186, a HC CDR3 comprising the sequence of SEQ ID NO: 1187, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 1191, a LC CDR2 comprising the sequence of SEQ ID NO: 1192, and a LC CDR3 comprising the sequence of SEQ ID NO: 1193;(v) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3371, a HC CDR2 comprising the sequence of SEQ ID NO: 3372, a HC CDR3 comprising the sequence of SEQ ID NO: 3373, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3374, a LC CDR2 comprising the sequence of SEQ ID NO: 3375, and a LC CDR3 comprising the sequence of SEQ ID NO: 3376;(vi) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3381, a HC CDR2 comprising the sequence of SEQ ID NO: 3382, a HC CDR3 comprising the sequence of SEQ ID NO: 3383, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3384, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3386;(vi) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3391, a HC CDR2 comprising the sequence of SEQ ID NO: 3392, a HC CDR3 comprising the sequence of SEQ ID NO: 3393, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3394, a LC CDR2 comprising the sequence of SEQ ID NO: 3395, and a LC CDR3 comprising the sequence of SEQ ID NO: 3396;(vii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3401, a HC CDR2 comprising the sequence of SEQ ID NO: 3402, a HC CDR3 comprising the sequence of SEQ ID NO: 3403, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3404, a LC CDR2 comprising the sequence of SEQ ID NO: 3405, and a LC CDR3 comprising the sequence of SEQ ID NO: 3406;(viii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3411, a HC CDR2 comprising the sequence of SEQ ID NO: 3412, a HC CDR3 comprising the sequence of SEQ ID NO: 3413, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3414, a LC CDR2 comprising the sequence of SEQ ID NO: 3415, and a LC CDR3 comprising the sequence of SEQ ID NO: 3416;(ix) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3351, SEQ ID NO: 3421, or SEQ ID NO: 3702, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, a HC CDR3 comprising the sequence of SEQ ID NO: 3353, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3355, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356; or(x) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3351, SEQ ID NO: 3421, or SEQ ID NO: 3702, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, a HC CDR3 comprising the sequence of SEQ ID NO: 3353, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3443, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356.

[0372] In some embodiments, the first binder comprises a VH comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO: 3445, SEQ ID NO: 3448, SEQ ID NO: 3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO: 3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO: 3465, and SEQ ID NO: 3470.

[0373] In some embodiments, the first binder comprises a VH comprising any one sequence selected from the group consisting of: SEQ ID NO: 3445, SEQ ID NO: 3448, SEQ ID NO: 3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO: 3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO:3465, and SEQ ID NO: 3470.

[0374] In some embodiments, the first binder comprises a VL comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO: 3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO: 3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO: 3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

[0375] In some embodiments, the first binder comprises a VL comprising any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO: 3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO: 3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO:3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

[0376] In some embodiments, the first binder comprises:(i) a VH comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO: 3445, SEQ ID NO: 3448, SEQ ID NO: 3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO: 3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO:3465, and SEQ ID NO: 3470; and(ii) a VL comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO: 3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO: 3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO:3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

[0377] In some embodiments, the first binder comprises:(i) a VH comprising any one sequence selected from the group consisting of: SEQ ID NO: 3445, SEQ ID NO: 3448, SEQ ID NO: 3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO: 3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO: 3465, and SEQ ID NO: 3470; and(ii) a VL comprising any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO: 3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO: 3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO: 3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

[0378] In some embodiments, the first binder comprises:(i) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3445, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3446;(ii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3448, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3449;(iii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3450, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3451;(iv) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1346, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1349;(v) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1196, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1195;(v) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3455, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3456;(vi) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3457, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3458;(vii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3463, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3464;(viii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3465, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3466;(ix) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3470, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3471;(x) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1346, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3475; or(xi) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1346, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3476.

[0379] In some embodiments, the first binder comprises:(i) a VH comprising the sequence of SEQ ID NO: 3445, and a VL comprising the sequence of SEQ ID NO: 3446;(ii) a VH comprising the sequence of SEQ ID NO: 3448, and a VL comprising the sequence of SEQ ID NO: 3449;(iii) a VH comprising the sequence of SEQ ID NO: 3450, and a VL comprising the sequence of SEQ ID NO: 3451;(iv) a VH comprising the sequence of SEQ ID NO: 1346, and a VL comprising the sequence of SEQ ID NO: 1349;(v) a VH comprising the sequence of SEQ ID NO: 1196, and a VL comprising the sequence of SEQ ID NO: 1195;(vi) a VH comprising the sequence of SEQ ID NO: 3455, and a VL comprising the sequence of SEQ ID NO: 3456;(vii) a VH comprising the sequence of SEQ ID NO: 3457, and a VL comprising the sequence of SEQ ID NO: 3458;(viii) a VH comprising the sequence of SEQ ID NO: 3463, and a VL comprising the sequence of SEQ ID NO: 3464;(ix) a VH comprising the sequence of SEQ ID NO: 3465, and a VL comprising the sequence of SEQ ID NO: 3466;(x) a VH comprising the sequence of SEQ ID NO: 3470, and a VL comprising the sequence of SEQ ID NO: 3471;(xi) a VH comprising the sequence of SEQ ID NO: 1346, and a VL comprising the sequence of SEQ ID NO: 3475; or(xii) a VH comprising the sequence of SEQ ID NO: 1346, and a VL comprising the sequence of SEQ ID NO: 3476.

[0380] In some embodiments, the second binder comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 3 (HC CDR3) comprising the sequence of SEQ ID NO: 3343, SEQ ID NO: 3323, SEQ ID NO: 3353, SEQ ID NO: 1187, SEQ ID NO: 3373, SEQ ID NO: 3383, SEQ ID NO: 3393, SEQ ID NO: 3403, or SEQ ID NO: 3413.

[0381] In some embodiments, the second binder comprises a VH comprising a heavy chain complementarity determining region 1 (HC CDR1) comprising the sequence of SEQ ID NO: 3341, SEQ ID NO: 3321, SEQ ID NO: 3351, SEQ ID NO: 1190, SEQ ID NO: 3371, SEQ ID NO: 3381, SEQ ID NO: 3391, SEQ ID NO: 3401, SEQ ID NO: 3411, SEQ ID NO: 3421, or SEQ ID NO: 3702.

[0382] In some embodiments, the second binder comprises a VH comprising a heavy chain complementarity determining region 2 (HC CDR2) comprising the sequence of SEQ ID NO: 3342, SEQ ID NO: 3322, SEQ ID NO: 3352, SEQ ID NO: 1186, SEQ ID NO: 3372, SEQ ID NO: 3382, SEQ ID NO: 3392, SEQ ID NO: 3402, or SEQ ID NO: 3412.

[0383] In some embodiments, the second binder comprises a VH comprising:(i) a HC CDR1 comprising the sequence of SEQ ID NO: 3341, a HC CDR2 comprising the sequence of SEQ ID NO: 3342, and a HC CDR3 comprising the sequence of SEQ ID NO: 3343;(ii) a HC CDR1 comprising the sequence of SEQ ID NO: 3321, a HC CDR2 comprising the sequence of SEQ ID NO: 3322, and a HC CDR3 comprising the sequence of SEQ ID NO: 3323;(iii) a HC CDR1 comprising the sequence of SEQ ID NO: 3351, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, and a HC CDR3 comprising the sequence of SEQ ID NO: 3353;(iv) a HC CDR1 comprising the sequence of SEQ ID NO: 1190, a HC CDR2 comprising the sequence of SEQ ID NO: 1186, and a HC CDR3 comprising the sequence of SEQ ID NO: 1187;(v) a HC CDR1 comprising the sequence of SEQ ID NO: 3371, a HC CDR2 comprising the sequence of SEQ ID NO: 3372, and a HC CDR3 comprising the sequence of SEQ ID NO: 3373;(vi) a HC CDR1 comprising the sequence of SEQ ID NO: 3381, a HC CDR2 comprising the sequence of SEQ ID NO: 3382, and a HC CDR3 comprising the sequence of SEQ ID NO: 3383;(vii) a HC CDR1 comprising the sequence of SEQ ID NO: 3391, a HC CDR2 comprising the sequence of SEQ ID NO: 3392, and a HC CDR3 comprising the sequence of SEQ ID NO: 3393;(viii) a HC CDR1 comprising the sequence of SEQ ID NO: 3401, a HC CDR2 comprising the sequence of SEQ ID NO: 3402, and a HC CDR3 comprising the sequence of SEQ ID NO: 3403;(ix) a HC CDR1 comprising the sequence of SEQ ID NO: 3351, SEQ ID NO: 3421, or SEQ ID NO: 3702, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, and a HC CDR3 comprising the sequence of SEQ ID NO: 3353; or(x) a HC CDR1 comprising the sequence of SEQ ID NO: 3411, a HC CDR2 comprising the sequence of SEQ ID NO: 3412, and a HC CDR3 comprising the sequence of SEQ ID NO: 3413.

[0384] In some embodiments, the second binder comprises a light chain variable region (VL) comprising a light chain complementarity determining region 3 (LC CDR3) comprising the sequenceof SEQ ID NO: 3346, SEQ ID NO: 3326, SEQ ID NO: 3356, SEQ ID NO: 1193, SEQ ID NO: 3376, SEQ ID NO: 3386, SEQ ID NO: 3396, SEQ ID NO: 3406, or SEQ ID NO: 3416.

[0385] In some embodiments, the second binder comprises a VL comprising a light chain complementarity determining region 1 (LC CDR1) comprising the sequence of SEQ ID NO: 3344, SEQ ID NO: 3324, SEQ ID NO: 3354, SEQ ID NO: 1191, SEQ ID NO: 3374, SEQ ID NO: 3384, SEQ ID NO: 3394, SEQ ID NO: 3404, or SEQ ID NO: 3414.

[0386] In some embodiments, the second binder comprises a VL comprising a light chain complementarity determining region 2 (LC CDR2) comprising the sequence of SEQ ID NO: 3345, SEQ ID NO: 3325, SEQ ID NO: 3355, SEQ ID NO: 1192, SEQ ID NO: 3375, SEQ ID NO: 3395, SEQ ID NO: 3405, SEQ ID NO: 3415, or SEQ ID NO: 3443.

[0387] In some embodiments, the second binder comprises a VL comprising:(i) a LC CDR1 comprising the sequence of SEQ ID NO: 3344, a LC CDR2 comprising the sequence of SEQ ID NO: 3345, and a LC CDR3 comprising the sequence of SEQ ID NO: 3346;(ii) a LC CDR1 comprising the sequence of SEQ ID NO: 3324, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3326;(iii) a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3355, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356;(iv) a LC CDR1 comprising the sequence of SEQ ID NO: 1191, a LC CDR2 comprising the sequence of SEQ ID NO: 1192, and a LC CDR3 comprising the sequence of SEQ ID NO: 1193;(v) a LC CDR1 comprising the sequence of SEQ ID NO: 3374, a LC CDR2 comprising the sequence of SEQ ID NO: 3375, and a LC CDR3 comprising the sequence of SEQ ID NO: 3376;(vi) a LC CDR1 comprising the sequence of SEQ ID NO: 3384, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3386;(vii) a LC CDR1 comprising the sequence of SEQ ID NO: 3394, a LC CDR2 comprising the sequence of SEQ ID NO: 3395, and a LC CDR3 comprising the sequence of SEQ ID NO: 3396;(viii) a LC CDR1 comprising the sequence of SEQ ID NO: 3404, a LC CDR2 comprising the sequence of SEQ ID NO: 3405, and a LC CDR3 comprising the sequence of SEQ ID NO: 3406;(ix) a LC CDR1 comprising the sequence of SEQ ID NO: 3414, a LC CDR2 comprising the sequence of SEQ ID NO: 3415, and a LC CDR3 comprising the sequence of SEQ ID NO: 3416; or(x) a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3443, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356.

[0388] In some embodiments, the second binder comprises:(i) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3341, a HC CDR2 comprising the sequence of SEQ ID NO: 3342, a HC CDR3 comprising the sequence of SEQ ID NO: 3343, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3344, a LC CDR2 comprising the sequence of SEQ ID NO: 3345, and a LC CDR3 comprising the sequence of SEQ ID NO: 3346;(ii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3321, a HC CDR2 comprising the sequence of SEQ ID NO: 3322, a HC CDR3 comprising the sequence of SEQ ID NO:3323, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3324, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3326;(iii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3351, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, a HC CDR3 comprising the sequence of SEQ ID NO: 3353, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3355, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356;(iv) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 1190, a HC CDR2 comprising the sequence of SEQ ID NO: 1186, a HC CDR3 comprising the sequence of SEQ ID NO: 1187, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 1191, a LC CDR2 comprising the sequence of SEQ ID NO: 1192, and a LC CDR3 comprising the sequence of SEQ ID NO: 1193;(v) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3371, a HC CDR2 comprising the sequence of SEQ ID NO: 3372, a HC CDR3 comprising the sequence of SEQ ID NO: 3373, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3374, a LC CDR2 comprising the sequence of SEQ ID NO: 3375, and a LC CDR3 comprising the sequence of SEQ ID NO: 3376;(vi) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3381, a HC CDR2 comprising the sequence of SEQ ID NO: 3382, a HC CDR3 comprising the sequence of SEQ ID NO: 3383, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3384, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3386;(vii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3391, a HC CDR2 comprising the sequence of SEQ ID NO: 3392, a HC CDR3 comprising the sequence of SEQ ID NO: 3393, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3394, a LC CDR2 comprising the sequence of SEQ ID NO: 3395, and a LC CDR3 comprising the sequence of SEQ ID NO: 3396;(viii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3401, a HC CDR2 comprising the sequence of SEQ ID NO: 3402, a HC CDR3 comprising the sequence of SEQ ID NO: 3403, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3404, a LC CDR2 comprising the sequence of SEQ ID NO: 3405, and a LC CDR3 comprising the sequence of SEQ ID NO: 3406;(ix) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3411, a HC CDR2 comprising the sequence of SEQ ID NO: 3412, a HC CDR3 comprising the sequence of SEQ ID NO: 3413, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3414, a LC CDR2 comprising the sequence of SEQ ID NO: 3415, and a LC CDR3 comprising the sequence of SEQ ID NO: 3416;(x) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3351, SEQ ID NO: 3421, or SEQ ID NO: 3702, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, a HC CDR3 comprising the sequence of SEQ ID NO: 3353, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3355, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356; or(xi) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3351, SEQ ID NO: 3421, or SEQ ID NO: 3702, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, a HC CDR3 comprising the sequence of SEQ ID NO: 3353, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3443, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356.

[0389] In some embodiments, the second binder comprises a VH comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO:3445, SEQ ID NO: 3448, SEQ ID NO: 3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO:3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO: 3465, and SEQ ID NO: 3470.

[0390] In some embodiments, the second binder comprises a VH comprising any one sequence selected from the group consisting of: SEQ ID NO: 3445, SEQ ID NO: 3448, SEQ ID NO: 3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO: 3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO: 3465, and SEQ ID NO: 3470.

[0391] In some embodiments, the second binder comprises a VL comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO:3446, SEQ ID NO: 3449, SEQ ID NO: 3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO:3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO: 3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

[0392] In some embodiments, the second binder comprises a VL comprising any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO: 3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO: 3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO: 3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

[0393] In some embodiments, the second binder comprises:(i) a VH comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO: 3445, SEQ ID NO: 3448, SEQ ID NO: 3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO: 3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO:3465, and SEQ ID NO: 3470; and(ii) a VL comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO: 3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO: 3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO:3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

[0394] In some embodiments, the second binder comprises:(i) a VH comprising any one sequence selected from the group consisting of: SEQ ID NO: 3445, SEQ ID NO: 3448, SEQ ID NO: 3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO: 3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO: 3465, and SEQ ID NO: 3470; and(ii) a VL comprising any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO: 3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO: 3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO: 3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

[0395] In some embodiments, the second binder comprises:(i) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3445, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3446;(ii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3448, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3449;(iii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3450, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3451;(iv) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1346, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1349;(v) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1196, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1195;(vi) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3455, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3456;(vii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3457, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3458;(viii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3463, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3464;(ix) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3465, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3466;(x) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3470, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3471;(xi) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1346, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3475; or(xii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1346, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3476.

[0396] In some embodiments, the second binder comprises:(i) a VH comprising the sequence of SEQ ID NO: 3445, and a VL comprising the sequence of SEQ ID NO: 3446;(ii) a VH comprising the sequence of SEQ ID NO: 3448, and a VL comprising the sequence of SEQ ID NO: 3449;(iii) a VH comprising the sequence of SEQ ID NO: 3450, and a VL comprising the sequence of SEQ ID NO: 3451;(iv) a VH comprising the sequence of SEQ ID NO: 1346, and a VL comprising the sequence of SEQ ID NO: 1349;(v) a VH comprising the sequence of SEQ ID NO: 1196, and a VL comprising the sequence of SEQ ID NO: 1195;(vi) a VH comprising the sequence of SEQ ID NO: 3455, and a VL comprising the sequence of SEQ ID NO: 3456;(vii) a VH comprising the sequence of SEQ ID NO: 3457, and a VL comprising the sequence of SEQ ID NO: 3458;(viii) a VH comprising the sequence of SEQ ID NO: 3463, and a VL comprising the sequence of SEQ ID NO: 3464;(ix) a VH comprising the sequence of SEQ ID NO: 3465, and a VL comprising the sequence of SEQ ID NO: 3466;(x) a VH comprising the sequence of SEQ ID NO: 3470, and a VL comprising the sequence of SEQ ID NO: 3471;(xi) a VH comprising the sequence of SEQ ID NO: 1346, and a VL comprising the sequence of SEQ ID NO: 3475; or(xii) a VH comprising the sequence of SEQ ID NO: 1346, and a VL comprising the sequence of SEQ ID NO: 3476.

[0397] In some embodiments, the first binder and the second binder bind to different TCRpV regions.

[0398] In some embodiments, the first binder and the second binder bind to different TCRpV s belonging to different subfamilies.

[0399] In some embodiments, the first binder and the second binder bind to different members of the same TCRpV subfamily.

[0400] In some embodiments, the first binder comprises one or more heavy chain constant regions selected from the group consisting of IgGl heavy chain constant region or fragment thereof, IgG2 heavy chain constant region or fragment thereof, IgG3 heavy chain constant region or fragmentthereof, IgGAl heavy chain constant region or fragment thereof, IgGA2 heavy chain constant region or fragment thereof, IgG4 heavy chain constant region or fragment thereof, IgJ heavy chain constant region or fragment thereof, IgM heavy chain constant region or fragment thereof, IgD heavy chain constant region or fragment thereof, and IgE heavy chain constant region or fragment thereof.

[0401] In some embodiments, the first binder comprises a kappa light chain constant region or fragment thereof, a lambda light chain constant region or fragment thereof, or a combination thereof.

[0402] In some embodiments, the second binder comprises one or more heavy chain constant regions selected from the group consisting of IgGl heavy chain constant region or fragment thereof, IgG2 heavy chain constant region or fragment there-of, IgG3 heavy chain constant region or fragment thereof, IgGAl heavy chain constant region or fragment thereof, IgGA2 heavy chain constant region or fragment thereof, IgG4 heavy chain constant region or fragment thereof, IgJ heavy chain constant region or fragment thereof, IgM heavy chain constant region or fragment thereof, IgD heavy chain constant region or fragment thereof, and IgE heavy chain constant region or fragment thereof.

[0403] In some embodiments, the second binder comprises a kappa light chain constant region or fragment thereof, a lambda light chain constant region or fragment thereof, or a combination thereof.

[0404] In some embodiments, the first agent is a multifunctional molecule.

[0405] In some embodiments, the first agent is a multispecific molecule.

[0406] In some embodiments, the second agent is a multifunctional molecule.

[0407] In some embodiments, the second agent is a multispecific molecule.

[0408] In some embodiments, the first agent, the second agent, or a combination thereof comprises at least two non-contiguous polypeptide chains; wherein a first polypeptide chain of the at least two non-contiguous polypeptide chains comprises a first Fc region, and a second polypeptide chain of the at least two non-contiguous polypeptide chains comprises a second Fc region; and wherein the first Fc region and the second Fc region comprise an Fc interface with a knob-in-a hole.

[0409] In some embodiments, the first Fc region, the second Fc region, or a combination thereof comprises an Asn297Ala mutation, a Leu234Ala / Leu235Ala mutation, or a combination thereof.

[0410] In some embodiments, the first agent is a multispecific molecule that further comprises one or more of a tumor-targeting moiety, a cytokine molecule, a stromal modifying moiety, or an immune cell engager.

[0411] In some embodiments, the second agent is a multispecific molecule that further comprises one or more of a tumor-targeting moiety, a cytokine molecule, a stromal modifying moiety, or an immune cell engager.

[0412] In some embodiments, the first agent comprises the following configuration:A-, B-[dimerization module] -C, -D, wherein:(a) the dimerization module comprises a first immunoglobulin chain constant region and a second immunoglobulin chain constant region;(b) A and C are linked to the first immunoglobulin chain constant region; and B and D are linked to the second immunoglobulin chain constant region;(c) A, B, C, and D are independently (i) absent; (ii) the first binder; (iii) the tumor targeting moiety, (iv) the cytokine molecule; (v) stromal modifying moiety; or (vi) the immune cell engager; and wherein at least one, two, or three of A, B, C, and D comprises the first binder.

[0413] In some embodiments, the second agent comprises the following configuration:A-, B-[dimerization module] -C, -D, wherein:(a) the dimerization module comprises a first immunoglobulin chain constant region and a second immunoglobulin chain constant region;(b) A and C are linked to the first immunoglobulin chain constant region; and B and D are linked to the second immunoglobulin chain constant region;(c) A, B, C, and D are independently (i) absent; (ii) the second binder; (iii) the tumor targeting moiety, (iv) the cytokine molecule; (v) stromal modifying moiety; or (vi) the immune cell engager; and wherein at least one, two, or three of A, B, C, and D comprises the second binder.

[0414] In some embodiments, the first immunoglobulin chain constant region comprises the first fragment crystalizable region (Fc region) and the second first immunoglobulin chain constant region comprises the second fragment crystallizable region (Fc region).

[0415] In some embodiments, dimerization of the first Fc region and the second Fc region is enhanced by providing an Fc interface of the first Fc region and the second Fc region with one or more of a paired cavity-protuberance, an electrostatic interaction, or a strand-exchange, such that a greater ratio of heteromultimer to homomultimer forms relative to a non-engineered interface.

[0416] In some embodiments, the immune cell engager is selected from the group consisting of a T cell engager, an NK cell engager, a B cell engager, a dendritic cell engager, a macrophage cell engager, and any combination thereof.

[0417] In some embodiments, the cytokine molecule is selected from the group consisting of interleukin-2 (IL-2) or functional variant thereof, interleu-kin-7 (IL-7) or functional variant thereof, interleukin- 12 (IL-12) or functional variant thereof, interleukin- 15 (IL-15) or functional variant thereof, interleukin- 18 (IL- 18) or functional variant thereof, interleukin-21 (IL-21) or functional variant thereof, interferon gamma or functional variant thereof, and any combination thereof.

[0418] In some embodiments, the cytokine molecule comprises interleukin-2 (IL-2) or functional variant thereof.

[0419] In some embodiments, the interleukin-2 (IL-2) or functional variant thereof comprises the sequence of SEQ ID NO : 2270 or SEQ ID NO : 2191.

[0420] In some embodiments, the cytokine molecule comprises interleukin- 15 (IL- 15) or functional variant thereof.

[0421] In some embodiments, the interleukin- 15 (IL- 15) or functional variant thereof comprises the sequence of SEQ ID NO: 2170.

[0422] In some embodiments, the cytokine molecule further comprises an IL15Ralpha dimerizing domain covalently linked the interleukin- 15 (IL-15) or functional variant thereof.

[0423] In some embodiments, the IL15Ralpha dimerizing domain comprises an IL- 15 receptor alpha sushi domain or functional variant thereof.

[0424] In some embodiments, the IL15Ralpha dimerizing domain comprises the sequence of SEQ ID NO: 3472.

[0425] In some embodiments, the interleukin- 15 (IL- 15) or functional variant thereof is covalently linked to the IL15Ralpha dimerizing domain via a link-er.

[0426] In some embodiments, the interleukin- 15 (IL- 15) or functional variant thereof is covalently linked to the IL15Ralpha dimerizing domain via a linker comprising the sequence of SEQ ID NO: 3473.

[0427] In some embodiments, the cytokine molecule comprises the sequence of SEQ ID NO: 3474.

[0428] In some embodiments, the stromal modifying moiety is selected from the group consisting of a hyaluronidase, a collagenase, a chondroitinase, and a matrix metalloproteinase.

[0429] In some embodiments, the tumor-targeting moiety binds to a cancer antigen.

[0430] In some embodiments, the tumor-targeting moiety binds to a cancer antigen.

[0431] In some embodiments, the cancer antigen is present on a hematological cancer, a solid tumor, a metastatic cancer, a soft tissue tumor, a metastatic lesion, or a combination thereof.

[0432] In some embodiments, the cancer antigen is a tumor antigen, a stromal antigen, or a hematological antigen.

