Materials and methods for modulating T cell-mediated immunity

Abstract

Anti-TRGV9 antibodies or antigen-binding fragments thereof are described. Nucleic acids encoding the antibodies, compositions containing the antibodies, and methods of producing the antibodies and using the antibodies to treat or prevent diseases such as cancer are also described.

Description

Technical field

[0001] (Cross reference to related application) This application is filed May 8, 2019, U.S. Patent Application No. 62 / 844,959, filed May 8, 2019, U.S. Patent Application No. 62 / 844,966, filed May 8, 2019. No. 62 / 844,970 filed May 8, 2019; No. 62 / 844,976 filed May 8, 2019; and No. 62 / 844,995 filed May 8, 2019 , each of which is incorporated herein by reference in its entirety.

[0002] (field of invention) The present invention includes, inter alia, anti-TRGV9 molecules, including anti-TRGV9 antibodies, anti-TRGV9 / anti-cancer associated antigen bispecific antibodies, and nucleic acids and expression vectors encoding the antibodies, recombinant cells containing the vectors, and antibodies. Regarding the composition. Also provided are methods of making antibodies and methods of using antibodies to kill cancer cells.

[0003] (reference to sequence listing submitted electronically) This application has been submitted electronically via EFS-Web as a Sequence Listing in ASCII format with a file name of "14620-021-228_SEQLIST" and a creation date of May 4, 2020, with a size of 349,509 bytes. Includes sequence listing. The Sequence Listing submitted via EFS-Web is part of this specification and is hereby incorporated by reference in its entirety. [Outline of the invention] [Means for solving the problem]

[0004] In one aspect, provided herein are antibodies that bind to T Cell Receptor Gamma Variable 9 (T Cell Receptor Gamma Variable 9, TRGV9). In some embodiments, an antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL).

[0005] In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) a VH complementarity determining region (CDR) 1 having the amino acid sequence of SEQ ID NO:1, SEQ ID NO:2; a VH comprising a VH CDR2 having an amino acid sequence and a VH CDR3 having an amino acid sequence of SEQ ID NO:31; and (ii) a VL CDR1 having an amino acid sequence of SEQ ID NO:4, a VL CDR2 having an amino acid sequence of SEQ ID NO:5, and VL, which contains the VL CDR3 having the amino acid sequence of SEQ ID NO:6. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:34. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO:8. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:34 and a VL having the amino acid sequence of SEQ ID NO:8. In some embodiments, the antibody specifically binds TRGV9. In other embodiments, TRGV9 is present on the surface of γδ T cells. In some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype. In some embodiments, the antibody is a bispecific antibody. In certain embodiments, antibodies are multivalent. In other embodiments, the antibody is capable of binding at least three antigens. In some embodiments, an antibody can bind to at least 5 antigens.

[0006] In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) a VH CDR1 having the amino acid sequence of SEQ ID NO:1, a VH CDR2 having the amino acid sequence of SEQ ID NO:2, and SEQ ID NO:32; and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 4, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VL CDR3 having the amino acid sequence of SEQ ID NO: 6. including, VL and including. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:35. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO:8. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:35 and a VL having the amino acid sequence of SEQ ID NO:8. In some embodiments, the antibody specifically binds TRGV9. In other embodiments, TRGV9 is present on the surface of γδ T cells. In some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype. In some embodiments, the antibody is a bispecific antibody. In certain embodiments, antibodies are multivalent. In other embodiments, the antibody is capable of binding at least three antigens. In some embodiments, an antibody can bind to at least 5 antigens.

[0007] In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) a VH CDR1 having the amino acid sequence of SEQ ID NO:1, a VH CDR2 having the amino acid sequence of SEQ ID NO:2, and SEQ ID NO:33; and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 4, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VL CDR3 having the amino acid sequence of SEQ ID NO: 6. including, VL and including. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:36. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO:8. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:36 and a VL having the amino acid sequence of SEQ ID NO:8. In some embodiments, the antibody specifically binds TRGV9. In other embodiments, TRGV9 is present on the surface of γδ T cells. In some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype. In some embodiments, the antibody is a bispecific antibody. In certain embodiments, antibodies are multivalent. In other embodiments, the antibody is capable of binding at least three antigens. In some embodiments, an antibody can bind to at least 5 antigens.

[0008] In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:1, VH CDR2 having the amino acid sequence of SEQ ID NO:76, and SEQ ID NO:3. and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 77, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VL CDR3 having the amino acid sequence of SEQ ID NO: 6. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:60, VH CDR2 having the amino acid sequence of SEQ ID NO:61, and SEQ ID NO:62 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 63, VL CDR2 having the amino acid sequence of SEQ ID NO: 64, and VL CDR3 having the amino acid sequence of SEQ ID NO: 6. including, VL and including. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:65. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO:66. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:65 and a VL having the amino acid sequence of SEQ ID NO:66. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:67. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO:68. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:67 and a VL having the amino acid sequence of SEQ ID NO:68. In some embodiments, the antibody specifically binds TRGV9. In other embodiments, TRGV9 is present on the surface of γδ T cells. In some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype. In some embodiments, the antibody is a bispecific antibody. In certain embodiments, antibodies are multivalent. In other embodiments, the antibody is capable of binding at least three antigens. In some embodiments, an antibody can bind to at least 5 antigens.

[0009] In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:98, VH CDR2 having the amino acid sequence of SEQ ID NO:99, and SEQ ID NO:100 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 101, VL CDR2 having the amino acid sequence of SEQ ID NO: 102, and VL CDR3 having the amino acid sequence of SEQ ID NO: 103. including, VL and including. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:104. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO:105. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:104 and a VL having the amino acid sequence of SEQ ID NO:105. In some embodiments, the antibody specifically binds TRGV9. In other embodiments, TRGV9 is present on the surface of γδ T cells. In some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype. In some embodiments, the antibody is a bispecific antibody. In certain embodiments, antibodies are multivalent. In other embodiments, the antibody is capable of binding at least three antigens. In some embodiments, an antibody can bind to at least 5 antigens.

[0010] In another aspect, provided herein are antibodies that bind to TRGV9, the antibodies comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO:107, VH CDR2 having the amino acid sequence of SEQ ID NO:108, and SEQ ID NO:109 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 110, VL CDR2 having the amino acid sequence of SEQ ID NO: 111, and VL CDR3 having the amino acid sequence of SEQ ID NO: 112. including, VL and including. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:113. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO:114. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:113 and a VL having the amino acid sequence of SEQ ID NO:114. In some embodiments, the antibody specifically binds TRGV9. In other embodiments, TRGV9 is present on the surface of γδ T cells. In some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype. In some embodiments, the antibody is a bispecific antibody. In certain embodiments, antibodies are multivalent. In other embodiments, the antibody is capable of binding at least three antigens. In some embodiments, an antibody can bind to at least 5 antigens.

[0011] In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:117, VH CDR2 having the amino acid sequence of SEQ ID NO:118, and SEQ ID NO:119 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 120, VL CDR2 having the amino acid sequence of SEQ ID NO: 121, and VL CDR3 having the amino acid sequence of SEQ ID NO: 122. including, VL and including. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:123. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO:124. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:123 and a VL having the amino acid sequence of SEQ ID NO:124. In some embodiments, the antibody specifically binds TRGV9. In other embodiments, TRGV9 is present on the surface of γδ T cells. In some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype. In some embodiments, the antibody is a bispecific antibody. In certain embodiments, antibodies are multivalent. In other embodiments, the antibody is capable of binding at least three antigens. In some embodiments, an antibody can bind to at least 5 antigens.

[0012] In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:127, VH CDR2 having the amino acid sequence of SEQ ID NO:128, and SEQ ID NO:129 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 130, VL CDR2 having the amino acid sequence of SEQ ID NO: 131, and VL CDR3 having the amino acid sequence of SEQ ID NO: 132. including, VL and including. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:133. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO:134. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:133 and a VL having the amino acid sequence of SEQ ID NO:134. In some embodiments, the antibody specifically binds TRGV9. In other embodiments, TRGV9 is present on the surface of γδ T cells. In some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype. In some embodiments, the antibody is a bispecific antibody. In certain embodiments, antibodies are multivalent. In other embodiments, the antibody is capable of binding at least three antigens. In some embodiments, an antibody can bind to at least 5 antigens.

[0013] Also provided are nucleic acids encoding antibodies that bind to TRGV9 provided herein. Also provided is a vector comprising a nucleic acid encoding an antibody that binds to TRGV9 provided herein. Also provided is a host cell containing a vector comprising a nucleic acid encoding an antibody that binds to TRGV9 provided herein. Also provided is a kit comprising a vector comprising a nucleic acid encoding an antibody that binds to TRGV9 provided herein and a package therefor.

[0014] Also provided is a pharmaceutical composition comprising an antibody that binds to TRGV9 provided herein and a pharmaceutically acceptable carrier. Also provided is a method of producing a pharmaceutical composition, the method comprising combining the antibody with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition.

[0015] Also provided is a method of activating a γδ T cell that expresses TRGV9, the method comprising contacting the γδ T cell with an antibody that binds TRGV9 provided herein. In some embodiments, the contacting results in increased CD69, CD25, and / or granzyme B expression compared to control γδ T cells expressing TRGV9. Also provided is a method of inactivating a γδ T cell that expresses TRGV9, the method comprising contacting the γδ T cell with an antibody that binds TRGV9 provided herein. Also provided are methods of blocking activation of γδ T cells that express TRGV9, the methods comprising contacting the γδ T cells with an antibody that binds TRGV9 provided herein. Also provided is a method of modulating the activity of a TRGV9-expressing γδ T cell, the method comprising contacting the γδ T cell with an antibody that binds TRGV9 provided herein.

[0016] In another aspect, a bispecific antibody is described herein comprising (a) a first binding domain that binds TRGV9 and (b) a second binding domain that binds a second target that is not TRGV9. provided to In certain embodiments, the first binding domain of the bispecific antibody specifically binds TRGV9. In some embodiments, TRGV9 is present on the surface of γδ T cells. In some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype.

[0017] In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 3 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:4, a VL CDR2 having the amino acid sequence of SEQ ID NO:5, and a VL CDR3 having the amino acid sequence of SEQ ID NO:6. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:7. In some embodiments, the first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:8. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:7 and a VL having the amino acid sequence of SEQ ID NO:8. In certain embodiments, the first binding domain of the bispecific antibody specifically binds TRGV9. In some embodiments, TRGV9 is present on the surface of γδ T cells. In some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype.

[0018] In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 31 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:4, a VL CDR2 having the amino acid sequence of SEQ ID NO:5, and a VL CDR3 having the amino acid sequence of SEQ ID NO:6. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:34. In some embodiments, the first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:8. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:34 and a VL having the amino acid sequence of SEQ ID NO:8. In certain embodiments, the first binding domain of the bispecific antibody specifically binds TRGV9. In some embodiments, TRGV9 is present on the surface of γδ T cells. In some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype.

[0019] In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 32 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:4, a VL CDR2 having the amino acid sequence of SEQ ID NO:5, and a VL CDR3 having the amino acid sequence of SEQ ID NO:6. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:35. In some embodiments, the first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:8. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:35 and a VL having the amino acid sequence of SEQ ID NO:8. In certain embodiments, the first binding domain of the bispecific antibody specifically binds TRGV9. In some embodiments, TRGV9 is present on the surface of γδ T cells. In some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype.

[0020] In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 33 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:4, a VL CDR2 having the amino acid sequence of SEQ ID NO:5, and a VL CDR3 having the amino acid sequence of SEQ ID NO:6. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:36. In some embodiments, the first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:8. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:36 and a VL having the amino acid sequence of SEQ ID NO:8. In certain embodiments, the first binding domain of the bispecific antibody specifically binds TRGV9. In some embodiments, TRGV9 is present on the surface of γδ T cells. In some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype.

[0021] In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 76, and VH CDR3 having the amino acid sequence of SEQ ID NO: 3 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:77, a VL CDR2 having the amino acid sequence of SEQ ID NO:5, and a VL CDR3 having the amino acid sequence of SEQ ID NO:6. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 60, VH CDR2 having the amino acid sequence of SEQ ID NO: 61, and VH CDR3 having the amino acid sequence of SEQ ID NO: 62 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:63, a VL CDR2 having the amino acid sequence of SEQ ID NO:64, and a VL CDR3 having the amino acid sequence of SEQ ID NO:6. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:65. In some embodiments, the first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:66. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:65 and a VL having the amino acid sequence of SEQ ID NO:66. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:67. In some embodiments, the first binding domain comprises VL having the amino acid sequence of SEQ ID NO:68. In some embodiments, the first binding domain, VH having the amino acid sequence of SEQ ID NO:67, and VL having the amino acid sequence of SEQ ID NO:68. In certain embodiments, the first binding domain of the bispecific antibody specifically binds TRGV9. In some embodiments, TRGV9 is present on the surface of γδ T cells. In some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype.

[0022] In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:89, VH CDR2 having the amino acid sequence of SEQ ID NO:90, and VH CDR3 having the amino acid sequence of SEQ ID NO:91 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:92, a VL CDR2 having the amino acid sequence of SEQ ID NO:93, and a VL CDR3 having the amino acid sequence of SEQ ID NO:94. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:95. In some embodiments, the first binding domain comprises VL having the amino acid sequence of SEQ ID NO:96. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:95 and a VL having the amino acid sequence of SEQ ID NO:96. In certain embodiments, the first binding domain of the bispecific antibody specifically binds TRGV9. In some embodiments, TRGV9 is present on the surface of γδ T cells. In some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype.

[0023] In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:98, VH CDR2 having the amino acid sequence of SEQ ID NO:99, and VH CDR3 having the amino acid sequence of SEQ ID NO:100 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:101, a VL CDR2 having the amino acid sequence of SEQ ID NO:102, and a VL CDR3 having the amino acid sequence of SEQ ID NO:103. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:104. In some embodiments, the first binding domain comprises VL having the amino acid sequence of SEQ ID NO:105. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:104 and a VL having the amino acid sequence of SEQ ID NO:105. In certain embodiments, the first binding domain of the bispecific antibody specifically binds TRGV9. In some embodiments, TRGV9 is present on the surface of γδ T cells. In some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype.

[0024] In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 107, VH CDR2 having the amino acid sequence of SEQ ID NO: 108, and VH CDR3 having the amino acid sequence of SEQ ID NO: 109 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:110, a VL CDR2 having the amino acid sequence of SEQ ID NO:111, and a VL CDR3 having the amino acid sequence of SEQ ID NO:112. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:113. In some embodiments, the first binding domain comprises VL having the amino acid sequence of SEQ ID NO:114. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:113 and a VL having the amino acid sequence of SEQ ID NO:114. In certain embodiments, the first binding domain of the bispecific antibody specifically binds TRGV9. In some embodiments, TRGV9 is present on the surface of γδ T cells. In some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype.

[0025] In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 117, VH CDR2 having the amino acid sequence of SEQ ID NO: 118, and VH CDR3 having the amino acid sequence of SEQ ID NO: 119 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:120, a VL CDR2 having the amino acid sequence of SEQ ID NO:121, and a VL CDR3 having the amino acid sequence of SEQ ID NO:122. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:123. In some embodiments, the first binding domain comprises VL having the amino acid sequence of SEQ ID NO:124. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:123 and a VL having the amino acid sequence of SEQ ID NO:124. In certain embodiments, the first binding domain of the bispecific antibody specifically binds TRGV9. In some embodiments, TRGV9 is present on the surface of γδ T cells. In some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype.

[0026] In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 127, VH CDR2 having the amino acid sequence of SEQ ID NO: 128, and VH CDR3 having the amino acid sequence of SEQ ID NO: 129 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:130, a VL CDR2 having the amino acid sequence of SEQ ID NO:131, and a VL CDR3 having the amino acid sequence of SEQ ID NO:132. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:133. In some embodiments, the first binding domain comprises VL having the amino acid sequence of SEQ ID NO:134. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:133 and a VL having the amino acid sequence of SEQ ID NO:134. In certain embodiments, the first binding domain of the bispecific antibody specifically binds TRGV9. In some embodiments, TRGV9 is present on the surface of γδ T cells. In some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype.

[0027] In another embodiment, a bispecific antibody comprising (a) a first binding domain that binds TRGV9 and (b) a second binding domain that binds a cancer antigen present on the surface of a cancer cell provided herein. In some embodiments, the antigen on the surface of cancer cells is a tumor-specific antigen, tumor-associated antigen, or neoantigen. In certain embodiments, the first binding domain of the bispecific antibody specifically binds TRGV9. In some embodiments, TRGV9 is present on the surface of γδ T cells. In some embodiments, cancer cells are killed when the bispecific antibody binds to TRGV9 on the surface of γδ T cells and the antigen on the surface of cancer cells. In some embodiments, the first binding domain is humanized, the second binding domain is humanized, or both the first binding domain and the second binding domain are human has been made In some embodiments the bispecific antibody is an IgG antibody. In some embodiments, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype.

[0028] In another aspect, provided herein is a bispecific antibody comprising (a) a first binding domain that binds TRGV9 and (b) a second binding domain that binds CD123. In certain embodiments, the first binding domain of the bispecific antibody specifically binds TRGV9. In some embodiments, TRGV9 is present on the surface of γδ T cells. In some embodiments, CD123 is on the surface of the cell. In certain embodiments, TRGV9 is present on the surface of γδ T cells and CD123 is on the surface of the cells. In some embodiments, when the bispecific antibody binds to TRGV9 on the surface of a γδ T cell and CD123 on the surface of the cell, the cell with CD123 on its surface is killed. In some embodiments, CD123 is on the surface of cancer cells. In certain embodiments, TRGV9 is present on the surface of γδ T cells and CD123 is on the surface of cancer cells. In some embodiments, cancer cells are killed when the bispecific antibody binds to TRGV9 on the surface of a γδ T cell and CD123 on the surface of the cell. In some embodiments, the first binding domain is humanized, the second binding domain is humanized, or both the first binding domain and the second binding domain are human has been made In some embodiments the bispecific antibody is an IgG antibody. In some embodiments, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype.

[0029] In another aspect, provided herein are bispecific antibodies, the antibody comprising (a) a first binding domain that binds TRGV9 and (b) a second binding domain that binds CD123. , the second binding domain comprises: (i) a VH CDR1 having the amino acid sequence of SEQ ID NO:9, a VH CDR2 having the amino acid sequence of SEQ ID NO:10, and a VH CDR3 having the amino acid sequence of SEQ ID NO:11; (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:12, a VL CDR2 having the amino acid sequence of SEQ ID NO:13, and a VL CDR3 having the amino acid sequence of SEQ ID NO:14; In some embodiments, the second binding domain comprises a VH having the amino acid sequence of SEQ ID NO:15. In some embodiments, the second binding domain comprises a VL having the amino acid sequence of SEQ ID NO:16. In some embodiments, the second binding domain comprises a VH having the amino acid sequence of SEQ ID NO:15 and a VL having the amino acid sequence of SEQ ID NO:16. In some embodiments, CD123 is on the surface of the cell. In certain embodiments, TRGV9 is present on the surface of γδ T cells and CD123 is on the surface of the cells. In some embodiments, when the bispecific antibody binds to TRGV9 on the surface of a γδ T cell and CD123 on the surface of the cell, the cell with CD123 on its surface is killed. In some embodiments, CD123 is on the surface of cancer cells. In certain embodiments, TRGV9 is present on the surface of γδ T cells and CD123 is on the surface of cancer cells. In some embodiments, cancer cells are killed when the bispecific antibody binds to TRGV9 on the surface of a γδ T cell and CD123 on the surface of the cell. In some embodiments, the first binding domain is humanized, the second binding domain is humanized, or both the first binding domain and the second binding domain are human has been made In some embodiments the bispecific antibody is an IgG antibody. In some embodiments, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype.

[0030] In some embodiments of the various bispecific antibodies provided herein, the first binding domain that binds TRGV9 is a VH CDR1 having an amino acid sequence as provided herein, Including VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the first binding domain that binds TRGV9 comprises VH CDR1, VH CDR2, and VH CDR3 of a VH domain having amino acid sequences as provided herein. In some embodiments, the first binding domain that binds TRGV9 comprises VL CDR1, VL CDR2, and VL CDR3 of a VL domain having amino acid sequences as provided herein. In some embodiments, the first binding domain that binds TRGV9 is VH CDR1, VH CDR2, and VH CDR3 of a VH domain having the amino acid sequences as provided herein and VL CDR1, VL CDR2, and VL CDR3 of the VL domain having the amino acid sequences provided. In some embodiments, the first binding domain that binds TRGV9 comprises a VH domain having an amino acid sequence as provided herein. In some embodiments, the first binding domain that binds TRGV9 comprises a VL domain having an amino acid sequence as provided herein. In some embodiments, the first binding domain that binds TRGV9 is a VH domain having an amino acid sequence as provided herein and a VL domain having an amino acid sequence as provided herein. including.

[0031] Also, as provided herein, a bispecific comprising (a) a first binding domain that binds TRGV9 and (b) a second binding domain that binds a second target that is not TRGV9 A nucleic acid is provided that encodes a sexual antibody. Also provided is a vector comprising a nucleic acid encoding a bispecific antibody that binds to TRGV9 provided herein. Also provided is a host cell comprising a vector comprising a nucleic acid encoding a bispecific antibody that binds to TRGV9 provided herein. Also provided is a kit comprising a vector comprising a nucleic acid encoding a bispecific antibody that binds to TRGV9 provided herein and a package therefor.

[0032] Another embodiment comprises (a) a first binding domain that binds TRGV9, and (b) a second binding domain that binds a second target that is not TRGV9, and a pharmaceutically acceptable carrier. , pharmaceutical compositions are provided herein. Any of the bispecific antibodies provided herein are contemplated in pharmaceutical compositions. In certain embodiments, the second binding domain binds CD123.

[0033] In another aspect, provided herein are methods of directing γδ T cells expressing TRGV9 to cancer cells, the methods comprising contacting the γδ T cells with a bispecific antibody provided herein. Including. In some embodiments, the contacting directs γδ T cells to cancer cells.

[0034] In another aspect, provided herein is a method of inhibiting the growth or proliferation of a cancer cell that expresses a cancer antigen on its cell surface, the method comprising treating the cancer cell with a bispecific antibody provided herein. including contact with In some embodiments, contacting cancer cells with the pharmaceutical composition inhibits cancer cell growth or proliferation. In some embodiments, the cancer cell is in the presence of γδ T cells expressing TRGV9 while in contact with the bispecific antibody.

[0035] In another aspect, provided herein is a method for eliminating cancer cells in a subject, the method comprising administering to the subject an effective amount of a bispecific antibody as provided herein. include. In some embodiments, the subject is a subject in need of the method. In some embodiments, the subject is human.

[0036] In another aspect, provided herein is a method of activating a γδ T cell expressing TRGV9, the method comprising contacting the γδ T cell with a bispecific antibody as provided herein. Including.

[0037] Provided herein is an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises a. a first heavy chain (HC1); b. a second heavy chain (HC2); c. a first light chain (LC1); d. a second light chain (LC2); HC1 is related to LC1, HC2 is related to LC2, HC1 is i. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively; ii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31, respectively; iii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32, respectively, or iv. heavy chain complementarity determining region 1 (HCDR1), HCDR2, and HCDR3, comprising the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33, respectively; LC1 comprises a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, LCDR2, and LCDR2, respectively; HC2 and LC2 form the binding site for a second antigen. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof has at least 95% and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8. In another embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 comprising an amino acid sequence selected from SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36 , LC1 comprises the amino acid sequence of SEQ ID NO:8.

[0038] Also provided herein is an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises (a) HC1 and (b ) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, HC1 is related to LC1, HC2 is related to LC2, HC1 comprises HCDR1, HCDR2 and HCDR3 comprising the amino acid sequences of SEQ ID NO:1, SEQ ID NO:2 and SEQ ID NO:3 respectively, and LC1 comprises the amino acid sequences of SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6 respectively The LCDR1, LCDR2, and LCDR3 containing sequences form a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:7, wherein LC1 is An amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8. In another embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 comprising the amino acid sequence of SEQ ID NO:7 and LC1 comprises the amino acid sequence of SEQ ID NO:8.

[0039] Also provided herein is an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises (a) HC1 and (b ) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, HC1 is related to LC1, HC2 is related to LC2, HC1 comprises HCDR1, HCDR2 and HCDR3 comprising the amino acid sequences of SEQ ID NO:1, SEQ ID NO:2 and SEQ ID NO:31 respectively, and LC1 comprises the amino acid sequences of SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6 respectively The LCDR1, LCDR2, and LCDR3 containing sequences form a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:34, wherein LC1 is An amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8. In another embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 comprising the amino acid sequence of SEQ ID NO:34 and LC1 comprises the amino acid sequence of SEQ ID NO:8.

[0040] Also provided herein is an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises (a) HC1 and (b ) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, HC1 is related to LC1, HC2 is related to LC2, HC1 comprises HCDR1, HCDR2 and HCDR3 comprising the amino acid sequences of SEQ ID NO:1, SEQ ID NO:2 and SEQ ID NO:32 respectively, and LC1 comprises the amino acid sequences of SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6 respectively The LCDR1, LCDR2, and LCDR3 containing sequences form a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:35, wherein LC1 is An amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8. In another embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 comprising the amino acid sequence of SEQ ID NO:35 and LC1 comprises the amino acid sequence of SEQ ID NO:8.

[0041] Also provided herein is an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises (a) HC1 and (b ) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, HC1 is related to LC1, HC2 is related to LC2, HC1 comprises HCDR1, HCDR2 and HCDR3 comprising the amino acid sequences of SEQ ID NO:1, SEQ ID NO:2 and SEQ ID NO:33 respectively, and LC1 comprises the amino acid sequences of SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6 respectively The LCDR1, LCDR2, and LCDR3 containing sequences form a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:36, wherein LC1 is An amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8. In another embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 comprising the amino acid sequence of SEQ ID NO:36 and LC1 comprises the amino acid sequence of SEQ ID NO:8.