[0433] In some embodiments, the cancer antigen is selected from the group consisting of BCMA, CD19, CD20, CD22, FcRH5, PDL1, CD47, ganglioside 2 (GD2), prostate stem cell antigen (PSCA), prostate specific membrane antigen (PMSA), prostate-specific antigen (PSA), carcinoembryonic antigen (CEA), Ron Kinase, c-Met, Immature laminin receptor, TAG-72, BING-4, Calcium-activated chloride channel 2, Cyclin-Bl, 9D7, Ep-CAM, EphA3, Her2 / neu, Telomerase, SAP-1, Survivin, NY- ESO-l / LAGE-1, PRAME, SSX-2, Melan-A / MART-1, Gpl00 / pmell7, Tyrosinase, MC1R, p-catenin, BRCA1 / 2, CDK4, CML66, Fibronectin, p53, Ras, TGF-B receptor, AFP, ETA, MAGE, CA-125, BAGE, GAGE, CDC27, a actinin-4, TRPl / gp75, TRP2, gangliosides, WT1, Epidermal growth factor receptor (EGFR), MART-2, MUC1, MUC2, MUM1, MUM2, MUM3, NA88-1, NPM, OA1, OGT, RCC, RU11, RU12, SAGE, TRG, TSTA, Folate receptor alpha, LI -CAM, CAIX, gpA33, GD3, GM2, VEGFR, Integrins, Carbohydrates, IGF1R, TRAILR1, TRAILR2, RANKL, FAP, TGF-beta, hyaluronic acid, collagen, tenascin C, and tenascin W.

[0434] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3445, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3446, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0435] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3448, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3449, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0436] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3450, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3451, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0437] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3450, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3454 or the sequence of SEQ ID NO: 3501 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3451, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0438] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3454 or the sequence of SEQ ID NO: 3501 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 1349, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0439] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1196, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 1195, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0440] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3455, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3456, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0441] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3457, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3459, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3460,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3462 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2191, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3458, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3461.

[0442] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3463, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3459, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3460,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3462 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2191, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3464, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3461.

[0443] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3465, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3467, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3468,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3469 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2191, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3466, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3461.

[0444] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3470, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3471, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0445] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-15 or functional variant thereof comprising the sequence of SEQ ID NO: 2170, wherein the IL-15 or functional variant thereof is covalently linked to an IL15Ralpha dimerizing domain comprising the sequence of the SEQ ID NO: 3472 via a linker comprising the sequence of SEQ ID NO: 3473, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 1349, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0446] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-15 or functional variant thereof comprising the sequence of SEQ ID NO: 2170, wherein the IL-15 or functional variant thereof is covalently linked to an IL15Ralpha dimerizing domain comprising the sequence of the SEQ ID NO: 3472 via a linker comprising the sequence of SEQ ID NO: 3473, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3475, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0447] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-15 or functionalvariant thereof comprising the sequence of SEQ ID NO: 2170, wherein the IL-15 or functional variant thereof is covalently linked to an IL15Ralpha dimerizing domain comprising the sequence of the SEQ ID NO: 3472 via a linker comprising the sequence of SEQ ID NO: 3473, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3476, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0448] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3445, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3446, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0449] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3448, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3449, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0450] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3450, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649,wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3451, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0451] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3450, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3454 or the sequence of SEQ ID NO: 3501 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3451, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0452] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3454 or the sequence of SEQ ID NO: 3501 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 1349, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0453] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1196, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 1195, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0454] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3455, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3456, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0455] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3457, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3459, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3460,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3462 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2191, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3458, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3461.

[0456] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3463, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3459, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3460,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3462 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2191, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3464, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3461.

[0457] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3465, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3467, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3468,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3469 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2191, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3466, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3461.

[0458] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3470, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3471, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0459] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-15 or functional variant thereof comprising the sequence of SEQ ID NO: 2170, wherein the IL-15 or functional variant thereof is covalently linked to an IL15Ralpha dimerizing domain comprising the sequence of the SEQ ID NO: 3472 via a linker comprising the sequence of SEQ ID NO: 3473, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 1349, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0460] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-15 or functional variant thereof comprising the sequence of SEQ ID NO: 2170, wherein the IL-15 or functional variant thereof is covalently linked to an IL15Ralpha dimerizing domain comprising the sequence of the SEQ ID NO: 3472 via a linker comprising the sequence of SEQ ID NO: 3473, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3475, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0461] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-15 or functional variant thereof comprising the sequence of SEQ ID NO: 2170, wherein the IL-15 or functional variant thereof is covalently linked to an IL15Ralpha dimerizing domain comprising the sequence of the SEQ ID NO: 3472 via a linker comprising the sequence of SEQ ID NO: 3473, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3476, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

[0462] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3338;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3339.

[0463] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3318;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3319.

[0464] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3328;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3329.

[0465] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3328;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3350 or the sequence of SEQ ID NO: 3500; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3329.

[0466] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3349.

[0467] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3358;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3359.

[0468] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3368;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3369.

[0469] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3378;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3380; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3379.

[0470] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3388;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3390; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3389.

[0471] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3398;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3400; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3399.

[0472] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3408;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3409.

[0473] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3349.

[0474] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3428.

[0475] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3437.

[0476] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3338;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3339.

[0477] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3318;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3319.

[0478] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3328;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3329.

[0479] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3328;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3350 or the sequence of SEQ ID NO: 3500; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3329.

[0480] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3349.

[0481] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3358;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3359.

[0482] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3368;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3369.

[0483] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3378;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3380; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3379.

[0484] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3388;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3390; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3389.

[0485] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3398;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3400; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3399.

[0486] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3408;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3409.

[0487] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3349.

[0488] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3428.

[0489] In some embodiments, the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3437.

[0490] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3338;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3339.

[0491] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3318;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3319.

[0492] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3328;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3329.

[0493] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3328;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3350 or the sequence of SEQ ID NO: 3500; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3329.

[0494] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3349.

[0495] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3358;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3359.

[0496] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3368;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3369.

[0497] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3378;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3380; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3379.

[0498] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3388;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3390; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3389.

[0499] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3398;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3400; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3399.

[0500] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3408;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3409.

[0501] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3349.

[0502] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3428.

[0503] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3437.

[0504] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3338;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3339.

[0505] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3318;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3319.

[0506] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3328;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3329.

[0507] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3328;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3350 or the sequence of SEQ ID NO: 3500; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3329.

[0508] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3349.

[0509] In some embodiments, the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3358;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) t...

Claims

CLAIMSWHAT IS CLAIMED IS:

1. A method of treating a disease or condition in a subject in need thereof comprising administering a first agent that comprises a first binder that binds to a first target molecule to the subject, and administering a second agent that comprises a second binder that binds to a second target molecule to the subject, thereby treating the disease or condition in the subject; wherein an administration of the first agent is followed by an administration of the second agent; wherein the first target molecule and the second target molecule are independently selected from the group consisting of a T cell receptor alpha variable region (TCRaV) and a T cell receptor beta variable region (TCRpV); and wherein the first target molecule and the second target molecule are different.

2. The method of claim 1, wherein the first agent and the second agent are not concomitantly administered to the subject.

3. The method of claim 1 or 2, wherein administering the first agent comprises administering a therapeutically effective amount of the first agent to the subject.

4. The method of any one of claims 1-3, wherein administering the second agent comprises administering a therapeutically effective amount of the second agent to the subject.

5. The method of any one of claims 1-4, wherein the method is more effective to treat the disease or condition in the subject relative to a method in which the first agent is administered to the subject but not the second agent.

6. The method of any one of claims 1-5, wherein the method is more effective to treat the disease or condition in the subject relative to a method in which the second agent is administered to the subject but not the first agent.

7. The method of any one of claims 1-6, wherein the method is more effective to treat the disease or condition in the subject relative to a method in which the first agent is administered to the subject at a first administration and the first agent is administered to the subject subsequently at a second administration.

8. The method of any one of claims 1-7, wherein the method is more effective to treat the disease or condition in the subject relative to a method in which the second agent is administered to the subject at a first administration and the second agent is administered to the subject subsequently at a second administration.

9. The method of any one of claims 1-8, wherein the method is more effective to treat the disease or condition in the subject relative to a method in which the second agent is administered to the subject at a first administration and the first agent is administered to the subject subsequently at a second administration.

10. The method of any one of claims 1-9, wherein the administration of the first agent comprises one or more doses.

11. The method of any one of claims 1-10, wherein the administration of the first agent comprises two or more doses.

12. The method of any one of claims 1-11, wherein the administration of the first agent comprises one dose per week.

13. The method of any one of claims 1-11, wherein the administration of the first agent comprises two or more doses per week.

14. The method of any one of claims 1-11, wherein the first agent is administered to the subject once every two weeks.

15. The method of any one of claims 1-11, wherein the first agent is administered to the subject once every three weeks.

16. The method of any one of claims 1-12, wherein the first agent is administered to the subject once every week for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

17. The method of any one of claims 1-11 and 13, wherein the administration of the first agent comprises two or more doses per week for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

18. The method of any one of claims 1-11 and 14, wherein the first agent is administered to the subject once every two weeks for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

19. The method of any one of claims 1-11 and 15, wherein the first agent is administered to the subject once every three weeks for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

20. The method of any one of claims 1-19, wherein the administration of the second agent comprises one or more doses.

21. The method of any one of claims 1-20, wherein the administration of the second agent comprises two or more doses.

22. The method of any one of claims 1-21, wherein the administration of the second agent comprises one dose per week.

23. The method of any one of claims 1-21, wherein the administration of the second agent comprises two or more doses per week.

24. The method of any one of claims 1-21, wherein the second agent is administered to the subject once every two weeks.

25. The method of any one of claims 1-21, wherein the second agent is administered to the subject once every three weeks.

26. The method of any one of claims 1-22, wherein the second agent is administered to the subject once every week for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

27. The method of any one of claims 1-21 and 23, wherein the administration of the second agent comprises two or more doses per week for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

28. The method of any one of claims 1-21 and 24, wherein the second agent is administered to the subject once every two weeks for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

29. The method of any one of claims 1-21 and 25, wherein the second agent is administered to the subject once every three weeks for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

30. The method of any one of claims 1-29, wherein the administration of the first agent and the administration of the second agent is separated by one week.

31. The method of any one of claims 1-29, wherein the administration of the first agent and the administration of the second agent is separated by two or more weeks.

32. The method of any one of claims 1-29, wherein the administration of the first agent and the administration of the second agent is separated by 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 12 months.

33. The method of any one of claims 1-32, wherein the administration of the first agent and the second agent is repeated twice or more.

34. The method of any one of claims 1-12, 16, 20-23, 26, 30, 32, and 33, wherein the first agent and the second agent are administered to the subject according to a dosing regimen, wherein the dosing regimen comprises an administration of the first agent once every week for two weeks followed by an administration of the second agent once a week for two weeks, wherein the second agent is administered to the subject one week after the last administration of the first agent.

35. The method of claim 34, wherein the dosing regimen is repeated twice or more.

36. The method of claim 34 or 35, wherein the dosing regimen is repeated at the interval of one week.

37. The method of any one of claims 34-36, wherein the dosing regimen is repeated at the interval of 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 12 months.

38. The method of any one of claims 1-37, wherein the first agent and the second agent are administered to the subject in a same amount.

39. The method of any one of claims 1-37, wherein the first agent and the second agent are administered to the subject in different amounts.

40. The method of any one of claims 1-39, wherein the administration of the first agent comprises two or more doses, and each dose comprises a same amount of the first agent.

41. The method of any one of claims 1-39, wherein the administration of the first agent comprises two or more doses, and each dose comprises different amounts of the first agent.

42. The method of any one of claims 1-41, wherein the administration of the second agent comprises two or more doses, and each dose comprises a same amount of the second agent.

43. The method of any one of claims 1-41, wherein the administration of the second agent comprises two or more doses, and each dose comprises different amounts of the second agent.

44. The method of any one of claims 1-43, wherein the first agent is administered to the subject at a dose of from about 0.001 mg / kg to about 10 mg / kg.

45. The method of any one of claims 1-44, wherein the second agent is administered to the subject at a dose of from about 0.001 mg / kg to about 10 mg / kg.

46. The method of any one of claims 1-45, wherein the first agent is administered to the subject at a dose of about 0.3 mg / kg or about 1 mg / kg.

47. The method of any one of claims 1-46, wherein the second agent is administered to the subject at a dose of about 0.3 mg / kg or about 1 mg / kg.

48. The method of any one of claims 1-47, wherein the first target molecule is a first TCRpV, and the second target molecule is a second TCRpV, wherein the first TCRpV and the second TCRpV are different.

49. The method of any one of claims 1-45, wherein the first target molecule is a first TCRaV, and the second target molecule is a second TCRaV, wherein the first TCRaV and the second TCRaV are different.

50. The method of any one of claims 1-45, wherein the first target molecule is a TCRpV, and the second target molecule is a TCRaV.

51. The method of any one of claims 1-45, wherein the first target molecule is a TCRaV, and the second target molecule is a TCRpV.

52. The method of any one of claims 1-48 and 50, wherein the first target molecule is human TCRPV6.

53. The method of any one of claims 1-48 and 50, wherein the first target molecule is human TCRPV 10.

54. The method of any one of claims 1-48 and 51, wherein the second target molecule is human TCRPV15.

55. The method of any one of claims 1-48 and 51, wherein the second target molecule is human TCRPV27.

56. The method of any one of claims 1-48 and 51, wherein the second target molecule is human TCRPV5.

57. The method of any one of claims 1-48, 52, and 56, wherein the first target molecule is human TCRPV6, and the second target molecule is human TCRPV5.

58. The method of any one of claims 1-48, 52, and 56, wherein the first target molecule is human TCRPV6, and the second target molecule is human TCRPV15.

59. The method of any one of claims 1-48, 52, and 56, wherein the first target molecule is human TCRPV6, and the second target molecule is human TCRPV27.

60. The method of any one of claims 1-48, 53, and 56, wherein the first target molecule is human TCRpVIO, and the second target molecule is human TCRPV5.

61. The method of any one of claims 1-48, 53, and 56, wherein the first target molecule is human TCRpVIO, and the second target molecule is human TCRPV15.

62. The method of any one of claims 1-48, 53, and 56, wherein the first target molecule is human TCRpVIO, and the second target molecule is human TCRPV27.

63. The method of any one of claims 1-48 and 50, wherein the first target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV19, human TRBV20, or human TRBV28.

64. The method of any one of claims 1-48, 50, and 63, wherein the first target molecule is human TRBV5-1, human TRBV6-5, human TRBV10-1, human TRBV10-2, human TRBV10-3, human TRBV7-2, human TRBV7-3, human TRBV19, human TRBV20-1, or human TRBV28.

65. The method of any one of claims 1-45, 49, and 51, wherein the first target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30.

66. The method of any one of claims 1-45, 49, 51, and 65, wherein the first target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30.

67. The method of any one of claims 1-48 and 51, wherein the second target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV15, human TRBV27, human TRBV19, human TRBV20, or human TRBV28.

68. The method of any one of claims 1-48, 51, and 67, wherein the second target molecule is human TRBV5-1, human TRBV6-5, human TRBV10-1, human TRBV10-2, human TRBV10-3, human TRBV7-2, human TRBV7-3, human TRBV15, human TRBV27, human TRBV19, human TRBV20-1, or human TRBV28.

69. The method of any one of claims 1-45, 49, and 50, wherein the second target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30.

70. The method of any one of claims 1-45, 49, 50, and 69, wherein the second target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30.

71. The method of any one of claims 1 -48, 63 , 64, 67, and 68, wherein the first target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV19, human TRBV20, or human TRBV28, and the second target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV15, human TRBV27, human TRBV19, human TRBV20, or human TRBV28, wherein the first target molecule and the second target molecule are different.

72. The method of any one of claims 1-48, 63, 64, 67, 68, and 71, wherein the first target molecule and the second target molecule are: human TRBV5 and human TRBV5, respectively; human TRBV5 and human TRBV6, respectively; human TRBV5 and human TRBV10, respectively; human TRBV5 and human TRBV7, respectively;human TRBV5 and human TRBV19, respectively; human TRBV5 and human TRBV20, respectively; human TRBV5 and human TRBV28, respectively; human TRBV6 and human TRBV5, respectively; human TRBV6 and human TRBV6, respectively; human TRBV6 and human TRBV10, respectively; human TRBV6 and human TRBV7, respectively; human TRBV6 and human TRBV15, respectively; human TRBV6 and human TRBV27, respectively; human TRBV6 and human TRBV19, respectively; human TRBV6 and human TRBV20, respectively; human TRBV6 and human TRBV28, respectively; human TRBV1O and human TRBV5, respectively; human TRBV1O and human TRBV1O, respectively; human TRBV1O and human TRBV6, respectively; human TRBV1O and human TRBV7, respectively; human TRBV1O and human TRBV15, respectively; human TRBV1O and human TRBV27, respectively; human TRBV1O and human TRBV19, respectively; human TRBV1O and human TRBV20, respectively; human TRBV1O and human TRBV28, respectively; human TRBV7 and human TRBV5, respectively; human TRBV7 and human TRBV6, respectively; human TRBV7 and human TRBV1O, respectively; human TRBV7 and human TRBV7, respectively; human TRBV7 and human TRBV19, respectively; human TRBV7 and human TRBV20, respectively; human TRBV7 and human TRBV28, respectively; human TRBV19 and human TRBV5, respectively; human TRBV19 and human TRBV6, respectively; human TRBV19 and human TRBV1O, respectively; human TRBV19 and human TRBV7, respectively; human TRBV19 and human TRBV19, respectively; human TRBV19 and human TRBV20, respectively; human TRBV19 and human TRBV28, respectively; human TRBV20 and human TRBV5, respectively; human TRBV20 and human TRBV6, respectively; human TRBV20 and human TRBV1O, respectively;human TRBV20 and human TRBV7, respectively; human TRBV20 and human TRBV19, respectively; human TRBV20 and human TRBV20, respectively; human TRBV20 and human TRBV28, respectively; human TRBV28 and human TRBV5, respectively; human TRBV28 and human TRBV6, respectively; human TRBV28 and human TRBV10, respectively; human TRBV28 and human TRBV7, respectively; human TRBV28 and human TRBV19, respectively; human TRBV28 and human TRBV20, respectively; or human TRBV28 and human TRBV28, respectively.

73. The method of any one of claims 1-48, 63, 64, 67, and 68, wherein the first target molecule is human TRBV5-1, human TRBV6-5, human TRBV10-1, human TRBV10-2, human TRBV10-3, human TRBV7-2, human TRBV7-3, human TRBV19, human TRBV20-1, or human TRBV28, and the second target molecule is human TRBV5-1, human TRBV6-5, human TRBV10-1, human TRBV10-2, human TRBV10-3, human TRBV7-2, human TRBV7-3, human TRBV15, human TRBV27, human TRBV19, human TRBV20-1, or human TRBV28, wherein the first target molecule and the second target molecule are different.

74. The method of any one of claims 1-48, 63, 64, 67, 68, and 73, wherein the first target molecule and the second target molecule are: human TRBV5-1 and human TRBV6-5, respectively; human TRBV5-1 and human TRBV10-1, respectively; human TRBV5-1 and human TRBV10-2, respectively; human TRBV5-1 and human TRBV10-3, respectively; human TRBV5-1 and human TRBV7-2, respectively; human TRBV5-1 and human TRBV7-3, respectively; human TRBV5-1 and human TRBV19, respectively; human TRBV5-1 and human TRBV20-1, respectively; human TRBV5-1 and human TRBV28, respectively; human TRBV6-5 and human TRBV5-1, respectively; human TRBV6-5 and human TRBV7-2, respectively; human TRBV6-5 and human TRBV7-3, respectively; human TRBV6-5 and human TRBV15, respectively; human TRBV6-5 and human TRBV27, respectively; human TRBV6-5 and human TRBV19, respectively; human TRBV6-5 and human TRBV20-1, respectively; human TRBV6-5 and human TRBV28, respectively; human TRBV10-1 and human TRBV5-1, respectively;human TRBV10-1 and human TRBV7-2, respectively; human TRBV10-1 and human TRBV7-3, respectively; human TRBV10-1 and human TRBV15, respectively; human TRBV10-1 and human TRBV27, respectively; human TRBV10-1 and human TRBV19, respectively; human TRBV10-1 and human TRBV20-1, respectively; human TRBV10-1 and human TRBV28, respectively; human TRBV10-2 and human TRBV5-1, respectively; human TRBV10-2 and human TRBV7-2, respectively; human TRBV10-2 and human TRBV7-3, respectively; human TRBV10-2 and human TRBV15, respectively; human TRBV10-2 and human TRBV27, respectively; human TRBV10-2 and human TRBV19, respectively; human TRBV10-2 and human TRBV20-1, respectively; human TRBV10-2 and human TRBV28, respectively; human TRBV10-3 and human TRBV5-1, respectively; human TRBV10-3 and human TRBV7-2, respectively; human TRBV10-3 and human TRBV7-3, respectively; human TRBV10-3 and human TRBV15, respectively; human TRBV10-3 and human TRBV27, respectively; human TRBV10-3 and human TRBV19, respectively; human TRBV10-3 and human TRBV20-1, respectively; human TRBV10-3 and human TRBV28, respectively; human TRBV7-2 and human TRBV5-1, respectively; human TRBV7-2 and human TRBV6-5, respectively; human TRBV7-2 and human TRBV10-1, respectively; human TRBV7-2 and human TRBV10-2, respectively; human TRBV7-2 and human TRBV10-3, respectively; human TRBV7-2 and human TRBV7-3, respectively; human TRBV7-2 and human TRBV19, respectively; human TRBV7-2 and human TRBV20-1, respectively; human TRBV7-2 and human TRBV28, respectively; human TRBV7-3 and human TRBV5-1, respectively; human TRBV7-3 and human TRBV6-5, respectively; human TRBV7-3 and human TRBV10-1, respectively; human TRBV7-3 and human TRBV10-2, respectively; human TRBV7-3 and human TRBV10-3, respectively; human TRBV7-3 and human TRBV7-2, respectively;human TRBV7-3 and human TRBV19, respectively; human TRBV7-3 and human TRBV20-1, respectively; human TRBV7-3 and human TRBV28, respectively; human TRBV19 and human TRBV5-1, respectively; human TRBV19 and human TRBV6-5, respectively; human TRBV19 and human TRBV10-1, respectively; human TRBV19 and human TRBV10-2, respectively; human TRBV19 and human TRBV10-3, respectively; human TRBV19 and human TRBV7-2, respectively; human TRBV19 and human TRBV7-3, respectively; human TRBV19 and human TRBV20-1, respectively; human TRBV19 and human TRBV28, respectively; human TRBV20-1 and human TRBV5-1, respectively; human TRBV20-1 and human TRBV6-5, respectively; human TRBV20-1 and human TRBV10-1, respectively; human TRBV20-1 and human TRBV10-2, respectively; human TRBV20-1 and human TRBV10-3, respectively; human TRBV20-1 and human TRBV7-2, respectively; human TRBV20-1 and human TRBV7-3, respectively; human TRBV20-1 and human TRBV19, respectively; human TRBV20-1 and human TRBV28, respectively; human TRBV28 and human TRBV5-1, respectively; human TRBV28 and human TRBV6-5, respectively; human TRBV28 and human TRBV10-1, respectively; human TRBV28 and human TRBV10-2, respectively; human TRBV28 and human TRBV10-3, respectively; human TRBV28 and human TRBV7-2, respectively; human TRBV28 and human TRBV7-3, respectively; human TRBV28 and human TRBV19, respectively; or human TRBV28 and human TRBV20-1, respectively.

75. The method of any one of claims 1-45, 49, 65, 66, 69, and 70, wherein the first target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30, and the second target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30, wherein the first target molecule and the second target molecule are different.

76. The method of any one of claims 1-45, 49, 65, 66, 69, 70, and 75, wherein the first target molecule and the second target molecule are: human TRAV12 and human TRAV12, respectively;human TRAV12 and human TRAV13, respectively; human TRAV12 and human TRAV19, respectively; human TRAV12 and human TRAV21, respectively; human TRAV12 and human TRAV30, respectively; human TRAV13 and human TRAV12, respectively; human TRAV13 and human TRAV13, respectively; human TRAV13 and human TRAV19, respectively; human TRAV13 and human TRAV21, respectively; human TRAV13 and human TRAV30, respectively; human TRAV19 and human TRAV12, respectively; human TRAV19 and human TRAV13, respectively; human TRAV19 and human TRAV19, respectively; human TRAV19 and human TRAV21, respectively; human TRAV19 and human TRAV30, respectively; human TRAV21 and human TRAV12, respectively; human TRAV21 and human TRAV13, respectively; human TRAV21 and human TRAV19, respectively; human TRAV21 and human TRAV21, respectively; human TRAV21 and human TRAV30, respectively; human TRAV30 and human TRAV12, respectively; human TRAV30 and human TRAV13, respectively; human TRAV30 and human TRAV19, respectively; human TRAV30 and human TRAV21, respectively; or human TRAV30 and human TRAV30, respectively.

77. The method of any one of claims 1-45, 49, 65, 66, 69, and 70, wherein the first target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30, and the second target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30, wherein the first target molecule and the second target molecule are different.