[0042] Also provided herein is an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises (a) HC1 and (b ) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, HC1 is related to LC1, HC2 is related to LC2, HC1 comprises HCDR1, HCDR2 and HCDR3 comprising the amino acid sequences of SEQ ID NO:1, SEQ ID NO:76 and SEQ ID NO:3 respectively, and LC1 comprises the amino acid sequences of SEQ ID NO:77, SEQ ID NO:5 and SEQ ID NO:6 respectively The LCDR1, LCDR2, and LCDR3 containing sequences form a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:65, wherein LC1 is Include an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:66. In another embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 comprising the amino acid sequence of SEQ ID NO:65 and LC1 comprises the amino acid sequence of SEQ ID NO:66. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:67, wherein LC1 is Include amino acid sequences having at least 95% identity to the amino acid sequence of SEQ ID NO:68. In another embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 comprising the amino acid sequence of SEQ ID NO:67 and LC1 comprises the amino acid sequence of SEQ ID NO:68.

[0043] Also provided herein is an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises (a) HC1 and (b ) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, HC1 is related to LC1, HC2 is related to LC2, HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:60, SEQ ID NO:61, and SEQ ID NO:62, respectively, and LC1 comprises the amino acids of SEQ ID NO:63, SEQ ID NO:64, and SEQ ID NO:6, respectively. The LCDR1, LCDR2, and LCDR3 containing sequences form a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:65, wherein LC1 is Include an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:66. In another embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 comprising the amino acid sequence of SEQ ID NO:65 and LC1 comprises the amino acid sequence of SEQ ID NO:66. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:67, wherein LC1 is Include amino acid sequences having at least 95% identity to the amino acid sequence of SEQ ID NO:68. In another embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 comprising the amino acid sequence of SEQ ID NO:67 and LC1 comprises the amino acid sequence of SEQ ID NO:68.

[0044] Also provided herein is an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises (a) HC1 and (b ) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, HC1 is related to LC1, HC2 is related to LC2, HC1 comprises HCDR1, HCDR2 and HCDR3 comprising the amino acid sequences of SEQ ID NO:89, SEQ ID NO:90 and SEQ ID NO:91 respectively, and LC1 comprises the amino acid sequences of SEQ ID NO:92, SEQ ID NO:93 and SEQ ID NO:94 respectively The LCDR1, LCDR2, and LCDR3 containing sequences form a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:95, wherein LC1 is Include amino acid sequences having at least 95% identity to the amino acid sequence of SEQ ID NO:96. In another embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 comprising the amino acid sequence of SEQ ID NO:95 and LC1 comprises the amino acid sequence of SEQ ID NO:96.

[0045] Also provided herein is an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises (a) HC1 and (b ) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, HC1 is related to LC1, HC2 is related to LC2, HC1 comprises HCDR1, HCDR2 and HCDR3 comprising the amino acid sequences of SEQ ID NO:98, SEQ ID NO:99 and SEQ ID NO:100 respectively, and LC1 comprises the amino acids of SEQ ID NO:101, SEQ ID NO:102 and SEQ ID NO:103 respectively The LCDR1, LCDR2, and LCDR3 containing sequences form a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 104, wherein LC1 is Include amino acid sequences having at least 95% identity to the amino acid sequence of SEQ ID NO:105. In another embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 comprising the amino acid sequence of SEQ ID NO:104 and LC1 comprises the amino acid sequence of SEQ ID NO:105.

[0046] Also provided herein is an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises (a) HC1 and (b ) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, HC1 is related to LC1, HC2 is related to LC2, HC1 comprises HCDR1, HCDR2 and HCDR3 comprising the amino acid sequences of SEQ ID NO:107, SEQ ID NO:108 and SEQ ID NO:109 respectively, and LC1 comprises the amino acids of SEQ ID NO:110, SEQ ID NO:111 and SEQ ID NO:112 respectively The LCDR1, LCDR2, and LCDR3 containing sequences form a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 113, wherein LC1 is Include amino acid sequences having at least 95% identity to the amino acid sequence of SEQ ID NO:114. In another embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 comprising the amino acid sequence of SEQ ID NO:113 and LC1 comprises the amino acid sequence of SEQ ID NO:114.

[0047] Also provided herein is an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises (a) HC1 and (b ) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, HC1 is related to LC1, HC2 is related to LC2, HC1 comprises HCDR1, HCDR2 and HCDR3 comprising the amino acid sequences of SEQ ID NO:117, SEQ ID NO:118 and SEQ ID NO:119 respectively, and LC1 comprises the amino acids of SEQ ID NO:120, SEQ ID NO:121 and SEQ ID NO:122 respectively The LCDR1, LCDR2, and LCDR3 containing sequences form a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 123, wherein LC1 is Include amino acid sequences having at least 95% identity to the amino acid sequence of SEQ ID NO:124. In another embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 comprising the amino acid sequence of SEQ ID NO:123 and LC1 comprises the amino acid sequence of SEQ ID NO:124.

[0048] Also provided herein is an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises (a) HC1 and (b ) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, HC1 is related to LC1, HC2 is related to LC2, HC1 comprises HCDR1, HCDR2 and HCDR3 comprising the amino acid sequences of SEQ ID NO:127, SEQ ID NO:128 and SEQ ID NO:129 respectively, and LC1 comprises the amino acids of SEQ ID NO:130, SEQ ID NO:131 and SEQ ID NO:132 respectively The LCDR1, LCDR2, and LCDR3 containing sequences form a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 133, wherein LC1 is Include amino acid sequences having at least 95% identity to the amino acid sequence of SEQ ID NO:134. In another embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 comprising the amino acid sequence of SEQ ID NO:133 and LC1 comprises the amino acid sequence of SEQ ID NO:134.

[0049] In another embodiment, the binding site for the first antigen binds TRGV9 on γδ T cells.

[0050] In another embodiment, the binding site for the second antigen binds to a cancer antigen present on the surface of cancer cells.

[0051] In another embodiment, the bispecific antibody binds TRGV9 present on the surface of γδ T cells, and binding of the cancer antigen present on the surface of cancer cells results in killing of the cancer cells.

[0052] In another embodiment, the TRGV9 bispecific antibody comprises humanized HC1 and humanized LC1.

[0053] In another embodiment, HC2 and LC2 of the TRGV9 antibody bind CD123.

[0054] In another embodiment, the bispecific antibody or antigen-binding fragment thereof is of the IgG1, IgG2, IgG3, or IgG4 isotype.

[0055] In certain embodiments, the bispecific antibody or antigen-binding fragment thereof is of the IgG4 isotype.

[0056] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof has an EC of less than about 500 pM 50 induces γδ T cell-dependent cytotoxicity of cancer cells in vitro.

[0057] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof has an EC of less than about 300 pM 50 induces γδ T cell-dependent cytotoxicity of cancer cells in vitro.

[0058] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof has an EC of less than about 160 pM 50 induces γδ T cell-dependent cytotoxicity of cancer cells in vitro.

[0059] In one embodiment, EC 50 is assessed in a mixture of γδ T effector cells and Kasumi3 AML target cells.

[0060] In another embodiment, the ratio of effector cells to target cells is from about 0.01:1 to about 5:1.

[0061] In yet another embodiment, the ratio of effector cells to target cells is from about 0.1:1 to about 2:1.

[0062] In certain embodiments, the ratio of effector cells to target cells is about 1:1.

[0063] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof is multivalent.

[0064] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof is capable of binding at least three antigens.

[0065] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof is capable of binding at least five antigens.

[0066] Also provided is an isolated γδ T cell bispecific antibody or antigen-binding fragment thereof, wherein the isolated γδ T cell bispecific antibody or antigen-binding fragment thereof comprises a. HC1 and b. HC2 and c.LC1 and d. including LC2 and HC1 is related to LC1, HC2 is related to LC2, HC1 and LC1 form the binding site for the first antigen on γδ T cells, HC2 and LC2 form a binding site for a second antigen.

[0067] Also comprising a first means capable of specifically binding to the T cell receptor gamma chain and a second means capable of specifically binding to a target molecule that is not the T cell receptor gamma chain, Bispecific antibodies are provided herein.

[0068] Also provided are processes for making molecules capable of specifically binding to two or more target molecules, the molecules yielding oligopeptides or polypeptides capable of binding to the T cell receptor gamma chain. Providing a functional step to obtain an oligopeptide or polypeptide capable of binding to a target, a T cell receptor gamma chain and a molecule capable of specifically binding to a target molecule. and the step of performing a function.

[0069] In one embodiment, the steps are repeated n times to serve the function of obtaining an oligopeptide or polypeptide capable of binding to a target that specifically binds the T cell receptor gamma chain and n target molecules. It further comprises n steps, where n is at least 2, to perform the function of providing the molecule capable of producing the molecule.

[0070] Provided herein is an isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof, a. HC1 and b. HC2 and c.LC1 and d. including LC2 and HC1 is related to LC1, HC2 is related to LC2, HC1 is i. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively; ii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31, respectively; iii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32, respectively, or iv. HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for a first antigen that specifically binds Vγ9; HC2 comprises HCDR1, HCDR2 and HCDR3 comprising the amino acid sequences of SEQ ID NO:9, SEQ ID NO:10 and SEQ ID NO:11 respectively, and LC2 comprises the amino acids of SEQ ID NO:12, SEQ ID NO:13 and SEQ ID NO:14 respectively LCDR1, LCDR2, and LCDR3 containing sequences form a binding site for a second antigen that specifically binds to CD123. In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment is directed to an amino acid sequence selected from SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36 HC1 comprises an amino acid sequence with at least 95% identity, and LC1 comprises an amino acid sequence with at least 95% identity to the amino acid sequence of SEQ ID NO:8. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises an amino acid sequence selected from SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36 HC1, LC1 comprising the amino acid sequence of SEQ ID NO:8. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC2 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:15. , LC2 comprise an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:16. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC2 comprising the amino acid sequence of SEQ ID NO:15 and LC2 comprises the amino acid sequence of SEQ ID NO:16.

[0071] Also provided herein are isolated anti-TRGV9 / anti-CD123 bispecific antibodies, or antigen-binding fragments thereof, comprising (a) HC1, (b) HC2, (c) LC1, (d) HC2, HC1 related to LC1, HC2 related to LC2, HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively. and LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for a first antigen that specifically binds Vγ9 HC2 comprises HCDR1, HCDR2 and HCDR3 comprising the amino acid sequences of SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11 respectively, and LC2 comprises SEQ ID NO: 12, SEQ ID NO: 13 and SEQ ID NO: 14 respectively to form a binding site for a second antigen that specifically binds to CD123. In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises an amino acid sequence having at least 95% identity to the selected amino acid sequence of SEQ ID NO:7. and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO:7 and LC1 comprises the amino acid sequence of SEQ ID NO:8. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC2 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:15. , LC2 comprise an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:16. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC2 comprising the amino acid sequence of SEQ ID NO:15 and LC2 comprises the amino acid sequence of SEQ ID NO:16.

[0072] Also provided herein are isolated anti-TRGV9 / anti-CD123 bispecific antibodies, or antigen-binding fragments thereof, comprising (a) HC1, (b) HC2, (c) LC1, (d) HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31, respectively. and LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for a first antigen that specifically binds Vγ9 HC2 comprises HCDR1, HCDR2 and HCDR3 comprising the amino acid sequences of SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11 respectively, and LC2 comprises SEQ ID NO: 12, SEQ ID NO: 13 and SEQ ID NO: 14 respectively to form a binding site for a second antigen that specifically binds to CD123. In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises an amino acid sequence having at least 95% identity to the selected amino acid sequence of SEQ ID NO:34. and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO:34 and LC1 comprises the amino acid sequence of SEQ ID NO:8. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC2 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:15. , LC2 comprise an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:16. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC2 comprising the amino acid sequence of SEQ ID NO:15 and LC2 comprises the amino acid sequence of SEQ ID NO:16.

[0073] Also provided herein are isolated anti-TRGV9 / anti-CD123 bispecific antibodies, or antigen-binding fragments thereof, comprising (a) HC1, (b) HC2, (c) LC1, (d) HC2, HC1 is related to LC1, HC2 is related to LC2, and HC1 is HCDR1, HCDR2, and HCDR3, which comprise the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32, respectively. and LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for a first antigen that specifically binds Vγ9 HC2 comprises HCDR1, HCDR2 and HCDR3 comprising the amino acid sequences of SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11 respectively, and LC2 comprises SEQ ID NO: 12, SEQ ID NO: 13 and SEQ ID NO: 14 respectively to form a binding site for a second antigen that specifically binds to CD123. In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises an amino acid sequence having at least 95% identity to the selected amino acid sequence of SEQ ID NO:35. and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO:35 and LC1 comprises the amino acid sequence of SEQ ID NO:8. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC2 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:15. , LC2 comprise an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:16. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC2 comprising the amino acid sequence of SEQ ID NO:15 and LC2 comprises the amino acid sequence of SEQ ID NO:16.

[0074] Also provided herein are isolated anti-TRGV9 / anti-CD123 bispecific antibodies, or antigen-binding fragments thereof, comprising (a) HC1, (b) HC2, (c) LC1, (d) HC2, HC1 is related to LC1, HC2 is related to LC2, and HC1 is HCDR1, HCDR2, and HCDR3, which comprise the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33, respectively. and LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for a first antigen that specifically binds Vγ9 HC2 comprises HCDR1, HCDR2 and HCDR3 comprising the amino acid sequences of SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11 respectively, and LC2 comprises SEQ ID NO: 12, SEQ ID NO: 13 and SEQ ID NO: 14 respectively to form a binding site for a second antigen that specifically binds to CD123. In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises an amino acid sequence having at least 95% identity to the selected amino acid sequence of SEQ ID NO:36. and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO:36 and LC1 comprises the amino acid sequence of SEQ ID NO:8. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC2 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:15. , LC2 comprise an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:16. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC2 comprising the amino acid sequence of SEQ ID NO:15 and LC2 comprises the amino acid sequence of SEQ ID NO:16.

[0075] Also provided herein are isolated anti-TRGV9 / anti-CD123 bispecific antibodies, or antigen-binding fragments thereof, comprising (a) HC1, (b) HC2, (c) LC1, (d) HC2, HC1 related to LC1, HC2 related to LC2, and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 76, and SEQ ID NO: 3, respectively. and LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:77, SEQ ID NO:5, and SEQ ID NO:6, respectively, to form a binding site for a first antigen that specifically binds Vγ9 HC2 comprises HCDR1, HCDR2 and HCDR3 comprising the amino acid sequences of SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11 respectively, and LC2 comprises SEQ ID NO: 12, SEQ ID NO: 13 and SEQ ID NO: 14 respectively to form a binding site for a second antigen that specifically binds to CD123. In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises an amino acid sequence having at least 95% identity to the selected amino acid sequence of SEQ ID NO:65. and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:66. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO:65 and LC1 comprises the amino acid sequence of SEQ ID NO:66. In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises an amino acid sequence having at least 95% identity to the selected amino acid sequence of SEQ ID NO:67. and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:68. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO:67 and LC1 comprises the amino acid sequence of SEQ ID NO:68. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC2 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:15. , LC2 comprise an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:16. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC2 comprising the amino acid sequence of SEQ ID NO:15 and LC2 comprises the amino acid sequence of SEQ ID NO:16.

[0076] Also provided herein are isolated anti-TRGV9 / anti-CD123 bispecific antibodies, or antigen-binding fragments thereof, comprising (a) HC1, (b) HC2, (c) LC1, (d) HCDR1, HCDR2, and HCDR3, comprising the amino acid sequences of SEQ ID NO: 60, SEQ ID NO: 61, and SEQ ID NO: 62, respectively. and LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:63, SEQ ID NO:64, and SEQ ID NO:65, respectively, to form a binding site for a first antigen that specifically binds Vγ9 HC2 comprises HCDR1, HCDR2 and HCDR3 comprising the amino acid sequences of SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11 respectively, and LC2 comprises SEQ ID NO: 12, SEQ ID NO: 13 and SEQ ID NO: 14 respectively to form a binding site for a second antigen that specifically binds to CD123. In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises an amino acid sequence having at least 95% identity to the selected amino acid sequence of SEQ ID NO:65. and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:66. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO:65 and LC1 comprises the amino acid sequence of SEQ ID NO:66. In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises an amino acid sequence having at least 95% identity to the selected amino acid sequence of SEQ ID NO:67. and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:68. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO:67 and LC1 comprises the amino acid sequence of SEQ ID NO:68. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC2 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:15. , LC2 comprise an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:16. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC2 comprising the amino acid sequence of SEQ ID NO:15 and LC2 comprises the amino acid sequence of SEQ ID NO:16.

[0077] Also provided herein are isolated anti-TRGV9 / anti-CD123 bispecific antibodies, or antigen-binding fragments thereof, comprising (a) HC1, (b) HC2, (c) LC1, (d) HCDR1, HCDR2, and HCDR3, comprising the amino acid sequences of SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, respectively. and LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:92, SEQ ID NO:93, and SEQ ID NO:94, respectively, to form a binding site for a first antigen that specifically binds Vγ9 HC2 comprises HCDR1, HCDR2 and HCDR3 comprising the amino acid sequences of SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11 respectively, and LC2 comprises SEQ ID NO: 12, SEQ ID NO: 13 and SEQ ID NO: 14 respectively to form a binding site for a second antigen that specifically binds to CD123. In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises an amino acid sequence having at least 95% identity to the selected amino acid sequence of SEQ ID NO:95. and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:96. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO:95 and LC1 comprises the amino acid sequence of SEQ ID NO:96. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC2 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:15. , LC2 comprise an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:16. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC2 comprising the amino acid sequence of SEQ ID NO:15 and LC2 comprises the amino acid sequence of SEQ ID NO:16.

[0078] Also provided herein are isolated anti-TRGV9 / anti-CD123 bispecific antibodies, or antigen-binding fragments thereof, comprising (a) HC1, (b) HC2, (c) LC1, (d) LC2, HC1 is related to LC1, HC2 is related to LC2, and HC1 is HCDR1, HCDR2, and HCDR3, which comprise the amino acid sequences of SEQ ID NO: 98, SEQ ID NO: 99, and SEQ ID NO: 100, respectively. and LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 103, respectively, to form a binding site for a first antigen that specifically binds Vγ9 HC2 comprises HCDR1, HCDR2 and HCDR3 comprising the amino acid sequences of SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11 respectively, and LC2 comprises SEQ ID NO: 12, SEQ ID NO: 13 and SEQ ID NO: 14 respectively to form a binding site for a second antigen that specifically binds to CD123. In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises an amino acid sequence having at least 95% identity to the selected amino acid sequence of SEQ ID NO:104. and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:105. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO:104 and LC1 comprises the amino acid sequence of SEQ ID NO:105. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC2 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:15. , LC2 comprise an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:16. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC2 comprising the amino acid sequence of SEQ ID NO:15 and LC2 comprises the amino acid sequence of SEQ ID NO:16.

[0079] Also provided herein are isolated anti-TRGV9 / anti-CD123 bispecific antibodies, or antigen-binding fragments thereof, comprising (a) HC1, (b) HC2, (c) LC1, (d) HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 109, respectively. and LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 110, SEQ ID NO: 111, and SEQ ID NO: 112, respectively, to form a binding site for a first antigen that specifically binds Vγ9 HC2 comprises HCDR1, HCDR2 and HCDR3 comprising the amino acid sequences of SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11 respectively, and LC2 comprises SEQ ID NO: 12, SEQ ID NO: 13 and SEQ ID NO: 14 respectively to form a binding site for a second antigen that specifically binds to CD123. In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises an amino acid sequence having at least 95% identity to the selected amino acid sequence of SEQ ID NO:113. and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:114. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO:113 and LC1 comprises the amino acid sequence of SEQ ID NO:114. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC2 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:15. , LC2 comprise an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:16. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC2 comprising the amino acid sequence of SEQ ID NO:15 and LC2 comprises the amino acid sequence of SEQ ID NO:16.

[0080] Also provided herein are isolated anti-TRGV9 / anti-CD123 bispecific antibodies, or antigen-binding fragments thereof, comprising (a) HC1, (b) HC2, (c) LC1, (d) HC2, HC1 is related to LC1, HC2 is related to LC2, and HC1 is HCDR1, HCDR2, and HCDR3, which comprise the amino acid sequences of SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 119, respectively. and LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 120, SEQ ID NO: 121, and SEQ ID NO: 122, respectively, to form a binding site for a first antigen that specifically binds Vγ9 HC2 comprises HCDR1, HCDR2 and HCDR3 comprising the amino acid sequences of SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11 respectively, and LC2 comprises SEQ ID NO: 12, SEQ ID NO: 13 and SEQ ID NO: 14 respectively to form a binding site for a second antigen that specifically binds to CD123. In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises an amino acid sequence having at least 95% identity to the selected amino acid sequence of SEQ ID NO:123. and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:124. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO:123 and LC1 comprises the amino acid sequence of SEQ ID NO:124. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC2 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:15. , LC2 comprise an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:16. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC2 comprising the amino acid sequence of SEQ ID NO:15 and LC2 comprises the amino acid sequence of SEQ ID NO:16.

[0081] Also provided herein are isolated anti-TRGV9 / anti-CD123 bispecific antibodies, or antigen-binding fragments thereof, comprising (a) HC1, (b) HC2, (c) LC1, (d) LC2, HC1 is related to LC1, HC2 is related to LC2, and HC1 is HCDR1, HCDR2, and HCDR3, which comprise the amino acid sequences of SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 129, respectively. and LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 130, SEQ ID NO: 131, and SEQ ID NO: 132, respectively, to form a binding site for a first antigen that specifically binds to Vγ9 HC2 comprises HCDR1, HCDR2 and HCDR3 comprising the amino acid sequences of SEQ ID NO: 9, SEQ ID NO: 10 and SEQ ID NO: 11 respectively, and LC2 comprises SEQ ID NO: 12, SEQ ID NO: 13 and SEQ ID NO: 14 respectively to form a binding site for a second antigen that specifically binds to CD123. In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises an amino acid sequence having at least 95% identity to the selected amino acid sequence of SEQ ID NO:133. and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:134. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO:133 and LC1 comprises the amino acid sequence of SEQ ID NO:134. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC2 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:15. , LC2 comprise an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:16. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC2 comprising the amino acid sequence of SEQ ID NO:15 and LC2 comprises the amino acid sequence of SEQ ID NO:16.

[0082] In another embodiment, TRGV9 is on the surface of γδ T cells.

[0083] In another embodiment, CD123 is on the surface of tumor cells or CD34+ stem cells.

[0084] In another embodiment, binding of the bispecific antibody to TRGV9 present on the surface of γδ T cells and binding of CD123 on the surface of cancer cells results in robust killing of cancer cells.

[0085] In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof comprises humanized HC1 and humanized LC1.

[0086] In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises humanized HC2 and humanized LC2.

[0087] In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof is of the IgG1, IgG2, IgG3, or IgG4 isotype. In certain embodiments, bispecific antibodies are of the IgG4 isotype.

[0088] In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof has an EC of less than about 500 pM 50 induces γδ T cell-dependent cytotoxicity of cancer cells in vitro.

[0089] In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof has an EC of less than about 300 pM 50 induces γδ T cell-dependent cytotoxicity of cancer cells in vitro.

[0090] In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof has an EC of less than about 160 pM 50 induces γδ T cell-dependent cytotoxicity of cancer cells in vitro.

[0091] In one embodiment, EC 50 is assessed in a mixture of γδ T effector cells and Kasumi3 AML target cells.

[0092] In another embodiment, the ratio of effector cells to target cells is from about 0.01:1 to about 5:1.

[0093] In yet another embodiment, the ratio of effector cells to target cells is from about 0.1:1 to about 2:1.

[0094] In certain embodiments, the ratio of effector cells to target cells is about 1:1.

[0095] Also provided herein is a method of making the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof provided herein, the method comprising: Culturing a cell containing a nucleic acid encoding the anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof under conditions that produce the antigen-binding fragment, and recovering the bispecific antibody or antigen-binding fragment thereof including doing.

[0096] In another aspect, provided herein is an isolated TRGV9 bispecific antibody or antigen epitope binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigen epitope binding fragment thereof comprises a first A binding site for an antigen and a binding site for a second antigen, the binding site for the first antigen binding to a TRGV9 epitope on a γδ T cell and the binding site for the second antigen binding to the surface of a target cell. Binding to the epitope of the second antigen above, binding of the TRGV9 epitope on the γδ T cell and binding of the second antigen epitope on the target cell results in killing of the target cell.

[0097] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises a. HC1 and b. HC2 and c.LC1 and d. including LC2 and HC1 is related to LC1, HC2 is related to LC2, HC1 is i. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively; ii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31, respectively; iii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32, respectively, or iv. HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33, respectively; LC1 comprises LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, respectively, to form a binding site for the first antigen; form binding sites for antigenic epitopes of In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment has at least 95% identity to an amino acid sequence selected from SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36. and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 comprising an amino acid sequence selected from SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36, wherein LC1 comprises the sequence Contains the amino acid sequence of number 8.

[0098] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises (a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1. , HC2 is related to LC2, HC1 comprises HCDR1, HCDR2, and HCDR3, comprising the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively; LC1 comprises SEQ ID NO: 4, sequence No. 5, and LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO: 6 form a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen epitope. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:7, and LC1 is It includes amino acid sequences that have at least 95% identity to the amino acid sequence. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO:7 and LC1 comprises the amino acid sequence of SEQ ID NO:8.

[0099] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises (a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1. , HC2 is related to LC2, HC1 comprises HCDR1, HCDR2, and HCDR3, comprising the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31, respectively; LC1, respectively, SEQ ID NO: 4, sequence No. 5, and LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO: 6 form a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen epitope. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:34, and LC1 is It includes amino acid sequences that have at least 95% identity to the amino acid sequence. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO:34 and LC1 comprising the amino acid sequence of SEQ ID NO:8.

[0100] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises (a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1. , HC2 is related to LC2, HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32, respectively; LC1 comprises SEQ ID NO: 4, sequence No. 5, and LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO: 6 form a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen epitope. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:35, and LC1 is It includes amino acid sequences that have at least 95% identity to the amino acid sequence. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO:35 and LC1 comprising the amino acid sequence of SEQ ID NO:8.

[0101] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises (a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1. , HC2 is related to LC2, HC1 comprises HCDR1, HCDR2, and HCDR3, comprising the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33, respectively; LC1, respectively, SEQ ID NO: 4, sequence No. 5, and LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO: 6 form a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen epitope. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:36, and LC1 comprises It includes amino acid sequences that have at least 95% identity to the amino acid sequence. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO:36 and LC1 comprising the amino acid sequence of SEQ ID NO:8.

[0102] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises (a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1. , HC2 is related to LC2, HC1 comprises HCDR1, HCDR2, and HCDR3, comprising the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 76, and SEQ ID NO: 3, respectively; LC1, respectively, SEQ ID NO: 77, sequence No. 5, and LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO: 6 form a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen epitope. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:65, and LC1 is It includes amino acid sequences that have at least 95% identity to the amino acid sequence. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO:65 and LC1 comprises the amino acid sequence of SEQ ID NO:66. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:67, and LC1 is It includes amino acid sequences that have at least 95% identity to the amino acid sequence. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO:67 and LC1 comprises the amino acid sequence of SEQ ID NO:68.

[0103] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises (a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1. , HC2 is related to LC2, HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 60, SEQ ID NO: 61, and SEQ ID NO: 62, respectively; LC1 comprises SEQ ID NO: 63, sequence No. 64, and LCDR1, LCDR2, and LCDR2 comprising the amino acid sequence of SEQ ID NO:6 form a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen epitope. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:65, and LC1 is It includes amino acid sequences that have at least 95% identity to the amino acid sequence. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO:65 and LC1 comprises the amino acid sequence of SEQ ID NO:66. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:67, and LC1 is It includes amino acid sequences that have at least 95% identity to the amino acid sequence. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO:67 and LC1 comprises the amino acid sequence of SEQ ID NO:68.

[0104] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises (a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1. , HC2 is related to LC2, HC1 comprises HCDR1, HCDR2, and HCDR3, comprising the amino acid sequences of SEQ ID NO:89, SEQ ID NO:90, and SEQ ID NO:91, respectively; LC1, respectively, SEQ ID NO:92, sequence No. 93, and LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO:94 form a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen epitope. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:95, and LC1 is It includes amino acid sequences that have at least 95% identity to the amino acid sequence. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO:95 and LC1 comprises the amino acid sequence of SEQ ID NO:96.

[0105] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises (a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1. , HC2 is related to LC2, HC1 comprises HCDR1, HCDR2, and HCDR3, comprising the amino acid sequences of SEQ ID NO: 98, SEQ ID NO: 99, and SEQ ID NO: 100, respectively; LC1, respectively, SEQ ID NO: 101, sequence No. 102, and LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO: 103 form a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen epitope. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:104, and LC1 is It includes amino acid sequences that have at least 95% identity to the amino acid sequence. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO:104 and LC1 comprises the amino acid sequence of SEQ ID NO:105.

[0106] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises (a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1. , HC2 is related to LC2, HC1 comprises HCDR1, HCDR2, and HCDR3, comprising the amino acid sequences of SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 109, respectively; LC1, respectively, SEQ ID NO: 110, sequence LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of number 111 and SEQ ID NO: 112 form a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen epitope. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:113, and LC1 is It includes amino acid sequences that have at least 95% identity to the amino acid sequence. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO:113 and LC1 comprises the amino acid sequence of SEQ ID NO:114.

[0107] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises (a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1. , HC2 is related to LC2, HC1 comprises HCDR1, HCDR2, and HCDR3, comprising the amino acid sequences of SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 119, respectively; LC1, respectively, SEQ ID NO: 120, sequence LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of No. 121 and SEQ ID NO: 122 form a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen epitope. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:123, and LC1 comprises It includes amino acid sequences that have at least 95% identity to the amino acid sequence. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO:123 and LC1 comprises the amino acid sequence of SEQ ID NO:124.

[0108] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises (a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1. , HC2 is related to LC2, HC1 comprises HCDR1, HCDR2, and HCDR3, comprising the amino acid sequences of SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 129, respectively; LC1, respectively, SEQ ID NO: 130, sequence LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of numbers 131 and SEQ ID NO: 132 form a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen epitope. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:133, and LC1 is It includes amino acid sequences that have at least 95% identity to the amino acid sequence. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO:133 and LC1 comprises the amino acid sequence of SEQ ID NO:134.

[0109] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises humanized HC1 and humanized LC.

[0110] In another embodiment, the TRGV9 bispecific antibody or antigen binding fragment binds to a CD123 epitope.

[0111] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC2 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:15, and LC2 comprises It includes amino acid sequences that have at least 95% identity to the amino acid sequence.

[0112] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC2 comprising the amino acid sequence of SEQ ID NO:15 and LC2 comprises the amino acid sequence of SEQ ID NO:16.

[0113] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof is of IgG1, IgG2, and IgG3, or IgG4 isotypes. In certain embodiments, the bispecific antibody or antigen-binding fragment thereof is of the IgG4 isotype.

[0114] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof has an EC of less than about 500 pM 50 induces γδ T cell-dependent cytotoxicity of cancer cells in vitro.

[0115] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof has an EC of less than about 300 pM 50 induces γδ T cell-dependent cytotoxicity of cancer cells in vitro.

[0116] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof has an EC of less than about 160 pM 50 induces γδ T cell-dependent cytotoxicity of cancer cells in vitro.

[0117] In one embodiment, EC 50 is assessed in a mixture of γδ T effector cells and Kasumi3 AML target cells.

[0118] In another embodiment, the ratio of effector cells to target cells is from about 0.01:1 to about 5:1. In another embodiment, the ratio of effector cells to target cells is from about 0.1:1 to about 2:1. In certain embodiments, the ratio of effector cells to target cells is about 1:1.

[0119] Also provided is an isolated γδ T cell bispecific antibody or antigen-binding fragment thereof, wherein the isolated γδ T cell bispecific antibody or antigen-binding fragment thereof comprises a binding site for a first antigen epitope and a binding site for a second antigen epitope, wherein the binding site for the first antigen epitope binds to the first antigen on the γδ T cell, and the binding site for the second antigen epitope binds to the first antigen on the target cell. Binding to a second antigenic epitope on the surface, binding of the first antigenic epitope on the γδ T cell and binding of the second antigenic epitope on the target cell results in killing of the target cell.

[0120] In another aspect, provided herein is an isolated nucleic acid encoding a TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises: a. HC1 and b. HC2 and c.LC1 and d. including LC2 and HC1 is related to LC1, HC2 is related to LC2, HC1 is i. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively; ii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31, respectively; iii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32, respectively, or iv. HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33, respectively; LC1 comprises LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, respectively, to form a binding site for the first antigen; form the binding site for the antigen of In one embodiment, the isolated nucleic acid comprises HC1 comprising an amino acid sequence having at least 95% identity to an amino acid sequence selected from SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36 Encoding a TRGV9 bispecific antibody, LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8. In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 comprising an amino acid sequence selected from SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36, wherein LC1 is , which contains the amino acid sequence of SEQ ID NO:8.

[0121] In another aspect, provided herein is an isolated nucleic acid encoding a TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises (a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is SEQ ID NO: 1 and SEQ ID NO: respectively. 2, and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:3, and LC1 comprising LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, respectively. , form the binding site for the first antigen, and HC2 and LC2 form the binding site for the second antigen. In one embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:7; containing an amino acid sequence having at least 95% identity to the amino acid sequence of In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 comprising the amino acid sequence of SEQ ID NO:7 and LC1 comprising the amino acid sequence of SEQ ID NO:8.

[0122] In another aspect, provided herein is an isolated nucleic acid encoding a TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises (a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is SEQ ID NO: 1 and SEQ ID NO: respectively. 2, and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 31, and LC1 comprising LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. , form the binding site for the first antigen, and HC2 and LC2 form the binding site for the second antigen. In one embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:34, and LC1 is SEQ ID NO:8 containing an amino acid sequence having at least 95% identity to the amino acid sequence of In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 comprising the amino acid sequence of SEQ ID NO:34 and LC1 comprising the amino acid sequence of SEQ ID NO:8.

[0123] In another aspect, provided herein is an isolated nucleic acid encoding a TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises (a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is SEQ ID NO: 1 and SEQ ID NO: respectively. 2, and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:32, and LC1 comprising LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, respectively. , form the binding site for the first antigen, and HC2 and LC2 form the binding site for the second antigen. In one embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:35; containing an amino acid sequence having at least 95% identity to the amino acid sequence of In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 comprising the amino acid sequence of SEQ ID NO:35 and LC1 comprising the amino acid sequence of SEQ ID NO:8.

[0124] In another aspect, provided herein is an isolated nucleic acid encoding a TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises (a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is SEQ ID NO: 1 and SEQ ID NO: respectively. 2, and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:33, and LC1 comprising LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, respectively. , form the binding site for the first antigen, and HC2 and LC2 form the binding site for the second antigen. In one embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:36, and LC1 is SEQ ID NO:8 containing an amino acid sequence having at least 95% identity to the amino acid sequence of In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 comprising the amino acid sequence of SEQ ID NO:36 and LC1 comprising the amino acid sequence of SEQ ID NO:8.

[0125] In another aspect, provided herein is an isolated nucleic acid encoding a TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises (a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is SEQ ID NO: 1 and SEQ ID NO: respectively. 76, and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 3, and LC1 comprising LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO: 77, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. , form the binding site for the first antigen, and HC2 and LC2 form the binding site for the second antigen. In one embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:65, and LC1 is SEQ ID NO:66 containing an amino acid sequence having at least 95% identity to the amino acid sequence of In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 comprising the amino acid sequence of SEQ ID NO:65 and LC1 comprising the amino acid sequence of SEQ ID NO:66. In one embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:67, and LC1 is SEQ ID NO:68 containing an amino acid sequence having at least 95% identity to the amino acid sequence of In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 comprising the amino acid sequence of SEQ ID NO:67 and LC1 comprising the amino acid sequence of SEQ ID NO:68.

[0126] In another aspect, provided herein is an isolated nucleic acid encoding a TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises (a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is SEQ ID NO: 60 and SEQ ID NO: 60, respectively. HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 61, and SEQ ID NO: 62, and LC1 comprising LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 64, and SEQ ID NO: 6, respectively. , form the binding site for the first antigen, and HC2 and LC2 form the binding site for the second antigen. In one embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:65, and LC1 is SEQ ID NO:66 containing an amino acid sequence having at least 95% identity to the amino acid sequence of In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 comprising the amino acid sequence of SEQ ID NO:65 and LC1 comprising the amino acid sequence of SEQ ID NO:66. In one embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:67, and LC1 is SEQ ID NO:68 containing an amino acid sequence having at least 95% identity to the amino acid sequence of In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 comprising the amino acid sequence of SEQ ID NO:67 and LC1 comprising the amino acid sequence of SEQ ID NO:68.

[0127] In another aspect, provided herein is an isolated nucleic acid encoding a TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises (a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is SEQ ID NO:89 and SEQ ID NO:89, respectively. HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:90 and SEQ ID NO:91, and LC1 comprising LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO:92, SEQ ID NO:93, and SEQ ID NO:94, respectively. , form the binding site for the first antigen, and HC2 and LC2 form the binding site for the second antigen. In one embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:95, and LC1 is SEQ ID NO:96 containing an amino acid sequence having at least 95% identity to the amino acid sequence of In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 comprising the amino acid sequence of SEQ ID NO:95 and LC1 comprising the amino acid sequence of SEQ ID NO:96.

[0128] In another aspect, provided herein is an isolated nucleic acid encoding a TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises (a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is SEQ ID NO:98 and SEQ ID NO:98, respectively. 99, and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 100, and LC1 comprising LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 103, respectively. , form the binding site for the first antigen, and HC2 and LC2 form the binding site for the second antigen. In one embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:104, and LC1 is SEQ ID NO:105 containing an amino acid sequence having at least 95% identity to the amino acid sequence of In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 comprising the amino acid sequence of SEQ ID NO:104 and LC1 comprising the amino acid sequence of SEQ ID NO:105.

[0129] In another aspect, provided herein is an isolated nucleic acid encoding a TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises (a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is SEQ ID NO: 107, SEQ ID NO: 107, respectively. HCDR1, HCDR2 and HCDR3 comprising the amino acid sequences of SEQ ID NO: 108, and SEQ ID NO: 109, and LC1 comprising LCDR1, LCDR2 and LCDR2 comprising the amino acid sequences of SEQ ID NO: 110, SEQ ID NO: 111 and SEQ ID NO: 112, respectively. , form the binding site for the first antigen, and HC2 and LC2 form the binding site for the second antigen. In one embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:113, and LC1 is SEQ ID NO:114 containing an amino acid sequence having at least 95% identity to the amino acid sequence of In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 comprising the amino acid sequence of SEQ ID NO:113 and LC1 comprising the amino acid sequence of SEQ ID NO:114.

[0130] In another aspect, provided herein is an isolated nucleic acid encoding a TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises (a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is SEQ ID NO: 117 and SEQ ID NO: 117, respectively. HCDR1, HCDR2 and HCDR3 comprising the amino acid sequences of SEQ ID NO: 118, and SEQ ID NO: 119, and LC1 comprising LCDR1, LCDR2 and LCDR2 comprising the amino acid sequences of SEQ ID NO: 120, SEQ ID NO: 121 and SEQ ID NO: 122, respectively , form the binding site for the first antigen, and HC2 and LC2 form the binding site for the second antigen. In one embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:123, and LC1 is SEQ ID NO:124 containing an amino acid sequence having at least 95% identity to the amino acid sequence of In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 comprising the amino acid sequence of SEQ ID NO:123 and LC1 comprising the amino acid sequence of SEQ ID NO:124.

[0131] In another aspect, provided herein is an isolated nucleic acid encoding a TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises (a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is SEQ ID NO: 127 and SEQ ID NO: 127, respectively. HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 128, and SEQ ID NO: 129; , form the binding site for the first antigen, and HC2 and LC2 form the binding site for the second antigen. In one embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:133, and LC1 is SEQ ID NO:134 containing an amino acid sequence having at least 95% identity to the amino acid sequence of In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 comprising the amino acid sequence of SEQ ID NO:133 and LC1 comprising the amino acid sequence of SEQ ID NO:134.

[0132] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising a binding site comprising a first antigen that binds TRGV9 on γδ T cells.

[0133] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising a binding site for a second antigen that binds to a cancer antigen present on the surface of cancer cells.

[0134] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody, binding of the bispecific antibody to TRGV9 present on the surface of γδ T cells and cancer present on the surface of cancer cells. Antigen binding results in cancer cell death.

[0135] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody and HC1 and LC1 are humanized.

[0136] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody and HC2 and LC2 bind CD123.

[0137] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody, and the bispecific antibody or antigen-binding fragment thereof is of the IgG1, IgG2, IgG3, or IgG4 isotype.

[0138] In certain embodiments, the bispecific antibody or antigen-binding fragment thereof is of the IgG4 isotype.

[0139] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody, wherein the bispecific antibody or antigen-binding fragment thereof has an EC of less than about 500 pM 50 induces γδ T cell-dependent cytotoxicity of cancer cells in vitro.

[0140] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody, wherein the bispecific antibody or antigen-binding fragment thereof has an EC of less than about 300 pM 50 induces γδ T cell-dependent cytotoxicity of cancer cells in vitro.

[0141] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody, wherein the bispecific antibody or antigen-binding fragment thereof has an EC of less than about 160 pM 50 induces γδ T cell-dependent cytotoxicity of cancer cells in vitro.

[0142] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody and comprises an EC 50 is assessed in a mixture of γδ T effector cells and Kasumi3 AML target cells.

[0143] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody and the effector to target cell ratio is from about 0.01:1 to about 5:1. In one embodiment, the ratio of effector cells to target cells is from about 0.1:1 to about 2:1. In yet another embodiment, the ratio of effector cells to target cells is about 1:1.

[0144] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody, and the bispecific antibody or antigen-binding fragment thereof is multivalent.

[0145] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody, and the bispecific antibody or antigen-binding fragment thereof is capable of binding at least three antigens.

[0146] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody, and the bispecific antibody or antigen-binding fragment thereof is capable of binding at least five antigens.

[0147] Also provided are vectors comprising the isolated nucleic acids provided herein.

[0148] Also provided are host cells containing the vectors provided herein.

[0149] Also provided are kits comprising the vectors provided herein and packaging therefor.

[0150] Pharmaceutical compositions are provided herein, the pharmaceutical compositions comprising (A) an isolated TRGV9 bispecific antibody, or antigen-binding fragment thereof, comprising: a. HC1 and b. HC2 and c.LC1 and d. including LC2 and HC1 related to LC1, HC2 related to LC2, HC1 related to i. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively; ii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31, respectively; iii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32, respectively, or iv. HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33, respectively; LC1 comprises LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for the first antigen; an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof that forms a binding site for the antigen of (B) a pharmaceutically acceptable carrier; In one embodiment, the pharmaceutical composition comprises HC1 comprising an amino acid sequence having at least 95% identity to an amino acid sequence selected from SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36; LC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8. In another embodiment, the pharmaceutical composition comprises HC1 comprising an amino acid sequence selected from SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36 and LC1 comprising the amino acid sequence of SEQ ID NO:8 , including bispecific antibodies.

[0151] Also provided herein is a pharmaceutical composition comprising (A) an isolated TRGV9 bispecific antibody, or an antigen-binding fragment thereof, comprising (a) HC1 and (b) HC2 and (c) LC1 and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively. HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences, wherein LC1 comprises LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively; an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof that forms a binding site, wherein HC2 and LC2 form a binding site for a second antigen; and (B) a pharmaceutically acceptable carrier; including. In one embodiment, the pharmaceutical composition comprises an HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:7 and a HC1 having at least 95% identity to the amino acid sequence of SEQ ID NO:8. and LC1 comprising an amino acid sequence having a bispecific antibody. In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HC1 comprising the amino acid sequence of SEQ ID NO:7 and LC1 comprising the amino acid sequence of SEQ ID NO:8.

[0152] Also provided herein is a pharmaceutical composition comprising (A) an isolated TRGV9 bispecific antibody, or an antigen-binding fragment thereof, comprising (a) HC1 and (b) HC2 and (c) LC1 and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31, respectively. HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences, wherein LC1 comprises LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively; an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof that forms a binding site, wherein HC2 and LC2 form a binding site for a second antigen; and (B) a pharmaceutically acceptable carrier; including. In one embodiment, the pharmaceutical composition comprises an HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:34 and a HC1 having at least 95% identity to the amino acid sequence of SEQ ID NO:8. and LC1 comprising an amino acid sequence having a bispecific antibody. In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HC1 comprising the amino acid sequence of SEQ ID NO:34 and LC1 comprising the amino acid sequence of SEQ ID NO:8.

[0153] Also provided herein is a pharmaceutical composition comprising (A) an isolated TRGV9 bispecific antibody, or an antigen-binding fragment thereof, comprising (a) HC1 and (b) HC2 and (c) LC1 and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32, respectively. HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences, wherein LC1 comprises LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively; an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof that forms a binding site, wherein HC2 and LC2 form a binding site for a second antigen; and (B) a pharmaceutically acceptable carrier; including. In one embodiment, the pharmaceutical composition comprises an HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:35 and a HC1 having at least 95% identity to the amino acid sequence of SEQ ID NO:8. and LC1 comprising an amino acid sequence having a bispecific antibody. In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HC1 comprising the amino acid sequence of SEQ ID NO:35 and LC1 comprising the amino acid sequence of SEQ ID NO:8.

[0154] Also provided herein is a pharmaceutical composition comprising (A) an isolated TRGV9 bispecific antibody, or an antigen-binding fragment thereof, comprising (a) HC1 and (b) HC2 and (c) LC1 and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33, respectively. HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences, wherein LC1 comprises LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively; an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof that forms a binding site, wherein HC2 and LC2 form a binding site for a second antigen; and (B) a pharmaceutically acceptable carrier; including. In one embodiment, the pharmaceutical composition comprises an HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:36 and a HC1 having at least 95% identity to the amino acid sequence of SEQ ID NO:8. and LC1 comprising an amino acid sequence having a bispecific antibody. In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HC1 comprising the amino acid sequence of SEQ ID NO:36 and LC1 comprising the amino acid sequence of SEQ ID NO:8.

[0155] Also provided herein is a pharmaceutical composition comprising (A) an isolated TRGV9 bispecific antibody, or an antigen-binding fragment thereof, comprising (a) HC1 and (b) HC2 and (c) LC1 and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is SEQ ID NO: 1, SEQ ID NO: 76, and SEQ ID NO: 3, respectively. HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences, wherein LC1 comprises LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO: 77, SEQ ID NO: 5, and SEQ ID NO: 6, respectively; an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof that forms a binding site, wherein HC2 and LC2 form a binding site for a second antigen; and (B) a pharmaceutically acceptable carrier; including. In one embodiment, the pharmaceutical composition comprises an HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:65 and a HC1 having at least 95% identity to the amino acid sequence of SEQ ID NO:66. and LC1 comprising an amino acid sequence having a bispecific antibody. In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HC1 comprising the amino acid sequence of SEQ ID NO:65 and LC1 comprising the amino acid sequence of SEQ ID NO:66. In one embodiment, the pharmaceutical composition comprises an HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:67 and a HC1 having at least 95% identity to the amino acid sequence of SEQ ID NO:68. and LC1 comprising an amino acid sequence having a bispecific antibody. In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HC1 comprising the amino acid sequence of SEQ ID NO:67 and LC1 comprising the amino acid sequence of SEQ ID NO:68.

[0156] Also provided herein is a pharmaceutical composition comprising (A) an isolated TRGV9 bispecific antibody, or an antigen-binding fragment thereof, comprising (a) HC1 and (b) HC2 and (c) LC1 and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is SEQ ID NO: 60, SEQ ID NO: 61, and SEQ ID NO: 62, respectively. HCDR1, HCDR2, and HCDR3 comprising amino acid sequences, wherein LC1 comprises LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 64, and SEQ ID NO: 6, respectively; an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof that forms a binding site, wherein HC2 and LC2 form a binding site for a second antigen; and (B) a pharmaceutically acceptable carrier; including. In one embodiment, the pharmaceutical composition comprises an HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:65 and a HC1 having at least 95% identity to the amino acid sequence of SEQ ID NO:66. and LC1 comprising an amino acid sequence having a bispecific antibody. In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HC1 comprising the amino acid sequence of SEQ ID NO:65 and LC1 comprising the amino acid sequence of SEQ ID NO:66. In one embodiment, the pharmaceutical composition comprises an HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:67 and a HC1 having at least 95% identity to the amino acid sequence of SEQ ID NO:68. and LC1 comprising an amino acid sequence having a bispecific antibody. In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HC1 comprising the amino acid sequence of SEQ ID NO:67 and LC1 comprising the amino acid sequence of SEQ ID NO:68.

[0157] Also provided herein is a pharmaceutical composition comprising (A) an isolated TRGV9 bispecific antibody, or an antigen-binding fragment thereof, comprising (a) HC1 and (b) HC2 and (c) LC1 and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, respectively. HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences, wherein LC1 comprises LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO: 92, SEQ ID NO: 93, and SEQ ID NO: 94, respectively; an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof that forms a binding site, wherein HC2 and LC2 form a binding site for a second antigen; and (B) a pharmaceutically acceptable carrier; including. In one embodiment, the pharmaceutical composition comprises an HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:95 and a HC1 having at least 95% identity to the amino acid sequence of SEQ ID NO:96. and LC1 comprising an amino acid sequence having a bispecific antibody. In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HC1 comprising the amino acid sequence of SEQ ID NO:95 and LC1 comprising the amino acid sequence of SEQ ID NO:96.

[0158] Also provided herein is a pharmaceutical composition comprising (A) an isolated TRGV9 bispecific antibody, or an antigen-binding fragment thereof, comprising (a) HC1 and (b) HC2 and (c) LC1 and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is SEQ ID NO: 98, SEQ ID NO: 99, and SEQ ID NO: 100, respectively. HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences, wherein LC1 comprises LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 103, respectively; an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof that forms a binding site, wherein HC2 and LC2 form a binding site for a second antigen; and (B) a pharmaceutically acceptable carrier; including. In one embodiment, the pharmaceutical composition comprises an HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:104 and a HC1 having at least 95% identity to the amino acid sequence of SEQ ID NO:105. and LC1 comprising an amino acid sequence having a bispecific antibody. In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HC1 comprising the amino acid sequence of SEQ ID NO:104 and LC1 comprising the amino acid sequence of SEQ ID NO:105.

[0159] Also provided herein is a pharmaceutical composition comprising (A) an isolated TRGV9 bispecific antibody, or an antigen-binding fragment thereof, comprising (a) HC1 and (b) HC2 and (c) LC1 and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 109, respectively. HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences, wherein LC1 comprises LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO: 110, SEQ ID NO: 111, and SEQ ID NO: 112, respectively; an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof that forms a binding site, wherein HC2 and LC2 form a binding site for a second antigen; and (B) a pharmaceutically acceptable carrier; including. In one embodiment, the pharmaceutical composition comprises an HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:113 and a HC1 having at least 95% identity to the amino acid sequence of SEQ ID NO:114. and LC1 comprising an amino acid sequence having a bispecific antibody. In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HC1 comprising the amino acid sequence of SEQ ID NO:113 and LC1 comprising the amino acid sequence of SEQ ID NO:114.

[0160] Also provided herein is a pharmaceutical composition comprising (A) an isolated TRGV9 bispecific antibody, or an antigen-binding fragment thereof, comprising (a) HC1 and (b) HC2 and (c) LC1 and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 119, respectively. HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences, wherein LC1 comprises LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO: 120, SEQ ID NO: 121, and SEQ ID NO: 122, respectively; an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof that forms a binding site, wherein HC2 and LC2 form a binding site for a second antigen; and (B) a pharmaceutically acceptable carrier; including. In one embodiment, the pharmaceutical composition comprises an HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:123 and a HC1 having at least 95% identity to the amino acid sequence of SEQ ID NO:124. and LC1 comprising an amino acid sequence having a bispecific antibody. In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HC1 comprising the amino acid sequence of SEQ ID NO:123 and LC1 comprising the amino acid sequence of SEQ ID NO:124.

[0161] Also provided herein is a pharmaceutical composition comprising (A) an isolated TRGV9 bispecific antibody, or an antigen-binding fragment thereof, comprising (a) HC1 and (b) HC2 and (c) LC1 and (d) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 129, respectively. HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences, wherein LC1 comprises LCDR1, LCDR2, and LCDR2 comprising the amino acid sequences of SEQ ID NO: 130, SEQ ID NO: 131, and SEQ ID NO: 132, respectively, to a first antigen; an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof that forms a binding site, wherein HC2 and LC2 form a binding site for a second antigen; and (B) a pharmaceutically acceptable carrier; including. In one embodiment, the pharmaceutical composition comprises an HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:133 and a HC1 having at least 95% identity to the amino acid sequence of SEQ ID NO:134. and LC1 comprising an amino acid sequence having a bispecific antibody. In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HC1 comprising the amino acid sequence of SEQ ID NO:133 and LC1 comprising the amino acid sequence of SEQ ID NO:134.