78. The method of any one of claims 1-45, 49, 65, 66, 69, 70, and 77, wherein the first target molecule and the second target molecule are: human TRAV12-2 and human TRAV13-1, respectively; human TRAV12-2 and human TRAV19, respectively; human TRAV12-2 and human TRAV21, respectively; human TRAV12-2 and human TRAV30, respectively; human TRAV13-1 and human TRAV12-2, respectively; human TRAV13-1 and human TRAV19, respectively; human TRAV13-1 and human TRAV21, respectively; human TRAV13-1 and human TRAV30, respectively;human TRAV19 and human TRAV12-2, respectively; human TRAV19 and human TRAV13-1, respectively; human TRAV19 and human TRAV21, respectively; human TRAV19 and human TRAV30, respectively; human TRAV21 and human TRAV12-2, respectively; human TRAV21 and human TRAV13-1, respectively; human TRAV21 and human TRAV19, respectively; human TRAV21 and human TRAV30, respectively; human TRAV30 and human TRAV12-2, respectively; human TRAV30 and human TRAV13-1, respectively; human TRAV30 and human TRAV19, respectively; or human TRAV30 and human TRAV21, respectively.

79. The method of any one of claims 1-45, 50, 63, 64, 69, and 70, wherein the first target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV19, human TRBV20, or human TRBV28, and the second target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30.

80. The method of any one of claims 1-45, 50, 63, 64, 69, 70, and 79, wherein the first target molecule and the second target molecule are: human TRBV5 and human TRAV12, respectively; human TRBV5 and human TRAV13, respectively; human TRBV5 and human TRAV19, respectively; human TRBV5 and human TRAV21, respectively; human TRBV5 and human TRAV30, respectively; human TRBV6 and human TRAV12, respectively; human TRBV6 and human TRAV13, respectively; human TRBV6 and human TRAV19, respectively; human TRBV6 and human TRAV21, respectively; human TRBV6 and human TRAV30, respectively; human TRBV10 and human TRAV12, respectively; human TRBV10 and human TRAV13, respectively; human TRBV10 and human TRAV19, respectively; human TRBV10 and human TRAV21, respectively; human TRBV10 and human TRAV30, respectively; human TRBV7 and human TRAV12, respectively; human TRBV7 and human TRAV13, respectively; human TRBV7 and human TRAV19, respectively; human TRBV7 and human TRAV21, respectively; human TRBV7 and human TRAV30, respectively;human TRBV19 and human TRAV12, respectively; human TRBV19 and human TRAV13, respectively; human TRBV19 and human TRAV19, respectively; human TRBV19 and human TRAV21, respectively; human TRBV19 and human TRAV30, respectively; human TRBV20 and human TRAV12, respectively; human TRBV20 and human TRAV13, respectively; human TRBV20 and human TRAV19, respectively; human TRBV20 and human TRAV21, respectively; human TRBV20 and human TRAV30, respectively; human TRBV28 and human TRAV12, respectively; human TRBV28 and human TRAV13, respectively; human TRBV28 and human TRAV19, respectively; human TRBV28 and human TRAV21, respectively; or human TRBV28 and human TRAV30, respectively.

81. The method of any one of claims 1-45, 50, 63, 64, 69, and 70, wherein the first target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV19, human TRBV20, or human TRBV28, and the second target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30.

82. The method of any one of claims 1-45, 50, 63, 64, 69, 70, and 81, wherein the first target molecule and the second target molecule are: human TRBV5 and human TRAV12-2, respectively; human TRBV5 and human TRAV13-1, respectively; human TRBV5 and human TRAV19, respectively; human TRBV5 and human TRAV21, respectively; human TRBV5 and human TRAV30, respectively; human TRBV6 and human TRAV12-2, respectively; human TRBV6 and human TRAV13-1, respectively; human TRBV6 and human TRAV19, respectively; human TRBV6 and human TRAV21, respectively; human TRBV6 and human TRAV30, respectively; human TRBV10 and human TRAV12-2, respectively; human TRBV10 and human TRAV13-1, respectively; human TRBV10 and human TRAV19, respectively; human TRBV10 and human TRAV21, respectively; human TRBV10 and human TRAV30, respectively; human TRBV7 and human TRAV12-2, respectively; human TRBV7 and human TRAV13-1, respectively;human TRBV7 and human TRAV19, respectively; human TRBV7 and human TRAV21, respectively; human TRBV7 and human TRAV30, respectively; human TRBV19 and human TRAV12-2, respectively; human TRBV19 and human TRAV13-1, respectively; human TRBV19 and human TRAV19, respectively; human TRBV19 and human TRAV21, respectively; human TRBV19 and human TRAV30, respectively; human TRBV20 and human TRAV12-2, respectively; human TRBV20 and human TRAV13-1, respectively; human TRBV20 and human TRAV19, respectively; human TRBV20 and human TRAV21, respectively; human TRBV20 and human TRAV30, respectively; human TRBV28 and human TRAV12-2, respectively; human TRBV28 and human TRAV13-1, respectively; human TRBV28 and human TRAV19, respectively; human TRBV28 and human TRAV21, respectively; or human TRBV28 and human TRAV30, respectively.

83. The method of any one of claims 1-45, 50, 63, 64, 69, and 70, wherein the first target molecule is human TRBV5-1, human TRBV6-5, human TRBV10-1, human TRBV10-2, human TRBV10-3, human TRBV7-2, human TRBV7-3, human TRBV19, human TRBV20-1, or human TRBV28, and the second target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30.

84. The method of any one of claims 1-45, 50, 63, 64, 69, 70, and 83, wherein the first target molecule and the second target molecule are: human TRBV5-1 and human TRAV12, respectively; human TRBV5-1 and human TRAV13, respectively; human TRBV5-1 and human TRAV19, respectively; human TRBV5-1 and human TRAV21, respectively; human TRBV5-1 and human TRAV30, respectively; human TRBV6-5 and human TRAV12, respectively; human TRBV6-5 and human TRAV13, respectively; human TRBV6-5 and human TRAV19, respectively; human TRBV6-5 and human TRAV21, respectively; human TRBV6-5 and human TRAV30, respectively; human TRBV10-1 and human TRAV12, respectively; human TRBV10-1 and human TRAV13, respectively; human TRBV10-1 and human TRAV19, respectively;human TRBV10-1 and human TRAV21, respectively; human TRBV10-1 and human TRAV30, respectively; human TRBV10-2 and human TRAV12, respectively; human TRBV10-2 and human TRAV13, respectively; human TRBV10-2 and human TRAV19, respectively; human TRBV10-2 and human TRAV21, respectively; human TRBV10-2 and human TRAV30, respectively; human TRBV10-3 and human TRAV12, respectively; human TRBV10-3 and human TRAV13, respectively; human TRBV10-3 and human TRAV19, respectively; human TRBV10-3 and human TRAV21, respectively; human TRBV10-3 and human TRAV30, respectively; human TRBV7-2 and human TRAV12, respectively; human TRBV7-2 and human TRAV13, respectively; human TRBV7-2 and human TRAV19, respectively; human TRBV7-2 and human TRAV21, respectively; human TRBV7-2 and human TRAV30, respectively; human TRBV7-3 and human TRAV12, respectively; human TRBV7-3 and human TRAV13, respectively; human TRBV7-3 and human TRAV19, respectively; human TRBV7-3 and human TRAV21, respectively; human TRBV7-3 and human TRAV30, respectively; human TRBV19 and human TRAV12, respectively; human TRBV19 and human TRAV13, respectively; human TRBV19 and human TRAV19, respectively; human TRBV19 and human TRAV21, respectively; human TRBV19 and human TRAV30, respectively; human TRBV20-1 and human TRAV12, respectively; human TRBV20-1 and human TRAV13, respectively; human TRBV20-1 and human TRAV19, respectively; human TRBV20-1 and human TRAV21, respectively; human TRBV20-1 and human TRAV30, respectively; human TRBV28 and human TRAV12, respectively; human TRBV28 and human TRAV13, respectively; human TRBV28 and human TRAV19, respectively; human TRBV28 and human TRAV21, respectively; or human TRBV28 and human TRAV30, respectively.

85. The method of any one of claims 1-45, 50, 63, 64, 69, and 70, wherein the first target molecule is human TRBV5-1, human TRBV6-5, human TRBV10-1, human TRBV10-2, human TRBV10-3, human TRBV7-2, human TRBV7-3, human TRBV19, human TRBV20-1, or human TRBV28, and the second target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30.

86. The method of any one of claims 1-45, 50, 63, 64, 69, 70, and 85, wherein the first target molecule and the second target molecule are: human TRBV5-1 and human TRAV12-2, respectively; human TRBV5-1 and human TRAV13-1, respectively; human TRBV5-1 and human TRAV19, respectively; human TRBV5-1 and human TRAV21, respectively; human TRBV5-1 and human TRAV30, respectively; human TRBV6-5 and human TRAV12-2, respectively; human TRBV6-5 and human TRAV13-1, respectively; human TRBV6-5 and human TRAV19, respectively; human TRBV6-5 and human TRAV21, respectively; human TRBV6-5 and human TRAV30, respectively; human TRBV10-1 and human TRAV12-2, respectively; human TRBV10-1 and human TRAV13-1, respectively; human TRBV10-1 and human TRAV19, respectively; human TRBV10-1 and human TRAV21, respectively; human TRBV10-1 and human TRAV30, respectively; human TRBV10-2 and human TRAV12-2, respectively; human TRBV10-2 and human TRAV13-1, respectively; human TRBV10-2 and human TRAV19, respectively; human TRBV10-2 and human TRAV21, respectively; human TRBV10-2 and human TRAV30, respectively; human TRBV10-3 and human TRAV12-2, respectively; human TRBV10-3 and human TRAV13-1, respectively; human TRBV10-3 and human TRAV19, respectively; human TRBV10-3 and human TRAV21, respectively; human TRBV10-3 and human TRAV30, respectively; human TRBV7-2 and human TRAV12-2, respectively; human TRBV7-2 and human TRAV13-1, respectively; human TRBV7-2 and human TRAV19, respectively; human TRBV7-2 and human TRAV21, respectively; human TRBV7-2 and human TRAV30, respectively; human TRBV7-3 and human TRAV12-2, respectively;human TRBV7-3 and human TRAV13-1, respectively; human TRBV7-3 and human TRAV19, respectively; human TRBV7-3 and human TRAV21, respectively; human TRBV7-3 and human TRAV30, respectively; human TRBV19 and human TRAV12-2, respectively; human TRBV19 and human TRAV13-1, respectively; human TRBV19 and human TRAV19, respectively; human TRBV19 and human TRAV21, respectively; human TRBV19 and human TRAV30, respectively; human TRBV20-1 and human TRAV12-2, respectively; human TRBV20-1 and human TRAV13-1, respectively; human TRBV20-1 and human TRAV19, respectively; human TRBV20-1 and human TRAV21, respectively; human TRBV20-1 and human TRAV30, respectively; human TRBV28 and human TRAV12-2, respectively; human TRBV28 and human TRAV13-1, respectively; human TRBV28 and human TRAV19, respectively; human TRBV28 and human TRAV21, respectively; or human TRBV28 and human TRAV30, respectively.

87. The method of any one of claims 1-45, 51, and 65-68, wherein the first target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30, and the second target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV19, human TRBV20, or human TRBV28.

88. The method of any one of claims 1-45, 51, 65-68, and 87, wherein the first target molecule and the second target molecule are: human TRAV12 and human TRBV5, respectively; human TRAV12 and human TRBV6, respectively; human TRAV12 and human TRBV10, respectively; human TRAV12 and human TRBV7, respectively; human TRAV12 and human TRBV19, respectively; human TRAV12 and human TRBV20, respectively; human TRAV12 and human TRBV28, respectively; human TRAV13 and human TRBV5, respectively; human TRAV13 and human TRBV6, respectively; human TRAV13 and human TRBV10, respectively; human TRAV13 and human TRBV7, respectively; human TRAV13 and human TRBV19, respectively; human TRAV13 and human TRBV20, respectively; human TRAV13 and human TRBV28, respectively;human TRAV19 and human TRBV5, respectively; human TRAV19 and human TRBV6, respectively; human TRAV19 and human TRBV10, respectively; human TRAV19 and human TRBV7, respectively; human TRAV19 and human TRBV19, respectively; human TRAV19 and human TRBV20, respectively; human TRAV19 and human TRBV28, respectively; human TRAV21 and human TRBV5, respectively; human TRAV21 and human TRBV6, respectively; human TRAV21 and human TRBV1O, respectively; human TRAV21 and human TRBV7, respectively; human TRAV21 and human TRBV19, respectively; human TRAV21 and human TRBV20, respectively; human TRAV21 and human TRBV28, respectively; human TRAV3O and human TRBV5, respectively; human TRAV3O and human TRBV6, respectively; human TRAV3O and human TRBV1O, respectively; human TRAV3O and human TRBV7, respectively; human TRAV3O and human TRBV19, respectively; human TRAV3O and human TRBV20, respectively; or human TRAV30 and human TRBV28, respectively.

89. The method of any one of claims 1-45, 51, 65, and 66-68, wherein the first target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30, and the second target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV19, human TRBV20, or human TRBV28.

90. The method of any one of claims 1-45, 51, 65, 66-68, and 89, wherein the first target molecule and the second target molecule are: human TRAV12-2 and human TRBV5, respectively; human TRAV12-2 and human TRBV6, respectively; human TRAV12-2 and human TRBV10, respectively; human TRAV12-2 and human TRBV7, respectively; human TRAV12-2 and human TRBV19, respectively; human TRAV12-2 and human TRBV20, respectively; human TRAV12-2 and human TRBV28, respectively; human TRAV13-1 and human TRBV5, respectively; human TRAV13-1 and human TRBV6, respectively; human TRAV13-1 and human TRBV10, respectively; human TRAV13-1 and human TRBV7, respectively; human TRAV13-1 and human TRBV19, respectively;human TRAV13-1 and human TRBV20, respectively; human TRAV13-1 and human TRBV28, respectively; human TRAV19 and human TRBV5, respectively; human TRAV19 and human TRBV6, respectively; human TRAV19 and human TRBV10, respectively; human TRAV19 and human TRBV7, respectively; human TRAV19 and human TRBV19, respectively; human TRAV19 and human TRBV20, respectively; human TRAV19 and human TRBV28, respectively; human TRAV21 and human TRBV5, respectively; human TRAV21 and human TRBV6, respectively; human TRAV21 and human TRBV1O, respectively; human TRAV21 and human TRBV7, respectively; human TRAV21 and human TRBV19, respectively; human TRAV21 and human TRBV20, respectively; human TRAV21 and human TRBV28, respectively; human TRAV3O and human TRBV5, respectively; human TRAV3O and human TRBV6, respectively; human TRAV3O and human TRBV1O, respectively; human TRAV3O and human TRBV7, respectively; human TRAV3O and human TRBV19, respectively; human TRAV3O and human TRBV20, respectively; or human TRAV30 and human TRBV28, respectively.

91. The method of any one of claims 1-45, 51, and 65-68, wherein the first target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30, and the second target molecule is human TRBV5-1, human TRBV6-5, human TRBV10-1, human TRBV10-2, human TRBV10-3, human TRBV7-2, human TRBV7-3, human TRBV19, human TRBV20-1, or human TRBV28.

92. The method of any one of claims 1-45, 51, 65-68, and 91, wherein the first target molecule and the second target molecule are: human TRAV12 and human TRBV5-1, respectively; human TRAV12 and human TRBV6-5, respectively; human TRAV12 and human TRBV10-1, respectively; human TRAV12 and human TRBV10-2, respectively; human TRAV12 and human TRBV10-3, respectively; human TRAV12 and human TRBV7-2, respectively; human TRAV12 and human TRBV7-3, respectively; human TRAV12 and human TRBV19, respectively; human TRAV12 and human TRBV20-1, respectively;human TRAV12 and human TRBV28, respectively; human TRAV13 and human TRBV5-1, respectively; human TRAV13 and human TRBV6-5, respectively; human TRAV13 and human TRBV10-1, respectively; human TRAV13 and human TRBV10-2, respectively; human TRAV13 and human TRBV10-3, respectively; human TRAV13 and human TRBV7-2, respectively; human TRAV13 and human TRBV7-3, respectively; human TRAV13 and human TRBV19, respectively; human TRAV13 and human TRBV20-1, respectively; human TRAV13 and human TRBV28, respectively; human TRAV19 and human TRBV5-1, respectively; human TRAV19 and human TRBV6-5, respectively; human TRAV19 and human TRBV10-1, respectively; human TRAV19 and human TRBV10-2, respectively; human TRAV19 and human TRBV10-3, respectively; human TRAV19 and human TRBV7-2, respectively; human TRAV19 and human TRBV7-3, respectively; human TRAV19 and human TRBV19, respectively; human TRAV19 and human TRBV20-1, respectively; human TRAV19 and human TRBV28, respectively; human TRAV21 and human TRBV5-1, respectively; human TRAV21 and human TRBV6-5, respectively; human TRAV21 and human TRBV10-1, respectively; human TRAV21 and human TRBV10-2, respectively; human TRAV21 and human TRBV10-3, respectively; human TRAV21 and human TRBV7-2, respectively; human TRAV21 and human TRBV7-3, respectively; human TRAV21 and human TRBV19, respectively; human TRAV21 and human TRBV20-1, respectively; human TRAV21 and human TRBV28, respectively; human TRAV30 and human TRBV5-1, respectively; human TRAV30 and human TRBV6-5, respectively; human TRAV30 and human TRBV10-1, respectively; human TRAV30 and human TRBV10-2, respectively; human TRAV30 and human TRBV10-3, respectively; human TRAV30 and human TRBV7-2, respectively; human TRAV30 and human TRBV7-3, respectively; human TRAV30 and human TRBV19, respectively;human TRAV30 and human TRBV20-1, respectively; or human TRAV30 and human TRBV28, respectively.

93. The method of any one of claims 1-45, 51, and 65-68, wherein the first target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30, and the second target molecule is human TRBV5-1, human TRBV6-5, human TRBV 10-1, human TRBV 10-2, human TRBV 10-3, human TRBV7-2, human TRBV7-3, human TRBV19, human TRBV20-1, or human TRBV28.

94. The method of any one of claims 1-45, 51, 65-68, and 93, wherein the first target molecule and the second target molecule are: human TRAV12-2 and human TRBV5-1, respectively; human TRAV12-2 and human TRBV6-5, respectively; human TRAV12-2 and human TRBV 10-1, respectively; human TRAV12-2 and human TRBV 10-2, respectively; human TRAV12-2 and human TRBV 10-3, respectively; human TRAV12-2 and human TRBV7-2, respectively; human TRAV12-2 and human TRBV7-3, respectively; human TRAV12-2 and human TRBV 19, respectively; human TRAV12-2 and human TRBV20-1, respectively; human TRAV12-2 and human TRBV28, respectively; human TRAV13-1 and human TRBV5-1, respectively; human TRAV13-1 and human TRBV6-5, respectively; human TRAV13-1 and human TRBV 10-1, respectively; human TRAV13-1 and human TRBV 10-2, respectively; human TRAV13-1 and human TRBV 10-3, respectively; human TRAV13-1 and human TRBV7-2, respectively; human TRAV13-1 and human TRBV7-3, respectively; human TRAV13-1 and human TRBV 19, respectively; human TRAV13-1 and human TRBV20-1, respectively; human TRAV13-1 and human TRBV28, respectively; human TRAV19 and human TRBV5-1, respectively; human TRAV19 and human TRBV6-5, respectively; human TRAV19 and human TRBV 10-1, respectively; human TRAV19 and human TRBV 10-2, respectively; human TRAV19 and human TRBV10-3, respectively; human TRAV19 and human TRBV7-2, respectively; human TRAV19 and human TRBV7-3, respectively; human TRAV19 and human TRBV 19, respectively; human TRAV19 and human TRBV20-1, respectively; human TRAV19 and human TRBV28, respectively;human TRAV21 and human TRBV5-1, respectively; human TRAV21 and human TRBV6-5, respectively; human TRAV21 and human TRBV10-1, respectively; human TRAV21 and human TRBV10-2, respectively; human TRAV21 and human TRBV10-3, respectively; human TRAV21 and human TRBV7-2, respectively; human TRAV21 and human TRBV7-3, respectively; human TRAV21 and human TRBV19, respectively; human TRAV21 and human TRBV20-1, respectively; human TRAV21 and human TRBV28, respectively; human TRAV30 and human TRBV5-1, respectively; human TRAV30 and human TRBV6-5, respectively; human TRAV30 and human TRBV10-1, respectively; human TRAV30 and human TRBV10-2, respectively; human TRAV30 and human TRBV10-3, respectively; human TRAV30 and human TRBV7-2, respectively; human TRAV30 and human TRBV7-3, respectively; human TRAV30 and human TRBV19, respectively; human TRAV30 and human TRBV20-1, respectively; or human TRAV30 and human TRBV28, respectively.

95. The method of any one of claims 1-94, wherein the first binder comprises a full antibody or antigen-binding fragment thereof, a bivalent antibody, bispecific antibody, or a biparatopic antibody.

96. The method of any one of claims 1-95, wherein the second binder comprises a full antibody or antigen-binding fragment thereof, a bivalent antibody, bispecific antibody, or a biparatopic antibody.

97. The method of claim 95 or 96, wherein the antigen-binding fragment is a Fab, F(ab')2, Fv, a single chain Fv (scFv), a single domain antibody, a diabody, a single domain antibody, or a camelid antibody.

98. The method of any one of claims 1-97, wherein the first binder comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 3 (HC CDR3) comprising the sequence of SEQ ID NO: 3343, SEQ ID NO: 3323, SEQ ID NO: 3353, SEQ ID NO: 1187, SEQ ID NO: 3373, SEQ ID NO: 3383, SEQ ID NO: 3393, SEQ ID NO: 3403, or SEQ ID NO: 3413.

99. The method of any one of claims 1-98, wherein the first binder comprises a VH comprising a heavy chain complementarity determining region 1 (HC CDR1) comprising the sequence of SEQ ID NO: 3341, SEQ ID NO: 3321, SEQ ID NO: 3351, SEQ ID NO: 1190, SEQ ID NO: 3371, SEQ ID NO: 3381, SEQ ID NO: 3391, SEQ ID NO: 3401, SEQ ID NO: 3411, SEQ ID NO: 3421, or SEQ ID NO: 3702.

100. The method of any one of claims 1-99, wherein the first binder comprises a VH comprising a heavy chain complementarity determining region 2 (HC CDR2) comprising the sequence of SEQ ID NO: 3342, SEQ ID NO: 3322, SEQ ID NO: 3352, SEQ ID NO: 1186, SEQ ID NO: 3372, SEQ ID NO: 3382, SEQ ID NO: 3392, SEQ ID NO: 3402, or SEQ ID NO: 3412.

101. The method of any one of claims 1-100, wherein the first binder comprises a VH comprising:(i) a HC CDR1 comprising the sequence of SEQ ID NO: 3341, a HC CDR2 comprising the sequence of SEQ ID NO: 3342, and a HC CDR3 comprising the sequence of SEQ ID NO: 3343;(ii) a HC CDR1 comprising the sequence of SEQ ID NO: 3321, a HC CDR2 comprising the sequence of SEQ ID NO: 3322, and a HC CDR3 comprising the sequence of SEQ ID NO: 3323;(iii) a HC CDR1 comprising the sequence of SEQ ID NO: 3351, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, and a HC CDR3 comprising the sequence of SEQ ID NO: 3353;(iv) a HC CDR1 comprising the sequence of SEQ ID NO: 1190, a HC CDR2 comprising the sequence of SEQ ID NO: 1186, and a HC CDR3 comprising the sequence of SEQ ID NO: 1187;(v) a HC CDR1 comprising the sequence of SEQ ID NO: 3371, a HC CDR2 comprising the sequence of SEQ ID NO: 3372, and a HC CDR3 comprising the sequence of SEQ ID NO: 3373;(vi) a HC CDR1 comprising the sequence of SEQ ID NO: 3381, a HC CDR2 comprising the sequence of SEQ ID NO: 3382, and a HC CDR3 comprising the sequence of SEQ ID NO: 3383;(vii) a HC CDR1 comprising the sequence of SEQ ID NO: 3391, a HC CDR2 comprising the sequence of SEQ ID NO: 3392, and a HC CDR3 comprising the sequence of SEQ ID NO: 3393;(viii) a HC CDR1 comprising the sequence of SEQ ID NO: 3401, a HC CDR2 comprising the sequence of SEQ ID NO: 3402, and a HC CDR3 comprising the sequence of SEQ ID NO: 3403;(ix) a HC CDR1 comprising the sequence of SEQ ID NO: 3351, SEQ ID NO: 3421, or SEQ ID NO: 3702, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, and a HC CDR3 comprising the sequence of SEQ ID NO: 3353; or(x) a HC CDR1 comprising the sequence of SEQ ID NO: 3411, a HC CDR2 comprising the sequence of SEQ ID NO: 3412, and a HC CDR3 comprising the sequence of SEQ ID NO: 3413.

102. The method of any one of claims 1-101, wherein the first binder comprises a light chain variable region (VL) comprising a light chain complementarity determining region 3 (LC CDR3) comprising the sequence of SEQ ID NO: 3346, SEQ ID NO: 3326, SEQ ID NO: 3356, SEQ ID NO:1193, SEQ ID NO: 3376, SEQ ID NO: 3386, SEQ ID NO: 3396, SEQ ID NO: 3406, or SEQ ID NO: 3416.