[0162] In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising a binding site for a first antigen that binds TRGV9 on γδ T cells.

[0163] In another embodiment, the pharmaceutical composition comprises a bispecific antibody, wherein the binding site for the second antigen binds to a cancer antigen present on the surface of cancer cells.

[0164] In another embodiment, the pharmaceutical composition comprises a bispecific antibody, wherein binding of the bispecific antibody to TRGV9 present on the surface of γδ T cells and cancer antigen present on the surface of cancer cells Binding results in cancer cell death.

[0165] In another embodiment, the pharmaceutical composition comprises a bispecific antibody and HC1 and LC1 are humanized.

[0166] In another embodiment, the pharmaceutical composition comprises a bispecific antibody, wherein HC2 and LC2 bind CD123.

[0167] In another embodiment, the pharmaceutical composition comprises a bispecific antibody, wherein the bispecific antibody or antigen-binding fragment thereof is of the IgG1, IgG2, IgG3, or IgG4 isotype.

[0168] Also provided are methods of directing Vγ9-expressing γδ T cells to cancer cells, the methods comprising contacting the Vγ9-expressing γδ T cells with a pharmaceutical composition provided herein, wherein the Vγ9-expressing γδ T cells are Contacting with the pharmaceutical composition targets Vγ9-expressing γδ T cells to cancer cells.

[0169] Also provided are methods of inhibiting the growth or proliferation of cancer cells that express cancer antigens on their cell surface, the methods comprising contacting the cancer cells with a pharmaceutical composition provided herein, comprising: with the pharmaceutical composition inhibits cancer cell growth or proliferation.

[0170] In one embodiment, the cancer cell is in the presence of Vγ9-expressing γδ T cells while in contact with the anti-TRGV9 bispecific antibody or antigen-binding fragment thereof.

[0171] Also provided are methods for doing so in a subject in need of treatment for cancer, the methods comprising: a. identifying a subject in need of cancer treatment; b. administering a pharmaceutical composition provided herein to a subject in need thereof; Administering the pharmaceutical composition to a subject in need thereof treats cancer in the subject.

[0172] Also provided is a method of activating Vγ9-expressing γδ T cells, the method comprising contacting the Vγ9-expressing γδ T cells with a pharmaceutical composition provided herein, wherein the Vγ9-expressing γδ T cells are treated with a pharmaceutical composition. Contacting with the substance results in increased CD69, CD25, and / or granzyme B expression compared to control Vγ9-expressing γδ T cells.

[0173] Also provided are methods of producing the pharmaceutical compositions provided herein, the methods comprising combining the bispecific antibody or antigen-binding fragment thereof with a pharmaceutically acceptable carrier to produce the pharmaceutical composition. Including getting. [Brief description of the drawing]

[0174] The foregoing summary, as well as the following detailed description of specific embodiments of the present application, will be better understood when read in conjunction with the accompanying drawings. However, it should be understood that the application is not limited to the precise embodiments shown in the drawings.

Figure 1

Figure 2

[0175] Various publications, articles, and patents are cited or described in the background art and throughout this specification. Each of these references is incorporated herein by reference in its entirety. Discussion of documents, operations, materials, devices, articles, etc. contained herein is intended to provide a context for the invention. Such discussion is not an admission that any or all of these items constitute prior art to any invention disclosed or claimed.

[0176] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Otherwise, certain terms used herein shall have the meanings set forth herein.

[0177] It should be noted that as used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. There is

[0178] Unless otherwise specified, any numerical values, such as concentrations or concentration ranges, recited herein are to be understood in all instances as being modified by the term "about." Accordingly, numerical values ​​typically include ±10% of the stated value. For example, a concentration of 1 mg / mL includes 0.9 mg / mL to 1.1 mg / mL. Similarly, the concentration range of 1%-10% (w / v) includes 0.9% (w / v)-11% (w / v). As used herein, the use of numerical ranges includes all possible subranges, all subranges within the range, including integers and fractions of values ​​within the range, unless the context clearly dictates otherwise. explicitly include the individual numerical values ​​of

[0179] Unless stated otherwise, the term "at least" preceding an element in a series should be understood to refer to all elements in the series. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments described herein. Such equivalents are intended to be encompassed by this invention.

[0180] As used herein, the terms “comprises,” “comprising,” “includes,” “including,” “has,” “having,” "Contains" or "containing" or any other variation thereof is intended to include the stated integer or group of integers, but other than these other integers or exclude integer groups, which are intended to be non-exclusive or non-restrictive. For example, a composition, mixture, process, method, article, or apparatus that includes a set of elements is not necessarily limited to those elements only, and is not explicitly listed or includes such compositions, mixtures, It may include other elements not inherent in the process, method, article, or apparatus. Further, unless expressly stated to the contrary, "or" refers to an inclusive "or" and not to an exclusive "or." For example, the condition A or B is such that if A is true (or exists) and B is false (or does not exist) then A is false (or does not exist) and B is true (or exists ), and if both A and B are true (or exist).

[0181] As used herein, the conjunctive term “and / or” between multiple listed elements is understood to encompass both individual and combined options. For example, when two elements are connected by "and / or," a first alternative refers to the applicability of the first element without the second element. The second option refers to the second element being applicable without the first. A third option refers to the first and second elements being applicable together. Any one of these alternatives is understood to be implied and thus satisfy the requirements of the term "and / or" as used herein. It is understood that the simultaneous applicability of two or more of the alternatives is also included in the meaning and thus satisfies the requirements of the term "and / or".

[0182] As used herein, the term "consists of" or variations such as "consist of" or "consisting of" are used throughout the specification and claims. When , any recited integer or group of integers is included, but indicates that no additional integer or group of integers is added to the specified method, structure, or composition.

[0183] As used herein, the term "consists essentially of" or variations such as "consist essentially of" or "consisting essentially of" when used throughout the specification and claims encompasses any recited integer or group of integers, optionally substantively the basic or novel property of the specified method, structure, or composition. It is also meant to include any recited integer or group of integers that do not vary systematically. See M.P.E.P. §2111.03.

[0184] As used herein, "subject" means any animal, eg, mammal, eg, human. As used herein, the term "mammal" includes any mammal. Examples of mammals include, but are not limited to, cows, horses, sheep, pigs, cats, dogs, mice, rats, rabbits, guinea pigs, monkeys, humans, etc. or, for example, humans.

[0185] The terms “about,” “approximately,” “approximately,” “substantially,” and like terms used herein when referring to dimensions or characteristics of components are understood by those skilled in the art. In addition, it should also be understood that the stated dimensions / features are not exact boundaries or parameters and do not exclude minor deviations from those that are functionally the same or similar. At a minimum, such references involving numerical parameters, using art-accepted mathematical and industrial principles (e.g., rounding, measurement, or other systematic errors, manufacturing tolerances, etc.) The least significant digit will include invariant variations.

[0186] The terms "identical" or "percent identity" refer to two or more nucleic acid or polypeptide sequences (e.g., anti-TRGV9 / anti-cancer associated antigen bispecific antibody and polynucleotide encoding same, Anti-TRGV9 / anti-CD123 bispecific antibody and polynucleotide encoding same, TRGV9 polypeptide and TRGV9 / polynucleotide encoding same, CD123 polypeptide and CD123 polynucleotide encoding same) Relatedly, they are the same, or a certain percentage of the same when compared and aligned for maximum correspondence, as determined using one of the following sequence comparison algorithms or by visual inspection. refers to a sequence or subsequence of two or more amino acid residues or nucleotides that are

[0187] For sequence comparison, typically one sequence acts as a reference sequence, to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are entered into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. The sequence comparison algorithm then calculates the percent sequence identities for the test sequences relative to the reference sequence, based on the specified program parameters.

[0188] Optimal alignment of sequences for comparison can be determined, for example, by the local homology algorithm of Smith & Waterman, Adv. Appl. Math. 2:482 (1981), the homology of Needleman & Wunsch, J. Mol. Biol. USA 85:2444 (1988), computerized implementations of these algorithms (Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., GAP, BESTFIT, FASTA, and TFASTA in Madison, WI) or visual inspection (generally, Current Protocols in Molecular Biology, F.M. Ausubel et al., eds., Current Protocols, a joint venture between Greene Publishing Associates, Inc. and John Wiley & Sons, Inc., (1995 Supplement) (see Ausubel).

[0189] Examples of suitable algorithms for determining percent sequence identity and sequence similarity are Altschul et al. (1990) J. Mol. Biol. 215:403-410, and Altschul et al. (1997) Nucleic Acids. The BLAST and BLAST 2.0 algorithms described in Res. 25:3389-3402, respectively. Software for performing BLAST analyzes is publicly available through the National Center for Biotechnology Information. The algorithm first evaluates the number of words of length W in the query sequence that either match when aligned with words of the same length in the database sequence, or satisfy some positive valued threshold score T. It involves identifying high-scoring sequence pairs (HSPs) by identifying short words. T is referred to as the neighborhood word score threshold (Altschul et al., supra). These initial neighborhood word hits act as seeds for initiating searches to find longer HSPs containing them. Word hits are then extended in both directions along each sequence for as long as the cumulative alignment score can be increased.

[0190] Cumulative scores are calculated using, for nucleotide sequences, the parameters M (reward score for a pair of matching residues; always >0) and N (penalty score for mismatching residues; always <0). For amino acid sequences, a scoring matrix is ​​used to calculate the cumulative score. when the cumulative alignment score drops from its maximum score by an amount X, when accumulation of alignments of one or more negative scoring residues brings the cumulative score below zero, or any sequence Stop extending word hits in each direction when the end of the is reached. The BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment. The BLASTN program (for nucleotide sequences) uses as defaults a wordlength (W) of 11, an expectation of 10, M=5, N=-4, and a comparison of both strands. For amino acid sequences, the BLASTP program uses as defaults a wordlength (W) of 3, an expectation (E) of 10, and the BLOSUM62 scoring matrix (Henikoff & Henikoff, Proc. Natl. Acad. Sci. USA 89:10915). 1989)).

[0191] In addition to calculating percent sequence identity, the BLAST algorithm also performs statistical analysis of the similarity between two sequences (see, eg, Karlin & Altschul, Proc. Nat'l. Acad. Sci. USA 90:5873-5787). 1993)). One measure of similarity provided by the BLAST algorithm is the minimum sum probability (P(N)), which provides an indication of the probability that a match between two nucleotide or amino acid sequences would occur by chance. For example, a nucleic acid is considered similar to a reference sequence if the minimum sum probability of comparing the test nucleic acid to the reference nucleic acid is less than about 0.1, less than about 0.01, or less than about 0.001.

[0192] A further indication that two nucleic acid sequences or polypeptides are substantially identical is that the polypeptide encoded by the first nucleic acid is identical to the polypeptide encoded by the second nucleic acid, as described below. to be immunologically cross-reactive with the peptide. Thus, a polypeptide is typically substantially identical to a second polypeptide, eg, the two peptides differ only by conservative substitutions. Another indication that two nucleic acid sequences are substantially identical is that the two molecules hybridize to each other under stringent conditions.

[0193] As used herein, the term "polynucleotide" is also referred to interchangeably as "nucleic acid molecule", "nucleotide" or "nucleic acid" and is unmodified RNA or DNA or modified RNA or DNA It refers to any polyribonucleotide or polydeoxyribonucleotide. "Polynucleotide" includes, but is not limited to, single- and double-stranded DNA, DNA that is a mixture of single- and double-stranded regions, single- and double-stranded RNA, and RNA that is a mixture of single- and double-stranded regions, hybrids comprising DNA and RNA that may be single-stranded or more typically double-stranded or a mixture of single- and double-stranded regions molecule. In addition, "polynucleotide" refers to triple-stranded regions comprising RNA or DNA or both RNA and DNA. The term polynucleotide also includes DNAs or RNAs containing one or more modified bases and DNAs or RNAs with backbones modified for stability or for other reasons. "Modified" bases include, for example, tritylated bases and unusual bases such as inosine. Various modifications can be made to DNA and RNA. Thus, "polynucleotide" includes chemically, enzymatically, or metabolically modified forms of polynucleotides typically found in nature, as well as chemical forms that have the characteristics of viral and cellular DNA and RNA. . "Polynucleotide" also embraces relatively short nucleic acid strands, often called oligonucleotides.

[0194] As used herein, the term "vector" refers to a replicon into which another nucleic acid segment can be operatively inserted to effect replication or expression of that segment.

[0195] As used herein, the term "host cell" refers to a cell that contains a nucleic acid molecule provided herein. A "host cell" can be any type of cell, eg, a primary cell, a cell in culture, or a cell derived from a cell line. In one embodiment, a "host cell" is a cell transfected with a nucleic acid molecule provided herein. In another embodiment, the "host cell" is the progeny or potential progeny of such a transfected cell. The progeny of a cell may or may not be identical to the parent cell due, for example, to mutations or environmental influences that may occur in subsequent generations, or to integration of nucleic acid molecules into the host cell genome.

[0196] As used herein, the term "expression" refers to the biosynthesis of a gene product. Such terms include transcription of the gene into RNA. Such terms also include translation of RNA into one or more polypeptides and further include all naturally occurring post-transcriptional and post-translational modifications. The bispecific antibody that is expressed can be present in the cytoplasm of the host cell, in an extracellular environment such as the growth medium of a cell culture, or can be anchored to the cell membrane.

[0197] As used herein, the terms "peptide," "polypeptide," or "protein" can refer to molecules composed of amino acids and can be recognized as proteins by those of ordinary skill in the art. The conventional one-letter or three-letter code for amino acid residues is used herein. The terms "peptide," "polypeptide," and "protein" can be used interchangeably herein to refer to polymers of amino acids of any length. The polymer can be linear or branched, can contain modified amino acids, and can be interrupted by non-amino acids. The term also includes amino acid polymers that are naturally modified or modified by intervention. For example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation or modification, such as conjugation with a labeling component. Definitions also include, for example, polypeptides containing one or more analogs of amino acids (including, for example, unnatural amino acids, etc.), as well as other modifications known in the art.

[0198] The peptide sequences described herein are written according to the usual convention, with the N-terminal region of the peptide on the left and the C-terminal region on the right. Isomeric forms of amino acids are known, but unless explicitly indicated otherwise, the L-form of the amino acid is shown.

[0199] antibody Provided herein are anti-TRGV9 antibodies or antigen-binding fragments thereof, nucleic acids and expression vectors encoding the antibodies, recombinant cells containing the vectors, and compositions comprising the antibodies. Also provided herein are anti-TRGV9 bispecific antibodies or antigen-binding fragments thereof, nucleic acids encoding the antibodies and expression vectors, recombinant cells containing the vectors, and compositions comprising the bispecific antibodies. . Also provided are anti-TRGV9 / anti-CD123 bispecific antibodies or antigen-binding fragments thereof, nucleic acids and expression vectors encoding the bispecific antibodies, recombinant cells containing the vectors, and compositions comprising the bispecific antibodies. provided herein. Also provided are methods of making the antibodies and methods of using the antibodies to treat diseases, including cancer. Antibodies disclosed herein have high affinity binding to TRGV9 and / or high affinity binding to CD123, high specificity to TRGV9 and / or high specificity to CD123, and high specificity to TRGV9 and / or high specificity to CD123, and alone or with other anti-cancer therapies. It has one or more desirable functional properties including, but not limited to, the ability to treat or prevent cancer when administered in combination.

[0200] As used herein, the term "antibody" is used broadly and includes antibody molecules and antibody fragments, including human, humanized, composite and chimeric antibodies, which are immunoglobulins or monoclonal or polyclonal. Generally, antibodies are proteins or peptide chains that exhibit binding specificity for a particular antigen. The structure of antibodies is known. Immunoglobulins can be assigned to five major classes (ie, IgA, IgD, IgE, IgG, and IgM) depending on the amino acid sequence of their heavy chain constant domains. IgA and IgG are further subdivided into the isotypes IgA1, IgA2, IgG1, IgG2, IgG3 and IgG4. Thus, the antibodies provided herein can be of any of the five major classes or corresponding subclasses. In certain embodiments, the antibodies provided herein are IgG1. In some embodiments, an antibody provided herein is IgG2. In some embodiments, an antibody provided herein is IgG3. In some embodiments, an antibody provided herein is IgG4. Antibody light chains in vertebrate species can be assigned to one of two distinct types, kappa and lambda, based on the amino acid sequences of their constant domains. Accordingly, the antibodies provided herein may contain a kappa or lambda light chain constant domain. According to certain embodiments, the antibodies provided herein comprise heavy and / or light chain constant regions derived from rat or human antibodies.

[0201] In addition to heavy and light constant domains, antibodies contain antigen-binding regions consisting of a light chain variable region and a heavy chain variable region, each of which has three domains (ie, complementarity determining regions 1-3; CDR1, CDR2 , and CDR3). A "CDR" is one of the three hypervariable regions (HCDR1, HCDR2, or HCDR3) within the non-framework regions of an immunoglobulin (Ig or antibody) VH β-sheet framework, or an antibody VL β-sheet Refers to one of the three hypervariable regions (LCDR1, LCDR2, or LCDR3) within the non-framework regions of the framework. Thus, CDRs are variable region sequences interspersed within framework region sequences. CDR regions are well known to those of skill in the art and have been defined, for example, by Kabat as the most hypervariable regions within antibody variable (V) domains (Kabat et al., J. Biol. Chem. 252 : 6609-6616 (1977), Kabat, Adv. Prot. Chem. 32:1-75 (1978)). CDR region sequences have also been structurally defined by Chothia as residues that are not part of the conserved β-sheet framework and are therefore capable of adapting to different conformations. Chothia and Lesk, J. Mol. Biol. 196:901-917 (1987)). Both terms are well recognized in the art. CDR region sequences are also defined by AbM, Contact, and IMGT. Exemplary CDR region sequences are illustrated herein, eg, in the Sequence Listing and tables provided in the Examples below. The locations of CDRs within canonical antibody variable regions have been determined by the non-nuclear structure of a number of structures (Al-Lazikani et al., J. Mol. Biol. 273:927-948 (1997), Morea et al. , Methods 20:267-279 (2000)). Because the number of residues within hypervariable regions varies in different antibodies, additional residues to canonical positions are conventionally assigned according to the standard variable region numbering scheme (Al-Lazikani et al., supra (1997)). ), followed by a, b, c, and so on. Such nomenclature is well known to those skilled in the art.

[0202] The light chain variable region CDR1 domain is referred to interchangeably herein as LCDR1 or VL CDR1. The light chain variable region CDR2 domain is referred to interchangeably herein as LCDR2 or VL CDR2. Light chain variable region CDR3 domains are referred to interchangeably herein as LCDR3 or VL CDR3. Heavy chain variable region CDR1 domains are referred to herein interchangeably as HCDR1 or VH CDR1. Heavy chain variable region CDR2 domains are referred to interchangeably herein as HCDR2 or VH CDR2. The heavy chain variable region CDR1 domain is referred to interchangeably herein as HCDR3 or VH CDR3.

[0203] As used herein, the term "hypervariable region", such as VH or VL, refers to regions of antibody variable regions that are hypervariable in sequence and / or form structurally defined loops. In general, antibodies contain six hypervariable regions, three of VH (HCDR1, HCDR2, HCDR3) and three of VL (LCDR1, LCDR2, LCDR3). A number of hypervariable region delineations have been used and are encompassed herein. "Kabat" CDRs are based on sequence variability and are the most commonly used (see, e.g., Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda , MD. (1991)). "Chothia" refers instead to the location of structural loops (see, eg, Chothia and Lesk, J. Mol. Biol. 196:901-917 (1987)). The ends of the Chothia CDR-HCDR1 loops when numbered using the Kabat numbering convention vary from H32 to H34 depending on the length of the loop (this is because the Kabat numbering scheme is divided into H35A and H35B). To place the insert, if neither 35A nor 35B is present the loop ends at 32, if only 35A is present the loop ends at 33, if both 35A and 35B are present the loop ends at 34 ). The "AbM" hypervariable regions represent a compromise between the Kabat CDRs and the Chothia structural loops and are used by Oxford Molecular's AbM antibody modeling software (e.g. Martin, in Antibody Engineering, Vol. 2, Chapter 3, Springer See Verlag). "Contact" hypervariable regions are based on analysis of available composite crystal structures.

[0204] Recently, a universal numbering system has been developed and widely adopted (ImMunoGeneTics (IMGT) Information System® (Lafranc et al., Dev. Comp. Immunol. 27(1):55-77 (2003 ))). IMGT is an integrated information system dedicated to immunoglobulin (IG), T cell receptor (TR), and the major histocompatibility complex (MHC) of humans and other vertebrates. . As used herein, CDRs are meant both in terms of amino acid sequence and position in the light or heavy chain. Because the "positions" of CDRs within the structure of immunoglobulin variable domains are conserved among species and occur in structures called loops, a numbering system is used that aligns variable domain sequences according to structural features. CDR and framework residues are readily identified by . This information can be used to graft and replace CDR residues from one species of immunoglobulin into an acceptor framework, typically from a human antibody. A further numbering system (AHon) has been developed by Honegger and Pluckthun, J. Mol. Biol. 309:657-670 (2001). For example, correspondence between numbering systems, including Kabat numbering and IMGT-specific numbering systems, is well known to those of skill in the art (e.g., Kabat, supra, Chothia and Lesk, supra, Martin, supra, Lefranc et al., see above). The exemplary system presented herein combines Kabat and Chothia.

[0205]

table 1

[0206] Hypervariable regions may include "extended hypervariable regions" such as: 24-36 or 24-34 in the VL (LCDR1), 46-56 or 50-56 (LCDR2), and 89-97 or 89-96 (LCDR3), and 26-35 or 26-35A in VH (HCDR1), 50-65 or 49-65 (HCDR2), and 93-102, 94-102, or 95-102 (HCDR3). CDR sequences reflecting each of the above numbering schemes, contained in the sequence listing, are provided herein.

[0207] The term "constant region" or "constant domain" refers to the carboxy-terminal portions of light and heavy chains that are not directly involved in binding an antibody to antigen, but that exhibit various effector functions, such as interaction with Fc receptors. This term refers to portions of immunoglobulin molecules that have more conserved amino acid sequences compared to other portions of immunoglobulins, the variable regions that contain the antigen-binding sites. The constant region may contain the CH1, CH2, and CH3 regions of the heavy chain and the CL region of the light chain.

[0208] The term "framework" or "FR" residues are those variable region residues that flank the CDRs. FR residues are present, for example, in chimeric antibodies, human antibodies, human domain antibodies, diabodies, linear antibodies, and bispecific antibodies. FR residues are variable domain residues other than hypervariable region residues or CDR residues.

[0209] As used herein, the term "isolated antibody" refers to an antibody that is substantially free of other antibodies with different antigenic specificity (e.g., an isolated antibody that specifically binds TRGV9 An isolated antibody that is substantially free of antibodies that do not bind to Vγ9 and that specifically binds CD123 is substantially free of antibodies that do not bind to CD123). Moreover, an isolated antibody is substantially free of other cellular material and / or chemicals.

[0210] As used herein, the term "monoclonal antibody" refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies that make up the population have naturally occurring variations that may be present in minute amounts. are identical except The monoclonal antibodies provided herein can be made by hybridoma technology, phage display technology, single lymphocyte gene cloning technology, or recombinant DNA methods. For example, monoclonal antibodies can be produced by a hybridoma comprising B cells obtained from a transgenic non-human animal such as a transgenic mouse or rat, and having a genome comprising human heavy and light chain transgenes.

[0211] As used herein, the term "antigen-binding fragment" includes e.g. diabodies, Fab, Fab', F(ab')2, Fv fragments, disulfide stabilized Fv fragments (dsFv), (dsFv) 2, bispecific dsFv (dsFv-dsFv'), disulfide stabilized diabodies (ds diabodies), single chain antibody molecules (scFv), single domain antibody (sdAb) scFv dimers (bivalent diabodies), Multispecific antibodies, camelized single domain antibodies, nanobodies, domain antibodies, bivalent domain antibodies formed from a portion of an antibody comprising one or more CDRs, or antigen-binding but intact antibody structures It refers to an antibody fragment, such as any other antibody fragment, not including. An antigen-binding fragment can bind to the same antigen that the parent antibody or parent antibody fragment binds. According to certain embodiments, the antigen binding fragment comprises the light chain variable region, the light chain constant region and the Fd fragment of the heavy chain. According to other particular embodiments, antigen-binding fragments include Fab and F(ab').

[0212] As used herein, the term "single-chain antibody" comprises a heavy chain variable region and a light chain variable region connected by a short peptide of about 15 to about 20 amino acids. refers to antibodies. As used herein, the term "single domain antibody" refers to a conventional single domain antibody in the art comprising a heavy chain variable region and a heavy chain constant region or only a heavy chain variable region. .

[0213] As used herein, the term "human antibody" refers to an antibody produced by a human or an amino acid sequence corresponding to an antibody produced by a human produced using any technique known in the art. refers to an antibody that has This definition of human antibody includes intact or full-length antibodies, fragments thereof, and / or antibodies comprising at least one human heavy and / or light chain polypeptide.

[0214] As used herein, the term "humanized antibody" means that the antigen-binding properties of the antibody are retained, but modifications have been made to increase sequence homology to that of a human antibody such that the antigen is less antigenic in the human body. means a non-human antibody raised against.

[0215] As used herein, the term "chimeric antibody" refers to an antibody in which the amino acid sequences of the immunoglobulin molecule are derived from two or more species. Both the light and heavy chain variable regions are often antibody variables derived from a single species of mammal (e.g., mouse, rat, rabbit, etc.) with the desired specificity, affinity, and potency. The constant region corresponds to the sequence of an antibody from another species of mammal (eg, human) to avoid eliciting an immune response in that species.

[0216] As used herein, the term "multispecific antibody" refers to an antibody comprising a plurality of immunoglobulin variable domain sequences, a first immunoglobulin variable domain sequence of the plurality binding to a first epitope Having specificity, the second immunoglobulin variable domain sequence of the plurality has binding specificity for a second epitope. In certain embodiments, the first and second epitopes are non-overlapping or substantially non-overlapping. In certain embodiments, the first and second epitopes are on different antigens, eg, different proteins (or subunits of different multimeric proteins). In certain embodiments, the multispecific antibody comprises a third, fourth, or fifth immunoglobulin variable domain. In certain embodiments, the multispecific antibody is a bispecific antibody molecule, a trispecific antibody branch, or a tetraspecific antibody molecule.

[0217] As used herein, the term "bispecific antibody" refers to a multispecific antibody that binds no more than two epitopes or no more than two antigens. Bispecific antibodies comprise a first immunoglobulin variable domain sequence with binding specificity for a first epitope (e.g., an epitope on the TRGV9 antigen), and a second epitope (e.g., a tumor-associated antigen (e.g., CD123 It is characterized by a second immunoglobulin variable domain sequence that has binding specificity for an epitope on an antigen). In certain embodiments, the first and second epitopes are on different antigens, eg, different proteins (or subunits of different multimeric proteins). In certain embodiments, a bispecific antibody comprises a heavy chain variable domain sequence and a light chain variable domain sequence with binding specificity for a first epitope and a heavy chain variable domain sequence with binding specificity for a second epitope. and light chain variable domain sequences. In certain embodiments, a bispecific antibody comprises a half-antibody or fragment thereof with binding specificity for a first epitope and a half-antibody or fragment thereof with binding specificity for a second epitope. In certain embodiments, bispecific antibodies comprise an scFv or fragment thereof with binding specificity for a first epitope and an scFv or fragment thereof with binding specificity for a second epitope. In one embodiment, the first epitope is located on TRGV9 and the second epitope is located on CD123. In one embodiment, the first epitope is located on TRGV9 and the second epitope is PD-1, PD-L1, CTLA-4, EGFR, HER-2, CD19, CD20, CD3, and / or others. cancer-associated immunosuppressive factors or surface antigens of

[0218] As used herein, the term "half-antibody" refers to one immunoglobulin heavy chain related to one immunoglobulin light chain. An exemplary half-antibody is shown in SEQ ID NO:17. One skilled in the art will readily appreciate that half-antibodies can include fragments thereof, and can also have an antigen-binding domain consisting of a single variable domain, eg, from Camelidae.

[0219] As used herein, the term "TRGV9" refers to a polypeptide capable of forming a γδ T cell receptor when expressed on the surface of a cell. TRGV9-expressing γδ T cells are the first T cells to develop in the human fetus and are the major γδ T cell subset in healthy adult peripheral blood cells. The term "TRGV9" refers to any TRGV9 variant, isoform, which can be expressed naturally by cells (including T cells) or on cells transfected with a gene or cDNA encoding the polypeptide. Including forms, and species homologues. Unless otherwise specified, TRGV9 is human TRGV9 in certain embodiments. The human TRGV9 amino acid sequence is provided by GenBank Accession No. NG_001336.2.

[0220] The term "CD123" refers to a molecule found on cells that helps signal interleukin-3, a soluble cytokine that is important in the immune system. CD123 may also be referred to as the "interleukin-3 receptor." The receptor belongs to the type I cytokine receptor family and is a heterodimer with a unique alpha chain paired with a common beta subunit (betac or CD131). The CD123 receptor can be found on pluripotent progenitor cells, induce tyrosine phosphorylation within the cell, and promote proliferation and differentiation within hematopoietic cell lines. CD123 can also be expressed in acute myeloid leukemia (AML) subtypes. The term "CD123", unless otherwise specified, can be expressed naturally by cells (including T cells) or on cells transfected with a gene or cDNA encoding the polypeptide, any In certain embodiments, "CD123" is human CD123. The human CD123 amino acid sequence is provided by GenBank Accession No. AY789109.1.

[0221] As used herein, an antibody that "specifically binds to TRGV9" means that TRGV9, e.g., human TRGV9, -7 M or less, e.g., 1 x 10 -8 M or less, 5×10 -9 M or less, 1 x 10 -9 M or less, 5×10 -10 M or less, or 1×10 -10 Refers to antibodies that bind with a KD of M or less. The term "KD" refers to the dissociation constant obtained from the ratio of Kd to Ka (ie, Kd / Ka) and expressed as molarity (M). KD values ​​for antibodies can be determined using methods in the art in view of the present disclosure. For example, the KD of an antibody can be determined by using surface plasmon resonance, such as by using a biosensor system such as the Biacore® system, or using a biolayer interferometry technique such as the Octet RED96 system. can be obtained by

[0222] As used herein, an antigen-binding domain or antigen-binding fragment that "specifically binds to a tumor-associated antigen" refers to a tumor-associated antigen of 1 x 10 -7 M or less, e.g., 1 x 10 -8 M or less, 5×10 -9 M or less, 1 x 10 -9 M or less, 5×10 -10 M or less, or 1×10 -10 Refers to an antigen-binding domain or antigen-binding fragment that binds with a KD of M or less.

[0223] The term "KD" refers to the dissociation constant obtained from the ratio of Kd to Ka (ie, Kd / Ka) and expressed as molarity (M). KD values ​​for antibodies can be determined using methods in the art in view of the present disclosure. For example, the KD of an antigen-binding domain or antigen-binding fragment can be determined by using surface plasmon resonance, such as by using a biosensor system such as the Biacore® system, or a biolayer interface such as the Octet RED96 system. It can be determined by using ferrometry techniques.

[0224] As used herein, an antibody that "specifically binds to CD123" refers to CD123, e.g., human CD123, at 1 x 10 -7 M or less, e.g., 1 x 10 -8 M or less, 5×10 -9 M or less, 1 x 10 -9 M or less, 5×10 -10 M or less, or 1×10 -10 Refers to antibodies that bind with a KD of M or less. The term "KD" refers to the dissociation constant obtained from the ratio of Kd to Ka (ie, Kd / Ka) and expressed as molarity (M). KD values ​​for antibodies can be determined using methods in the art in view of the present disclosure. For example, the KD of an antibody can be determined by using surface plasmon resonance, such as by using a biosensor system such as the Biacore® system, or using a biolayer interferometry technique such as the Octet RED96 system. can be obtained by

[0225] The lower the value of the KD for an antibody, the higher the affinity that antibody binds to its target antigen.

[0226] In one aspect, provided herein are antibodies that bind to TRGV9. In some embodiments, an antibody comprises a heavy chain variable region and a light chain variable region. In some embodiments, the TRGV9 antibody is not a single domain antibody or Nanobody. In some embodiments, the TRGV1 antibody is a humanized antibody.

[0227] In certain embodiments, an antibody comprising the VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 of any one of the antibodies described herein. TRGV9 antibodies are provided herein. In some embodiments, provided herein are anti-TRGV9 antibodies that comprise the VH region of any one of the antibodies described herein. In some embodiments, provided herein are anti-TRGV9 antibodies that comprise the VL region of any one of the antibodies described herein. In some embodiments, an anti-TRGV9 antibody comprising the VH region of any one of the antibodies described herein and the VL region of any one of the antibodies described herein is provided herein. In some embodiments, provided herein are anti-TRGV9 antibodies that comprise the VH CDR1, VH CDR2, and VH CDR3 of any one of the antibodies described herein. In some embodiments, provided herein are anti-TRGV9 antibodies that comprise VL CDR1, VL CDR2, and VL CDR3 of any one of the antibodies described herein. In some embodiments, the VH CDR1, VH CDR2, and VH CDR3 of any one of the antibodies described herein and the VL CDR1 of any one of the antibodies described herein , VL CDR2, and VL CDR3 are provided herein. Representative VH and VL amino acid sequences, including the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the TRGV9 antibodies provided herein, can be found in the Sequence Listing and Tables 1-31. provided to

[0228] In certain embodiments, TRGV9 having the VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 of any one of the antibodies described herein Provided herein are anti-TRGV9 bispecific antibodies comprising a binding domain that binds to. In some embodiments, provided herein is an anti-TRGV9 bispecific antibody comprising a binding domain that binds TRGV9 with the VH region of any one of the antibodies described herein . In some embodiments, provided herein is an anti-TRGV9 bispecific antibody comprising a binding domain that binds TRGV9 with the VL region of any one of the antibodies described herein . In some embodiments, binds TRGV9 having the VH region of any one of the antibodies described herein and the VL region of any one of the antibodies described herein Provided herein are anti-TRGV9 bispecific antibodies comprising a binding domain. In some embodiments, an anti-TRGV9 bispecific antibody comprising a binding domain that binds TRGV9 with VH CDR1, VH CDR2, and VH CDR3 of any one of the antibodies described herein provided. In some embodiments, an anti-TRGV9 bispecific antibody comprising a binding domain that binds TRGV9 having VL CDR1, VL CDR2, and VL CDR3 of any one of the antibodies described herein provided herein. In some embodiments, the VH CDR1, VH CDR2, and VH CDR3 of any one of the antibodies described herein and the VL CDR1, VL of any one of the antibodies described herein Provided herein is an anti-TRGV9 bispecific antibody comprising a binding domain that binds TRGV9 with CDR2 and VL CDR3.

[0229] In certain embodiments, an anti-TRGV9 antibody is a bispecific antibody. In some embodiments, the anti-TRGV9 bispecific antibody comprises the VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or the anti-CD123 antibody provided herein. or a second binding domain that binds CD123 with the VL CDR3. In some embodiments, the anti-TRGV9 bispecific antibody further comprises a second binding domain that binds CD123 with the VH region of an anti-CD123 antibody provided herein. In some embodiments, the anti-TRGV9 bispecific antibody further comprises a second binding domain that binds CD123 with the VL region of an anti-CD123 antibody provided herein. In some embodiments, the anti-TRGV9 bispecific antibody binds CD123 having the VH region of an anti-CD123 antibody provided herein and the VL region of an anti-CD123 antibody provided herein. further comprising a second binding domain. In some embodiments, the anti-TRGV9 bispecific antibody further comprises a second binding domain that binds CD123 having the VH CDR1, VH CDR2, and VH CDR3 of an anti-CD123 antibody provided herein. include. In some embodiments, the anti-TRGV9 bispecific antibody further comprises a second binding domain that binds CD123 having the VL CDR1, VL CDR2, and VL CDR3 of an anti-CD123 antibody provided herein. include. In some embodiments, the anti-TRGV9 bispecific antibody comprises VH CDR1, VH CDR2, and VH CDR3 of an anti-CD123 antibody provided herein and VL of an anti-CD123 antibody provided herein. It further comprises a second binding domain that binds CD123 having CDR1, VL CDR2, and VL CDR3.

[0230] In certain embodiments, anti-TRGV9 antibodies that are intact antibodies are provided. In other embodiments, anti-TRGV9 antibodies are provided, and antigen-binding fragments of anti-TRGV9 antibodies are provided. In some embodiments, an antigen-binding fragment of an anti-TRGV9 antibody is a functional fragment. In some embodiments, the antigen-binding fragment is a diabody. In some embodiments, the antigen binding fragment is a Fab. In some embodiments, the antigen-binding fragment is a Fab'. In some embodiments, the antigen-binding fragment is F(ab')2. In some embodiments, the antigen binding fragment is an Fv fragment. In some embodiments, the antigen binding fragment is a disulfide stabilized Fv fragment (dsFv). In some embodiments, the antigen binding fragment is (dsFv) 2 is. In some embodiments, the antigen-binding fragment is a bispecific dsFv (dsFv-dsFv'). In some embodiments, the antigen-binding fragment is a disulfide-stabilized diabody (ds diabody). In some embodiments, the antigen-binding fragment is a single-chain antibody molecule (scFv). In some embodiments, the antigen-binding fragment is a single domain antibody (sdAb). In some embodiments, the antigen-binding fragment is a scFv dimer (bivalent diabody). In some embodiments, antigen-binding fragments are multispecific antibodies formed from portions of antibodies that contain one or more CDRs. In some embodiments, the antigen-binding fragment is a camelized single domain antibody. In some embodiments, the antigen-binding fragment is a nanobody. In some embodiments, the antigen-binding fragment is a domain antibody. In some embodiments, the antigen binding fragment is a bivalent domain antibody. In some embodiments, an antigen-binding fragment is an antibody fragment that binds antigen but does not include the complete antibody structure.

[0231] In certain embodiments, an anti-TRGV9 antibody comprises a VH region and a VL region. In some embodiments, an anti-TRGV9 antibody is not a single chain antibody. In some embodiments, an anti-TRGV9 antibody is not a single domain antibody. In some embodiments, an anti-TRGV9 antibody is not a Nanobody. In certain embodiments, an anti-TRGV9 antibody is not a VHH antibody. In certain embodiments, the anti-TRGV9 antibody is not a llama antibody. In some embodiments, anti-TRGV9 bispecific antibodies do not comprise single chain antibodies. In some embodiments, anti-TRGV9 bispecific antibodies do not comprise single domain antibodies. In certain embodiments, the anti-TRGV9 bispecific antibody does not comprise a Nanobody. In certain embodiments, anti-TRGV9 bispecific antibodies do not comprise VHH antibodies. In certain embodiments, an anti-TRGV9 bispecific antibody does not comprise a llama antibody. In some embodiments, an anti-TRGV9 antibody is a multispecific antibody. In other embodiments, the anti-TRGV9 antibody is a bispecific antibody. In certain embodiments, multispecific antibodies comprise antigen-binding fragments of anti-TRGV9 antibodies provided herein. In other embodiments, the bispecific antibody comprises an antigen-binding fragment of an anti-TRGV9 antibody provided herein. In some embodiments, the anti-TRGV9 antibody is an agonistic antibody. In certain embodiments, anti-TRGV9 antibodies activate γδ T cells. In other embodiments, the anti-TRGV9 antibody is an antagonist antibody. In certain embodiments, anti-TRGV9 antibodies inactivate γδ T cells. In some embodiments, the anti-TRGV9 antibody blocks γδ T cell activation. In some embodiments, the anti-TRGV9 antibody modulates the activity of γδ T cells. In some embodiments, the anti-TRGV9 antibody neither activates nor inactivates γδ T cell activity. In certain embodiments, the γδ T cells are human γδ T cells. In certain embodiments, bispecific antibodies are provided comprising the TRGV9 antibodies provided herein in knob-in-hole format. In some embodiments, the anti-TRGV9 antibodies provided herein may be included in bispecific antibodies. In some embodiments, the anti-TRGV9 bispecific antibodies provided herein may be included in multispecific antibodies. In certain embodiments, the bispecific antibodies provided herein comprise a first binding domain comprising an anti-TRGV9 antibody provided herein that binds to a first TRGV9 epitope; and a second binding domain comprising an anti-TRGV9 antibody provided herein that binds to a TRGV9 epitope, wherein the first TRGV9 epitope and the second TRGV9 epitope are not the same. In certain embodiments, the TRGV9 antibodies or antigen-binding fragments thereof provided herein specifically bind to TRGV9. In certain embodiments, the TRGV9 antibodies or antigen-binding fragments thereof provided herein do not bind to an epitope of V52.

[0232] In another aspect, provided herein are antibodies that bind to TRGV9, wherein the antibodies are (i) VH CDR1, VH CDR2 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO:34. and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO:8. . In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) a VH CDR1 having the amino acid sequence of SEQ ID NO:1, a VH CDR2 having the amino acid sequence of SEQ ID NO:2, and SEQ ID NO:31; and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 4, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VL CDR3 having the amino acid sequence of SEQ ID NO: 6. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:196, VH CDR2 having the amino acid sequence of SEQ ID NO:197, and SEQ ID NO:198 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 199, VL CDR2 having the amino acid sequence of SEQ ID NO: 200, and VL CDR3 having the amino acid sequence of SEQ ID NO: 201. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:202, VH CDR2 having the amino acid sequence of SEQ ID NO:203, and SEQ ID NO:204 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:205, VL CDR2 having the amino acid sequence of SEQ ID NO:206, and VL CDR3 having the amino acid sequence of SEQ ID NO:207. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:208, VH CDR2 having the amino acid sequence of SEQ ID NO:209, and SEQ ID NO:210 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:211, VL CDR2 having the amino acid sequence of SEQ ID NO:212, and VL CDR3 having the amino acid sequence of SEQ ID NO:213. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:214, VH CDR2 having the amino acid sequence of SEQ ID NO:215, and SEQ ID NO:216 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:217, VL CDR2 having the amino acid sequence of SEQ ID NO:218, and VL CDR3 having the amino acid sequence of SEQ ID NO:219. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:214, VH CDR2 having the amino acid sequence of SEQ ID NO:702, and SEQ ID NO:703 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:217, VL CDR2 having the amino acid sequence of SEQ ID NO:218, and VL CDR3 having the amino acid sequence of SEQ ID NO:219. including, VL and including. In another aspect, provided herein are antibodies that bind to TRGV9, the antibodies comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO:220, VH CDR2 having the amino acid sequence of SEQ ID NO:221, and SEQ ID NO:222 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:223, VL CDR2 having the amino acid sequence of SEQ ID NO:224, and VL CDR3 having the amino acid sequence of SEQ ID NO:225. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:226, VH CDR2 having the amino acid sequence of SEQ ID NO:227, and SEQ ID NO:228. and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:229, VL CDR2 having the amino acid sequence of SEQ ID NO:230, and VL CDR3 having the amino acid sequence of SEQ ID NO:231. including, VL and including. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:34. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO:8. Antibodies include a VH having the amino acid sequence of SEQ ID NO:34 and a VL having the amino acid sequence of SEQ ID NO:8. In some embodiments, the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:34. In some embodiments, the antibody comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8. In some embodiments, the antibody is at least 95% identical to the amino acid sequence of SEQ ID NO:8 with a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:34 and VL, including an amino acid sequence having

[0233] In another aspect, provided herein are antibodies that bind to TRGV9, wherein the antibodies are (i) VH CDR1, VH CDR2 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO:35. and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO:8. . In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) a VH CDR1 having the amino acid sequence of SEQ ID NO:1, a VH CDR2 having the amino acid sequence of SEQ ID NO:2, and SEQ ID NO:32; and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 4, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VL CDR3 having the amino acid sequence of SEQ ID NO: 6. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:232, VH CDR2 having the amino acid sequence of SEQ ID NO:233, and SEQ ID NO:234 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:235, VL CDR2 having the amino acid sequence of SEQ ID NO:236, and VL CDR3 having the amino acid sequence of SEQ ID NO:237. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:238, VH CDR2 having the amino acid sequence of SEQ ID NO:239, and SEQ ID NO:240 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:241, VL CDR2 having the amino acid sequence of SEQ ID NO:242, and VL CDR3 having the amino acid sequence of SEQ ID NO:243. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO:244, VH CDR2 having the amino acid sequence of SEQ ID NO:245, and SEQ ID NO:246 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:247, VL CDR2 having the amino acid sequence of SEQ ID NO:248, and VL CDR3 having the amino acid sequence of SEQ ID NO:249. including, VL and including. In another aspect, provided herein are antibodies that bind to TRGV9, the antibodies comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO:250, VH CDR2 having the amino acid sequence of SEQ ID NO:251, and SEQ ID NO:252 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:253, VL CDR2 having the amino acid sequence of SEQ ID NO:254, and VL CDR3 having the amino acid sequence of SEQ ID NO:255. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:250, VH CDR2 having the amino acid sequence of SEQ ID NO:704, and SEQ ID NO:705 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:253, VL CDR2 having the amino acid sequence of SEQ ID NO:254, and VL CDR3 having the amino acid sequence of SEQ ID NO:255. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:256, VH CDR2 having the amino acid sequence of SEQ ID NO:257, and SEQ ID NO:258. and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:259, VL CDR2 having the amino acid sequence of SEQ ID NO:260, and VL CDR3 having the amino acid sequence of SEQ ID NO:261. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:262, VH CDR2 having the amino acid sequence of SEQ ID NO:263, and SEQ ID NO:264 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:265, VL CDR2 having the amino acid sequence of SEQ ID NO:266, and VL CDR3 having the amino acid sequence of SEQ ID NO:267. including, VL and including. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:35. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO:8. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:35 and a VL having the amino acid sequence of SEQ ID NO:8. In some embodiments, the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:35. In some embodiments, the antibody comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8. In some embodiments, the antibody is at least 95% identical to the amino acid sequence of SEQ ID NO:8 with a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:35 and VL, including an amino acid sequence having

[0234] In another aspect, provided herein are antibodies that bind to TRGV9, wherein the antibodies are (i) VH CDR1, VH CDR2 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO:36. and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO:8. . In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) a VH CDR1 having the amino acid sequence of SEQ ID NO:1, a VH CDR2 having the amino acid sequence of SEQ ID NO:2, and SEQ ID NO:33; and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 4, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VL CDR3 having the amino acid sequence of SEQ ID NO: 6. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:268, VH CDR2 having the amino acid sequence of SEQ ID NO:269, and SEQ ID NO:270 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:271, VL CDR2 having the amino acid sequence of SEQ ID NO:272, and VL CDR3 having the amino acid sequence of SEQ ID NO:273. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO:274, VH CDR2 having the amino acid sequence of SEQ ID NO:275, and SEQ ID NO:276 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:277, VL CDR2 having the amino acid sequence of SEQ ID NO:278, and VL CDR3 having the amino acid sequence of SEQ ID NO:279. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:280, VH CDR2 having the amino acid sequence of SEQ ID NO:281, and SEQ ID NO:282 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:283, VL CDR2 having the amino acid sequence of SEQ ID NO:284, and VL CDR3 having the amino acid sequence of SEQ ID NO:285. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:286, VH CDR2 having the amino acid sequence of SEQ ID NO:287, and SEQ ID NO:288. and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:289, VL CDR2 having the amino acid sequence of SEQ ID NO:290, and VL CDR3 having the amino acid sequence of SEQ ID NO:291. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:286, VH CDR2 having the amino acid sequence of SEQ ID NO:706, and SEQ ID NO:707 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:289, VL CDR2 having the amino acid sequence of SEQ ID NO:290, and VL CDR3 having the amino acid sequence of SEQ ID NO:291. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:292, VH CDR2 having the amino acid sequence of SEQ ID NO:293, and SEQ ID NO:294 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:295, VL CDR2 having the amino acid sequence of SEQ ID NO:296, and VL CDR3 having the amino acid sequence of SEQ ID NO:297. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:298, VH CDR2 having the amino acid sequence of SEQ ID NO:299, and SEQ ID NO:300 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:301, VL CDR2 having the amino acid sequence of SEQ ID NO:302, and VL CDR3 having the amino acid sequence of SEQ ID NO:303. including, VL and including. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:36. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO:8. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:36 and a VL having the amino acid sequence of SEQ ID NO:8. In some embodiments, the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:36. In some embodiments, the antibody comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8. In some embodiments, the antibody is at least 95% identical to the amino acid sequence of SEQ ID NO:8 with a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:36 and VL, including an amino acid sequence having

[0235] In another aspect, provided herein are antibodies that bind to TRGV9, wherein the antibodies are (i) VH CDR1, VH CDR2 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO:65. and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 66. . In another aspect, provided herein are antibodies that bind to TRGV9, wherein the antibodies are (i) VH CDR1, VH CDR2 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO:67. and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 68. . In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:1, VH CDR2 having the amino acid sequence of SEQ ID NO:76, and SEQ ID NO:3. and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 77, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VL CDR3 having the amino acid sequence of SEQ ID NO: 6. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:60, VH CDR2 having the amino acid sequence of SEQ ID NO:61, and SEQ ID NO:62 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 63, VL CDR2 having the amino acid sequence of SEQ ID NO: 64, and VL CDR3 having the amino acid sequence of SEQ ID NO: 6. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:304, VH CDR2 having the amino acid sequence of SEQ ID NO:305, and SEQ ID NO:306 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:307, VL CDR2 having the amino acid sequence of SEQ ID NO:308, and VL CDR3 having the amino acid sequence of SEQ ID NO:309. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:310, VH CDR2 having the amino acid sequence of SEQ ID NO:311, and SEQ ID NO:312 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:313, VL CDR2 having the amino acid sequence of SEQ ID NO:314, and VL CDR3 having the amino acid sequence of SEQ ID NO:315. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO:316, VH CDR2 having the amino acid sequence of SEQ ID NO:317, and SEQ ID NO:318 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:319, VL CDR2 having the amino acid sequence of SEQ ID NO:320, and VL CDR3 having the amino acid sequence of SEQ ID NO:321. including, VL and including. In another aspect, provided herein are antibodies that bind to TRGV9, the antibodies comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO:322, VH CDR2 having the amino acid sequence of SEQ ID NO:323, and SEQ ID NO:324 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:325, VL CDR2 having the amino acid sequence of SEQ ID NO:326, and VL CDR3 having the amino acid sequence of SEQ ID NO:327. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:322, VH CDR2 having the amino acid sequence of SEQ ID NO:708, and SEQ ID NO:709 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:325, VL CDR2 having the amino acid sequence of SEQ ID NO:326, and VL CDR3 having the amino acid sequence of SEQ ID NO:327. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:328, VH CDR2 having the amino acid sequence of SEQ ID NO:329, and SEQ ID NO:330 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:331, VL CDR2 having the amino acid sequence of SEQ ID NO:332, and VL CDR3 having the amino acid sequence of SEQ ID NO:333. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:334, VH CDR2 having the amino acid sequence of SEQ ID NO:335, and SEQ ID NO:336 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:337, VL CDR2 having the amino acid sequence of SEQ ID NO:338, and VL CDR3 having the amino acid sequence of SEQ ID NO:339. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:340, VH CDR2 having the amino acid sequence of SEQ ID NO:341, and SEQ ID NO:342 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:343, VL CDR2 having the amino acid sequence of SEQ ID NO:344, and VL CDR3 having the amino acid sequence of SEQ ID NO:345. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO:346, VH CDR2 having the amino acid sequence of SEQ ID NO:347, and SEQ ID NO:348 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:349, VL CDR2 having the amino acid sequence of SEQ ID NO:350, and VL CDR3 having the amino acid sequence of SEQ ID NO:351. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:352, VH CDR2 having the amino acid sequence of SEQ ID NO:353, and SEQ ID NO:354 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:355, VL CDR2 having the amino acid sequence of SEQ ID NO:356, and VL CDR3 having the amino acid sequence of SEQ ID NO:357. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:358, VH CDR2 having the amino acid sequence of SEQ ID NO:359, and SEQ ID NO:360 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:361, VL CDR2 having the amino acid sequence of SEQ ID NO:362, and VL CDR3 having the amino acid sequence of SEQ ID NO:363. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:358, VH CDR2 having the amino acid sequence of SEQ ID NO:710, and SEQ ID NO:711 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:361, VL CDR2 having the amino acid sequence of SEQ ID NO:362, and VL CDR3 having the amino acid sequence of SEQ ID NO:363. including, VL and including. In another aspect, provided herein are antibodies that bind to TRGV9, the antibodies comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO:364, VH CDR2 having the amino acid sequence of SEQ ID NO:365, and SEQ ID NO:366 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:367, VL CDR2 having the amino acid sequence of SEQ ID NO:368, and VL CDR3 having the amino acid sequence of SEQ ID NO:369. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:370, VH CDR2 having the amino acid sequence of SEQ ID NO:371, and SEQ ID NO:372 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:373, VL CDR2 having the amino acid sequence of SEQ ID NO:374, and VL CDR3 having the amino acid sequence of SEQ ID NO:375. including, VL and including. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:65. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO:66. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:65 and a VL having the amino acid sequence of SEQ ID NO:66. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:67. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO:68. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:67 and a VL having the amino acid sequence of SEQ ID NO:68. In some embodiments, the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO:71. In some embodiments, the antibody comprises a light chain having the amino acid sequence of SEQ ID NO:72. In some embodiments, the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO:71 and a light chain having the amino acid sequence of SEQ ID NO:72. In some embodiments, the antibody comprises the amino acid sequence of SEQ ID NO:70. In some embodiments, the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO:74. In some embodiments, the antibody comprises a light chain having the amino acid sequence of SEQ ID NO:75. In some embodiments, the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO:74 and a light chain having the amino acid sequence of SEQ ID NO:75.In some embodiments, the antibody comprises the amino acid sequence of SEQ ID NO:73. In some embodiments, the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:65. In some embodiments, the antibody comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:66. In some embodiments, the antibody is at least 95% identical to the amino acid sequence of SEQ ID NO:66 with a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:65. and VL, including an amino acid sequence having In some embodiments, the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:67. In some embodiments, the antibody comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:68. In some embodiments, the antibody is at least 95% identical to the amino acid sequence of SEQ ID NO:68 with a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:67 and VL, including an amino acid sequence having In some embodiments, the antibody comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:71. In some embodiments, the antibody comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:72. Including chains. In some embodiments, the antibody is at least 95% identical to the amino acid sequence of SEQ ID NO:72 with a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:71. and a light chain comprising a unique amino acid sequence. In some embodiments, the antibody comprises the amino acid sequence of SEQ ID NO:70. In some embodiments, the antibody comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:74. In some embodiments, the antibody comprises a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:75. In some embodiments, the antibody is at least 95% identical to the amino acid sequence of SEQ ID NO:75 with a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:74. and a light chain comprising a unique amino acid sequence. In some embodiments, the antibody comprises the amino acid sequence of SEQ ID NO:73.