103. The method of any one of claims 1-102, wherein the first binder comprises a VL comprising a light chain complementarity determining region 1 (LC CDR1) comprising the sequence of SEQ ID NO: 3344, SEQ ID NO: 3324, SEQ ID NO: 3354, SEQ ID NO: 1191, SEQ ID NO: 3374, SEQ ID NO: 3384, SEQ ID NO: 3394, SEQ ID NO: 3404, or SEQ ID NO: 3414.

104. The method of any one of claims 1-103, wherein the first binder comprises a VL comprising a light chain complementarity determining region 2 (LC CDR2) comprising the sequence of SEQ ID NO: 3345, SEQ ID NO: 3325, SEQ ID NO: 3355, SEQ ID NO: 1192, SEQ ID NO: 3375, SEQ ID NO: 3395, SEQ ID NO: 3405, SEQ ID NO: 3415, or SEQ ID NO: 3443.

105. The method of any one of claims 1-104, wherein the first binder comprises a VL comprising:(i) a LC CDR1 comprising the sequence of SEQ ID NO: 3344, a LC CDR2 comprising the sequence of SEQ ID NO: 3345, and a LC CDR3 comprising the sequence of SEQ ID NO: 3346;(ii) a LC CDR1 comprising the sequence of SEQ ID NO: 3324, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3326;(iii) a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3355, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356;(iv) a LC CDR1 comprising the sequence of SEQ ID NO: 1191, a LC CDR2 comprising the sequence of SEQ ID NO: 1192, and a LC CDR3 comprising the sequence of SEQ ID NO: 1193;(v) a LC CDR1 comprising the sequence of SEQ ID NO: 3374, a LC CDR2 comprising the sequence of SEQ ID NO: 3375, and a LC CDR3 comprising the sequence of SEQ ID NO: 3376;(vi) a LC CDR1 comprising the sequence of SEQ ID NO: 3384, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3386;(vii) a LC CDR1 comprising the sequence of SEQ ID NO: 3394, a LC CDR2 comprising the sequence of SEQ ID NO: 3395, and a LC CDR3 comprising the sequence of SEQ ID NO: 3396;(viii) a LC CDR1 comprising the sequence of SEQ ID NO: 3404, a LC CDR2 comprising the sequence of SEQ ID NO: 3405, and a LC CDR3 comprising the sequence of SEQ ID NO: 3406;(ix) a LC CDR1 comprising the sequence of SEQ ID NO: 3414, a LC CDR2 comprising the sequence of SEQ ID NO: 3415, and a LC CDR3 comprising the sequence of SEQ ID NO: 3416; or(x) a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3443, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356.

106. The method of any one of claims 1-105, wherein the first binder comprises:(i) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3341, a HC CDR2 comprising the sequence of SEQ ID NO: 3342, a HC CDR3 comprising the sequence of SEQ ID NO: 3343, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3344, a LC CDR2 comprising the sequence of SEQ ID NO: 3345, and a LC CDR3 comprising the sequence of SEQ ID NO: 3346;(ii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3321, a HC CDR2 comprising the sequence of SEQ ID NO: 3322, a HC CDR3 comprising the sequence of SEQ ID NO: 3323, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3324, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3326;(iii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3351, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, a HC CDR3 comprising the sequence of SEQ ID NO: 3353, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3355, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356;(iv) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 1190, a HC CDR2 comprising the sequence of SEQ ID NO: 1186, a HC CDR3 comprising the sequence of SEQ ID NO: 1187, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO:1191, a LC CDR2 comprising the sequence of SEQ ID NO: 1192, and a LC CDR3 comprising the sequence of SEQ ID NO: 1193;(v) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3371, a HC CDR2 comprising the sequence of SEQ ID NO: 3372, a HC CDR3 comprising the sequence of SEQ ID NO: 3373, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3374, a LC CDR2 comprising the sequence of SEQ ID NO: 3375, and a LC CDR3 comprising the sequence of SEQ ID NO: 3376;(vi) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3381, a HC CDR2 comprising the sequence of SEQ ID NO: 3382, a HC CDR3 comprising the sequence of SEQ ID NO: 3383, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3384, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3386;(vii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3391, a HC CDR2 comprising the sequence of SEQ ID NO: 3392, a HC CDR3 comprising the sequence of SEQ ID NO: 3393, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3394, a LC CDR2 comprising the sequence of SEQ ID NO: 3395, and a LC CDR3 comprising the sequence of SEQ ID NO: 3396;(viii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3401, a HC CDR2 comprising the sequence of SEQ ID NO: 3402, a HC CDR3 comprising the sequence of SEQ ID NO: 3403, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3404, a LC CDR2 comprising the sequence of SEQ ID NO: 3405, and a LC CDR3 comprising the sequence of SEQ ID NO: 3406;(ix) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3411, a HC CDR2 comprising the sequence of SEQ ID NO: 3412, a HC CDR3 comprising the sequence of SEQ ID NO: 3413, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3414, a LC CDR2 comprising the sequence of SEQ ID NO: 3415, and a LC CDR3 comprising the sequence of SEQ ID NO: 3416;(x) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3351, SEQ ID NO: 3421, or SEQ ID NO: 3702, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, a HC CDR3 comprising the sequence of SEQ ID NO: 3353, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3355, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356; or(xi) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3351, SEQ ID NO: 3421, or SEQ ID NO: 3702, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, a HC CDR3 comprising the sequence of SEQ ID NO: 3353, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3443, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356.

107. The method of any one of claims 1-106, wherein the first binder comprises a VH comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO: 3445, SEQ ID NO: 3448, SEQ ID NO: 3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO: 3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO: 3465, and SEQ ID NO: 3470.

108. The method of any one of claims 1-107, wherein the first binder comprises a VH comprising any one sequence selected from the group consisting of: SEQ ID NO: 3445, SEQ ID NO: 3448, SEQ ID NO: 3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO: 3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO: 3465, and SEQ ID NO: 3470.

109. The method of any one of claims 1-108, wherein the first binder comprises a VL comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO: 3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO: 3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO: 3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

110. The method of any one of claims 1-109, wherein the first binder comprises a VL comprising any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO: 3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO: 3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO: 3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

111. The method of any one of claims 1-110, wherein the first binder comprises:(i) a VH comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO: 3445, SEQ ID NO: 3448, SEQ ID NO:3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO: 3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO: 3465, and SEQ ID NO: 3470; and(ii) a VL comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO:3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO: 3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO: 3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

112. The method of any one of claims 1-111, wherein the first binder comprises:(i) a VH comprising any one sequence selected from the group consisting of: SEQ ID NO: 3445,SEQ ID NO: 3448, SEQ ID NO: 3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO:3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO: 3465, and SEQ ID NO: 3470; and(ii) a VL comprising any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO: 3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO:3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO: 3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

113. The method of any one of claims 1-112, wherein the first binder comprises:(i) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ IDNO: 3445, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3446;(ii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3448, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3449;(iii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3450, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3451;(iv) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1346, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1349;(v) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1196, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1195;(vi) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3455, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3456;(vii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3457, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3458;(viii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3463, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3464;(ix) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3465, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3466;(x) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3470, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3471;(xi) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1346, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3475; or(xii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1346, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3476.

114. The method of any one of claims 1-113, wherein the first binder comprises:(i) a VH comprising the sequence of SEQ ID NO: 3445, and a VL comprising the sequence ofSEQ ID NO: 3446;(ii) a VH comprising the sequence of SEQ ID NO: 3448, and a VL comprising the sequence of SEQ ID NO: 3449;(iii) a VH comprising the sequence of SEQ ID NO: 3450, and a VL comprising the sequence of SEQ ID NO: 3451;(iv) a VH comprising the sequence of SEQ ID NO: 1346, and a VL comprising the sequence of SEQ ID NO: 1349;(v) a VH comprising the sequence of SEQ ID NO: 1196, and a VL comprising the sequence of SEQ ID NO: 1195;(vi) a VH comprising the sequence of SEQ ID NO: 3455, and a VL comprising the sequence of SEQ ID NO: 3456;(vii) a VH comprising the sequence of SEQ ID NO: 3457, and a VL comprising the sequence of SEQ ID NO: 3458;(viii) a VH comprising the sequence of SEQ ID NO: 3463, and a VL comprising the sequence of SEQ ID NO: 3464;(ix) a VH comprising the sequence of SEQ ID NO: 3465, and a VL comprising the sequence of SEQ ID NO: 3466;(x) a VH comprising the sequence of SEQ ID NO: 3470, and a VL comprising the sequence of SEQ ID NO: 3471;(xi) a VH comprising the sequence of SEQ ID NO: 1346, and a VL comprising the sequence of SEQ ID NO: 3475; or(xii) a VH comprising the sequence of SEQ ID NO: 1346, and a VL comprising the sequence of SEQ ID NO: 3476.

115. The method of any one of claims 1-114, wherein the second binder comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 3 (HC CDR3) comprising the sequence of SEQ ID NO: 3343, SEQ ID NO: 3323, SEQ ID NO: 3353, SEQ ID NO: 1187, SEQ ID NO: 3373, SEQ ID NO: 3383, SEQ ID NO: 3393, SEQ ID NO: 3403, or SEQ ID NO: 3413.

116. The method of any one of claims 1-115, wherein the second binder comprises a VH comprising a heavy chain complementarity determining region 1 (HC CDR1) comprising the sequence of SEQ ID NO: 3341, SEQ ID NO: 3321, SEQ ID NO: 3351, SEQ ID NO: 1190, SEQ ID NO: 3371, SEQ ID NO: 3381, SEQ ID NO: 3391, SEQ ID NO: 3401, SEQ ID NO: 3411, SEQ ID NO: 3421, or SEQ ID NO: 3702.

117. The method of any one of claims 1-116, wherein the second binder comprises a VH comprising a heavy chain complementarity determining region 2 (HC CDR2) comprising the sequence of SEQ ID NO: 3342, SEQ ID NO: 3322, SEQ ID NO: 3352, SEQ ID NO: 1186, SEQ ID NO: 3372, SEQ ID NO: 3382, SEQ ID NO: 3392, SEQ ID NO: 3402, or SEQ ID NO: 3412.

118. The method of any one of claims 1-117, wherein the second binder comprises a VH comprising:(i) a HC CDR1 comprising the sequence of SEQ ID NO: 3341, a HC CDR2 comprising the sequence of SEQ ID NO: 3342, and a HC CDR3 comprising the sequence of SEQ ID NO: 3343;(ii) a HC CDR1 comprising the sequence of SEQ ID NO: 3321, a HC CDR2 comprising the sequence of SEQ ID NO: 3322, and a HC CDR3 comprising the sequence of SEQ ID NO: 3323;(iii) a HC CDR1 comprising the sequence of SEQ ID NO: 3351, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, and a HC CDR3 comprising the sequence of SEQ ID NO: 3353;(iv) a HC CDR1 comprising the sequence of SEQ ID NO: 1190, a HC CDR2 comprising the sequence of SEQ ID NO: 1186, and a HC CDR3 comprising the sequence of SEQ ID NO: 1187;(v) a HC CDR1 comprising the sequence of SEQ ID NO: 3371, a HC CDR2 comprising the sequence of SEQ ID NO: 3372, and a HC CDR3 comprising the sequence of SEQ ID NO: 3373;(vi) a HC CDR1 comprising the sequence of SEQ ID NO: 3381, a HC CDR2 comprising the sequence of SEQ ID NO: 3382, and a HC CDR3 comprising the sequence of SEQ ID NO: 3383;(vii) a HC CDR1 comprising the sequence of SEQ ID NO: 3391, a HC CDR2 comprising the sequence of SEQ ID NO: 3392, and a HC CDR3 comprising the sequence of SEQ ID NO: 3393;(viii) a HC CDR1 comprising the sequence of SEQ ID NO: 3401, a HC CDR2 comprising the sequence of SEQ ID NO: 3402, and a HC CDR3 comprising the sequence of SEQ ID NO: 3403;(ix) a HC CDR1 comprising the sequence of SEQ ID NO: 3351, SEQ ID NO: 3421, or SEQ ID NO: 3702, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, and a HC CDR3 comprising the sequence of SEQ ID NO: 3353; or(x) a HC CDR1 comprising the sequence of SEQ ID NO: 3411, a HC CDR2 comprising the sequence of SEQ ID NO: 3412, and a HC CDR3 comprising the sequence of SEQ ID NO: 3413.

119. The method of any one of claims 1-118, wherein the second binder comprises a light chain variable region (VL) comprising a light chain complementarity determining region 3 (LC CDR3) comprising the sequence of SEQ ID NO: 3346, SEQ ID NO: 3326, SEQ ID NO: 3356, SEQ ID NO: 1193, SEQ ID NO: 3376, SEQ ID NO: 3386, SEQ ID NO: 3396, SEQ ID NO: 3406, or SEQ ID NO: 3416.

120. The method of any one of claims 1-119, wherein the second binder comprises a VL comprising a light chain complementarity determining region 1 (LC CDR1) comprising the sequence of SEQ ID NO: 3344, SEQ ID NO: 3324, SEQ ID NO: 3354, SEQ ID NO: 1191, SEQ ID NO: 3374, SEQ ID NO: 3384, SEQ ID NO: 3394, SEQ ID NO: 3404, or SEQ ID NO: 3414.

121. The method of any one of claims 1-120, wherein the second binder comprises a VL comprising a light chain complementarity determining region 2 (LC CDR2) comprising the sequence of SEQ ID NO: 3345, SEQ ID NO: 3325, SEQ ID NO: 3355, SEQ ID NO: 1192, SEQ ID NO: 3375, SEQ ID NO: 3395, SEQ ID NO: 3405, SEQ ID NO: 3415, or SEQ ID NO: 3443.

122. The method of any one of claims 1-121, wherein the second binder comprises a VL comprising:(i) a LC CDR1 comprising the sequence of SEQ ID NO: 3344, a LC CDR2 comprising the sequence of SEQ ID NO: 3345, and a LC CDR3 comprising the sequence of SEQ ID NO: 3346;(ii) a LC CDR1 comprising the sequence of SEQ ID NO: 3324, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3326;(iii) a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3355, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356;(iv) a LC CDR1 comprising the sequence of SEQ ID NO: 1191, a LC CDR2 comprising the sequence of SEQ ID NO: 1192, and a LC CDR3 comprising the sequence of SEQ ID NO: 1193;(v) a LC CDR1 comprising the sequence of SEQ ID NO: 3374, a LC CDR2 comprising the sequence of SEQ ID NO: 3375, and a LC CDR3 comprising the sequence of SEQ ID NO: 3376;(vi) a LC CDR1 comprising the sequence of SEQ ID NO: 3384, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3386;(vii) a LC CDR1 comprising the sequence of SEQ ID NO: 3394, a LC CDR2 comprising the sequence of SEQ ID NO: 3395, and a LC CDR3 comprising the sequence of SEQ ID NO: 3396;(viii) a LC CDR1 comprising the sequence of SEQ ID NO: 3404, a LC CDR2 comprising the sequence of SEQ ID NO: 3405, and a LC CDR3 comprising the sequence of SEQ ID NO: 3406;(ix) a LC CDR1 comprising the sequence of SEQ ID NO: 3414, a LC CDR2 comprising the sequence of SEQ ID NO: 3415, and a LC CDR3 comprising the sequence of SEQ ID NO: 3416; or(x) a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3443, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356.

123. The method of any one of claims 1-122, wherein the second binder comprises:(i) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3341, a HC CDR2 comprising the sequence of SEQ ID NO: 3342, a HC CDR3 comprising the sequence of SEQ ID NO: 3343, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3344, a LC CDR2 comprising the sequence of SEQ ID NO: 3345, and a LC CDR3 comprising the sequence of SEQ ID NO: 3346;(ii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3321, a HC CDR2 comprising the sequence of SEQ ID NO: 3322, a HC CDR3 comprising the sequence of SEQ ID NO: 3323, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3324, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3326;(iii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3351, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, a HC CDR3 comprising the sequence of SEQ ID NO: 3353, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3355, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356;(iv) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 1190, a HC CDR2 comprising the sequence of SEQ ID NO: 1186, a HC CDR3 comprising the sequence of SEQ ID NO: 1187, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO:1191, a LC CDR2 comprising the sequence of SEQ ID NO: 1192, and a LC CDR3 comprising the sequence of SEQ ID NO: 1193;(v) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3371, a HC CDR2 comprising the sequence of SEQ ID NO: 3372, a HC CDR3 comprising the sequence of SEQ ID NO: 3373, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO:3374, a LC CDR2 comprising the sequence of SEQ ID NO: 3375, and a LC CDR3 comprising the sequence of SEQ ID NO: 3376;(vi) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3381, a HC CDR2 comprising the sequence of SEQ ID NO: 3382, a HC CDR3 comprising the sequence of SEQ ID NO: 3383, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3384, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3386;(vii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3391, a HC CDR2 comprising the sequence of SEQ ID NO: 3392, a HC CDR3 comprising the sequence of SEQ ID NO: 3393, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3394, a LC CDR2 comprising the sequence of SEQ ID NO: 3395, and a LC CDR3 comprising the sequence of SEQ ID NO: 3396;(viii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3401, a HC CDR2 comprising the sequence of SEQ ID NO: 3402, a HC CDR3 comprising the sequence of SEQ ID NO: 3403, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3404, a LC CDR2 comprising the sequence of SEQ ID NO: 3405, and a LC CDR3 comprising the sequence of SEQ ID NO: 3406;(ix) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3411, a HC CDR2 comprising the sequence of SEQ ID NO: 3412, a HC CDR3 comprising the sequence of SEQ ID NO: 3413, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3414, a LC CDR2 comprising the sequence of SEQ ID NO: 3415, and a LC CDR3 comprising the sequence of SEQ ID NO: 3416;(x) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3351, SEQ ID NO: 3421, or SEQ ID NO: 3702, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, a HC CDR3 comprising the sequence of SEQ ID NO: 3353, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3355, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356; or(xi) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3351, SEQ ID NO: 3421, or SEQ ID NO: 3702, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, a HC CDR3 comprising the sequence of SEQ ID NO: 3353, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3443, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356.

124. The method of any one of claims 1-123, wherein the second binder comprises a VH comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO: 3445, SEQ ID NO: 3448, SEQ ID NO: 3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO: 3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO: 3465, and SEQ ID NO: 3470.

125. The method of any one of claims 1-124, wherein the second binder comprises a VH comprising any one sequence selected from the group consisting of: SEQ ID NO: 3445, SEQ ID NO:3448, SEQ ID NO: 3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO: 3455, SEQ ID NO:3457, SEQ ID NO: 3463, SEQ ID NO: 3465, and SEQ ID NO: 3470.

126. The method of any one of claims 1-125, wherein the second binder comprises a VL comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO: 3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO: 3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO: 3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

127. The method of any one of claims 1-126, wherein the second binder comprises a VL comprising any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO:3449, SEQ ID NO: 3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO: 3456, SEQ ID NO:3458, SEQ ID NO: 3464, SEQ ID NO: 3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

128. The method of any one of claims 1-127, wherein the second binder comprises:(i) a VH comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO: 3445, SEQ ID NO: 3448, SEQ ID NO:3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO: 3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO: 3465, and SEQ ID NO: 3470; and(ii) a VL comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO:3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO: 3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO: 3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

129. The method of any one of claims 1-128, wherein the second binder comprises:(i) a VH comprising any one sequence selected from the group consisting of: SEQ ID NO: 3445,SEQ ID NO: 3448, SEQ ID NO: 3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO:3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO: 3465, and SEQ ID NO: 3470; and(ii) a VL comprising any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO: 3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO:3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO: 3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

130. The method of any one of claims 1-129, wherein the second binder comprises:(i) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ IDNO: 3445, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3446;(ii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3448, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3449;(iii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3450, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3451;(iv) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1346, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1349;(v) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1196, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1195;(vi) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3455, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3456;(vii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3457, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3458;(viii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3463, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3464;(ix) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3465, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3466;(x) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3470, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3471;(xi) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1346, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3475; or(xii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1346, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3476.

131. The method of any one of claims 1-130, wherein the second binder comprises:(i) a VH comprising the sequence of SEQ ID NO: 3445, and a VL comprising the sequence ofSEQ ID NO: 3446;(ii) a VH comprising the sequence of SEQ ID NO: 3448, and a VL comprising the sequence of SEQ ID NO: 3449;(iii) a VH comprising the sequence of SEQ ID NO: 3450, and a VL comprising the sequence of SEQ ID NO: 3451;(iv) a VH comprising the sequence of SEQ ID NO: 1346, and a VL comprising the sequence of SEQ ID NO: 1349;(v) a VH comprising the sequence of SEQ ID NO: 1196, and a VL comprising the sequence of SEQ ID NO: 1195;(vi) a VH comprising the sequence of SEQ ID NO: 3455, and a VL comprising the sequence of SEQ ID NO: 3456;(vii) a VH comprising the sequence of SEQ ID NO: 3457, and a VL comprising the sequence of SEQ ID NO: 3458;(viii) a VH comprising the sequence of SEQ ID NO: 3463, and a VL comprising the sequence of SEQ ID NO: 3464;(ix) a VH comprising the sequence of SEQ ID NO: 3465, and a VL comprising the sequence of SEQ ID NO: 3466;(x) a VH comprising the sequence of SEQ ID NO: 3470, and a VL comprising the sequence of SEQ ID NO: 3471;(xi) a VH comprising the sequence of SEQ ID NO: 1346, and a VL comprising the sequence of SEQ ID NO: 3475; or(xii) a VH comprising the sequence of SEQ ID NO: 1346, and a VL comprising the sequence of SEQ ID NO: 3476.

132. The method of any one of claims 1-131, wherein the first binder and the second binder bind to different TCRpV regions.

133. The method of any one of claims 1-131, wherein the first binder and the second binder bind to different TCRpVs belonging to different subfamilies.

134. The method of any one of claims 1-131, wherein the first binder and the second binder bind to different members of the same TCRpV subfamily.

135. The method of any one of claims 1-134, wherein the first binder comprises one or more heavy chain constant regions selected from the group consisting of IgGl heavy chain constant region or fragment thereof, IgG2 heavy chain constant region or fragment thereof, IgG3 heavy chain constant region or fragment thereof, IgGAl heavy chain constant region or fragment thereof, IgGA2 heavy chain constant region or fragment thereof, IgG4 heavy chain constant region or fragment thereof, IgJ heavy chain constant region or fragment thereof, IgM heavy chain constant region or fragment thereof, IgD heavy chain constant region or fragment thereof, and IgE heavy chain constant region or fragment thereof.

136. The method of any one of claims 1-135, wherein the first binder comprises a kappa light chain constant region or fragment thereof, a lambda light chain constant region or fragment thereof, or a combination thereof.

137. The method of any one of claims 1-136, wherein the second binder comprises one or more heavy chain constant regions selected from the group consisting of IgGl heavy chain constant region or fragment thereof, IgG2 heavy chain constant region or fragment thereof, IgG3 heavy chain constant region or fragment thereof, IgGAl heavy chain constant region or fragment thereof, IgGA2 heavy chain constant region or fragment thereof, IgG4 heavy chain constant region or fragment thereof, IgJ heavy chain constant region or fragment thereof, IgM heavy chain constant region or fragment thereof, IgD heavy chain constant region or fragment thereof, and IgE heavy chain constant region or fragment thereof.

138. The method of any one of claims 1-137, wherein the second binder comprises a kappa light chain constant region or fragment thereof, a lambda light chain constant region or fragment thereof, or a combination thereof.

139. The method of any one of claims 1-138, wherein the first agent is a multifunctional molecule.

140. The method of any one of claims 1-139, wherein the first agent is a multispecific molecule.

141. The method of any one of claims 1-140, wherein the second agent is a multifunctional molecule.

142. The method of any one of claims 1-141, wherein the second agent is a multispecific molecule.

143. The method of any one of claims 1-142, wherein the first agent, the second agent, or a combination thereof comprises at least two non-contiguous polypeptide chains; wherein a first polypeptide chain of the at least two non-contiguous polypeptide chains comprises a first Fc region, and a second polypeptide chain of the at least two non-contiguous polypeptide chains comprises a second Fc region; and wherein the first Fc region and the second Fc region comprise an Fc interface with a knob-in- a hole.

144. The method of claim 143, wherein the first Fc region, the second Fc region, or a combination thereof comprises an Asn297Ala mutation, a Leu234Ala / Leu235Ala mutation, or a combination thereof.

145. The method of any one of claims 139-144, wherein the first agent is a multispecific molecule that further comprises one or more of a tumor-targeting moiety, a cytokine molecule, a stromal modifying moiety, or an immune cell engager.

146. The method of any one of claims 141-145, wherein the second agent is a multispecific molecule that further comprises one or more of a tumor-targeting moiety, a cytokine molecule, a stromal modifying moiety, or an immune cell engager.