[0236] In another aspect, provided herein are antibodies that bind to TRGV9, wherein the antibodies are (i) VH CDR1, VH CDR2 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 104. and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 105. . In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:98, VH CDR2 having the amino acid sequence of SEQ ID NO:99, and SEQ ID NO:100 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 101, VL CDR2 having the amino acid sequence of SEQ ID NO: 102, and VL CDR3 having the amino acid sequence of SEQ ID NO: 103. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:412, VH CDR2 having the amino acid sequence of SEQ ID NO:413, and SEQ ID NO:414 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:415, VL CDR2 having the amino acid sequence of SEQ ID NO:416, and VL CDR3 having the amino acid sequence of SEQ ID NO:417. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:418, VH CDR2 having the amino acid sequence of SEQ ID NO:419, and SEQ ID NO:420 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:421, VL CDR2 having the amino acid sequence of SEQ ID NO:422, and VL CDR3 having the amino acid sequence of SEQ ID NO:423. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:424, VH CDR2 having the amino acid sequence of SEQ ID NO:425, and SEQ ID NO:426 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:427, VL CDR2 having the amino acid sequence of SEQ ID NO:428, and VL CDR3 having the amino acid sequence of SEQ ID NO:429. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:430, VH CDR2 having the amino acid sequence of SEQ ID NO:431, and SEQ ID NO:432 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:433, VL CDR2 having the amino acid sequence of SEQ ID NO:434, and VL CDR3 having the amino acid sequence of SEQ ID NO:435. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:430, VH CDR2 having the amino acid sequence of SEQ ID NO:714, and SEQ ID NO:715 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:433, VL CDR2 having the amino acid sequence of SEQ ID NO:434, and VL CDR3 having the amino acid sequence of SEQ ID NO:435. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:436, VH CDR2 having the amino acid sequence of SEQ ID NO:437, and SEQ ID NO:438 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:439, VL CDR2 having the amino acid sequence of SEQ ID NO:440, and VL CDR3 having the amino acid sequence of SEQ ID NO:441. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:442, VH CDR2 having the amino acid sequence of SEQ ID NO:443, and SEQ ID NO:444 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:445, VL CDR2 having the amino acid sequence of SEQ ID NO:446, and VL CDR3 having the amino acid sequence of SEQ ID NO:447. including, VL and including. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:104. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO:105. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:104 and a VL having the amino acid sequence of SEQ ID NO:105. In some embodiments, the antibody comprises the amino acid sequence of SEQ ID NO:106. In some embodiments, the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:104. In some embodiments, the antibody comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:105. In some embodiments, the antibody is at least 95% identical to the amino acid sequence of SEQ ID NO:105 with a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:104 and VL, including an amino acid sequence having In some embodiments, the antibody comprises the amino acid sequence of SEQ ID NO:106.

[0237] In another aspect, provided herein are antibodies that bind to TRGV9, wherein the antibodies are (i) VH CDR1, VH CDR2 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 113. and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 114. . In another aspect, provided herein are antibodies that bind to TRGV9, the antibodies comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO:107, VH CDR2 having the amino acid sequence of SEQ ID NO:108, and SEQ ID NO:109 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 110, VL CDR2 having the amino acid sequence of SEQ ID NO: 111, and VL CDR3 having the amino acid sequence of SEQ ID NO: 112. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:448, VH CDR2 having the amino acid sequence of SEQ ID NO:449, and SEQ ID NO:450 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:451, VL CDR2 having the amino acid sequence of SEQ ID NO:452, and VL CDR3 having the amino acid sequence of SEQ ID NO:453. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:454, VH CDR2 having the amino acid sequence of SEQ ID NO:455, and SEQ ID NO:456 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 457, VL CDR2 having the amino acid sequence of SEQ ID NO: 458, and VL CDR3 having the amino acid sequence of SEQ ID NO: 459. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:460, VH CDR2 having the amino acid sequence of SEQ ID NO:461, and SEQ ID NO:462 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:463, VL CDR2 having the amino acid sequence of SEQ ID NO:464, and VL CDR3 having the amino acid sequence of SEQ ID NO:465. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:466, VH CDR2 having the amino acid sequence of SEQ ID NO:467, and SEQ ID NO:468 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:469, VL CDR2 having the amino acid sequence of SEQ ID NO:470, and VL CDR3 having the amino acid sequence of SEQ ID NO:471. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:466, VH CDR2 having the amino acid sequence of SEQ ID NO:716, and SEQ ID NO:717 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:469, VL CDR2 having the amino acid sequence of SEQ ID NO:470, and VL CDR3 having the amino acid sequence of SEQ ID NO:471. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:472, VH CDR2 having the amino acid sequence of SEQ ID NO:473, and SEQ ID NO:474 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:475, VL CDR2 having the amino acid sequence of SEQ ID NO:476, and VL CDR3 having the amino acid sequence of SEQ ID NO:477. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:478, VH CDR2 having the amino acid sequence of SEQ ID NO:479, and SEQ ID NO:480 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:481, VL CDR2 having the amino acid sequence of SEQ ID NO:482, and VL CDR3 having the amino acid sequence of SEQ ID NO:483. including, VL and including. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:113. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO:114. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:113 and a VL having the amino acid sequence of SEQ ID NO:114. In some embodiments, the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO:115. In some embodiments, the antibody comprises a light chain having the amino acid sequence of SEQ ID NO:116. In some embodiments, the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO:115 and a light chain having the amino acid sequence of SEQ ID NO:116. In some embodiments, the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:113. In some embodiments, the antibody comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:114. In some embodiments, the antibody is at least 95% identical to the amino acid sequence of SEQ ID NO:114 with a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:113 and VL, including an amino acid sequence having In some embodiments, the antibody comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:115. In some embodiments, the antibody comprises a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:116. In some embodiments, the antibody is at least 95% identical to the amino acid sequence of SEQ ID NO:116 with a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:115. and a light chain comprising a unique amino acid sequence.

[0238] In another aspect, provided herein are antibodies that bind to TRGV9, wherein the antibodies are (i) VH CDR1, VH CDR2 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 123. and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 124. . In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:117, VH CDR2 having the amino acid sequence of SEQ ID NO:118, and SEQ ID NO:119 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 120, VL CDR2 having the amino acid sequence of SEQ ID NO: 121, and VL CDR3 having the amino acid sequence of SEQ ID NO: 122. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:484, VH CDR2 having the amino acid sequence of SEQ ID NO:485, and SEQ ID NO:486 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:487, VL CDR2 having the amino acid sequence of SEQ ID NO:488, and VL CDR3 having the amino acid sequence of SEQ ID NO:489. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:490, VH CDR2 having the amino acid sequence of SEQ ID NO:491, and SEQ ID NO:492 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:493, VL CDR2 having the amino acid sequence of SEQ ID NO:494, and VL CDR3 having the amino acid sequence of SEQ ID NO:495. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO:496, VH CDR2 having the amino acid sequence of SEQ ID NO:497, and SEQ ID NO:498 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 499, VL CDR2 having the amino acid sequence of SEQ ID NO: 500, and VL CDR3 having the amino acid sequence of SEQ ID NO: 501. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:502, VH CDR2 having the amino acid sequence of SEQ ID NO:503, and SEQ ID NO:504 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:505, VL CDR2 having the amino acid sequence of SEQ ID NO:506, and VL CDR3 having the amino acid sequence of SEQ ID NO:507. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:502, VH CDR2 having the amino acid sequence of SEQ ID NO:718, and SEQ ID NO:719 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:505, VL CDR2 having the amino acid sequence of SEQ ID NO:506, and VL CDR3 having the amino acid sequence of SEQ ID NO:507. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:508, VH CDR2 having the amino acid sequence of SEQ ID NO:509, and SEQ ID NO:510 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:511, VL CDR2 having the amino acid sequence of SEQ ID NO:512, and VL CDR3 having the amino acid sequence of SEQ ID NO:513. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO:514, VH CDR2 having the amino acid sequence of SEQ ID NO:515, and SEQ ID NO:516 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:517, VL CDR2 having the amino acid sequence of SEQ ID NO:518, and VL CDR3 having the amino acid sequence of SEQ ID NO:519. including, VL and including. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:123. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO:124. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:123 and a VL having the amino acid sequence of SEQ ID NO:124. In some embodiments, the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO:125. In some embodiments, the antibody comprises a light chain having the amino acid sequence of SEQ ID NO:126. In some embodiments, the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO:125 and a light chain having the amino acid sequence of SEQ ID NO:126. In some embodiments, the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:123. In some embodiments, the antibody comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:124. In some embodiments, the antibody is at least 95% identical to the amino acid sequence of SEQ ID NO:124 with a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:123 and VL, including an amino acid sequence having In some embodiments, the antibody comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:125. In some embodiments, the antibody comprises a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:126. In some embodiments, the antibody is at least 95% identical to the amino acid sequence of SEQ ID NO:126 with a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:125. and a light chain comprising a unique amino acid sequence.

[0239] In another aspect, provided herein are antibodies that bind to TRGV9, wherein the antibodies are (i) VH CDR1, VH CDR2 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 133. and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 134. . In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:127, VH CDR2 having the amino acid sequence of SEQ ID NO:128, and SEQ ID NO:129 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 130, VL CDR2 having the amino acid sequence of SEQ ID NO: 131, and VL CDR3 having the amino acid sequence of SEQ ID NO: 132. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:520, VH CDR2 having the amino acid sequence of SEQ ID NO:521, and SEQ ID NO:522 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:523, VL CDR2 having the amino acid sequence of SEQ ID NO:524, and VL CDR3 having the amino acid sequence of SEQ ID NO:525. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO:526, VH CDR2 having the amino acid sequence of SEQ ID NO:527, and SEQ ID NO:528 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:529, VL CDR2 having the amino acid sequence of SEQ ID NO:530, and VL CDR3 having the amino acid sequence of SEQ ID NO:531. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:532, VH CDR2 having the amino acid sequence of SEQ ID NO:533, and SEQ ID NO:534 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:535, VL CDR2 having the amino acid sequence of SEQ ID NO:536, and VL CDR3 having the amino acid sequence of SEQ ID NO:537. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:538, VH CDR2 having the amino acid sequence of SEQ ID NO:539, and SEQ ID NO:540 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:541, VL CDR2 having the amino acid sequence of SEQ ID NO:542, and VL CDR3 having the amino acid sequence of SEQ ID NO:543. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:538, VH CDR2 having the amino acid sequence of SEQ ID NO:720, and SEQ ID NO:721 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:541, VL CDR2 having the amino acid sequence of SEQ ID NO:542, and VL CDR3 having the amino acid sequence of SEQ ID NO:543. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO:544, VH CDR2 having the amino acid sequence of SEQ ID NO:545, and SEQ ID NO:546 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:547, VL CDR2 having the amino acid sequence of SEQ ID NO:548, and VL CDR3 having the amino acid sequence of SEQ ID NO:549. including, VL and including. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:550, VH CDR2 having the amino acid sequence of SEQ ID NO:551, and SEQ ID NO:552 and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO:553, VL CDR2 having the amino acid sequence of SEQ ID NO:554, and VL CDR3 having the amino acid sequence of SEQ ID NO:555. including, VL and including. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:133. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO:134. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO:133 and a VL having the amino acid sequence of SEQ ID NO:134. In some embodiments, the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO:135. In some embodiments, the antibody comprises a light chain having the amino acid sequence of SEQ ID NO:136. In some embodiments, the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO:135 and a light chain having the amino acid sequence of SEQ ID NO:136. In some embodiments, the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:133. In some embodiments, the antibody comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:134. In some embodiments, the antibody is at least 95% identical to the amino acid sequence of SEQ ID NO:134 with a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:133 and VL, including an amino acid sequence having In some embodiments, the antibody comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:135. In some embodiments, the antibody comprises a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:136. In some embodiments, the antibody is at least 95% identical to the amino acid sequence of SEQ ID NO:136 with a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:135. and a light chain comprising a unique amino acid sequence.

[0240] In some embodiments, an anti-TRGV9 antibody is not a single chain antibody. In some embodiments, an anti-TRGV9 antibody is not a single domain antibody. In some embodiments, an anti-TRGV9 antibody is not a Nanobody. In certain embodiments, an anti-TRGV9 antibody is not a VHH antibody. In certain embodiments, the anti-TRGV9 antibody is not a llama antibody.

[0241] In some embodiments, the anti-TRGV9 antibodies provided herein do not comprise VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOS:730, 731, and 732, respectively. In some embodiments, the anti-TRGV9 antibodies provided herein do not comprise VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOS:733, 734, and 735, respectively. In some embodiments, the anti-TRGV9 antibodies provided herein do not comprise VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOS:736, 737, and 738, respectively. In some embodiments, the anti-TRGV9 antibodies provided herein do not comprise VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOS:739, 740, and 741, respectively. In some embodiments, the anti-TRGV9 antibodies provided herein do not comprise VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs:742, 743, and 744, respectively. In some embodiments, the anti-TRGV9 antibodies provided herein do not comprise VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs:745, 746, and 747, respectively. In some embodiments, the anti-TRGV9 antibodies provided herein do not comprise VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of SEQ ID NOs:748, 749, and 750, respectively. In some embodiments, an anti-TRGV9 antibody provided herein does not comprise a VH domain having the amino acid sequence of SEQ ID NO:751. In some embodiments, an anti-TRGV9 antibody provided herein does not comprise a VH domain having the amino acid sequence of SEQ ID NO:752. In some embodiments, an anti-TRGV9 antibody provided herein does not comprise a VH domain having the amino acid sequence of SEQ ID NO:753. In some embodiments, an anti-TRGV9 antibody provided herein does not comprise a VH domain having the amino acid sequence of SEQ ID NO:754. In some embodiments, an anti-TRGV9 antibody provided herein does not comprise a VH domain having the amino acid sequence of SEQ ID NO:755. In some embodiments, an anti-TRGV9 antibody provided herein does not comprise a VH domain having the amino acid sequence of SEQ ID NO:756. In some embodiments, an anti-TRGV9 antibody provided herein does not comprise a VH domain having the amino acid sequence of SEQ ID NO:757.

[0242] In another aspect, provided herein is an anti-TRGV9 antibody comprising a VH domain comprising a VH CDR3 having the amino acid sequence of APNxGzYTbDF (SEQ ID NO:758), wherein x is Y or M and z is , M or D, and b is I or L. In another aspect, provided herein is an anti-TRGV9 antibody comprising a VH domain comprising the amino acid sequence of SEQ ID NO:758. In another aspect, provided herein is an anti-TRGV9 antibody comprising a VH domain comprising a VH CDR1 having the amino acid sequence of GxTFzz (SEQ ID NO:761), wherein x is F, D, or G. , z is S or N. In another aspect, provided herein is an anti-TRGV9 antibody comprising a VH domain comprising the amino acid sequence of SEQ ID NO:761. In another aspect, provided herein is an anti-TRGV9 antibody comprising a VL domain comprising a VL CDR1 having the amino acid sequence of RxSQSz (SEQ ID NO:762), wherein x is A or S and Z is , V or L. In another aspect, provided herein is an anti-TRGV9 antibody comprising a VL domain comprising the amino acid sequence of SEQ ID NO:761.

[0243] In another aspect, provided herein are antibodies that bind to TRGV9, wherein the antibodies are (i) VH, including VH CDR1, VH CDR2, and VH CDR3; and (ii) VL CDR1, VL CDR2, and VL. VL, including CDR3. In some embodiments the VH CDR1 comprises a first polar amino acid. In some embodiments, the VH CDR1 includes a final polar uncharged amino acid. In some embodiments the VH CDR1 comprises at least one tyrosine. In some embodiments, the VH CDR1 comprises at least 20% hydrophobic amino acids. In some embodiments the VH CDR1 comprises at least two hydrophobic amino acids. In some embodiments, the VH CDR1 comprises at least about 40% hydrophobic amino acids. In some embodiments, the VH CDR1 comprises: the first polar amino acid, the last polar uncharged amino acid, at least one tyrosine, at least 20% hydrophobic amino acids, at least two hydrophobic amino acids, and at least about 40% hydrophobic amino acids. Any combination of two or more of the above VH CDR1 structural features is also contemplated. In some embodiments, the VH CDR2 comprises a polar amino acid at residue 13. In some embodiments, the VH CDR2 comprises a hydrophobicity at amino acid position 15. In some embodiments, the VH CDR2 comprises phenylalanine (F) or leucine (L) at position 15. In some embodiments, the VH CDR2 comprises a polar amino acid at position 14. In some embodiments, the VH CDR2 comprises a lysine (K) or serine (S) at position 14. In some embodiments, the VH CDR2 comprises a hydrophobic amino acid at position 2. In some embodiments, the VH CDR2 contains a hydrophobic amino acid at position 3. In some embodiments, the VH CDR2 comprises a polar penultimate amino acid. In some embodiments, the VH CDR2 comprises a polar amino acid at residue 13, a hydrophobic amino acid at position 15, phenylalanine (F) or leucine (L) at position 15, a polar amino acid at position 14, lysine (K ) or serine (S), a hydrophobic amino acid at position 2 or 3, and a polar penultimate amino acid. Any combination of two or more of the above VH CDR2 structural features is also contemplated. In some embodiments, the VH CDR3 does not contain a polar charged amino acid at position 3. In some embodiments, the VH CDR3 contains a hydrophobic or polar charged amino acid at position 7. In some embodiments, the VH CDR3 comprises a polar uncharged or hydrophobic amino acid at position 6. In some embodiments, the VH CDR3 does not contain a polar charged amino acid at position 3, a hydrophobic or polar charged amino acid at position 7, and a polar uncharged or hydrophobic amino acid at position 6. Any combination of two or more of the above VH CDR3 structural features is also contemplated. In some embodiments, the VL CDR1 contains a polar amino acid at position 4. In some embodiments, the VL CDR1 comprises a first amino acid that is polar charged. In some embodiments, the VL CDR1 comprises a polar uncharged or hydrophobic amino acid at position 2. In some embodiments, the VL CDR1 comprises a serine at position 3. In some embodiments, the VL CDR1 comprises a polar amino acid at position 5. In some embodiments, the VL CDR1 comprises a hydrophobic amino acid at position 6. In some embodiments, the VL CDR1 comprises a polar amino acid at position 4, the first amino acid that is polar charged, a polar uncharged or hydrophobic amino acid at position 2, a serine at position 3, a polar amino acid at position 5, and 6 containing hydrophobic amino acids. Any combination of two or more of the above VL CDR1 structural features is also contemplated. In some embodiments, the VL CDR2 contains a polar amino acid at position 7. In some embodiments, the VL CDR2 comprises a polar charged or hydrophobic amino acid at position 6. In some embodiments, the VL CDR2 contains a polar charged amino acid at position 3. In some embodiments, the VL CDR2 contains a polar uncharged amino acid at position 4. In some embodiments, the VL CDR2 contains a hydrophobic amino acid at position 2. In some embodiments, the VL CDR2 comprises a polar amino acid at position 7, a polar charged or hydrophobic amino acid at position 6, a polar charged amino acid at position 3, a polar uncharged amino acid at position 4, and a hydrophobic amino acid at position 2. include. Any combination of two or more of the above VL CDR2 structural features is also contemplated. In some embodiments, the VL CDR3 comprises a hydrophobic terminal amino acid. In some embodiments, the VL CDR3 contains a terminal tyrosine. In some embodiments, the VL CDR3 contains a polar uncharged amino acid at position 5. In some embodiments, the VL CDR3 contains a polar amino acid at position 2. In some embodiments, the VL CDR3 comprises a polar uncharged or hydrophobic amino acid at position 1. In some embodiments, the VL CDR3 comprises a hydrophobic amino acid at position 3. In some embodiments, the VL CDR3 comprises a hydrophilic or polar uncharged amino acid at position 6. In some embodiments, the VL CDR3 does not contain a polar or hydrophobic amino acid at position 7. In some embodiments, the VL CDR3 is a hydrophobic terminal amino acid, a terminal tyrosine, a polar uncharged amino acid at position 5, a polar amino acid at position 2, a polar uncharged or hydrophobic amino acid at position 1, a hydrophobic amino acid at position 3. , contains a hydrophilic or polar uncharged amino acid at position 6 and does not contain a polar or hydrophobic amino acid at position 7. Any combination of two or more of the above VL CDR3 structural features is also contemplated. In certain embodiments, residue position numbering follows exemplary numbering.

[0244] In some embodiments, an anti-TRGV9 antibody is a multispecific antibody. In other embodiments, the anti-TRGV9 antibody is a bispecific antibody. In certain embodiments, multispecific antibodies comprise antigen-binding fragments of anti-TRGV9 antibodies provided herein. In some embodiments, the multispecific antibody comprises a first binding domain that binds a first TRGV9 epitope and a second domain that binds a second TRGV9 epitope, wherein the first TRGV9 epitope and The second TRGV9 epitope is different. In certain embodiments, the multispecific antibody further comprises a third binding domain that binds a target that is not TRGV9.

[0245] In another aspect, a bispecific antibody is described herein comprising (a) a first binding domain that binds TRGV9 and (b) a second binding domain that binds a second target that is not TRGV9. provided to

[0246] In some embodiments, bispecific antibodies comprise a heavy chain variable region and a light chain variable region. In some embodiments, the first binding domain comprises a heavy chain variable region and a light chain variable region. In some embodiments, the second binding domain comprises a heavy chain variable region and a light chain variable region. In some embodiments, the first binding domain comprises a heavy chain variable region and a light chain variable region and the second binding domain comprises a heavy chain variable region and a light chain variable region. In some embodiments, the TRGV9 antibody is not a single domain antibody or Nanobody.

[0247] In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 7; and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO:8. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 3 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:4, a VL CDR2 having the amino acid sequence of SEQ ID NO:5, and a VL CDR3 having the amino acid sequence of SEQ ID NO:6. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 160, VH CDR2 having the amino acid sequence of SEQ ID NO: 161, and VH CDR3 having the amino acid sequence of SEQ ID NO: 162 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:163, a VL CDR2 having the amino acid sequence of SEQ ID NO:164, and a VL CDR3 having the amino acid sequence of SEQ ID NO:165. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 166, VH CDR2 having the amino acid sequence of SEQ ID NO: 167, and VH CDR3 having the amino acid sequence of SEQ ID NO: 168 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:169, a VL CDR2 having the amino acid sequence of SEQ ID NO:170, and a VL CDR3 having the amino acid sequence of SEQ ID NO:171. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 172, VH CDR2 having the amino acid sequence of SEQ ID NO: 173, and VH CDR3 having the amino acid sequence of SEQ ID NO: 174 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:175, a VL CDR2 having the amino acid sequence of SEQ ID NO:176, and a VL CDR3 having the amino acid sequence of SEQ ID NO:177. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 178, VH CDR2 having the amino acid sequence of SEQ ID NO: 179, and VH CDR3 having the amino acid sequence of SEQ ID NO: 180 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:181, a VL CDR2 having the amino acid sequence of SEQ ID NO:182, and a VL CDR3 having the amino acid sequence of SEQ ID NO:183. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 178, VH CDR2 having the amino acid sequence of SEQ ID NO: 700, and VH CDR3 having the amino acid sequence of SEQ ID NO: 701 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:181, a VL CDR2 having the amino acid sequence of SEQ ID NO:182, and a VL CDR3 having the amino acid sequence of SEQ ID NO:183. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 184, VH CDR2 having the amino acid sequence of SEQ ID NO: 185, and VH CDR3 having the amino acid sequence of SEQ ID NO: 186 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:187, a VL CDR2 having the amino acid sequence of SEQ ID NO:188, and a VL CDR3 having the amino acid sequence of SEQ ID NO:189. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 190, VH CDR2 having the amino acid sequence of SEQ ID NO: 191, and VH CDR3 having the amino acid sequence of SEQ ID NO: 192 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:193, a VL CDR2 having the amino acid sequence of SEQ ID NO:194, and a VL CDR3 having the amino acid sequence of SEQ ID NO:195. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:7. In some embodiments, the first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:8. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:7 and a VL having the amino acid sequence of SEQ ID NO:8. In some embodiments, the first binding domain comprises a heavy chain having the amino acid sequence of SEQ ID NO:23. In some embodiments, the first binding domain comprises a light chain having the amino acid sequence of SEQ ID NO:24. In some embodiments, the first binding domain comprises a heavy chain having the amino acid sequence of SEQ ID NO:23 and a light chain having the amino acid sequence of SEQ ID NO:24. In some embodiments, the first binding domain comprises the amino acid sequence of SEQ ID NO:17. In some embodiments, the first binding domain comprises a heavy chain having the amino acid sequence of SEQ ID NO:69. In some embodiments, the first binding domain comprises a light chain having the amino acid sequence of SEQ ID NO:24. In some embodiments, the first binding domain comprises a heavy chain having the amino acid sequence of SEQ ID NO:69 and a light chain having the amino acid sequence of SEQ ID NO:24. In some embodiments, the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:7. In some embodiments, the first binding domain comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8. In some embodiments, the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:7 and at least 95% to the amino acid sequence of SEQ ID NO:8. VL, which contains amino acid sequences with % identity. In some embodiments, the first binding domain comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:23. In some embodiments, the first binding domain comprises a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:24. In some embodiments, the first binding domain comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:23 and at least the amino acid sequence of SEQ ID NO:24. A light chain comprising an amino acid sequence with 95% identity. In some embodiments, the first binding domain comprises the amino acid sequence of SEQ ID NO:17. In some embodiments, the first binding domain comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:69. In some embodiments, the first binding domain comprises a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:24. In some embodiments, the first binding domain comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:69 and at least A light chain comprising an amino acid sequence with 95% identity.

[0248] In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 34; and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO:8. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 31 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:4, a VL CDR2 having the amino acid sequence of SEQ ID NO:5, and a VL CDR3 having the amino acid sequence of SEQ ID NO:6. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 196, VH CDR2 having the amino acid sequence of SEQ ID NO: 197, and VH CDR3 having the amino acid sequence of SEQ ID NO: 198 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:199, a VL CDR2 having the amino acid sequence of SEQ ID NO:200, and a VL CDR3 having the amino acid sequence of SEQ ID NO:201. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:202, VH CDR2 having the amino acid sequence of SEQ ID NO:203, and VH CDR3 having the amino acid sequence of SEQ ID NO:204 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:205, a VL CDR2 having the amino acid sequence of SEQ ID NO:206, and a VL CDR3 having the amino acid sequence of SEQ ID NO:207. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:208, VH CDR2 having the amino acid sequence of SEQ ID NO:209, and VH CDR3 having the amino acid sequence of SEQ ID NO:210 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:211, a VL CDR2 having the amino acid sequence of SEQ ID NO:212, and a VL CDR3 having the amino acid sequence of SEQ ID NO:213. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:214, VH CDR2 having the amino acid sequence of SEQ ID NO:215, and VH CDR3 having the amino acid sequence of SEQ ID NO:216 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:217, a VL CDR2 having the amino acid sequence of SEQ ID NO:218, and a VL CDR3 having the amino acid sequence of SEQ ID NO:219. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:214, VH CDR2 having the amino acid sequence of SEQ ID NO:702, and VH CDR3 having the amino acid sequence of SEQ ID NO:703 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:217, a VL CDR2 having the amino acid sequence of SEQ ID NO:218, and a VL CDR3 having the amino acid sequence of SEQ ID NO:219. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:220, VH CDR2 having the amino acid sequence of SEQ ID NO:221, and VH CDR3 having the amino acid sequence of SEQ ID NO:222 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:223, a VL CDR2 having the amino acid sequence of SEQ ID NO:224, and a VL CDR3 having the amino acid sequence of SEQ ID NO:225. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:226, VH CDR2 having the amino acid sequence of SEQ ID NO:227, and VH CDR3 having the amino acid sequence of SEQ ID NO:228 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:229, a VL CDR2 having the amino acid sequence of SEQ ID NO:230, and a VL CDR3 having the amino acid sequence of SEQ ID NO:231. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:34. In some embodiments, the first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:8. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:34 and a VL having the amino acid sequence of SEQ ID NO:8. In some embodiments, the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:34. In some embodiments, the first binding domain comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8. In some embodiments, the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:34 and at least 95% of the amino acid sequence of SEQ ID NO:8. VL, which contains amino acid sequences with % identity.

[0249] In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 35; and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO:8. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 32 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:4, a VL CDR2 having the amino acid sequence of SEQ ID NO:5, and a VL CDR3 having the amino acid sequence of SEQ ID NO:6. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:232, VH CDR2 having the amino acid sequence of SEQ ID NO:233, and VH CDR3 having the amino acid sequence of SEQ ID NO:234 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:235, a VL CDR2 having the amino acid sequence of SEQ ID NO:236, and a VL CDR3 having the amino acid sequence of SEQ ID NO:237. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:238, VH CDR2 having the amino acid sequence of SEQ ID NO:239, and VH CDR3 having the amino acid sequence of SEQ ID NO:240 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:241, a VL CDR2 having the amino acid sequence of SEQ ID NO:242, and a VL CDR3 having the amino acid sequence of SEQ ID NO:243. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:244, VH CDR2 having the amino acid sequence of SEQ ID NO:245, and VH CDR3 having the amino acid sequence of SEQ ID NO:246 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:247, a VL CDR2 having the amino acid sequence of SEQ ID NO:248, and a VL CDR3 having the amino acid sequence of SEQ ID NO:249. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:250, VH CDR2 having the amino acid sequence of SEQ ID NO:251, and VH CDR3 having the amino acid sequence of SEQ ID NO:252 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:253, a VL CDR2 having the amino acid sequence of SEQ ID NO:254, and a VL CDR3 having the amino acid sequence of SEQ ID NO:255. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:250, VH CDR2 having the amino acid sequence of SEQ ID NO:704, and VH CDR3 having the amino acid sequence of SEQ ID NO:705 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:253, a VL CDR2 having the amino acid sequence of SEQ ID NO:254, and a VL CDR3 having the amino acid sequence of SEQ ID NO:255. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:256, VH CDR2 having the amino acid sequence of SEQ ID NO:257, and VH CDR3 having the amino acid sequence of SEQ ID NO:258 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:259, a VL CDR2 having the amino acid sequence of SEQ ID NO:260, and a VL CDR3 having the amino acid sequence of SEQ ID NO:261. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:262, VH CDR2 having the amino acid sequence of SEQ ID NO:263, and VH CDR3 having the amino acid sequence of SEQ ID NO:264 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:265, a VL CDR2 having the amino acid sequence of SEQ ID NO:266, and a VL CDR3 having the amino acid sequence of SEQ ID NO:267. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:35. In some embodiments, the first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:8. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:35 and a VL having the amino acid sequence of SEQ ID NO:8. In some embodiments, the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:35. In some embodiments, the first binding domain comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8. In some embodiments, the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:35 and at least 95% of the amino acid sequence of SEQ ID NO:8. VL, which contains amino acid sequences with % identity.

[0250] In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 36; and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO:8. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 33 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:4, a VL CDR2 having the amino acid sequence of SEQ ID NO:5, and a VL CDR3 having the amino acid sequence of SEQ ID NO:6. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:268, VH CDR2 having the amino acid sequence of SEQ ID NO:269, and VH CDR3 having the amino acid sequence of SEQ ID NO:270 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:271, a VL CDR2 having the amino acid sequence of SEQ ID NO:272, and a VL CDR3 having the amino acid sequence of SEQ ID NO:273. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:274, VH CDR2 having the amino acid sequence of SEQ ID NO:275, and VH CDR3 having the amino acid sequence of SEQ ID NO:276 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:277, a VL CDR2 having the amino acid sequence of SEQ ID NO:278, and a VL CDR3 having the amino acid sequence of SEQ ID NO:279. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:280, VH CDR2 having the amino acid sequence of SEQ ID NO:281, and VH CDR3 having the amino acid sequence of SEQ ID NO:282 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:283, a VL CDR2 having the amino acid sequence of SEQ ID NO:284, and a VL CDR3 having the amino acid sequence of SEQ ID NO:285. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:286, VH CDR2 having the amino acid sequence of SEQ ID NO:287, and VH CDR3 having the amino acid sequence of SEQ ID NO:288 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:289, a VL CDR2 having the amino acid sequence of SEQ ID NO:290, and a VL CDR3 having the amino acid sequence of SEQ ID NO:291. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:286, VH CDR2 having the amino acid sequence of SEQ ID NO:706, and VH CDR3 having the amino acid sequence of SEQ ID NO:707 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:289, a VL CDR2 having the amino acid sequence of SEQ ID NO:290, and a VL CDR3 having the amino acid sequence of SEQ ID NO:291. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:292, VH CDR2 having the amino acid sequence of SEQ ID NO:293, and VH CDR3 having the amino acid sequence of SEQ ID NO:294 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:295, a VL CDR2 having the amino acid sequence of SEQ ID NO:296, and a VL CDR3 having the amino acid sequence of SEQ ID NO:297. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:298, VH CDR2 having the amino acid sequence of SEQ ID NO:299, and VH CDR3 having the amino acid sequence of SEQ ID NO:300 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:301, a VL CDR2 having the amino acid sequence of SEQ ID NO:302, and a VL CDR3 having the amino acid sequence of SEQ ID NO:303. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:36. In some embodiments, the first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:8. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:36 and a VL having the amino acid sequence of SEQ ID NO:8. In some embodiments, the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:36. In some embodiments, the first binding domain comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8. In some embodiments, the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:36 and at least 95% of the amino acid sequence of SEQ ID NO:8. VL, which contains amino acid sequences with % identity.

[0251] In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 65; and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO:66. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 67; and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO:68. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 76, and VH CDR3 having the amino acid sequence of SEQ ID NO: 3 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:77, a VL CDR2 having the amino acid sequence of SEQ ID NO:5, and a VL CDR3 having the amino acid sequence of SEQ ID NO:6. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 60, VH CDR2 having the amino acid sequence of SEQ ID NO: 61, and VH CDR3 having the amino acid sequence of SEQ ID NO: 62 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:63, a VL CDR2 having the amino acid sequence of SEQ ID NO:64, and a VL CDR3 having the amino acid sequence of SEQ ID NO:6. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:304, VH CDR2 having the amino acid sequence of SEQ ID NO:305, and VH CDR3 having the amino acid sequence of SEQ ID NO:306 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:307, a VL CDR2 having the amino acid sequence of SEQ ID NO:308, and a VL CDR3 having the amino acid sequence of SEQ ID NO:309. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:310, VH CDR2 having the amino acid sequence of SEQ ID NO:311, and VH CDR3 having the amino acid sequence of SEQ ID NO:312 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:313, a VL CDR2 having the amino acid sequence of SEQ ID NO:314, and a VL CDR3 having the amino acid sequence of SEQ ID NO:315. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:316, VH CDR2 having the amino acid sequence of SEQ ID NO:317, and VH CDR3 having the amino acid sequence of SEQ ID NO:318 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:319, a VL CDR2 having the amino acid sequence of SEQ ID NO:320, and a VL CDR3 having the amino acid sequence of SEQ ID NO:321. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:322, VH CDR2 having the amino acid sequence of SEQ ID NO:323, and VH CDR3 having the amino acid sequence of SEQ ID NO:324 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:325, a VL CDR2 having the amino acid sequence of SEQ ID NO:326, and a VL CDR3 having the amino acid sequence of SEQ ID NO:327. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:322, VH CDR2 having the amino acid sequence of SEQ ID NO:708, and VH CDR3 having the amino acid sequence of SEQ ID NO:709 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:325, a VL CDR2 having the amino acid sequence of SEQ ID NO:326, and a VL CDR3 having the amino acid sequence of SEQ ID NO:327. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:328, VH CDR2 having the amino acid sequence of SEQ ID NO:329, and VH CDR3 having the amino acid sequence of SEQ ID NO:330 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:331, a VL CDR2 having the amino acid sequence of SEQ ID NO:332, and a VL CDR3 having the amino acid sequence of SEQ ID NO:333. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:334, VH CDR2 having the amino acid sequence of SEQ ID NO:335, and VH CDR3 having the amino acid sequence of SEQ ID NO:336 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:337, a VL CDR2 having the amino acid sequence of SEQ ID NO:338, and a VL CDR3 having the amino acid sequence of SEQ ID NO:339. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:340, VH CDR2 having the amino acid sequence of SEQ ID NO:341, and VH CDR3 having the amino acid sequence of SEQ ID NO:342 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:343, a VL CDR2 having the amino acid sequence of SEQ ID NO:344, and a VL CDR3 having the amino acid sequence of SEQ ID NO:345. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:346, VH CDR2 having the amino acid sequence of SEQ ID NO:347, and VH CDR3 having the amino acid sequence of SEQ ID NO:348 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:349, a VL CDR2 having the amino acid sequence of SEQ ID NO:350, and a VL CDR3 having the amino acid sequence of SEQ ID NO:351. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:352, VH CDR2 having the amino acid sequence of SEQ ID NO:353, and VH CDR3 having the amino acid sequence of SEQ ID NO:354 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:355, a VL CDR2 having the amino acid sequence of SEQ ID NO:356, and a VL CDR3 having the amino acid sequence of SEQ ID NO:357. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:358, VH CDR2 having the amino acid sequence of SEQ ID NO:359, and VH CDR3 having the amino acid sequence of SEQ ID NO:360 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:361, a VL CDR2 having the amino acid sequence of SEQ ID NO:362, and a VL CDR3 having the amino acid sequence of SEQ ID NO:363.In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:358, VH CDR2 having the amino acid sequence of SEQ ID NO:710, and VH CDR3 having the amino acid sequence of SEQ ID NO:711 and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO:361, a VL CDR2 having the amino acid sequence of SEQ ID NO:362, and a VL CDR3 having the amino acid sequence of SEQ ID NO:363. In another aspect, bispecific antibodies are provided herein, wherein the antibody comprises (a) a first binding domain that binds TRGV9 and (b) a second target that binds to a second target that is not TRGV9. wherein the first binding domain comprises (i) VH CDR1 having the amino acid sequence of SEQ ID NO:364, VH CDR2 having the amino acid se...

Claims

1. An antibody that binds to T cell receptor gamma variable 9 (TRGV9), the antibody comprising a heavy chain variable region (VH) and a light chain variable region (VL).

2. The antibody (i) a VH comprising a VH complementarity determining region (CDR) 1 having the amino acid sequence of SEQ ID NO: 1, a VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 31; (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 4, a VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and a VL CDR3 having the amino acid sequence of SEQ ID NO:

6.

3. The antibody of claim 2, wherein the antibody comprises a VH having the amino acid sequence of SEQ ID NO:

34.

4. The antibody of claim 2, wherein the antibody comprises a VL having the amino acid sequence of SEQ ID NO:

8.

5. The antibody of claim 2, wherein the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 34 and a VL having the amino acid sequence of SEQ ID NO:

8.

6. The antibody (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 1, a VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 32; (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 4, a VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and a VL CDR3 having the amino acid sequence of SEQ ID NO:

6.

7. The antibody of claim 6, wherein the antibody comprises a VH having the amino acid sequence of SEQ ID NO:

35.

8. The antibody of claim 6, wherein the antibody comprises a VL having the amino acid sequence of SEQ ID NO:

8.

9. The antibody of claim 6, wherein the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 35 and a VL having the amino acid sequence of SEQ ID NO:

8.

10. The antibody (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 1, a VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 33; (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 4, a VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and a VL CDR3 having the amino acid sequence of SEQ ID NO:

6.

11. The antibody of claim 10, wherein the antibody comprises a VH having the amino acid sequence of SEQ ID NO:

36.

12. The antibody of claim 10, wherein the antibody comprises a VL having the amino acid sequence of SEQ ID NO:

8.

13. The antibody of claim 10, wherein the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 36 and a VL having the amino acid sequence of SEQ ID NO:

8.

14. The antibody (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 1, a VH CDR2 having the amino acid sequence of SEQ ID NO: 76, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 3; (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 77, a VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and a VL CDR3 having the amino acid sequence of SEQ ID NO:

6.

15. The antibody (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 60, a VH CDR2 having the amino acid sequence of SEQ ID NO: 61, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 62; (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 63, a VL CDR2 having the amino acid sequence of SEQ ID NO: 64, and a VL CDR3 having the amino acid sequence of SEQ ID NO:

6.

16. The antibody of claim 14 or 15, wherein the antibody comprises a VH having the amino acid sequence of SEQ ID NO:

65.

17. The antibody of claim 14 or 15, wherein the antibody comprises a VL having the amino acid sequence of SEQ ID NO:

66.

18. The antibody of claim 14 or 15, wherein the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 65 and a VL having the amino acid sequence of SEQ ID NO:

66.

19. The antibody of claim 14 or 15, wherein the antibody comprises a VH having the amino acid sequence of SEQ ID NO:

67.

20. The antibody of claim 14 or 15, wherein the antibody comprises a VL having the amino acid sequence of SEQ ID NO:

68.

21. The antibody of claim 14 or 15, wherein the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 67 and a VL having the amino acid sequence of SEQ ID NO:

68.

22. The antibody (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 98, a VH CDR2 having the amino acid sequence of SEQ ID NO: 99, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 100; (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 101, a VL CDR2 having the amino acid sequence of SEQ ID NO: 102, and a VL CDR3 having the amino acid sequence of SEQ ID NO:

103.

23. The antibody of claim 22, wherein the antibody comprises a VH having the amino acid sequence of SEQ ID NO:

104.

24. The antibody of claim 22, wherein the antibody comprises a VL having the amino acid sequence of SEQ ID NO:

105.

25. The antibody of claim 22, wherein the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 104 and a VL having the amino acid sequence of SEQ ID NO:

105.

26. The antibody (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 107, a VH CDR2 having the amino acid sequence of SEQ ID NO: 108, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 109; (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 110, a VL CDR2 having the amino acid sequence of SEQ ID NO: 111, and a VL CDR3 having the amino acid sequence of SEQ ID NO:

112.

27. The antibody of claim 26, wherein the antibody comprises a VH having the amino acid sequence of SEQ ID NO:

113.

28. 27. The antibody of claim 26, wherein the antibody comprises a VL having the amino acid sequence of SEQ ID NO:

114.

29. The antibody of claim 26, wherein the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 113 and a VL having the amino acid sequence of SEQ ID NO:

114.

30. The antibody (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 117, a VH CDR2 having the amino acid sequence of SEQ ID NO: 118, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 119; (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 120, a VL CDR2 having the amino acid sequence of SEQ ID NO: 121, and a VL CDR3 having the amino acid sequence of SEQ ID NO:

122.

31. The antibody of claim 30, wherein the antibody comprises a VH having the amino acid sequence of SEQ ID NO:

123.

32. The antibody of claim 30, wherein the antibody comprises a VL having the amino acid sequence of SEQ ID NO:

124.

33. The antibody of claim 30, wherein the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 123 and a VL having the amino acid sequence of SEQ ID NO:

124.

34. The antibody (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 127, a VH CDR2 having the amino acid sequence of SEQ ID NO: 128, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 129; (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 130, a VL CDR2 having the amino acid sequence of SEQ ID NO: 131, and a VL CDR3 having the amino acid sequence of SEQ ID NO:

132.

35. The antibody of claim 34, wherein the antibody comprises a VH having the amino acid sequence of SEQ ID NO:

133.

36. The antibody of claim 34, wherein the antibody comprises a VL having the amino acid sequence of SEQ ID NO:

134.

37. The antibody of claim 34, wherein the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 133 and a VL having the amino acid sequence of SEQ ID NO:

134.

38. The antibody of any one of claims 1 to 37, wherein the TRGV9 is present on the surface of a γδ T cell.

39. The antibody of any one of claims 1 to 38, wherein the antibody is a humanized antibody.

40. The antibody of any one of claims 1 to 39, wherein the antibody is an IgG antibody.

41. 41. The antibody of claim 40, wherein the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody.

42. The antibody of any one of claims 1 to 41, wherein the antibody is multivalent.

43. 43. The antibody of claim 42, wherein the antibody is capable of binding to at least three antigens.

44. 43. The antibody of claim 42, wherein the antibody is capable of binding to at least five antigens.

45. A nucleic acid encoding the antibody of any one of claims 1 to 44.

46. A vector comprising the nucleic acid of claim 45.

47. A host cell comprising the vector of claim 45.

48. 46. ​​A kit comprising the vector of claim 45 and a package therefor.

49. A pharmaceutical composition comprising the antibody of any one of claims 1 to 44 and a pharmaceutically acceptable carrier.

50. 50. A method of producing the pharmaceutical composition of claim 49, comprising combining the antibody with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition.

51. 45. A method of activating γδ T cells expressing TRGV9, comprising contacting said γδ T cells with the antibody of any one of claims 1 to 44.

52. 52. The method of claim 51 , wherein said contacting results in increased CD69, CD25, and / or Granzyme B expression compared to control γδ T cells expressing TRGV9.

53. A bispecific antibody, (a) a first binding domain that binds to TRGV9; (b) a second binding domain that binds to a second target that is not TRGV9.

54. the first binding domain comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 1, a VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 3; (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 4, a VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and a VL CDR3 having the amino acid sequence of SEQ ID NO:

6.

55. 55. The bispecific antibody of claim 54, wherein the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:

7.

56. 55. The bispecific antibody of claim 54, wherein the first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:

8.

57. 55. The bispecific antibody of claim 54, wherein the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 7 and a VL having the amino acid sequence of SEQ ID NO:

8.

58. the first binding domain comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 1, a VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 31; (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 4, a VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and a VL CDR3 having the amino acid sequence of SEQ ID NO:

6.

59. 59. The bispecific antibody of claim 58, wherein the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:

34.

60. 59. The bispecific antibody of claim 58, wherein the first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:

8.

61. 59. The bispecific antibody of claim 58, wherein the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 34 and a VL having the amino acid sequence of SEQ ID NO:

8.

62. the first binding domain comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 1, a VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 32; (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 4, a VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and a VL CDR3 having the amino acid sequence of SEQ ID NO:

6.

63. 63. The bispecific antibody of claim 62, wherein the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:

35.

64. 63. The bispecific antibody of claim 62, wherein the first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:

8.

65. 63. The bispecific antibody of claim 62, wherein the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 35 and a VL having the amino acid sequence of SEQ ID NO:

8.

66. the first binding domain comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 1, a VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 33; (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 4, a VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and a VL CDR3 having the amino acid sequence of SEQ ID NO:

6.

67. 67. The bispecific antibody of claim 66, wherein the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:

36.

68. 67. The bispecific antibody of claim 66, wherein the first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:

8.

69. 67. The bispecific antibody of claim 66, wherein the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 36 and a VL having the amino acid sequence of SEQ ID NO:

8.

70. the first binding domain comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 1, a VH CDR2 having the amino acid sequence of SEQ ID NO: 76, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 3; (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 77, a VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and a VL CDR3 having the amino acid sequence of SEQ ID NO:

6.

71. the first binding domain comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 60, a VH CDR2 having the amino acid sequence of SEQ ID NO: 61, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 62; (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 63, a VL CDR2 having the amino acid sequence of SEQ ID NO: 64, and a VL CDR3 having the amino acid sequence of SEQ ID NO:

6.

72. 72. The bispecific antibody of claim 70 or 71, wherein the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:

65.

73. 72. The bispecific antibody of claim 70 or 71, wherein the first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:

66.

74. 72. The bispecific antibody of claim 70 or 71, wherein the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 65 and a VL having the amino acid sequence of SEQ ID NO:

66.

75. 72. The bispecific antibody of claim 70 or 71, wherein the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:

67.

76. 72. The bispecific antibody of claim 70 or 71, wherein the first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:

68.

77. 72. A bispecific antibody according to claim 70 or 71, wherein the first binding domain, a VH having the amino acid sequence of SEQ ID NO: 67, and a VL having the amino acid sequence of SEQ ID NO:

68.

78. the first binding domain comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 89, a VH CDR2 having the amino acid sequence of SEQ ID NO: 90, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 91; (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 92, a VL CDR2 having the amino acid sequence of SEQ ID NO: 93, and a VL CDR3 having the amino acid sequence of SEQ ID NO:

94.

79. 79. The bispecific antibody of claim 78, wherein the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:

95.

80. 79. The bispecific antibody of claim 78, wherein the first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:

96.

81. 79. The bispecific antibody of claim 78, wherein the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 95 and a VL having the amino acid sequence of SEQ ID NO:

96.

82. the first binding domain comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 98, a VH CDR2 having the amino acid sequence of SEQ ID NO: 99, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 100; (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 101, a VL CDR2 having the amino acid sequence of SEQ ID NO: 102, and a VL CDR3 having the amino acid sequence of SEQ ID NO:

103.

83. 83. The bispecific antibody of claim 82, wherein the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:

104.

84. 83. The bispecific antibody of claim 82, wherein the first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:

105.

85. 83. The bispecific antibody of claim 82, wherein the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 104 and a VL having the amino acid sequence of SEQ ID NO:

105.

86. the first binding domain comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 107, a VH CDR2 having the amino acid sequence of SEQ ID NO: 108, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 109; (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 110, a VL CDR2 having the amino acid sequence of SEQ ID NO: 111, and a VL CDR3 having the amino acid sequence of SEQ ID NO:

112.

87. 87. The bispecific antibody of claim 86, wherein the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:

113.

88. 87. The bispecific antibody of claim 86, wherein the first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:

114.

89. 87. The bispecific antibody of claim 86, wherein the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 113 and a VL having the amino acid sequence of SEQ ID NO:

114.

90. the first binding domain comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 117, a VH CDR2 having the amino acid sequence of SEQ ID NO: 118, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 119; (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 120, a VL CDR2 having the amino acid sequence of SEQ ID NO: 121, and a VL CDR3 having the amino acid sequence of SEQ ID NO:

122.

91. 91. The bispecific antibody of claim 90, wherein the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:

123.

92. 91. The bispecific antibody of claim 90, wherein the first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:

124.