147. The method of any one of claims 139-146, wherein the first agent comprises the following configuration:A-, B-[dimerization module] -C, -D, wherein:(a) the dimerization module comprises a first immunoglobulin chain constant region and a second immunoglobulin chain constant region;(b) A and C are linked to the first immunoglobulin chain constant region; and B and D are linked to the second immunoglobulin chain constant region;(c) A, B, C, and D are independently (i) absent; (ii) the first binder; (iii) the tumor targeting moiety, (iv) the cytokine molecule; (v) stromal modifying moiety; or (vi) the immune cell engager; and wherein at least one, two, or three of A, B, C, and D comprises the first binder.

148. The method of any one of claims 141-147, wherein the second agent comprises the following configuration:A-, B-[dimerization module] -C, -D,wherein:(a) the dimerization module comprises a first immunoglobulin chain constant region and a second immunoglobulin chain constant region;(b) A and C are linked to the first immunoglobulin chain constant region; and B and D are linked to the second immunoglobulin chain constant region;(c) A, B, C, and D are independently (i) absent; (ii) the second binder; (iii) the tumor targeting moiety, (iv) the cytokine molecule; (v) stromal modifying moiety; or (vi) the immune cell engager; and wherein at least one, two, or three of A, B, C, and D comprises the second binder.

149. The method of claim 147 or 148, wherein the first immunoglobulin chain constant region comprises the first fragment crystallizable region (Fc region) and the second first immunoglobulin chain constant region comprises the second fragment crystallizable region (Fc region).

150. The method of claim 149, wherein dimerization of the first Fc region and the second Fc region is enhanced by providing an Fc interface of the first Fc region and the second Fc region with one or more of a paired cavity-protuberance, an electrostatic interaction, or a strand-exchange, such that a greater ratio of heteromultimer to homomultimer forms relative to a non-engineered interface.

151. The method of any one of claims 145-150, wherein the immune cell engager is selected from the group consisting of a T cell engager, an NK cell engager, a B cell engager, a dendritic cell engager, a macrophage cell engager, and any combination thereof.

152. The method of any one of claims 145-151, wherein the cytokine molecule is selected from the group consisting of interleukin-2 (IL-2) or functional variant thereof, interleukin-7 (IL-7) or functional variant thereof, interleukin- 12 (IL-12) or functional variant thereof, interleukin- 15 (IL-15) or functional variant thereof, interleukin- 18 (IL- 18) or functional variant thereof, interleukin-21 (IL- 21) or functional variant thereof, interferon gamma or functional variant thereof, and any combination thereof.

153. The method of claim 152, wherein the cytokine molecule comprises interleukin-2 (IL-2) or functional variant thereof.

154. The method of claim 153, wherein the interleukin-2 (IL-2) or functional variant thereof comprises the sequence of SEQ ID NO: 2270 or SEQ ID NO: 2191.

155. The method of claim 152, wherein the cytokine molecule comprises interleukin- 15 (IL-15) or functional variant thereof.

156. The method of claim 155, wherein the interleukin- 15 (IL-15) or functional variant thereof comprises the sequence of SEQ ID NO: 2170.

157. The method of claim 155 or 156, wherein the cytokine molecule further comprises an IL15Ralpha dimerizing domain covalently linked the interleukin- 15 (IL- 15) or functional variant thereof.

158. The method of claim 157, wherein the IL15Ralpha dimerizing domain comprises an IL- 15 receptor alpha sushi domain or functional variant thereof.

159. The method of claim 157 or 158, wherein the IL15Ralpha dimerizing domain comprises the sequence of SEQ ID NO: 3472.

160. The method of any one of claims 157-159, wherein the interleukin- 15 (IL-15) or functional variant thereof is covalently linked to the IL15Ralpha dimerizing domain via a linker.

161. The method of claim 160, wherein the interleukin- 15 (IL- 15) or functional variant thereof is covalently linked to the IL15Ralpha dimerizing domain via a linker comprising the sequence of SEQ ID NO: 3473.

162. The method of any one of claims 155-161, wherein the cytokine molecule comprises the sequence of SEQ ID NO: 3474.

163. The method of any one of claims 145-162, wherein the stromal modifying moiety is selected from the group consisting of a hyaluronidase, a collagenase, a chondroitinase, and a matrix metalloproteinase .

164. The method of any one of claims 145-163, wherein the tumor-targeting moiety binds to a cancer antigen.

165. The method of claim 164, wherein the tumor-targeting moiety binds to a cancer antigen.

166. The method of claim 164 or 165, wherein the cancer antigen is present on a hematological cancer, a solid tumor, a metastatic cancer, a soft tissue tumor, a metastatic lesion, or a combination thereof.

167. The method of any one of claims 164-166, wherein the cancer antigen is a tumor antigen, a stromal antigen, or a hematological antigen.

168. The method of any one of claims 164-167, wherein the cancer antigen is selected from the group consisting of BCMA, CD19, CD20, CD22, FcRH5, PDL1, CD47, ganglioside 2 (GD2), prostate stem cell antigen (PSCA), prostate specific membrane antigen (PMSA), prostate-specific antigen (PSA), carcinoembryonic antigen (CEA), Ron Kinase, c-Met, Immature laminin receptor, TAG-72, BING-4, Calcium-activated chloride channel 2, Cyclin-Bl, 9D7, Ep-CAM, EphA3, Her2 / neu, Telomerase, SAP-1, Survivin, NY-ESO-l / LAGE-1, PRAME, SSX-2, Melan-A / MART-1, Gpl00 / pmell7, Tyrosinase, MC1R, P-catenin, BRCA1 / 2, CDK4, CML66, Fibronectin, p53, Ras, TGF-B receptor, AFP, ETA, MAGE, CA-125, BAGE, GAGE, CDC27, a actinin-4, TRPl / gp75, TRP2, gangliosides, WT1, Epidermal growth factor receptor (EGFR), MART-2, MUC1, MUC2, MUM1, MUM2, MUM3, NA88-1, NPM, OA1, OGT, RCC, RU11, RU12, SAGE, TRG, TSTA, Folate receptor alpha, Ll-CAM, CAIX, gpA33, GD3, GM2, VEGFR, Integrins, Carbohydrates, IGF1R, TRAILR1, TRAILR2, RANKL, FAP, TGF-beta, hyaluronic acid, collagen, tenascin C, and tenascin W.

169. The method of any one of claims 1-168, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3445, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3446, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

170. The method of any one of claims 1-168, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3448, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3449, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

171. The method of any one of claims 1-168, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3450, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3451, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

172. The method of any one of claims 1-168, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3450, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3454 or the sequence of SEQ ID NO: 3501 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3451, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

173. The method of any one of claims 1-168, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3454 or the sequence of SEQ ID NO: 3501 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 1349, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

174. The method of any one of claims 1-168, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1196, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 1195, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

175. The method of any one of claims 1-168, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3455, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3456, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

176. The method of any one of claims 1-168, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3457, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3459, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3460,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3462 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2191, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3458, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3461.

177. The method of any one of claims 1-168, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3463, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3459, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3460,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3462 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2191, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3464, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3461.

178. The method of any one of claims 1-168, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3465, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3467, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3468,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3469 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2191, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3466, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3461.

179. The method of any one of claims 1-168, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3470, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3471, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

180. The method of any one of claims 1-168, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 15 or functional variant thereof comprising the sequence of SEQ ID NO: 2170, wherein the IL- 15 or functional variant thereof is covalently linked to an IL15Ralpha dimerizing domain comprising the sequence of the SEQ ID NO: 3472 via a linker comprising the sequence of SEQ ID NO: 3473, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 1349, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

181. The method of any one of claims 1-168, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 15 or functional variant thereof comprising the sequence of SEQ ID NO: 2170, wherein the IL- 15 or functional variant thereof is covalently linked to an IL15Ralpha dimerizing domain comprising the sequence of the SEQ ID NO: 3472 via a linker comprising the sequence of SEQ ID NO: 3473, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3475, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

182. The method of any one of claims 1-168, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 15 or functional variant thereof comprising the sequence of SEQ ID NO: 2170, wherein the IL- 15 or functional variant thereof is covalently linked to an IL15Ralpha dimerizing domain comprising the sequence of the SEQ ID NO: 3472 via a linker comprising the sequence of SEQ ID NO: 3473, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3476, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

183. The method of any one of claims 1-182, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3445, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3446, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

184. The method of any one of claims 1-182, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3448, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3449, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

185. The method of any one of claims 1-182, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3450, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3451, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

186. The method of any one of claims 1-182, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3450, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3454 or the sequence of SEQ ID NO: 3501 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3451, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

187. The method of any one of claims 1-182, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3454 or the sequence of SEQ ID NO: 3501 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 1349, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

188. The method of any one of claims 1-182, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1196, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 1195, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

189. The method of any one of claims 1-182, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3455, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3456, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

190. The method of any one of claims 1-182, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3457, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3459, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3460,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3462 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2191, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3458, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3461.

191. The method of any one of claims 1-182, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3463, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3459, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3460,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3462 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2191, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3464, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3461.

192. The method of any one of claims 1-182, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3465, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3467, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3468,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3469 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2191, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3466, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3461.

193. The method of any one of claims 1-182, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3470, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3471, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

194. The method of any one of claims 1-182, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,-SOO-(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 15 or functional variant thereof comprising the sequence of SEQ ID NO: 2170, wherein the IL- 15 or functional variant thereof is covalently linked to an IL15Ralpha dimerizing domain comprising the sequence of the SEQ ID NO: 3472 via a linker comprising the sequence of SEQ ID NO: 3473, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 1349, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

195. The method of any one of claims 1-182, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 15 or functional variant thereof comprising the sequence of SEQ ID NO: 2170, wherein the IL- 15 or functional variant thereof is covalently linked to an IL15Ralpha dimerizing domain comprising the sequence of the SEQ ID NO: 3472 via a linker comprising the sequence of SEQ ID NO: 3473, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3475, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

196. The method of any one of claims 1-182, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 15 or functional variant thereof comprising the sequence of SEQ ID NO: 2170, wherein the IL- 15 or functional variant thereof is covalently linked to an IL15Ralpha dimerizing domain comprising the sequence of the SEQ ID NO: 3472 via a linker comprising the sequence of SEQ ID NO: 3473, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3476, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

197. The method of any one of claims 1-196, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3338;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3339.

198. The method of any one of claims 1-196, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3318;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3319.

199. The method of any one of claims 1-196, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3328;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3329.

200. The method of any one of claims 1-196, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3328;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3350 or the sequence of SEQ ID NO: 3500; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3329.

201. The method of any one of claims 1-196, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3349.

202. The method of any one of claims 1-196, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3358;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3359.

203. The method of any one of claims 1-196, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3368;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3369.

204. The method of any one of claims 1-196, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3378;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3380; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3379.

205. The method of any one of claims 1-196, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3388;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3390; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3389.

206. The method of any one of claims 1-196, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3398;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3400; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3399.

207. The method of any one of claims 1-196, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3408;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3409.

208. The method of any one of claims 1-196, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3349.

209. The method of any one of claims 1-196, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3428.

210. The method of any one of claims 1-196, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3437.

211. The method of any one of claims 1-210, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3338;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3339.

212. The method of any one of claims 1-210, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3318;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3319.

213. The method of any one of claims 1-210, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3328;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3329.

214. The method of any one of claims 1-210, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3328;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3350 or the sequence of SEQ ID NO: 3500; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3329.

215. The method of any one of claims 1-210, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3348 or the sequence ofSEQ ID NO: 3502;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3349.

216. The method of any one of claims 1-210, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3358;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3359.

217. The method of any one of claims 1-210, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3368;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3369.

218. The method of any one of claims 1-210, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3378;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3380; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3379.

219. The method of any one of claims 1-210, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3388;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3390; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3389.

220. The method of any one of claims 1-210, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3398;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3400; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3399.

221. The method of any one of claims 1-210, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3408;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3409.

222. The method of any one of claims 1-210, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3348 or the sequence ofSEQ ID NO: 3502;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3349.

223. The method of any one of claims 1-210, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3348 or the sequence ofSEQ ID NO: 3502;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3428.

224. The method of any one of claims 1-210, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3348 or the sequence ofSEQ ID NO: 3502;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3437.

225. The method of any one of claims 1-224, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3338;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3339.

226. The method of any one of claims 1-224, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3318;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3319.

227. The method of any one of claims 1-224, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3328;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3329.

228. The method of any one of claims 1-224, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3328;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3350 or the sequence of SEQ ID NO: 3500; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3329.

229. The method of any one of claims 1-224, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3349.

230. The method of any one of claims 1-224, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3358;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3359.

231. The method of any one of claims 1-224, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3368;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3369.

232. The method of any one of claims 1-224, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3378;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3380; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3379.

233. The method of any one of claims 1-224, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3388;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3390; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3389.

234. The method of any one of claims 1-224, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3398;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3400; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3399.

235. The method of any one of claims 1-224, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3408;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3409.

236. The method of any one of claims 1-224, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3349.

237. The method of any one of claims 1-224, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3428.

238. The method of any one of claims 1-224, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3437.

239. The method of any one of claims 1-238, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3338;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3339.

240. The method of any one of claims 1-238, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3318;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3319.

241. The method of any one of claims 1-238, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3328;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3329.

242. The method of any one of claims 1-238, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3328;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3350 or the sequence of SEQ ID NO: 3500; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3329.

243. The method of any one of claims 1-238, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3348 or the sequence ofSEQ ID NO: 3502;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3349.

244. The method of any one of claims 1-238, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3358;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3359.

245. The method of any one of claims 1-238, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the firstpolypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3368;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3369.

246. The method of any one of claims 1-238, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3378;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3380; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3379.

247. The method of any one of claims 1-238, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3388;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3390; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3389.

248. The method of any one of claims 1-238, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3398;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3400; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3399.

249. The method of any one of claims 1-238, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3408;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3409.

250. The method of any one of claims 1-238, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3348 or the sequence ofSEQ ID NO: 3502;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3349.

251. The method of any one of claims 1-238, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3348 or the sequence ofSEQ ID NO: 3502;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3428.

252. The method of any one of claims 1-238, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3348 or the sequence ofSEQ ID NO: 3502;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3437.

253. The method of any one of claims 1-252, wherein the disease or condition is cancer.

254. The method of claim 253, wherein the cancer is a solid tumor.

255. The method of claim 254, wherein the solid tumor is melanoma, pancreatic cancer, breast cancer, colorectal cancer, lung cancer, skin cancer, ovarian cancer, or liver cancer.

256. The method of claim 253 or 254, wherein the solid tumor is selected from the group consisting of high mutational burden (TMB-H), microsatellite instability / DNA mismatch repair (MSI- H / dMMR), virally associated tumor, metastatic triple-negative breast cancer (mTNBC), relapsed and refractory epithelial ovarian cancer, metastatic castration-resistant prostate cancer (mCRPC), K-Ras wild type CRC, K-Ras mutant CRC, and primary stage IV or recurrent non-small cell lung cancer (NSCLC).

257. The method of claim 256, wherein the virally associated tumor comprises Merkel cell carcinoma, cervical cancer, oropharyngeal cancer, anal cancer, penile cancer, vaginal cancer, or vulvar cancer.

258. The method of claim 253, wherein the cancer is a hematological cancer.

259. The method of claim 258, wherein the hematological cancer is a B-cell or T cell malignancy.

260. The method of claim 259, wherein the B-cell or T cell malignancy is Hodgkin’s lymphoma,Non-Hodgkin’s lymphoma, acute myeloid leukemia (AML), chronic myeloid leukemia, myelodysplastic syndrome, multiple myeloma, or acute lymphocytic leukemia.

261. The method of claim 260, wherein the Non-Hodgkin’s lymphoma is B cell lymphoma, diffuse large B cell lymphoma, follicular lymphoma, chronic lymphocytic leukemia, mantle cell lymphoma, marginal zone B-cell lymphoma, Burkitt lymphoma, lymphoplasmacytic lymphoma, or hairy cell leukemia.

262. The method of any one of claims 1-261, wherein the administering comprises administering a first pharmaceutical composition comprising the first agent, and a second pharmaceutical composition comprising the second agent, wherein the first pharmaceutical composition and the second pharmaceutical composition independently further comprises a pharmaceutically acceptable excipient, carrier or diluent.

263. A combination therapy for treating a disease or condition in a subject in need thereof comprising administering a first agent that comprises a first binder that binds to a first target molecule to the subject, and administering a second agent that comprises a second binder that binds to a second target molecule to the subject, thereby treating the disease or condition in the subject; wherein an administration of the first agent is followed by an administration of the second agent; wherein the first target molecule and the second target molecule are independently selected from the group consisting of a T cell receptor alpha variable region (TCRaV) and a T cell receptor beta variable region (TCRpV); and wherein the first target molecule and the second target molecule are different.

264. The combination therapy of claim 263, wherein the first agent and the second agent are not concomitantly administered to the subject.

265. The combination therapy of claim 263 or 264, wherein administering the first agent comprises administering a therapeutically effective amount of the first agent to the subject.

266. The combination therapy of any one of claims 263-265, wherein administering the second agent comprises administering a therapeutically effective amount of the second agent to the subject.

267. The combination therapy of any one of claims 263-266, wherein the combination therapy is more effective to treat the disease or condition in the subject relative to a method in which the first agent is administered to the subject but not the second agent.

268. The combination therapy of any one of claims 263-267, wherein the combination therapy is more effective to treat the disease or condition in the subject relative to a method in which the second agent is administered to the subject but not the first agent.

269. The combination therapy of any one of claims 263-268, wherein the combination therapy is more effective to treat the disease or condition in the subject relative to a method in which the first agent is administered to the subject at a first administration and the first agent is administered to the subject subsequently at a second administration.

270. The combination therapy of any one of claims 263-269, wherein the combination therapy is more effective to treat the disease or condition in the subject relative to a method in which the second agent is administered to the subject at a first administration and the second agent is administered to the subject subsequently at a second administration.

271. The combination therapy of any one of claims 263-270, wherein the combination therapy is more effective to treat the disease or condition in the subject relative to a method in which the second agent is administered to the subject at a first administration and the second agent is administered to the subject subsequently at a second administration.

272. The combination therapy of any one of claims 263-271, wherein the administration of the first agent comprises one or more doses.

273. The combination therapy of any one of claims 263-272, wherein the administration of the first agent comprises two or more doses.

274. The combination therapy of any one of claims 263-273, wherein the administration of the first agent comprises one dose per week.

275. The combination therapy of any one of claims 263-273, wherein the administration of the first agent comprises two or more doses per week.

276. The combination therapy of any one of claims 263-273, wherein the first agent is administered to the subject once every two weeks.

277. The combination therapy of any one of claims 263-273, wherein the first agent is administered to the subject once every three weeks.

278. The combination therapy of any one of claims 263-274 wherein the first agent is administered to the subject once every week for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

279. The combination therapy of any one of claims 263-273 and 275, wherein the administration of the first agent comprises two or more doses per week for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

280. The combination therapy of any one of claims 263-273 and 276, wherein the first agent is administered to the subject once every two week for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

281. The combination therapy of any one of claims 263-273 and 277, wherein the first agent is administered to the subject once every three week for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

282. The combination therapy of any one of claims 263-281, wherein the administration of the second agent comprises one or more doses.

283. The combination therapy of any one of claims 263-282, wherein the administration of the second agent comprises two or more doses.

284. The combination therapy of any one of claims 263-283, wherein the administration of the second agent comprises one dose per week.

285. The combination therapy of any one of claims 263-283, wherein the administration of the second agent comprises two or more doses per week.

286. The combination therapy of any one of claims 263-283, wherein the second agent is administered to the subject once every two weeks.

287. The combination therapy of any one of claims 263-283, wherein the second agent is administered to the subject once every three weeks.

288. The combination therapy of any one of claims 263-282, wherein the second agent is administered to the subject once every week for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

289. The combination therapy of any one of claims 263-282 and 285, wherein the administration of the second agent comprises two or more doses per week for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

290. The combination therapy of any one of claims 263-282 and 286, wherein the second agent is administered to the subject once every two weeks for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

291. The combination therapy of any one of claims 263-282 and 287, wherein the second agent is administered to the subject once every three weeks for at least 1, 2, 3, or 4 weeks, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 months, or at least 1, 2, or 3 years.

292. The combination therapy of any one of claims 263-291, wherein the administration of the first agent and the administration of the second agent is separated by one week.

293. The combination therapy of any one of claims 263-291, wherein the administration of the first agent and the administration of the second agent is separated by two or more weeks.

294. The combination therapy of any one of claims 263-291, wherein the administration of the first agent and the administration of the second agent is separated by 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 12 months.

295. The combination therapy of any one of claims 263-294, wherein the administration of the first agent and the second agent is repeated twice or more.

296. The combination therapy of any one of the preceding claims, wherein the first agent and the second agent are administered to the subject according to a dosing regimen, wherein the dosing regimen comprises an administration of the first agent once every week for two weeks followed by an administration of the second agent once a week for two weeks, wherein the second agent is administered to the subject one week after the last administration of the first agent.

297. The combination therapy of claim 296, wherein the dosing regimen is repeated twice or more.

298. The combination therapy of claim 296 or 297, wherein the dosing regimen is repeated at the interval of one week.

299. The combination therapy of any one of claims 296-298, wherein the dosing regimen is repeated at the interval of 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 1 week, 2 weeks, 3 weeks, 4 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 12 months.

300. The combination therapy of any one of claims 263-299, wherein the first agent and the second agent are administered to the subject in a same amount.

301. The combination therapy of any one of claims 263-299, wherein the first agent and the second agent are administered to the subject in different amounts.

302. The combination therapy of any one of claims 263-301, wherein the administration of the first agent comprises two or more doses, and each dose comprises a same amount of the first agent.

303. The combination therapy of any one of claims 263-301, wherein the administration of the first agent comprises two or more doses, and each dose comprises different amounts of the first agent.

304. The combination therapy of any one of claims 263-303, wherein the administration of the second agent comprises two or more doses, and each dose comprises a same amount of the second agent.

305. The combination therapy of any one of claims 263-303, wherein the administration of the second agent comprises two or more doses, and each dose comprises different amounts of the second agent.

306. The combination therapy of any one of claims 263-305, wherein the first agent is administered to the subject at a dose of from about 0.001 mg / kg to about 10 mg / kg.

307. The combination therapy of any one of claims 263-306, wherein the second agent is administered to the subject at a dose of from about 0.001 mg / kg to about 10 mg / kg.

308. The combination therapy of any one of claims 263-307, wherein the first agent is administered to the subject at a dose of about 0.3 mg / kg or about 1 mg / kg.

309. The combination therapy of any one of claims 263-308, wherein the second agent is administered to the subject at a dose of about 0.3 mg / kg or about 1 mg / kg.

310. The combination therapy of any one of claims 263-309, wherein the first target molecule is a first TCRpV, and the second target molecule is a second TCRpV, wherein the first TCRpV and the second TCRpV are different.

311. The combination therapy of any one of claims 263-307, wherein the first target molecule is a first TCRaV, and the second target molecule is a second TCRaV, wherein the first TCRaV and the second TCRaV are different.

312. The combination therapy of any one of claims 263-307, wherein the first target molecule is a TCRpV, and the second target molecule is a TCRaV.

313. The combination therapy of any one of claims 263-307, wherein the first target molecule is a TCRaV, and the second target molecule is a TCRpV.

314. The combination therapy of any one of the preceding claims, wherein the first target molecule is human TCRPV6.

315. The combination therapy of any one of the preceding claims, wherein the first target molecule is human TCRpV 10.

316. The combination therapy of any one of the preceding claims, wherein the second target molecule is human TCRPV15.

317. The combination therapy of any one of the preceding claims, wherein the second target molecule is human TCRPV27.

318. The combination therapy of any one of the preceding claims, wherein the second target molecule is human TCRPV5.

319. The combination therapy of any one of the preceding claims, wherein the first target molecule is human TCRPV6, and the second target molecule is human TCRPV5.

320. The combination therapy of any one of the preceding claims, wherein the first target molecule is human TCRPV6, and the second target molecule is human TCRpV 15.

321. The combination therapy of any one of the preceding claims, wherein the first target molecule is human TCRPV6, and the second target molecule is human TCRPV27.

322. The combination therapy of any one of the preceding claims, wherein the first target molecule is human TCRpV 10, and the second target molecule is human TCRPV5.

323. The combination therapy of any one of the preceding claims, wherein the first target molecule is human TCRpV 10, and the second target molecule is human TCRPV15.

324. The combination therapy of any one of the preceding claims, wherein the first target molecule is human TCRpVIO, and the second target molecule is human TCRPV27.

325. The combination therapy of any one of the preceding claims, wherein the first target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV19, human TRBV20, or human TRBV28.

326. The combination therapy of any one of the preceding claims, wherein the first target molecule is human TRBV5-1, human TRBV6-5, human TRBV10-1, human TRBV10-2, human TRBV10-3, human TRBV7-2, human TRBV7-3, human TRBV19, human TRBV20-1, or human TRBV28.

327. The combination therapy of any one of the preceding claims, wherein the first target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30.

328. The combination therapy of any one of the preceding claims, wherein the first target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30.

329. The combination therapy of any one of the preceding claims, wherein the second target molecule is human TRBV5, human TRBV15, human TRBV27, human TRBV6, human TRBV10, human TRBV7, human TRBV19, human TRBV20, or human TRBV28.

330. The combination therapy of any one of the preceding claims, wherein the second target molecule is human TRBV5-1, human TRBV6-5, human TRBV10-1, human TRBV10-2, human TRBV10-3, human TRBV7-2, human TRBV7-3, human TRBV15, human TRBV27, human TRBV19, human TRBV20-1, or human TRBV28.

331. The combination therapy of any one of the preceding claims, wherein the second target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30.

332. The combination therapy of any one of the preceding claims, wherein the second target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30.

333. The combination therapy of any one of the preceding claims, wherein the first target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV19, humanTRBV20, or human TRBV28, and the second target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV15, human TRBV27, human TRBV19, human TRBV20, or human TRBV28, wherein the first target molecule and the second target molecule are different.

334. The combination therapy of any one of the preceding claims, wherein the first target molecule and the second target molecule are: human TRBV5 and human TRBV5, respectively; human TRBV5 and human TRBV6, respectively; human TRBV5 and human TRBV10, respectively; human TRBV5 and human TRBV7, respectively; human TRBV5 and human TRBV19, respectively; human TRBV5 and human TRBV20, respectively; human TRBV5 and human TRBV28, respectively; human TRBV6 and human TRBV5, respectively; human TRBV6 and human TRBV6, respectively; human TRBV6 and human TRBV10, respectively; human TRBV6 and human TRBV7, respectively; human TRBV6 and human TRBV15, respectively; human TRBV6 and human TRBV27, respectively; human TRBV6 and human TRBV19, respectively; human TRBV6 and human TRBV20, respectively; human TRBV6 and human TRBV28, respectively; human TRBV10 and human TRBV5, respectively; human TRBV10 and human TRBV6, respectively; human TRBV10 and human TRBV10, respectively; human TRBV10 and human TRBV7, respectively; human TRBV10 and human TRBV15, respectively; human TRBV10 and human TRBV27, respectively; human TRBV10 and human TRBV19, respectively; human TRBV10 and human TRBV20, respectively; human TRBV10 and human TRBV28, respectively;human TRBV7 and human TRBV5, respectively; human TRBV7 and human TRBV6, respectively; human TRBV7 and human TRBV10, respectively; human TRBV7 and human TRBV7, respectively; human TRBV7 and human TRBV19, respectively; human TRBV7 and human TRBV20, respectively; human TRBV7 and human TRBV28, respectively;human TRBV19 and human TRBV5, respectively; human TRBV19 and human TRBV6, respectively; human TRBV19 and human TRBV10, respectively; human TRBV19 and human TRBV7, respectively; human TRBV19 and human TRBV19, respectively; human TRBV19 and human TRBV20, respectively; human TRBV19 and human TRBV28, respectively; human TRBV20 and human TRBV5, respectively; human TRBV20 and human TRBV6, respectively; human TRBV20 and human TRBV1O, respectively; human TRBV20 and human TRBV7, respectively; human TRBV20 and human TRBV19, respectively; human TRBV20 and human TRBV20, respectively; human TRBV20 and human TRBV28, respectively; human TRBV28 and human TRBV5, respectively; human TRBV28 and human TRBV6, respectively; human TRBV28 and human TRBV1O, respectively; human TRBV28 and human TRBV7, respectively; human TRBV28 and human TRBV19, respectively; human TRBV28 and human TRBV20, respectively; or human TRBV28 and human TRBV28, respectively.

335. The combination therapy of any one of the preceding claims, wherein the first target molecule is human TRBV5-1, human TRBV6-5, human TRBV10-1, human TRBV10-2, human TRBV10-3, human TRBV7-2, human TRBV7-3, human TRBV19, human TRBV20-1, or human TRBV28, and the second target molecule is human TRBV5-1, human TRBV6-5, human TRBV10-1, human TRBV10-2, human TRBV10-3, human TRBV7-2, human TRBV7-3, human TRBV15, human TRBV27, human TRBV19, human TRBV20-1, or human TRBV28, wherein the first target molecule and the second target molecule are different.

336. The combination therapy of any one of the preceding claims, wherein the first target molecule and the second target molecule are:Human TRBV5-1 and human TRBV6-5, respectively; human TRBV5-1 and human TRBV10-1, respectively; human TRBV5-1 and human TRBV10-2, respectively; human TRBV5-1 and human TRBV10-3, respectively; human TRBV5-1 and human TRBV7-2, respectively; human TRBV5-1 and human TRBV7-3, respectively; human TRBV5-1 and human TRBV19, respectively; human TRBV5-1 and human TRBV20-1, respectively; human TRBV5-1 and human TRBV28, respectively;human TRBV6-5 and human TRBV5-1, respectively; human TRBV6-5 and human TRBV7-2, respectively; human TRBV6-5 and human TRBV7-3, respectively; human TRBV6-5 and human TRBV15, respectively; human TRBV6-5 and human TRBV27, respectively; human TRBV6-5 and human TRBV19, respectively; human TRBV6-5 and human TRBV20-1, respectively; human TRBV6-5 and human TRBV28, respectively; human TRBV10-1 and human TRBV5-1, respectively; human TRBV10-1 and human TRBV7-2, respectively; human TRBV10-1 and human TRBV7-3, respectively; human TRBV10-1 and human TRBV15, respectively; human TRBV10-1 and human TRBV27, respectively; human TRBV10-1 and human TRBV19, respectively; human TRBV10-1 and human TRBV20-1, respectively; human TRBV10-1 and human TRBV28, respectively; human TRBV10-2 and human TRBV5-1, respectively; human TRBV10-2 and human TRBV7-2, respectively; human TRBV10-2 and human TRBV7-3, respectively; human TRBV10-2 and human TRBV15, respectively; human TRBV10-2 and human TRBV27, respectively; human TRBV10-2 and human TRBV19, respectively; human TRBV10-2 and human TRBV20-1, respectively; human TRBV10-2 and human TRBV28, respectively; human TRBV10-3 and human TRBV5-1, respectively; human TRBV10-3 and human TRBV7-2, respectively; human TRBV10-3 and human TRBV7-3, respectively; human TRBV10-3 and human TRBV15, respectively; human TRBV10-3 and human TRBV27, respectively; human TRBV10-3 and human TRBV19, respectively; human TRBV10-3 and human TRBV20-1, respectively; human TRBV10-3 and human TRBV28, respectively; human TRBV7-2 and human TRBV5-1, respectively; human TRBV7-2 and human TRBV6-5, respectively; human TRBV7-2 and human TRBV10-1, respectively; human TRBV7-2 and human TRBV10-2, respectively; human TRBV7-2 and human TRBV10-3, respectively; human TRBV7-2 and human TRBV7-3, respectively;human TRBV7-2 and human TRBV19, respectively; human TRBV7-2 and human TRBV20-1, respectively; human TRBV7-2 and human TRBV28, respectively; human TRBV7-3 and human TRBV5-1, respectively; human TRBV7-3 and human TRBV6-5, respectively; human TRBV7-3 and human TRBV10-1, respectively; human TRBV7-3 and human TRBV10-2, respectively; human TRBV7-3 and human TRBV10-3, respectively; human TRBV7-3 and human TRBV7-2, respectively; human TRBV7-3 and human TRBV19, respectively; human TRBV7-3 and human TRBV20-1, respectively; human TRBV7-3 and human TRBV28, respectively; human TRBV19 and human TRBV5-1, respectively; human TRBV19 and human TRBV6-5, respectively; human TRBV19 and human TRBV10-1, respectively; human TRBV19 and human TRBV10-2, respectively; human TRBV19 and human TRBV10-3, respectively; human TRBV19 and human TRBV7-2, respectively; human TRBV19 and human TRBV7-3, respectively; human TRBV19 and human TRBV20-1, respectively; human TRBV19 and human TRBV28, respectively; human TRBV20-1 and human TRBV5-1, respectively; human TRBV20-1 and human TRBV6-5, respectively; human TRBV20-1 and human TRBV10-1, respectively; human TRBV20-1 and human TRBV10-2, respectively; human TRBV20-1 and human TRBV10-3, respectively; human TRBV20-1 and human TRBV7-2, respectively; human TRBV20-1 and human TRBV7-3, respectively; human TRBV20-1 and human TRBV19, respectively; human TRBV20-1 and human TRBV28, respectively; human TRBV28 and human TRBV5-1, respectively; human TRBV28 and human TRBV6-5, respectively; human TRBV28 and human TRBV10-1, respectively; human TRBV28 and human TRBV10-2, respectively; human TRBV28 and human TRBV10-3, respectively; human TRBV28 and human TRBV7-2, respectively; human TRBV28 and human TRBV7-3, respectively; human TRBV28 and human TRBV19, respectively; orhuman TRBV28 and human TRBV20-1, respectively.

337. The combination therapy of any one of the preceding claims, wherein the first target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30, and the second target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30, wherein the first target molecule and the second target molecule are different.

338. The combination therapy of any one of the preceding claims, wherein the first target molecule and the second target molecule are: human TRAV12 and human TRAV12, respectively; human TRAV12 and human TRAV13, respectively; human TRAV12 and human TRAV19, respectively; human TRAV12 and human TRAV21, respectively; human TRAV12 and human TRAV30, respectively; human TRAV13 and human TRAV12, respectively; human TRAV13 and human TRAV13, respectively; human TRAV13 and human TRAV19, respectively; human TRAV13 and human TRAV21, respectively; human TRAV13 and human TRAV30, respectively; human TRAV19 and human TRAV12, respectively; human TRAV19 and human TRAV13, respectively; human TRAV19 and human TRAV19, respectively; human TRAV19 and human TRAV21, respectively; human TRAV19 and human TRAV30, respectively; human TRAV21 and human TRAV12, respectively; human TRAV21 and human TRAV13, respectively; human TRAV21 and human TRAV19, respectively; human TRAV21 and human TRAV21, respectively; human TRAV21 and human TRAV30, respectively; human TRAV30 and human TRAV12, respectively; human TRAV30 and human TRAV13, respectively; human TRAV30 and human TRAV19, respectively; human TRAV30 and human TRAV21, respectively; or human TRAV30 and human TRAV30, respectively.

339. The combination therapy of any one of the preceding claims, wherein the first target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30, and the second target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30, wherein the first target molecule and the second target molecule are different.

340. The combination therapy of any one of the preceding claims, wherein the first target molecule and the second target molecule are: human TRAV12-2 and human TRAV13-1, respectively; human TRAV12-2 and human TRAV19, respectively; human TRAV12-2 and human TRAV21, respectively; human TRAV12-2 and human TRAV30, respectively; human TRAV13-1 and human TRAV12-2, respectively; human TRAV13-1 and human TRAV19, respectively; human TRAV13-1 and human TRAV21, respectively; human TRAV13-1 and human TRAV30, respectively; human TRAV19 and human TRAV12-2, respectively; human TRAV19 and human TRAV13-1, respectively; human TRAV19 and human TRAV21, respectively; human TRAV19 and human TRAV30, respectively; human TRAV21 and human TRAV12-2, respectively; human TRAV21 and human TRAV13-1, respectively; human TRAV21 and human TRAV19, respectively; human TRAV21 and human TRAV30, respectively; human TRAV30 and human TRAV12-2, respectively; human TRAV30 and human TRAV13-1, respectively; human TRAV30 and human TRAV19, respectively; or human TRAV30 and human TRAV21, respectively.

341. The combination therapy of any one of the preceding claims, wherein the first target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV19, human TRBV20, or human TRBV28, and the second target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30.

342. The combination therapy of any one of the preceding claims, wherein the first target molecule and the second target molecule are: human TRBV5 and human TRAV12, respectively; human TRBV5 and human TRAV13, respectively; human TRBV5 and human TRAV19, respectively; human TRBV5 and human TRAV21, respectively; human TRBV5 and human TRAV30, respectively; human TRBV6 and human TRAV12, respectively; human TRBV6 and human TRAV13, respectively; human TRBV6 and human TRAV19, respectively; human TRBV6 and human TRAV21, respectively; human TRBV6 and human TRAV30, respectively; human TRBV10 and human TRAV12, respectively;human TRBV10 and human TRAV13, respectively; human TRBV1O and human TRAV19, respectively; human TRBV1O and human TRAV21, respectively; human TRBV1O and human TRAV3O, respectively; human TRBV7 and human TRAV12, respectively; human TRBV7 and human TRAV13, respectively; human TRBV7 and human TRAV19, respectively; human TRBV7 and human TRAV21, respectively; human TRBV7 and human TRAV3O, respectively; human TRBV19 and human TRAV12, respectively; human TRBV19 and human TRAV13, respectively; human TRBV19 and human TRAV19, respectively; human TRBV19 and human TRAV21, respectively; human TRBV19 and human TRAV3O, respectively; human TRBV20 and human TRAV12, respectively; human TRBV20 and human TRAV13, respectively; human TRBV20 and human TRAV19, respectively; human TRBV20 and human TRAV21, respectively; human TRBV20 and human TRAV3O, respectively; human TRBV28 and human TRAV12, respectively; human TRBV28 and human TRAV13, respectively; human TRBV28 and human TRAV19, respectively; human TRBV28 and human TRAV21, respectively; or human TRBV28 and human TRAV30, respectively.

343. The combination therapy of any one of the preceding claims, wherein the first target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV19, human TRBV20, or human TRBV28, and the second target molecule is human TRAV12-2, human TRAV13- 1, human TRAV19, human TRAV21, or human TRAV30.

344. The combination therapy of any one of the preceding claims, wherein the first target molecule and the second target molecule are: human TRBV5 and human TRAV12-2, respectively; human TRBV5 and human TRAV13-1, respectively; human TRBV5 and human TRAV19, respectively; human TRBV5 and human TRAV21, respectively; human TRBV5 and human TRAV30, respectively; human TRBV6 and human TRAV12-2, respectively; human TRBV6 and human TRAV13-1, respectively; human TRBV6 and human TRAV19, respectively;human TRBV6 and human TRAV21, respectively; human TRBV6 and human TRAV30, respectively; human TRBV10 and human TRAV12-2, respectively; human TRBV1O and human TRAV13-1, respectively; human TRBV1O and human TRAV19, respectively; human TRBV1O and human TRAV21, respectively; human TRBV1O and human TRAV3O, respectively; human TRBV7 and human TRAV12-2, respectively; human TRBV7 and human TRAV13-1, respectively; human TRBV7 and human TRAV19, respectively; human TRBV7 and human TRAV21, respectively; human TRBV7 and human TRAV3O, respectively; human TRBV19 and human TRAV12-2, respectively; human TRBV19 and human TRAV13-1, respectively; human TRBV19 and human TRAV19, respectively; human TRBV19 and human TRAV21, respectively; human TRBV19 and human TRAV3O, respectively; human TRBV20 and human TRAV12-2, respectively; human TRBV20 and human TRAV13-1, respectively; human TRBV20 and human TRAV19, respectively; human TRBV20 and human TRAV21, respectively; human TRBV20 and human TRAV3O, respectively; human TRBV28 and human TRAV12-2, respectively; human TRBV28 and human TRAV13-1, respectively; human TRBV28 and human TRAV19, respectively; human TRBV28 and human TRAV21, respectively; or human TRBV28 and human TRAV30, respectively.

345. The combination therapy of any one of the preceding claims, wherein the first target molecule is human TRBV5-1, human TRBV6-5, human TRBV10-1, human TRBV10-2, human TRBV10-3, human TRBV7-2, human TRBV7-3, human TRBV19, human TRBV20-1, or human TRBV28, and the second target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30.

346. The combination therapy of any one of the preceding claims, wherein the first target molecule and the second target molecule are: human TRBV5-1 and human TRAV12, respectively; human TRBV5-1 and human TRAV13, respectively; human TRBV5-1 and human TRAV19, respectively; human TRBV5-1 and human TRAV21, respectively;human TRBV5-1 and human TRAV30, respectively; human TRBV6-5 and human TRAV12, respectively; human TRBV6-5 and human TRAV13, respectively; human TRBV6-5 and human TRAV19, respectively; human TRBV6-5 and human TRAV21, respectively; human TRBV6-5 and human TRAV30, respectively; human TRBV10-1 and human TRAV12, respectively; human TRBV10-1 and human TRAV13, respectively; human TRBV10-1 and human TRAV19, respectively; human TRBV10-1 and human TRAV21, respectively; human TRBV10-1 and human TRAV30, respectively; human TRBV10-2 and human TRAV12, respectively; human TRBV10-2 and human TRAV13, respectively; human TRBV10-2 and human TRAV19, respectively; human TRBV10-2 and human TRAV21, respectively; human TRBV10-2 and human TRAV30, respectively; human TRBV10-3 and human TRAV12, respectively; human TRBV10-3 and human TRAV13, respectively; human TRBV10-3 and human TRAV19, respectively; human TRBV10-3 and human TRAV21, respectively; human TRBV10-3 and human TRAV30, respectively; human TRBV7-2 and human TRAV12, respectively; human TRBV7-2 and human TRAV13, respectively; human TRBV7-2 and human TRAV19, respectively; human TRBV7-2 and human TRAV21, respectively; human TRBV7-2 and human TRAV30, respectively; human TRBV7-3 and human TRAV12, respectively; human TRBV7-3 and human TRAV13, respectively; human TRBV7-3 and human TRAV19, respectively; human TRBV7-3 and human TRAV21, respectively; human TRBV7-3 and human TRAV30, respectively; human TRBV19 and human TRAV12, respectively; human TRBV19 and human TRAV13, respectively; human TRBV19 and human TRAV19, respectively; human TRBV19 and human TRAV21, respectively; human TRBV19 and human TRAV30, respectively; human TRBV20-1 and human TRAV12, respectively; human TRBV20-1 and human TRAV13, respectively;human TRBV20-1 and human TRAV19, respectively; human TRBV20-1 and human TRAV21, respectively; human TRBV20-1 and human TRAV30, respectively; human TRBV28 and human TRAV12, respectively; human TRBV28 and human TRAV13, respectively; human TRBV28 and human TRAV19, respectively; human TRBV28 and human TRAV21, respectively; or human TRBV28 and human TRAV30, respectively.

347. The combination therapy of any one of the preceding claims, wherein the first target molecule is human TRBV5-1, human TRBV6-5, human TRBV10-1, human TRBV10-2, human TRBV10-3, human TRBV7-2, human TRBV7-3, human TRBV19, human TRBV20-1, or human TRBV28, and the second target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30.

348. The combination therapy of any one of the preceding claims, wherein the first target molecule and the second target molecule are: human TRBV5-1 and human TRAV12-2, respectively; human TRBV5-1 and human TRAV13-1, respectively; human TRBV5-1 and human TRAV19, respectively; human TRBV5-1 and human TRAV21, respectively; human TRBV5-1 and human TRAV30, respectively; human TRBV6-5 and human TRAV12-2, respectively; human TRBV6-5 and human TRAV13-1, respectively; human TRBV6-5 and human TRAV19, respectively; human TRBV6-5 and human TRAV21, respectively; human TRBV6-5 and human TRAV30, respectively; human TRBV10-1 and human TRAV12-2, respectively; human TRBV10-1 and human TRAV13-1, respectively; human TRBV10-1 and human TRAV19, respectively; human TRBV10-1 and human TRAV21, respectively; human TRBV10-1 and human TRAV30, respectively; human TRBV10-2 and human TRAV12-2, respectively; human TRBV10-2 and human TRAV13-1, respectively; human TRBV10-2 and human TRAV19, respectively; human TRBV10-2 and human TRAV21, respectively; human TRBV10-2 and human TRAV30, respectively; human TRBV10-3 and human TRAV12-2, respectively; human TRBV10-3 and human TRAV13-1, respectively; human TRBV10-3 and human TRAV19, respectively;human TRBV10-3 and human TRAV21, respectively; human TRBV10-3 and human TRAV30, respectively; human TRBV7-2 and human TRAV12-2, respectively; human TRBV7-2 and human TRAV13-1, respectively; human TRBV7-2 and human TRAV19, respectively; human TRBV7-2 and human TRAV21, respectively; human TRBV7-2 and human TRAV30, respectively; human TRBV7-3 and human TRAV12-2, respectively; human TRBV7-3 and human TRAV13-1, respectively; human TRBV7-3 and human TRAV19, respectively; human TRBV7-3 and human TRAV21, respectively; human TRBV7-3 and human TRAV30, respectively; human TRBV19 and human TRAV12-2, respectively; human TRBV19 and human TRAV13-1, respectively; human TRBV19 and human TRAV19, respectively; human TRBV19 and human TRAV21, respectively; human TRBV19 and human TRAV30, respectively; human TRBV20-1 and human TRAV12-2, respectively; human TRBV20-1 and human TRAV13-1, respectively; human TRBV20-1 and human TRAV19, respectively; human TRBV20-1 and human TRAV21, respectively; human TRBV20-1 and human TRAV30, respectively; human TRBV28 and human TRAV12-2, respectively; human TRBV28 and human TRAV13-1, respectively; human TRBV28 and human TRAV19, respectively; human TRBV28 and human TRAV21, respectively; or human TRBV28 and human TRAV30, respectively.

349. The combination therapy of any one of the preceding claims, wherein the first target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30, and the second target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV19, human TRBV20, or human TRBV28.

350. The combination therapy of any one of the preceding claims, wherein the first target molecule and the second target molecule are: human TRAV12 and human TRBV5, respectively; human TRAV12 and human TRBV6, respectively; human TRAV12 and human TRBV10, respectively; human TRAV12 and human TRBV7, respectively; human TRAV12 and human TRBV19, respectively;human TRAV12 and human TRBV20, respectively; human TRAV12 and human TRBV28, respectively; human TRAV13 and human TRBV5, respectively; human TRAV13 and human TRBV6, respectively; human TRAV13 and human TRBV10, respectively; human TRAV13 and human TRBV7, respectively; human TRAV13 and human TRBV19, respectively; human TRAV13 and human TRBV20, respectively; human TRAV13 and human TRBV28, respectively; human TRAV19 and human TRBV5, respectively; human TRAV19 and human TRBV6, respectively; human TRAV19 and human TRBV1O, respectively; human TRAV19 and human TRBV7, respectively; human TRAV19 and human TRBV19, respectively; human TRAV19 and human TRBV20, respectively; human TRAV19 and human TRBV28, respectively; human TRAV21 and human TRBV5, respectively; human TRAV21 and human TRBV6, respectively; human TRAV21 and human TRBV1O, respectively; human TRAV21 and human TRBV7, respectively; human TRAV21 and human TRBV19, respectively; human TRAV21 and human TRBV20, respectively; human TRAV21 and human TRBV28, respectively; human TRAV3O and human TRBV5, respectively; human TRAV3O and human TRBV6, respectively; human TRAV3O and human TRBV1O, respectively; human TRAV3O and human TRBV7, respectively; human TRAV3O and human TRBV19, respectively; human TRAV3O and human TRBV20, respectively; or human TRAV30 and human TRBV28, respectively.

351. The combination therapy of any one of the preceding claims, wherein the first target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30, and the second target molecule is human TRBV5, human TRBV6, human TRBV10, human TRBV7, human TRBV19, human TRBV20, or human TRBV28.

352. The combination therapy of any one of the preceding claims, wherein the first target molecule and the second target molecule are: human TRAV12-2 and human TRBV5, respectively; human TRAV12-2 and human TRBV6, respectively; human TRAV12-2 and human TRBV10, respectively;human TRAV12-2 and human TRBV7, respectively; human TRAV12-2 and human TRBV19, respectively; human TRAV12-2 and human TRBV20, respectively; human TRAV12-2 and human TRBV28, respectively; human TRAV13-1 and human TRBV5, respectively; human TRAV13-1 and human TRBV6, respectively; human TRAV13-1 and human TRBV10, respectively; human TRAV13-1 and human TRBV7, respectively; human TRAV13-1 and human TRBV19, respectively; human TRAV13-1 and human TRBV20, respectively; human TRAV13-1 and human TRBV28, respectively; human TRAV19 and human TRBV5, respectively; human TRAV19 and human TRBV6, respectively; human TRAV19 and human TRBV1O, respectively; human TRAV19 and human TRBV7, respectively; human TRAV19 and human TRBV19, respectively; human TRAV19 and human TRBV20, respectively; human TRAV19 and human TRBV28, respectively; human TRAV21 and human TRBV5, respectively; human TRAV21 and human TRBV6, respectively; human TRAV21 and human TRBV1O, respectively; human TRAV21 and human TRBV7, respectively; human TRAV21 and human TRBV19, respectively; human TRAV21 and human TRBV20, respectively; human TRAV21 and human TRBV28, respectively; human TRAV3O and human TRBV5, respectively; human TRAV3O and human TRBV6, respectively; human TRAV3O and human TRBV1O, respectively; human TRAV3O and human TRBV7, respectively; human TRAV3O and human TRBV19, respectively; human TRAV3O and human TRBV20, respectively; or human TRAV30 and human TRBV28, respectively.

353. The combination therapy of any one of the preceding claims, wherein the first target molecule is human TRAV12, human TRAV13, human TRAV19, human TRAV21, or human TRAV30, and the second target molecule is human TRBV5-1, human TRBV6-5, human TRBV10-1, human TRBV10-2, human TRBV10-3, human TRBV7-2, human TRBV7-3, human TRBV19, human TRBV20-1, or human TRBV28.

354. The combination therapy of any one of the preceding claims, wherein the first target molecule and the second target molecule are:human TRAV12 and human TRBV5-1, respectively; human TRAV12 and human TRBV6-5, respectively; human TRAV12 and human TRBV10-1, respectively; human TRAV12 and human TRBV10-2, respectively; human TRAV12 and human TRBV10-3, respectively; human TRAV12 and human TRBV7-2, respectively; human TRAV12 and human TRBV7-3, respectively; human TRAV12 and human TRBV19, respectively; human TRAV12 and human TRBV20-1, respectively; human TRAV12 and human TRBV28, respectively; human TRAV13 and human TRBV5-1, respectively; human TRAV13 and human TRBV6-5, respectively; human TRAV13 and human TRBV10-1, respectively; human TRAV13 and human TRBV10-2, respectively; human TRAV13 and human TRBV10-3, respectively; human TRAV13 and human TRBV7-2, respectively; human TRAV13 and human TRBV7-3, respectively; human TRAV13 and human TRBV19, respectively; human TRAV13 and human TRBV20-1, respectively; human TRAV13 and human TRBV28, respectively; human TRAV19 and human TRBV5-1, respectively; human TRAV19 and human TRBV6-5, respectively; human TRAV19 and human TRBV10-1, respectively; human TRAV19 and human TRBV10-2, respectively; human TRAV19 and human TRBV10-3, respectively; human TRAV19 and human TRBV7-2, respectively; human TRAV19 and human TRBV7-3, respectively; human TRAV19 and human TRBV19, respectively; human TRAV19 and human TRBV20-1, respectively; human TRAV19 and human TRBV28, respectively; human TRAV21 and human TRBV5-1, respectively; human TRAV21 and human TRBV6-5, respectively; human TRAV21 and human TRBV10-1, respectively; human TRAV21 and human TRBV10-2, respectively; human TRAV21 and human TRBV10-3, respectively; human TRAV21 and human TRBV7-2, respectively; human TRAV21 and human TRBV7-3, respectively; human TRAV21 and human TRBV19, respectively; human TRAV21 and human TRBV20-1, respectively;human TRAV21 and human TRBV28, respectively; human TRAV30 and human TRBV5-1, respectively; human TRAV30 and human TRBV6-5, respectively; human TRAV30 and human TRBV10-1, respectively; human TRAV30 and human TRBV10-2, respectively; human TRAV30 and human TRBV10-3, respectively; human TRAV30 and human TRBV7-2, respectively; human TRAV30 and human TRBV7-3, respectively; human TRAV30 and human TRBV19, respectively; human TRAV30 and human TRBV20-1, respectively; or human TRAV30 and human TRBV28, respectively.

355. The combination therapy of any one of the preceding claims, wherein the first target molecule is human TRAV12-2, human TRAV13-1, human TRAV19, human TRAV21, or human TRAV30, and the second target molecule is human TRBV5-1, human TRBV6-5, human TRBV 10-1, human TRBV 10-2, human TRBV 10-3, human TRBV7-2, human TRBV7-3, human TRBV19, human TRBV20-1, or human TRBV28.

356. The combination therapy of any one of the preceding claims, wherein the first target molecule and the second target molecule are: human TRAV12-2 and human TRBV5-1, respectively; human TRAV12-2 and human TRBV6-5, respectively; human TRAV12-2 and human TRBV 10-1, respectively; human TRAV12-2 and human TRBV 10-2, respectively; human TRAV12-2 and human TRBV 10-3, respectively; human TRAV12-2 and human TRBV7-2, respectively; human TRAV12-2 and human TRBV7-3, respectively; human TRAV12-2 and human TRBV 19, respectively; human TRAV12-2 and human TRBV20-1, respectively; human TRAV12-2 and human TRBV28, respectively; human TRAV13-1 and human TRBV5-1, respectively; human TRAV13-1 and human TRBV6-5, respectively; human TRAV13-1 and human TRBV 10-1, respectively; human TRAV13-1 and human TRBV 10-2, respectively; human TRAV13-1 and human TRBV 10-3, respectively; human TRAV13-1 and human TRBV7-2, respectively; human TRAV13-1 and human TRBV7-3, respectively; human TRAV13-1 and human TRBV 19, respectively; human TRAV13-1 and human TRBV20-1, respectively; human TRAV13-1 and human TRBV28, respectively; human TRAV19 and human TRBV5-1, respectively;human TRAV19 and human TRBV6-5, respectively; human TRAV19 and human TRBV10-1, respectively; human TRAV19 and human TRBV10-2, respectively; human TRAV19 and human TRBV10-3, respectively; human TRAV19 and human TRBV7-2, respectively; human TRAV19 and human TRBV7-3, respectively; human TRAV19 and human TRBV19, respectively; human TRAV19 and human TRBV20-1, respectively; human TRAV19 and human TRBV28, respectively; human TRAV21 and human TRBV5-1, respectively; human TRAV21 and human TRBV6-5, respectively; human TRAV21 and human TRBV10-1, respectively; human TRAV21 and human TRBV10-2, respectively; human TRAV21 and human TRBV10-3, respectively; human TRAV21 and human TRBV7-2, respectively; human TRAV21 and human TRBV7-3, respectively; human TRAV21 and human TRBV19, respectively; human TRAV21 and human TRBV20-1, respectively; human TRAV21 and human TRBV28, respectively; human TRAV30 and human TRBV5-1, respectively; human TRAV30 and human TRBV6-5, respectively; human TRAV30 and human TRBV10-1, respectively; human TRAV30 and human TRBV10-2, respectively; human TRAV30 and human TRBV10-3, respectively; human TRAV30 and human TRBV7-2, respectively; human TRAV30 and human TRBV7-3, respectively; human TRAV30 and human TRBV19, respectively; human TRAV30 and human TRBV20-1, respectively; or human TRAV30 and human TRBV28, respectively.

357. The combination therapy of any one of claims 263-356, wherein the first binder comprises a full antibody or antigen-binding fragment thereof, a bivalent antibody, bispecific antibody, or a biparatopic antibody.

358. The combination therapy of any one of claims 263-357, wherein the second binder comprises a full antibody or antigen-binding fragment thereof, a bivalent antibody, bispecific antibody, or a biparatopic antibody.

359. The combination therapy of claim 357 or 358, wherein the antigen-binding fragment is a Fab, F(ab')2, Fv, a single chain Fv (scFv), a single domain antibody, a diabody (dAb), a single domain antibody, or a camelid antibody.

360. The combination therapy of any one of claims 263-359, wherein the first binder comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 3 (HC CDR3) comprising the sequence of SEQ ID NO: 3343, SEQ ID NO: 3323, SEQ ID NO: 3353, SEQ ID NO: 1187, SEQ ID NO: 3373, SEQ ID NO: 3383, SEQ ID NO: 3393, SEQ ID NO: 3403, or SEQ ID NO: 3413.

361. The combination therapy of any one of claims 263-360, wherein the first binder comprises a VH comprising a heavy chain complementarity determining region 1 (HC CDR1) comprising the sequence of SEQ ID NO: 3341, SEQ ID NO: 3321, SEQ ID NO: 3351, SEQ ID NO: 1190, SEQ ID NO: 3371, SEQ ID NO: 3381, SEQ ID NO: 3391, SEQ ID NO: 3401, SEQ ID NO: 3411, SEQ ID NO: 3421, or SEQ ID NO: 3702.

362. The combination therapy of any one of claims 263-361, wherein the first binder comprises a VH comprising a heavy chain complementarity determining region 2 (HC CDR2) comprising the sequence of SEQ ID NO: 3342, SEQ ID NO: 3322, SEQ ID NO: 3352, SEQ ID NO: 1186, SEQ ID NO: 3372, SEQ ID NO: 3382, SEQ ID NO: 3392, SEQ ID NO: 3402, or SEQ ID NO: 3412.

363. The combination therapy of any one of claims 263-362, wherein the first binder comprises a VH comprising:(i) a HC CDR1 comprising the sequence of SEQ ID NO: 3341, a HC CDR2 comprising the sequence of SEQ ID NO: 3342, and a HC CDR3 comprising the sequence of SEQ ID NO: 3343;(ii) a HC CDR1 comprising the sequence of SEQ ID NO: 3321, a HC CDR2 comprising the sequence of SEQ ID NO: 3322, and a HC CDR3 comprising the sequence of SEQ ID NO: 3323;(iii) a HC CDR1 comprising the sequence of SEQ ID NO: 3351, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, and a HC CDR3 comprising the sequence of SEQ ID NO: 3353;(iv) a HC CDR1 comprising the sequence of SEQ ID NO: 1190, a HC CDR2 comprising the sequence of SEQ ID NO: 1186, and a HC CDR3 comprising the sequence of SEQ ID NO: 1187;(v) a HC CDR1 comprising the sequence of SEQ ID NO: 3371, a HC CDR2 comprising the sequence of SEQ ID NO: 3372, and a HC CDR3 comprising the sequence of SEQ ID NO: 3373;(vi) a HC CDR1 comprising the sequence of SEQ ID NO: 3381, a HC CDR2 comprising the sequence of SEQ ID NO: 3382, and a HC CDR3 comprising the sequence of SEQ ID NO: 3383;(vii) a HC CDR1 comprising the sequence of SEQ ID NO: 3391, a HC CDR2 comprising the sequence of SEQ ID NO: 3392, and a HC CDR3 comprising the sequence of SEQ ID NO: 3393;(viii) a HC CDR1 comprising the sequence of SEQ ID NO: 3401, a HC CDR2 comprising the sequence of SEQ ID NO: 3402, and a HC CDR3 comprising the sequence of SEQ ID NO: 3403;(ix) a HC CDR1 comprising the sequence of SEQ ID NO: 3351, SEQ ID NO: 3421, or SEQ ID NO: 3702, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, and a HC CDR3 comprising the sequence of SEQ ID NO: 3353; or(x) a HC CDR1 comprising the sequence of SEQ ID NO: 3411, a HC CDR2 comprising the sequence of SEQ ID NO: 3412, and a HC CDR3 comprising the sequence of SEQ ID NO: 3413.

364. The combination therapy of any one of claims 263-363, wherein the first binder comprises a light chain variable region (VL) comprising a light chain complementarity determining region 3 (LC CDR3) comprising the sequence of SEQ ID NO: 3346, SEQ ID NO: 3326, SEQ ID NO: 3356, SEQ ID NO: 1193, SEQ ID NO: 3376, SEQ ID NO: 3386, SEQ ID NO: 3396, SEQ ID NO: 3406, or SEQ ID NO: 3416.

365. The combination therapy of any one of claims 263-364, wherein the first binder comprises a VL comprising a light chain complementarity determining region 1 (LC CDR1) comprising the sequence of SEQ ID NO: 3344, SEQ ID NO: 3324, SEQ ID NO: 3354, SEQ ID NO: 1191, SEQ ID NO: 3374, SEQ ID NO: 3384, SEQ ID NO: 3394, SEQ ID NO: 3404, or SEQ ID NO: 3414.

366. The combination therapy of any one of claims 263-365, wherein the first binder comprises a VL comprising a light chain complementarity determining region 2 (LC CDR2) comprising the sequence of SEQ ID NO: 3345, SEQ ID NO: 3325, SEQ ID NO: 3355, SEQ ID NO: 1192, SEQ ID NO: 3375, SEQ ID NO: 3395, SEQ ID NO: 3405, SEQ ID NO: 3415, or SEQ ID NO: 3443.

367. The combination therapy of any one of claims 263-366, wherein the first binder comprises a VL comprising:(i) a LC CDR1 comprising the sequence of SEQ ID NO: 3344, a LC CDR2 comprising the sequence of SEQ ID NO: 3345, and a LC CDR3 comprising the sequence of SEQ ID NO: 3346;(ii) a LC CDR1 comprising the sequence of SEQ ID NO: 3324, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3326;(iii) a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3355, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356;(iv) a LC CDR1 comprising the sequence of SEQ ID NO: 1191, a LC CDR2 comprising the sequence of SEQ ID NO: 1192, and a LC CDR3 comprising the sequence of SEQ ID NO: 1193;(v) a LC CDR1 comprising the sequence of SEQ ID NO: 3374, a LC CDR2 comprising the sequence of SEQ ID NO: 3375, and a LC CDR3 comprising the sequence of SEQ ID NO: 3376;(vi) a LC CDR1 comprising the sequence of SEQ ID NO: 3384, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3386;(vii) a LC CDR1 comprising the sequence of SEQ ID NO: 3394, a LC CDR2 comprising the sequence of SEQ ID NO: 3395, and a LC CDR3 comprising the sequence of SEQ ID NO: 3396;(viii) a LC CDR1 comprising the sequence of SEQ ID NO: 3404, a LC CDR2 comprising the sequence of SEQ ID NO: 3405, and a LC CDR3 comprising the sequence of SEQ ID NO: 3406;(ix) a LC CDR1 comprising the sequence of SEQ ID NO: 3414, a LC CDR2 comprising the sequence of SEQ ID NO: 3415, and a LC CDR3 comprising the sequence of SEQ ID NO: 3416; or(x) a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3443, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356.

368. The combination therapy of any one of claims 263-367, wherein the first binder comprises:(i) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3341, a HC CDR2 comprising the sequence of SEQ ID NO: 3342, a HC CDR3 comprising the sequence of SEQ ID NO: 3343, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3344, a LC CDR2 comprising the sequence of SEQ ID NO: 3345, and a LC CDR3 comprising the sequence of SEQ ID NO: 3346;(ii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3321, a HC CDR2 comprising the sequence of SEQ ID NO: 3322, a HC CDR3 comprising the sequence of SEQ ID NO: 3323, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3324, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3326;(iii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3351, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, a HC CDR3 comprising the sequence of SEQ ID NO: 3353, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3355, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356;(iv) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 1190, a HC CDR2 comprising the sequence of SEQ ID NO: 1186, a HC CDR3 comprising the sequence of SEQ ID NO: 1187, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO:1191, a LC CDR2 comprising the sequence of SEQ ID NO: 1192, and a LC CDR3 comprising the sequence of SEQ ID NO: 1193;(v) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3371, a HC CDR2 comprising the sequence of SEQ ID NO: 3372, a HC CDR3 comprising the sequence of SEQ ID NO: 3373, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO:3374, a LC CDR2 comprising the sequence of SEQ ID NO: 3375, and a LC CDR3 comprising the sequence of SEQ ID NO: 3376;(vi) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3381, a HC CDR2 comprising the sequence of SEQ ID NO: 3382, a HC CDR3 comprising the sequence of SEQ ID NO: 3383, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3384, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3386;(vii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3391, a HC CDR2 comprising the sequence of SEQ ID NO: 3392, a HC CDR3 comprising the sequence of SEQ ID NO: 3393, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3394, a LC CDR2 comprising the sequence of SEQ ID NO: 3395, and a LC CDR3 comprising the sequence of SEQ ID NO: 3396;(viii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3401, a HC CDR2 comprising the sequence of SEQ ID NO: 3402, a HC CDR3 comprising the sequence of SEQ ID NO: 3403, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3404, a LC CDR2 comprising the sequence of SEQ ID NO: 3405, and a LC CDR3 comprising the sequence of SEQ ID NO: 3406;(ix) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3411, a HC CDR2 comprising the sequence of SEQ ID NO: 3412, a HC CDR3 comprising the sequence of SEQ ID NO: 3413, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3414, a LC CDR2 comprising the sequence of SEQ ID NO: 3415, and a LC CDR3 comprising the sequence of SEQ ID NO: 3416;(x) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3351, SEQ ID NO: 3421, or SEQ ID NO: 3702, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, a HC CDR3 comprising the sequence of SEQ ID NO: 3353, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3355, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356; or(xi) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3351, SEQ ID NO: 3421, or SEQ ID NO: 3702, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, a HC CDR3 comprising the sequence of SEQ ID NO: 3353, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3443, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356.

369. The combination therapy of any one of claims 263-368, wherein the first binder comprises a VH comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO: 3445, SEQ ID NO: 3448, SEQ ID NO: 3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO: 3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO: 3465, and SEQ ID NO: 3470.

370. The combination therapy of any one of claims 263-369, wherein the first binder comprises a VH comprising any one sequence selected from the group consisting of: SEQ ID NO: 3445, SEQ IDNO: 3448, SEQ ID NO: 3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO: 3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO: 3465, and SEQ ID NO: 3470.

371. The combination therapy of any one of claims 263-370, wherein the first binder comprises a VL comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO: 3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO: 3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO: 3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

372. The combination therapy of any one of claims 263-371, wherein the first binder comprises a VL comprising any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO: 3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO: 3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO: 3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

373. The combination therapy of any one of claims 263-372, wherein the first binder comprises:(i) a VH comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO: 3445, SEQ ID NO: 3448, SEQ ID NO:3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO: 3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO: 3465, and SEQ ID NO: 3470; and(ii) a VL comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO:3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO: 3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO: 3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

374. The combination therapy of any one of claims 263-373, wherein the first binder comprises:(i) a VH comprising any one sequence selected from the group consisting of: SEQ ID NO: 3445,SEQ ID NO: 3448, SEQ ID NO: 3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO:3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO: 3465, and SEQ ID NO: 3470; and(ii) a VL comprising any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO: 3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO:3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO: 3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

375. The combination therapy of any one of claims 263-374, wherein the first binder comprises:(i) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ IDNO: 3445, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3446;(ii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3448, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3449;(iii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3450, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3451;(iv) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1346, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1349;(v) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1196, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1195;(vi) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3455, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3456;(vii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3457, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3458;(viii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3463, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3464;(ix) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3465, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3466;(x) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3470, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3471;(xi) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1346, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3475; or(xii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1346, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3476.

376. The combination therapy of any one of claims 263-375, wherein the first binder comprises:(i) a VH comprising the sequence of SEQ ID NO: 3445, and a VL comprising the sequence ofSEQ ID NO: 3446;(ii) a VH comprising the sequence of SEQ ID NO: 3448, and a VL comprising the sequence of SEQ ID NO: 3449;(iii) a VH comprising the sequence of SEQ ID NO: 3450, and a VL comprising the sequence of SEQ ID NO: 3451;(iv) a VH comprising the sequence of SEQ ID NO: 1346, and a VL comprising the sequence of SEQ ID NO: 1349;(v) a VH comprising the sequence of SEQ ID NO: 1196, and a VL comprising the sequence of SEQ ID NO: 1195;(vi) a VH comprising the sequence of SEQ ID NO: 3455, and a VL comprising the sequence of SEQ ID NO: 3456;(vii) a VH comprising the sequence of SEQ ID NO: 3457, and a VL comprising the sequence of SEQ ID NO: 3458;(viii) a VH comprising the sequence of SEQ ID NO: 3463, and a VL comprising the sequence of SEQ ID NO: 3464;(ix) a VH comprising the sequence of SEQ ID NO: 3465, and a VL comprising the sequence of SEQ ID NO: 3466;(x) a VH comprising the sequence of SEQ ID NO: 3470, and a VL comprising the sequence of SEQ ID NO: 3471;(xi) a VH comprising the sequence of SEQ ID NO: 1346, and a VL comprising the sequence of SEQ ID NO: 3475; or(xii) a VH comprising the sequence of SEQ ID NO: 1346, and a VL comprising the sequence of SEQ ID NO: 3476.

377. The combination therapy of any one of claims 263-376, wherein the second binder comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 3 (HC CDR3) comprising the sequence of SEQ ID NO: 3343, SEQ ID NO: 3323, SEQ ID NO: 3353, SEQ ID NO: 1187, SEQ ID NO: 3373, SEQ ID NO: 3383, SEQ ID NO: 3393, SEQ ID NO: 3403, or SEQ ID NO: 3413.

378. The combination therapy of any one of claims 263-377, wherein the second binder comprises a VH comprising a heavy chain complementarity determining region 1 (HC CDR1) comprising the sequence of SEQ ID NO: 3341, SEQ ID NO: 3321, SEQ ID NO: 3351, SEQ ID NO: 1190, SEQ ID NO: 3371, SEQ ID NO: 3381, SEQ ID NO: 3391, SEQ ID NO: 3401, SEQ ID NO: 3411, SEQ ID NO: 3421, or SEQ ID NO: 3702.

379. The combination therapy of any one of claims 263-378, wherein the second binder comprises a VH comprising a heavy chain complementarity determining region 2 (HC CDR2) comprising the sequence of SEQ ID NO: 3342, SEQ ID NO: 3322, SEQ ID NO: 3352, SEQ ID NO: 1186, SEQ ID NO: 3372, SEQ ID NO: 3382, SEQ ID NO: 3392, SEQ ID NO: 3402, or SEQ ID NO: 3412.

380. The combination therapy of any one of claims 263-379, wherein the second binder comprises a VH comprising:(i) a HC CDR1 comprising the sequence of SEQ ID NO: 3341, a HC CDR2 comprising the sequence of SEQ ID NO: 3342, and a HC CDR3 comprising the sequence of SEQ ID NO: 3343;(ii) a HC CDR1 comprising the sequence of SEQ ID NO: 3321, a HC CDR2 comprising the sequence of SEQ ID NO: 3322, and a HC CDR3 comprising the sequence of SEQ ID NO: 3323;(iii) a HC CDR1 comprising the sequence of SEQ ID NO: 3351, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, and a HC CDR3 comprising the sequence of SEQ ID NO: 3353;(iv) a HC CDR1 comprising the sequence of SEQ ID NO: 1190, a HC CDR2 comprising the sequence of SEQ ID NO: 1186, and a HC CDR3 comprising the sequence of SEQ ID NO: 1187;(v) a HC CDR1 comprising the sequence of SEQ ID NO: 3371, a HC CDR2 comprising the sequence of SEQ ID NO: 3372, and a HC CDR3 comprising the sequence of SEQ ID NO: 3373;(vi) a HC CDR1 comprising the sequence of SEQ ID NO: 3381, a HC CDR2 comprising the sequence of SEQ ID NO: 3382, and a HC CDR3 comprising the sequence of SEQ ID NO: 3383;(vii) a HC CDR1 comprising the sequence of SEQ ID NO: 3391, a HC CDR2 comprising the sequence of SEQ ID NO: 3392, and a HC CDR3 comprising the sequence of SEQ ID NO: 3393;(viii) a HC CDR1 comprising the sequence of SEQ ID NO: 3401, a HC CDR2 comprising the sequence of SEQ ID NO: 3402, and a HC CDR3 comprising the sequence of SEQ ID NO: 3403;(ix) a HC CDR1 comprising the sequence of SEQ ID NO: 3351, SEQ ID NO: 3421, or SEQ ID NO: 3702, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, and a HC CDR3 comprising the sequence of SEQ ID NO: 3353; or(x) a HC CDR1 comprising the sequence of SEQ ID NO: 3411, a HC CDR2 comprising the sequence of SEQ ID NO: 3412, and a HC CDR3 comprising the sequence of SEQ ID NO: 3413.

381. The combination therapy of any one of claims 263-380, wherein the second binder comprises a light chain variable region (VL) comprising a light chain complementarity determining region 3 (LC CDR3) comprising the sequence of SEQ ID NO: 3346, SEQ ID NO: 3326, SEQ ID NO: 3356, SEQ ID NO: 1193, SEQ ID NO: 3376, SEQ ID NO: 3386, SEQ ID NO: 3396, SEQ ID NO: 3406, or SEQ ID NO: 3416.

382. The combination therapy of any one of claims 263-381, wherein the second binder comprises a VL comprising a light chain complementarity determining region 1 (LC CDR1) comprising the sequence of SEQ ID NO: 3344, SEQ ID NO: 3324, SEQ ID NO: 3354, SEQ ID NO: 1191, SEQ ID NO: 3374, SEQ ID NO: 3384, SEQ ID NO: 3394, SEQ ID NO: 3404, or SEQ ID NO: 3414.

383. The combination therapy of any one of claims 263-382, wherein the second binder comprises a VL comprising a light chain complementarity determining region 2 (LC CDR2) comprising the sequence of SEQ ID NO: 3345, SEQ ID NO: 3325, SEQ ID NO: 3355, SEQ ID NO: 1192, SEQ ID NO: 3375, SEQ ID NO: 3395, SEQ ID NO: 3405, SEQ ID NO: 3415, or SEQ ID NO: 3443.

384. The combination therapy of any one of claims 263-383, wherein the second binder comprises a VL comprising:(i) a LC CDR1 comprising the sequence of SEQ ID NO: 3344, a LC CDR2 comprising the sequence of SEQ ID NO: 3345, and a LC CDR3 comprising the sequence of SEQ ID NO: 3346;(ii) a LC CDR1 comprising the sequence of SEQ ID NO: 3324, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3326;(iii) a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3355, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356;(iv) a LC CDR1 comprising the sequence of SEQ ID NO: 1191, a LC CDR2 comprising the sequence of SEQ ID NO: 1192, and a LC CDR3 comprising the sequence of SEQ ID NO: 1193;(v) a LC CDR1 comprising the sequence of SEQ ID NO: 3374, a LC CDR2 comprising the sequence of SEQ ID NO: 3375, and a LC CDR3 comprising the sequence of SEQ ID NO: 3376;(vi) a LC CDR1 comprising the sequence of SEQ ID NO: 3384, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3386;(vii) a LC CDR1 comprising the sequence of SEQ ID NO: 3394, a LC CDR2 comprising the sequence of SEQ ID NO: 3395, and a LC CDR3 comprising the sequence of SEQ ID NO: 3396;(viii) a LC CDR1 comprising the sequence of SEQ ID NO: 3404, a LC CDR2 comprising the sequence of SEQ ID NO: 3405, and a LC CDR3 comprising the sequence of SEQ ID NO: 3406;(ix) a LC CDR1 comprising the sequence of SEQ ID NO: 3414, a LC CDR2 comprising the sequence of SEQ ID NO: 3415, and a LC CDR3 comprising the sequence of SEQ ID NO: 3416; or(x) a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3443, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356.

385. The combination therapy of any one of claims 263-384, wherein the second binder comprises:(i) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3341, a HC CDR2 comprising the sequence of SEQ ID NO: 3342, a HC CDR3 comprising the sequence of SEQ ID NO: 3343, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3344, a LC CDR2 comprising the sequence of SEQ ID NO: 3345, and a LC CDR3 comprising the sequence of SEQ ID NO: 3346;(ii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3321, a HC CDR2 comprising the sequence of SEQ ID NO: 3322, a HC CDR3 comprising the sequence of SEQ ID NO: 3323, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3324, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3326;(iii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3351, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, a HC CDR3 comprising the sequence of SEQ ID NO: 3353, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3355, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356;(iv) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 1190, a HC CDR2 comprising the sequence of SEQ ID NO: 1186, a HC CDR3 comprising the sequence of SEQ ID NO: 1187, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO:1191, a LC CDR2 comprising the sequence of SEQ ID NO: 1192, and a LC CDR3 comprising the sequence of SEQ ID NO: 1193;(v) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3371, a HC CDR2 comprising the sequence of SEQ ID NO: 3372, a HC CDR3 comprising the sequence of SEQ ID NO: 3373, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3374, a LC CDR2 comprising the sequence of SEQ ID NO: 3375, and a LC CDR3 comprising the sequence of SEQ ID NO: 3376;(vi) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3381, a HC CDR2 comprising the sequence of SEQ ID NO: 3382, a HC CDR3 comprising the sequence of SEQ ID NO: 3383, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3384, a LC CDR2 comprising the sequence of SEQ ID NO: 3325, and a LC CDR3 comprising the sequence of SEQ ID NO: 3386;(vii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3391, a HC CDR2 comprising the sequence of SEQ ID NO: 3392, a HC CDR3 comprising the sequence of SEQ ID NO: 3393, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3394, a LC CDR2 comprising the sequence of SEQ ID NO: 3395, and a LC CDR3 comprising the sequence of SEQ ID NO: 3396;(viii) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3401, a HC CDR2 comprising the sequence of SEQ ID NO: 3402, a HC CDR3 comprising the sequence of SEQ ID NO: 3403, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3404, a LC CDR2 comprising the sequence of SEQ ID NO: 3405, and a LC CDR3 comprising the sequence of SEQ ID NO: 3406;(ix) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3411, a HC CDR2 comprising the sequence of SEQ ID NO: 3412, a HC CDR3 comprising the sequence of SEQ ID NO: 3413, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3414, a LC CDR2 comprising the sequence of SEQ ID NO: 3415, and a LC CDR3 comprising the sequence of SEQ ID NO: 3416;(x) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3351, SEQ ID NO: 3421, or SEQ ID NO: 3702, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, a HC CDR3 comprising the sequence of SEQ ID NO: 3353, and a VL comprising a LC CDR1comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3355, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356; or(xi) a VH comprising a HC CDR1 comprising the sequence of SEQ ID NO: 3351, SEQ ID NO: 3421, or SEQ ID NO: 3702, a HC CDR2 comprising the sequence of SEQ ID NO: 3352, a HC CDR3 comprising the sequence of SEQ ID NO: 3353, and a VL comprising a LC CDR1 comprising the sequence of SEQ ID NO: 3354, a LC CDR2 comprising the sequence of SEQ ID NO: 3443, and a LC CDR3 comprising the sequence of SEQ ID NO: 3356.

386. The combination therapy of any one of claims 263-385, wherein the second binder comprises a VH comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO: 3445, SEQ ID NO: 3448, SEQ ID NO: 3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO: 3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO:3465, and SEQ ID NO: 3470.

387. The combination therapy of any one of claims 263-386, wherein the second binder comprises a VH comprising any one sequence selected from the group consisting of: SEQ ID NO: 3445, SEQ ID NO: 3448, SEQ ID NO: 3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO: 3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO: 3465, and SEQ ID NO: 3470.

388. The combination therapy of any one of claims 263-387, wherein the second binder comprises a VL comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO: 3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO: 3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO:3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

389. The combination therapy of any one of claims 263-388, wherein the second binder comprises a VL comprising any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO: 3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO: 3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO: 3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

390. The combination therapy of any one of claims 263-389, wherein the second binder comprises:(i) a VH comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO: 3445, SEQ ID NO: 3448, SEQ ID NO:3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO: 3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO: 3465, and SEQ ID NO: 3470; and(ii) a VL comprising a sequence having at least 75% sequence identity to any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO:3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO: 3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO: 3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

391. The combination therapy of any one of claims 263-390, wherein the second binder comprises:(i) a VH comprising any one sequence selected from the group consisting of: SEQ ID NO: 3445, SEQ ID NO: 3448, SEQ ID NO: 3450, SEQ ID NO: 1346, SEQ ID NO: 1196, SEQ ID NO: 3455, SEQ ID NO: 3457, SEQ ID NO: 3463, SEQ ID NO: 3465, and SEQ ID NO: 3470; and(ii) a VL comprising any one sequence selected from the group consisting of: SEQ ID NO: 3446, SEQ ID NO: 3449, SEQ ID NO: 3451, SEQ ID NO: 1349, SEQ ID NO: 1195, SEQ ID NO: 3456, SEQ ID NO: 3458, SEQ ID NO: 3464, SEQ ID NO: 3466, SEQ ID NO: 3471, SEQ ID NO: 3475, and SEQ ID NO: 3476.

392. The combination therapy of any one of claims 263-391, wherein the second binder comprises:(i) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ IDNO: 3445, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3446;(ii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3448, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3449;(iii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3450, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3451;(iv) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1346, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1349;(v) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1196, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1195;(vi) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3455, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3456;(vii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3457, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3458;(viii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3463, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3464;(ix) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3465, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3466;(x) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3470, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3471;(xi) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1346, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3475; or(xii) a VH comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 1346, and a VL comprising a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3476.

393. The combination therapy of any one of claims 263-392, wherein the second binder comprises:(i) a VH comprising the sequence of SEQ ID NO: 3445, and a VL comprising the sequence ofSEQ ID NO: 3446;(ii) a VH comprising the sequence of SEQ ID NO: 3448, and a VL comprising the sequence of SEQ ID NO: 3449;(iii) a VH comprising the sequence of SEQ ID NO: 3450, and a VL comprising the sequence of SEQ ID NO: 3451;(iv) a VH comprising the sequence of SEQ ID NO: 1346, and a VL comprising the sequence of SEQ ID NO: 1349;(v) a VH comprising the sequence of SEQ ID NO: 1196, and a VL comprising the sequence of SEQ ID NO: 1195;(vi) a VH comprising the sequence of SEQ ID NO: 3455, and a VL comprising the sequence of SEQ ID NO: 3456;(vii) a VH comprising the sequence of SEQ ID NO: 3457, and a VL comprising the sequence of SEQ ID NO: 3458;(viii) a VH comprising the sequence of SEQ ID NO: 3463, and a VL comprising the sequence of SEQ ID NO: 3464;(ix) a VH comprising the sequence of SEQ ID NO: 3465, and a VL comprising the sequence of SEQ ID NO: 3466;(x) a VH comprising the sequence of SEQ ID NO: 3470, and a VL comprising the sequence of SEQ ID NO: 3471;(xi) a VH comprising the sequence of SEQ ID NO: 1346, and a VL comprising the sequence of SEQ ID NO: 3475; or(xii) a VH comprising the sequence of SEQ ID NO: 1346, and a VL comprising the sequence of SEQ ID NO: 3476.

394. The combination therapy of any one of claims 263-393, wherein the first binder and the second binder bind to different TCRpV regions.

395. The combination therapy of any one of claims 263-393, wherein the first binder and the second binder bind to different TCRpVs belonging to different subfamilies.

396. The combination therapy of any one of claims 263-393, wherein the first binder and the second binder bind to different members of the same TCRpV subfamily.

397. The combination therapy of any one of claims 263-396, wherein the first binder comprises one or more heavy chain constant regions selected from the group consisting of IgGl heavy chain constant region or fragment thereof, IgG2 heavy chain constant region or fragment thereof, IgG3 heavy chain constant region or fragment thereof, IgGAl heavy chain constant region or fragment thereof, IgGA2 heavy chain constant region or fragment thereof, IgG4 heavy chain constant region orfragment thereof, IgJ heavy chain constant region or fragment thereof, IgM heavy chain constant region or fragment thereof, IgD heavy chain constant region or fragment thereof, and IgE heavy chain constant region or fragment thereof.

398. The combination therapy of any one of claims 263-397, wherein the first binder comprises a kappa light chain constant region or fragment thereof, a lambda light chain constant region or fragment thereof, or a combination thereof.

399. The combination therapy of any one of claims 263-398, wherein the second binder comprises one or more heavy chain constant regions selected from the group consisting of IgGl heavy chain constant region or fragment thereof, IgG2 heavy chain constant region or fragment thereof, IgG3 heavy chain constant region or fragment thereof, IgGAl heavy chain constant region or fragment thereof, IgGA2 heavy chain constant region or fragment thereof, IgG4 heavy chain constant region or fragment thereof, IgJ heavy chain constant region or fragment thereof, IgM heavy chain constant region or fragment thereof, IgD heavy chain constant region or fragment thereof, and IgE heavy chain constant region or fragment thereof.

400. The combination therapy of any one of claims 263-399, wherein the second binder comprises a kappa light chain constant region or fragment thereof, a lambda light chain constant region or fragment thereof, or a combination thereof.

401. The combination therapy of any one of claims 263-400, wherein the first agent is a multifunctional molecule.

402. The combination therapy of any one of claims 263-401, wherein the first agent is a multispecific molecule.

403. The combination therapy of any one of claims 263-402, wherein the second agent is a multifunctional molecule.

404. The combination therapy of any one of claims 263-403, wherein the second agent is a multispecific molecule.

405. The combination therapy of any one of claims 263-404, wherein the first agent, the second agent, or a combination thereof comprises at least two non-contiguous polypeptide chains; wherein a first polypeptide chain of the at least two non-contiguous polypeptide chains comprises a first Fc region, and a second polypeptide chain of the at least two non-contiguous polypeptide chains comprises a second Fc region; and wherein the first Fc region and the second Fc region comprise an Fc interface with a knob-in- a hole.

406. The combination therapy of claim 405, wherein the first Fc region, the second Fc region, or a combination thereof comprises an Asn297Ala mutation, a Leu234Ala / Leu235Ala mutation, or a combination thereof.

407. The combination therapy of any one of claims 401-406, wherein the first agent is a multispecific molecule that further comprises one or more of a tumor-targeting moiety, a cytokine molecule, a stromal modifying moiety, or an immune cell engager.

408. The combination therapy of any one of claims 403-407, wherein the second agent is a multispecific molecule that further comprises one or more of a tumor-targeting moiety, a cytokine molecule, a stromal modifying moiety, or an immune cell engager.

409. The combination therapy of any one of claims 401-408, wherein the first agent comprises the following configuration:A-, B-[dimerization module] -C, -D, wherein:(a) the dimerization module comprises a first immunoglobulin chain constant region and a second immunoglobulin chain constant region;(b) A and C are linked to the first immunoglobulin chain constant region; and B and D are linked to the second immunoglobulin chain constant region;(c) A, B, C, and D are independently (i) absent; (ii) the first binder; (iii) the tumor targeting moiety, (iv) the cytokine molecule; (v) stromal modifying moiety; or (vi) the immune cell engager; and wherein at least one, two, or three of A, B, C, and D comprises the first binder.

410. The combination therapy of any one of claims 403-409, wherein the second agent comprises the following configuration:A-, B-[dimerization module] -C, -D, wherein:(a) the dimerization module comprises a first immunoglobulin chain constant region and a second immunoglobulin chain constant region;(b) A and C are linked to the first immunoglobulin chain constant region; and B and D are linked to the second immunoglobulin chain constant region;(c) A, B, C, and D are independently (i) absent; (ii) the second binder; (iii) the tumor targeting moiety, (iv) the cytokine molecule; (v) stromal modifying moiety; or (vi) the immune cell engager; and wherein at least one, two, or three of A, B, C, and D comprises the second binder.

411. The combination therapy of claim 409 or 410, wherein the first immunoglobulin chain constant region comprises the first fragment crystalizable region (Fc region) and the second first immunoglobulin chain constant region comprises the second fragment crystallizable region (Fc region).

412. The combination therapy of claim 411, wherein dimerization of the first Fc region and the second Fc region is enhanced by providing an Fc interface of the first Fc region and the second Fc region with one or more of a paired cavity-protuberance, an electrostatic interaction, or a strandexchange, such that a greater ratio of heteromultimer to homomultimer forms relative to a nonengineered interface.

413. The combination therapy of any one of claims 407-412, wherein the immune cell engager is selected from the group consisting of a T cell engager, an NK cell engager, a B cell engager, a dendritic cell engager, a macrophage cell engager, and any combination thereof.

414. The combination therapy of any one of claims 407-413, wherein the cytokine molecule is selected from the group consisting of interleukin-2 (IL-2) or functional variant thereof, interleukin-7 (IL-7) or functional variant thereof, interleukin- 12 (IL- 12) or functional variant thereof, interleukin- 15 (IL- 15) or functional variant thereof, interleukin- 18 (IL- 18) or functional variant thereof, interleukin- 21 (IL-21) or functional variant thereof, interferon gamma or functional variant thereof, and any combination thereof.

415. The combination therapy of claim 414, wherein the cytokine molecule comprises interleukin- 2 (IL-2) or functional variant thereof.

416. The combination therapy of claim 415, wherein the interleukin-2 (IL-2) or functional variant thereof comprises the sequence of SEQ ID NO: 2270 or SEQ ID NO: 2191.

417. The combination therapy of claim 414, wherein the cytokine molecule comprises interleukin- 15 (IL- 15) or functional variant thereof.

418. The combination therapy of claim 417, wherein the interleukin- 15 (IL- 15) or functional variant thereof comprises the sequence of SEQ ID NO: 2170.

419. The combination therapy of claim 414 or 418, wherein the cytokine molecule further comprises an IL15Ralpha dimerizing domain covalently linked the interleukin- 15 (IL-15) or functional variant thereof.

420. The combination therapy of claim 419, wherein the IL15Ralpha dimerizing domain comprises an IL- 15 receptor alpha sushi domain or functional variant thereof.

421. The combination therapy of claim 419 or 420, wherein the IL15Ralpha dimerizing domain comprises the sequence of SEQ ID NO: 3472.

422. The combination therapy of any one of claims 419-421, wherein the interleukin- 15 (IL-15) or functional variant thereof is covalently linked to the IL15Ralpha dimerizing domain via a linker.

423. The combination therapy of claim 422, wherein the interleukin- 15 (IL- 15) or functional variant thereof is covalently linked to the IL15Ralpha dimerizing domain via a linker comprising the sequence of SEQ ID NO: 3473.

424. The combination therapy of any one of claims 417-423, wherein the cytokine molecule comprises the sequence of SEQ ID NO: 3474.

425. The combination therapy of any one of claims 407-424, wherein the stromal modifying moiety is selected from the group consisting of a hyaluronidase, a collagenase, a chondroitinase, and a matrix metalloproteinase.

426. The combination therapy of any one of claims 407-425, wherein the tumor-targeting moiety binds to a cancer antigen.

427. The combination therapy of claim 426, wherein the tumor-targeting moiety binds to a cancer antigen.

428. The combination therapy of claim 426 or 427, wherein the cancer antigen is present on a hematological cancer, a solid tumor, a metastatic cancer, a soft tissue tumor, a metastatic lesion, or a combination thereof.

429. The combination therapy of any one of claims 426-428, wherein the cancer antigen is a tumor antigen, a stromal antigen, or a hematological antigen.

430. The combination therapy of any one of claims 426-429, wherein the cancer antigen is selected from the group consisting of BCMA, CD19, CD20, CD22, FcRH5, PDL1, CD47, ganglioside 2 (GD2), prostate stem cell antigen (PSCA), prostate specific membrane antigen (PMSA), prostatespecific antigen (PSA), carcinoembryonic antigen (CEA), Ron Kinase, c-Met, Immature laminin receptor, TAG-72, BING-4, Calcium -activated chloride channel 2, Cyclin-Bl, 9D7, Ep-CAM, EphA3, Her2 / neu, Telomerase, SAP-1, Survivin, NY-ESO-l / LAGE-1, PRAME, SSX-2, Melan- A / MART-1, Gpl00 / pmell7, Tyrosinase, MC1R, P-catenin, BRCA1 / 2, CDK4, CML66, Fibronectin, p53, Ras, TGF-B receptor, AFP, ETA, MAGE, CA-125, BAGE, GAGE, CDC27, a actinin-4, TRPl / gp75, TRP2, gangliosides, WT1, Epidermal growth factor receptor (EGFR), MART-2, MUC1, MUC2, MUM1, MUM2, MUM3, NA88-1, NPM, OA1, OGT, RCC, RU11, RU12, SAGE, TRG, TSTA, Folate receptor alpha, Ll-CAM, CAIX, gpA33, GD3, GM2, VEGFR, Integrins, Carbohydrates, IGF1R, TRAILR1, TRAILR2, RANKL, FAP, TGF-beta, hyaluronic acid, collagen, tenascin C, and tenascin W.

431. The combination therapy of any one of claims 263-430, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3445, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3446, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

432. The combination therapy of any one of claims 263-430, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3448, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3449, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

433. The combination therapy of any one of claims 263-430, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3450, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3451, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

434. The combination therapy of any one of claims 263-430, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3450, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3454 or the sequence of SEQ ID NO: 3501 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3451, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

435. The combination therapy of any one of claims 263-430, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3454 or the sequence of SEQ ID NO: 3501 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 1349, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

436. The combination therapy of any one of claims 263-430, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1196, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 1195, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

437. The combination therapy of any one of claims 263-430, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3455, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3456, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

438. The combination therapy of any one of claims 263-430, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3457, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3459, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3460,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3462 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2191, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3458, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3461.

439. The combination therapy of any one of claims 263-430, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3463, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3459, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3460,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3462 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2191, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3464, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3461.

440. The combination therapy of any one of claims 263-430, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3465, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3467, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3468,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3469 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2191, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3466, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3461.

441. The combination therapy of any one of claims 263-430, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3470, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3471, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

442. The combination therapy of any one of claims 263-430, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 15 or functional variant thereof comprising the sequence of SEQ ID NO: 2170, wherein the IL- 15 or functional variant thereof is covalently linked to an IL15Ralpha dimerizing domain comprising the sequence of the SEQ ID NO: 3472 via a linker comprising the sequence of SEQ ID NO: 3473, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 1349, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

443. The combination therapy of any one of claims 263-430, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 15 or functional variant thereof comprising the sequence of SEQ ID NO: 2170, wherein the IL- 15 or functional variant thereof is covalently linked to an IL15Ralpha dimerizing domain comprising the sequence of the SEQ ID NO: 3472 via a linker comprising the sequence of SEQ ID NO: 3473, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3475, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

444. The combination therapy of any one of claims 263-430, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 15 or functional variant thereof comprising the sequence of SEQ ID NO: 2170, wherein the IL- 15 or functional variant thereof is covalently linked to an IL15Ralpha dimerizing domain comprising the sequence of the SEQ ID NO: 3472 via a linker comprising the sequence of SEQ ID NO: 3473, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3476, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

445. The combination therapy of any one of claims 263-444, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3445, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3446, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

446. The combination therapy of any one of claims 263-444, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3448, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3449, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

447. The combination therapy of any one of claims 263-444, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3450, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3451, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

448. The combination therapy of any one of claims 263-444, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3450, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3454 or the sequence of SEQ ID NO: 3501 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3451, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

449. The combination therapy of any one of claims 263-444, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3454 or the sequence of SEQ ID NO: 3501 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL-2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 1349, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

450. The combination therapy of any one of claims 263-444, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1196, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 1195, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

451. The combination therapy of any one of claims 263-444, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3455, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linkercomprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3456, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

452. The combination therapy of any one of claims 263-444, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3457, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3459, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3460,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3462 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2191, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3458, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3461.

453. The combination therapy of any one of claims 263-444, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3463, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3459, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3460,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3462 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2191, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3464, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3461.

454. The combination therapy of any one of claims 263-444, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3465, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3467, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3468,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3469 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2191, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3466, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3461.

455. The combination therapy of any one of claims 263-444, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 3470, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3649, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3447,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 2 or functional variant thereof comprising the sequence of SEQ ID NO: 2270, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3471, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

456. The combination therapy of any one of claims 263-444, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 15 or functional variant thereof comprising the sequence of SEQ ID NO: 2170, wherein theIL- 15 or functional variant thereof is covalently linked to an IL15Ralpha dimerizing domain comprising the sequence of the SEQ ID NO: 3472 via a linker comprising the sequence of SEQ ID NO: 3473, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 1349, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

457. The combination therapy of any one of claims 263-444, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 15 or functional variant thereof comprising the sequence of SEQ ID NO: 2170, wherein the IL- 15 or functional variant thereof is covalently linked to an IL15Ralpha dimerizing domain comprising the sequence of the SEQ ID NO: 3472 via a linker comprising the sequence of SEQ ID NO: 3473, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3475, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

458. The combination therapy of any one of claims 263-444, wherein the second agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a VH comprising the sequence of SEQ ID NO: 1346, wherein the VH is linked to a heavy chain constant region comprising the sequence of SEQ ID NO: 3452 or the sequence of SEQ ID NO: 3504, wherein the heavy chain constant region comprises the first Fc region comprising the sequence of SEQ ID NO: 3453 or the sequence of SEQ ID NO: 3505,(ii) the second polypeptide chain comprises a cytokine molecule, wherein the cytokine molecule is linked to the second Fc region comprising the sequence of SEQ ID NO: 3648 via a linker comprising the sequence of SEQ ID NO: 3308, wherein the cytokine molecule comprises IL- 15 or functional variant thereof comprising the sequence of SEQ ID NO: 2170, wherein the IL- 15 or functional variant thereof is covalently linked to an IL15Ralpha dimerizing domaincomprising the sequence of the SEQ ID NO: 3472 via a linker comprising the sequence of SEQ ID NO: 3473, and(iii) the third polypeptide chain comprises a VL comprising the sequence of SEQ ID NO: 3476, wherein the VL is linked to a light chain constant region comprising the sequence of SEQ ID NO: 3644.

459. The combination therapy of any one of claims 263-458, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3338;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3339.

460. The combination therapy of any one of claims 263-459, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3318;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3319.

461. The combination therapy of any one of claims 263-459, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3328;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3329.

462. The combination therapy of any one of claims 263-459, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3328;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3350 or the sequence of SEQ ID NO: 3500; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3329.

463. The combination therapy of any one of claims 263-459, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3349.

464. The combination therapy of any one of claims 263-459, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3358;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3359.

465. The combination therapy of any one of claims 263-459, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3368;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3369.

466. The combination therapy of any one of claims 263-459, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the firstpolypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3378;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3380; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3379.

467. The combination therapy of any one of claims 263-459, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3388;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3390; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3389.

468. The combination therapy of any one of claims 263-459, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3398;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3400; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3399.

469. The combination therapy of any one of claims 263-459, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3408;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3409.

470. The combination therapy of any one of claims 263-459, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3349.

471. The combination therapy of any one of claims 263-459, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3428.

472. The combination therapy of any one of claims 263-459, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3348 or the sequence of SEQ ID NO: 3502;(ii) the second polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises a sequence having at least 75% sequence identity to the sequence of SEQ ID NO: 3437.

473. The combination therapy of any one of claims 263-472, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3338;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3339.

474. The combination therapy of any one of claims 263-472, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3318;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3319.

475. The combination therapy of any one of claims 263-472, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3328;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3329.

476. The combination therapy of any one of claims 263-472, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3328;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3350 or the sequence of SEQ ID NO: 3500; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3329.

477. The combination therapy of any one of claims 263-472, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3348 or the sequence ofSEQ ID NO: 3502;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3349.

478. The combination therapy of any one of claims 263-472, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3358;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3359.

479. The combination therapy of any one of claims 263-472, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3368;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence of SEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3369.

480. The combination therapy of any one of claims 263-472, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3378;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3380; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3379.

481. The combination therapy of any one of claims 263-472, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3388;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3390; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3389.

482. The combination therapy of any one of claims 263-472, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3398;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3400; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3399.

483. The combination therapy of any one of claims 263-472, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3408;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3340 or the sequence ofSEQ ID NO: 3503; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3409.

484. The combination therapy of any one of claims 263-472, wherein the first agent comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain, wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous, and wherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 3348 or the sequence ofSEQ ID NO: 3502;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 3420; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 3349.

485. The combination therapy...

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