93. 91. The bispecific antibody of claim 90, wherein the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 123 and a VL having the amino acid sequence of SEQ ID NO:

124.

94. the first binding domain comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 127, a VH CDR2 having the amino acid sequence of SEQ ID NO: 128, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 129; (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 130, a VL CDR2 having the amino acid sequence of SEQ ID NO: 131, and a VL CDR3 having the amino acid sequence of SEQ ID NO:

132.

95. 95. The bispecific antibody of claim 94, wherein the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:

133.

96. 95. The bispecific antibody of claim 94, wherein the first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:

134.

97. 95. The bispecific antibody of claim 94, wherein the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 133 and a VL having the amino acid sequence of SEQ ID NO:

134.

98. 98. The bispecific antibody of any one of claims 53 to 97, wherein the second target is a cancer antigen present on the surface of a cancer cell.

99. 99. The bispecific antibody of claim 98, wherein the antigen on the surface of the cancer cell is a tumor-specific antigen, a tumor-associated antigen, or a neoantigen.

100. 100. The bispecific antibody of any one of claims 53 to 99, wherein the second target is CD123.

101. the second binding domain comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 9, a VH CDR2 having the amino acid sequence of SEQ ID NO: 10, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 11; (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 12, a VL CDR2 having the amino acid sequence of SEQ ID NO: 13, and a VL CDR3 having the amino acid sequence of SEQ ID NO:

14.

102. 102. The bispecific antibody of claim 101 , wherein the second binding domain comprises a VH having the amino acid sequence of SEQ ID NO:

15.

103. 102. The bispecific antibody of claim 101, wherein the second binding domain comprises a VL having the amino acid sequence of SEQ ID NO:

16.

104. 102. The bispecific antibody of claim 101 , wherein the second binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 15 and a VL having the amino acid sequence of SEQ ID NO:

16.

105. The bispecific antibody of any one of claims 53 to 104, wherein the TRGV9 is present on the surface of a γδ T cell.

106. 105. The bispecific antibody of any one of claims 53 to 104, wherein the TRGV9 is present on the surface of a γδ T cell and the second target is a cancer antigen expressed on the surface of the cancer cell.

107. 107. The bispecific antibody of claim 106, wherein upon binding of said TRGV9 on the surface of said γδ T cell and said antigen on the surface of said cancer cell, said cancer cell is killed.

108. 108. The bispecific antibody of any one of claims 53 to 107, wherein the first binding domain is humanized, the second binding domain is humanized, or both the first binding domain and the second binding domain are humanized.

109. The bispecific antibody of any one of claims 53 to 108, wherein the bispecific antibody is an IgG antibody.

110. 110. The bispecific antibody of claim 109, wherein the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody.

111. A pharmaceutical composition comprising the bispecific antibody of any one of claims 53 to 110 and a pharmaceutically acceptable carrier.

112. 111. A method of directing γδ T cells expressing TRGV9 to cancer cells, comprising contacting said γδ T cells with the bispecific antibody of any one of claims 53 to 110, wherein said contacting directs said γδ T cells to said cancer cells.

113. 111. A method of inhibiting the growth or proliferation of cancer cells that express a cancer antigen on the cell surface, said method comprising contacting said cancer cells with the bispecific antibody of any one of claims 53 to 110, wherein contacting said cancer cells with said pharmaceutical composition inhibits the growth or proliferation of said cancer cells.

114. 114. The method of claim 113, wherein the cancer cells are in the presence of γδ T cells expressing TRGV9 while in contact with the bispecific antibody.

115. 111. A method for eliminating cancer cells in a subject, comprising administering to said subject an effective amount of a bispecific antibody according to any one of claims 53 to 110.

116. 116. The method of claim 115, wherein the subject is a subject in need of the method.

117. 117. The method of claim 115 or 116, wherein the subject is a human.

118. 111. A method of activating γδ T cells expressing TRGV9, comprising contacting said γδ T cells with the bispecific antibody of any one of claims 53 to 110.

119. 1. An isolated TRGV9 bispecific antibody or antigen-binding fragment thereof, comprising: a. a first heavy chain (HC1); and b. a second heavy chain (HC2); and c. the first light chain (LC1); d. a second light chain (LC2), HC1 is associated with LC1, HC2 is associated with LC2, (A) HC1 is i. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively; ii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31, respectively; iii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32, respectively; or iv. heavy chain complementarity determining region 1 (HCDR1), HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:33, respectively; LC1 comprises light chain complementarity determining region 1 (LCDR1), LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, respectively, and forms a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen; or (B) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:1, SEQ ID NO:76, and SEQ ID NO:3, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:77, SEQ ID NO:5, and SEQ ID NO:6, respectively, and forms a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen; or (C) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 60, SEQ ID NO: 61, and SEQ ID NO: 62, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:63, SEQ ID NO:64, and SEQ ID NO:6, respectively, and forms a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen; or (D) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:89, SEQ ID NO:90, and SEQ ID NO:91, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:92, SEQ ID NO:93, and SEQ ID NO:94, respectively, and forms a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen; or (E) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:98, SEQ ID NO:99, and SEQ ID NO:100, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:101, SEQ ID NO:102, and SEQ ID NO:103, respectively, and forms a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen; or (F) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 109, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:110, SEQ ID NO:111, and SEQ ID NO:112, respectively, and forms a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen; or (G) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 119, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:120, SEQ ID NO:121, and SEQ ID NO:122, respectively, and forms a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen; or (H) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 129, respectively; An isolated TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 130, SEQ ID NO: 131, and SEQ ID NO: 132, respectively, and forms a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen.

120. (A) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8; or (B) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 65, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 66; or (C) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 67, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 68; or (D) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 95, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 96; or (E) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 104, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 105; or (F) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 113, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 114; or (G) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 123, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 124; or (H) The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 119, wherein HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 133 and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:

134.

121. (A) HC1 comprises the amino acid sequence of SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36, and LC1 comprises the amino acid sequence of SEQ ID NO:8; or (B) HC1 comprises the amino acid sequence of SEQ ID NO: 65 and LC1 comprises the amino acid sequence of SEQ ID NO: 66; or (C) HC1 comprises the amino acid sequence of SEQ ID NO: 67 and LC1 comprises the amino acid sequence of SEQ ID NO: 68; or (D) HC1 comprises the amino acid sequence of SEQ ID NO: 95 and LC1 comprises the amino acid sequence of SEQ ID NO: 96; or (E) HC1 comprises the amino acid sequence of SEQ ID NO: 104 and LC1 comprises the amino acid sequence of SEQ ID NO: 105; or (F) HC1 comprises the amino acid sequence of SEQ ID NO: 113 and LC1 comprises the amino acid sequence of SEQ ID NO: 114; or (G) HC1 comprises the amino acid sequence of SEQ ID NO: 123 and LC1 comprises the amino acid sequence of SEQ ID NO: 124; or (H) The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 120, wherein HC1 comprises the amino acid sequence of SEQ ID NO: 133 and LC1 comprises the amino acid sequence of SEQ ID NO:

134.

122. 122. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of any one of claims 119-121, wherein the binding site for a first antigen binds to TRGV9 on γδ T cells.

123. 123. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of any one of claims 119 to 122, wherein the binding site for a second antigen binds to a cancer antigen present on the surface of a cancer cell.

124. 124. The isolated TRGV9 bispecific antibody or antigen-binding fragment of claim 123, wherein said binding of said bispecific antibody to TRGV9 present on the surface of the γδ T cell and said binding of said cancer antigen present on the surface of the cancer cell results in killing of the cancer cell.

125. 125. The isolated TRGV9 bispecific antibody or antigen-binding fragment of any one of claims 119 to 124, wherein HC1 and LC1 are humanized.

126. 126. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of any one of claims 119 to 125, wherein HC2 and LC2 bind to CD123.

127. 127. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of any one of claims 119-126, wherein the bispecific antibody or antigen-binding fragment thereof is an IgG1, IgG2, IgG3, or IgG4 isotype.

128. 128. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of any one of claims 119 to 127, wherein the bispecific antibody or antigen-binding fragment thereof is of the IgG4 isotype.

129. the bispecific antibody or antigen-binding fragment thereof has an EC ５０ 129. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of any one of claims 119 to 128, which induces γδ T cell-dependent cytotoxicity of cancer cells in vitro.

130. the bispecific antibody or antigen-binding fragment thereof has an EC ５０ 130. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 129, wherein the antibody induces γδ T cell-dependent cytotoxicity of cancer cells in vitro.

131. the bispecific antibody or antigen-binding fragment thereof has an EC ５０ 130. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 129, wherein the antibody induces γδ T cell-dependent cytotoxicity of cancer cells in vitro.

132. The EC ５０ 132. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of any one of claims 129-131, wherein said antibody or antigen-binding fragment is assessed on a mixture of γδ T effector cells and Kasumi3 AML target cells.

133. 133. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 132, wherein the effector cell to target cell ratio is from about 0.01:1 to about 5:

1.

134. 134. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 133, wherein the effector cell to target cell ratio is from about 0.1:1 to about 2:

1.

135. 135. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 134, wherein the effector cell to target cell ratio is about 1:

1.

136. 136. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of any one of claims 119 to 135, wherein the bispecific antibody or antigen-binding fragment thereof is multivalent.

137. 137. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 136, wherein the bispecific antibody or antigen-binding fragment thereof is capable of binding to at least three antigens.

138. 137. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 136, wherein the bispecific antibody or antigen-binding fragment thereof is capable of binding to at least five antigens.

139. 1. An isolated γδ T cell bispecific antibody or antigen-binding fragment thereof, comprising: a. HC1, and b. HC2; c. LC1; d. LC2; HC1 is associated with LC1, HC2 is associated with LC2, HC1 and LC1 form the binding site for the first antigen on γδ T cells; An isolated γδ T cell bispecific antibody or antigen-binding fragment thereof, wherein HC2 and LC2 form a binding site for a second antigen.

140. A bispecific antibody comprising a first means capable of specifically binding to a T-cell receptor gamma chain and a second means capable of specifically binding to a target molecule which is not a T-cell receptor gamma chain.

141. 1. A process for producing a molecule capable of specifically binding to two or more target molecules, said molecule comprising the steps of: obtaining an oligopeptide or polypeptide capable of binding to a T-cell receptor gamma chain; obtaining an oligopeptide or polypeptide capable of binding to the target; and providing a molecule capable of specifically binding to a T-cell receptor gamma chain and the target molecules.

142. 142. The process of claim 141, wherein the step functioning to obtain an oligopeptide or polypeptide capable of binding to a target is repeated n times, and further comprises n steps functioning to provide molecules capable of specifically binding to a T-cell receptor gamma chain and n target molecules, wherein n is at least 2.

143. 1. An isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof, comprising: a. HC1, and b. HC2; c. LC1; d. LC2; HC1 is associated with LC1, HC2 is associated with LC2, (A) HC1 is i. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively; ii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31, respectively; iii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32, respectively; or iv. comprising HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:33, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, respectively, and forms a binding site for a first antigen that specifically binds to Vγ9; or (B) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:1, SEQ ID NO:76, and SEQ ID NO:3, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:77, SEQ ID NO:5, and SEQ ID NO:6, respectively, and forms a binding site for a first antigen that specifically binds to Vγ9; or (C) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 60, SEQ ID NO: 61, and SEQ ID NO: 62, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:63, SEQ ID NO:64, and SEQ ID NO:6, respectively, and forms a binding site for a first antigen that specifically binds to Vγ9; or (D) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:89, SEQ ID NO:90, and SEQ ID NO:91, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:92, SEQ ID NO:93, and SEQ ID NO:94, respectively, and forms a binding site for a first antigen that specifically binds to Vγ9; or (E) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:98, SEQ ID NO:99, and SEQ ID NO:100, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 103, respectively, and forms a binding site for a first antigen that specifically binds to Vγ9; or (F) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 109, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:110, SEQ ID NO:111, and SEQ ID NO:112, respectively, and forms a binding site for a first antigen that specifically binds to Vγ9; or (G) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 119, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 120, SEQ ID NO: 121, and SEQ ID NO: 122, respectively, and forms a binding site for a first antigen that specifically binds to Vγ9; or (H) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 129, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 130, SEQ ID NO: 131, and SEQ ID NO: 132, respectively, and forms a binding site for a first antigen that specifically binds to Vγ9; 1. An isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof, wherein HC2 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:9, SEQ ID NO:10, and SEQ ID NO:11, respectively, and LC2 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:14, respectively, forming a binding site for a second antigen that specifically binds to CD123.

144. (A) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8; or (B) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 65, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 66; or (C) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 67, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 68; or (D) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 95, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 96; or (E) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 104, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 105; or (F) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 113, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 114; or (G) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 123, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 124; or (H) The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof of claim 143, wherein HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 133 and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:

134.

145. (A) HC1 comprises the amino acid sequence of SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36, and LC1 comprises the amino acid sequence of SEQ ID NO:8; or (B) HC1 comprises the amino acid sequence of SEQ ID NO: 65 and LC1 comprises the amino acid sequence of SEQ ID NO: 66; or (C) HC1 comprises the amino acid sequence of SEQ ID NO: 67 and LC1 comprises the amino acid sequence of SEQ ID NO: 68; or (D) HC1 comprises the amino acid sequence of SEQ ID NO: 95 and LC1 comprises the amino acid sequence of SEQ ID NO: 96; or (E) HC1 comprises the amino acid sequence of SEQ ID NO: 104 and LC1 comprises the amino acid sequence of SEQ ID NO: 105; or (F) HC1 comprises the amino acid sequence of SEQ ID NO: 113 and LC1 comprises the amino acid sequence of SEQ ID NO: 114; or (G) HC1 comprises the amino acid sequence of SEQ ID NO: 123 and LC1 comprises the amino acid sequence of SEQ ID NO: 124; or (H) The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof of claim 144, wherein HC1 comprises the amino acid sequence of SEQ ID NO: 133 and LC1 comprises the amino acid sequence of SEQ ID NO:

134.

146. 146. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof of any one of claims 143 to 145, wherein HC2 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 15 and LC2 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:

16.

147. 147. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof of claim 146, wherein HC2 comprises the amino acid sequence of SEQ ID NO: 15 and LC2 comprises the amino acid sequence of SEQ ID NO:

16.

148. 148. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof of any one of claims 143-147, wherein the TRGV9 is on the surface of a γδ T cell.

149. 149. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof of any one of claims 145 to 148, wherein the CD123 is on the surface of a tumor cell or a CD34+ stem cell.

150. 150. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof of any one of claims 143-149, wherein said binding of said bispecific antibody to TRGV9 present on the surface of the γδ T cell and said binding of CD123 on the surface of the cancer cell results in killing of the cancer cell.

151. 151. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof of any one of claims 143 to 150, wherein HC1 and LC1 are humanized.

152. 152. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof of any one of claims 143 to 151, wherein HC2 and LC2 are humanized.

153. 153. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof of any one of claims 143-152, wherein the bispecific antibody or antigen-binding fragment thereof is of the IgG1, IgG2, IgG3, or IgG4 isotype.

154. 154. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof of any one of claims 143-153, wherein the bispecific antibody or antigen-binding fragment thereof is of the IgG4 isotype.

155. the bispecific antibody or antigen-binding fragment thereof has an EC ５０ 155. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof of any one of claims 143 to 154, which induces γδ T cell-dependent cytotoxicity of cancer cells in vitro.

156. the bispecific antibody or antigen-binding fragment thereof has an EC ５０ 156. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof of claim 155, wherein the antibody or antigen-binding fragment induces γδ T cell-dependent cytotoxicity of cancer cells in vitro.

157. the bispecific antibody or antigen-binding fragment thereof has an EC ５０ 156. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof of claim 155, wherein the antibody or antigen-binding fragment induces γδ T cell-dependent cytotoxicity of cancer cells in vitro.

158. The EC ５０ 158. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof of any one of claims 155 to 157, wherein said antibody or antigen-binding fragment is assessed on a mixture of γδ T effector cells and Kasumi3 AML target cells.

159. 159. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof of claim 158, wherein the effector cell to target cell ratio is from about 0.01:1 to about 5:

1.

160. 160. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof of claim 159, wherein the effector cell to target cell ratio is from about 0.1:1 to about 2:

1.

161. 161. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof of claim 160, wherein the effector cell to target cell ratio is about 1:

1.

162. 162. A method of making the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof of any one of claims 143-161, comprising culturing a cell comprising nucleic acid encoding the anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof under conditions to produce the bispecific antibody or antigen-binding fragment thereof, and recovering the bispecific antibody or antigen-binding fragment thereof.

163. 1. An isolated TRGV9 bispecific antibody or antigen epitope-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigen epitope-binding fragment thereof comprises a binding site for a first antigen and a binding site for a second antigen, wherein the binding site for the first antigen binds to a TRGV9 epitope on a γδ T cell and the binding site for the second antigen binds to an epitope of the second antigen on the surface of a target cell, and wherein the binding of the TRGV9 epitope on the γδ T cell and the binding of the second antigen epitope on the target cell results in killing of the target cell.

164. 1. An isolated TRGV9 bispecific antibody or antigen-binding fragment thereof, comprising: a. HC1, and b. HC2; c. LC1; d. LC2; HC1 is associated with LC1, HC2 is associated with LC2, (A) HC1 is i. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively; ii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31, respectively; iii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32, respectively; or iv. comprising HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:33, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, respectively, to form a binding site for a first antigen; or (B) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:1, SEQ ID NO:76, and SEQ ID NO:3, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:77, SEQ ID NO:5, and SEQ ID NO:6, respectively, and forms a binding site for a first antigen; or (C) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 60, SEQ ID NO: 61, and SEQ ID NO: 62, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:63, SEQ ID NO:64, and SEQ ID NO:6, respectively, and forms a binding site for a first antigen; or (D) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:89, SEQ ID NO:90, and SEQ ID NO:91, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:92, SEQ ID NO:93, and SEQ ID NO:94, respectively, and forms a binding site for a first antigen; or (E) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:98, SEQ ID NO:99, and SEQ ID NO:100, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 103, respectively, and forms a binding site for a first antigen; or (F) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 109, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:110, SEQ ID NO:111, and SEQ ID NO:112, respectively, and forms a binding site for a first antigen; or (G) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 119, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 120, SEQ ID NO: 121, and SEQ ID NO: 122, respectively, to form a binding site for a first antigen; or (H) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 129, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 130, SEQ ID NO: 131, and SEQ ID NO: 132, respectively, and forms a binding site for a first antigen; An isolated TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein HC2 and LC2 form a binding site for a second antigen epitope.

165. (A) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8; or (B) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 65, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 66; or (C) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 67, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 68; or (D) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 95, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 96; or (E) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 104, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 105; or (F) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 113, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 114; or (G) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 123, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 124; or (H) The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 164, wherein HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 133, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:

134.

166. (A) HC1 comprises the amino acid sequence of SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36, and LC1 comprises the amino acid sequence of SEQ ID NO:8; or (B) HC1 comprises the amino acid sequence of SEQ ID NO: 65 and LC1 comprises the amino acid sequence of SEQ ID NO: 66; or (C) HC1 comprises the amino acid sequence of SEQ ID NO: 67 and LC1 comprises the amino acid sequence of SEQ ID NO: 68; or (D) HC1 comprises the amino acid sequence of SEQ ID NO: 95 and LC1 comprises the amino acid sequence of SEQ ID NO: 96; or (E) HC1 comprises the amino acid sequence of SEQ ID NO: 104 and LC1 comprises the amino acid sequence of SEQ ID NO: 105; or (F) HC1 comprises the amino acid sequence of SEQ ID NO: 113 and LC1 comprises the amino acid sequence of SEQ ID NO: 114; or (G) HC1 comprises the amino acid sequence of SEQ ID NO: 123 and LC1 comprises the amino acid sequence of SEQ ID NO: 124; or (H) The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 165, wherein HC1 comprises the amino acid sequence of SEQ ID NO: 133 and LC1 comprises the amino acid sequence of SEQ ID NO:

134.

167. 167. The isolated TRGV9 bispecific antibody or antigen-binding fragment of any one of claims 164 to 166, wherein HC1 and LC1 are humanized.

168. 168. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of any one of claims 164 to 167, wherein HC2 and LC2 bind to a CD123 epitope.

169. 169. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 168, wherein HC2 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 15, and LC2 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:

16.

170. 170. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 169, wherein HC2 comprises the amino acid sequence of SEQ ID NO: 15 and LC2 comprises the amino acid sequence of SEQ ID NO:

16.

171. 171. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of any one of claims 163-170, wherein the bispecific antibody or antigen-binding fragment thereof is an IgG1, IgG2, IgG3, or IgG4 isotype.

172. 172. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of any one of claims 163-171, wherein the bispecific antibody or antigen-binding fragment thereof is of the IgG4 isotype.

173. the bispecific antibody or antigen-binding fragment thereof has an EC ５０ 173. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of any one of claims 163 to 172, which induces γδ T cell-dependent cytotoxicity of cancer cells in vitro.

174. the bispecific antibody or antigen-binding fragment thereof has an EC ５０ 174. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 173, wherein the antibody induces γδ T cell-dependent cytotoxicity of cancer cells in vitro.

175. the bispecific antibody or antigen-binding fragment thereof has an EC ５０ 175. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 174, wherein the antibody or antigen-binding fragment induces γδ T cell-dependent cytotoxicity of cancer cells in vitro.

176. The EC ５０ 176. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of any one of claims 173 to 175, wherein said antibody or antigen-binding fragment is assessed on a mixture of γδ T effector cells and Kasumi3 AML target cells.

177. 177. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 176, wherein the effector cell to target cell ratio is from about 0.01:1 to about 5:

1.

178. 178. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 177, wherein the effector cell to target cell ratio is from about 0.1:1 to about 2:

1.

179. 179. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 178, wherein the effector cell to target cell ratio is about 1:

1.

180. 1. An isolated γδ T cell bispecific antibody or antigen-binding fragment thereof, said isolated γδ T cell bispecific antibody or antigen-binding fragment thereof comprising a binding site for a first antigen epitope and a binding site for a second antigen epitope, wherein the binding site for the first antigen epitope binds to a first antigen on a γδ T cell and the binding site for the second antigen epitope binds to an epitope of the second antigen on the surface of a target cell, and wherein the binding of the first antigen epitope on the γδ T cell and the binding of the second antigen epitope on the target cell results in killing of the target cell.

181. 1. An isolated nucleic acid encoding a TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises: a. HC1, and b. HC2; c. LC1; d. LC2; HC1 is associated with LC1, HC2 is associated with LC2, (A) HC1 is i. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively; ii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31, respectively; iii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32, respectively; or iv. comprising HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:33, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, respectively, to form a binding site for a first antigen; or (B) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:1, SEQ ID NO:76, and SEQ ID NO:3, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:77, SEQ ID NO:5, and SEQ ID NO:6, respectively, and forms a binding site for a first antigen; or (C) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 60, SEQ ID NO: 61, and SEQ ID NO: 62, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:63, SEQ ID NO:64, and SEQ ID NO:6, respectively, and forms a binding site for a first antigen; or (D) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:89, SEQ ID NO:90, and SEQ ID NO:91, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:92, SEQ ID NO:93, and SEQ ID NO:94, respectively, and forms a binding site for a first antigen; or (E) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:98, SEQ ID NO:99, and SEQ ID NO:100, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 103, respectively, and forms a binding site for a first antigen; or (F) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 109, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:110, SEQ ID NO:111, and SEQ ID NO:112, respectively, and forms a binding site for a first antigen; or (G) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 119, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 120, SEQ ID NO: 121, and SEQ ID NO: 122, respectively, to form a binding site for a first antigen; or (H) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 129, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 130, SEQ ID NO: 131, and SEQ ID NO: 132, respectively, and forms a binding site for a first antigen; An isolated nucleic acid, wherein HC2 and LC2 form a binding site for a second antigen.

182. (A) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8; or (B) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 65, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 66; or (C) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 67, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 68; or (D) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 95, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 96; or (E) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 104, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 105; or (F) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 113, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 114; or (G) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 123, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 124; or (H) The isolated nucleic acid of claim 181, wherein HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 133, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:

134.

183. (A) HC1 comprises the amino acid sequence of SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36, and LC1 comprises the amino acid sequence of SEQ ID NO:8; or (B) HC1 comprises the amino acid sequence of SEQ ID NO: 65 and LC1 comprises the amino acid sequence of SEQ ID NO: 66; or (C) HC1 comprises the amino acid sequence of SEQ ID NO: 67 and LC1 comprises the amino acid sequence of SEQ ID NO: 68; or (D) HC1 comprises the amino acid sequence of SEQ ID NO: 95 and LC1 comprises the amino acid sequence of SEQ ID NO: 96; or (E) HC1 comprises the amino acid sequence of SEQ ID NO: 104 and LC1 comprises the amino acid sequence of SEQ ID NO: 105; or (F) HC1 comprises the amino acid sequence of SEQ ID NO: 113 and LC1 comprises the amino acid sequence of SEQ ID NO: 114; or (G) HC1 comprises the amino acid sequence of SEQ ID NO: 123 and LC1 comprises the amino acid sequence of SEQ ID NO: 124; or (H) The isolated nucleic acid of claim 182, wherein HC1 comprises the amino acid sequence of SEQ ID NO: 133 and LC1 comprises the amino acid sequence of SEQ ID NO:

134.

184. 184. The isolated nucleic acid of any one of claims 181-183, wherein the binding site for a first antigen binds to TRGV9 on a γδ T cell.

185. 185. The isolated nucleic acid of any one of claims 181 to 184, wherein the binding site for a second antigen binds to a cancer antigen present on the surface of a cancer cell.

186. 186. The isolated nucleic acid of Claim 185, wherein said binding of said bispecific antibody to TRGV9 present on the surface of said γδ T cell and said binding of said cancer antigen present on the surface of said cancer cell results in killing of said cancer cell.

187. 187. The isolated nucleic acid of any one of claims 181 to 186, wherein HC1 and LC1 are humanized.

188. 188. The isolated nucleic acid of any one of claims 181 to 187, wherein HC2 and LC2 bind to CD123.

189. 189. The isolated nucleic acid of any one of claims 181-188, wherein the bispecific antibody or antigen-binding fragment thereof is of the IgG1, IgG2, IgG3, or IgG4 isotype.

190. 190. The isolated nucleic acid of any one of claims 181 to 189, wherein the bispecific antibody or antigen-binding fragment thereof is of the IgG4 isotype.

191. the bispecific antibody or antigen-binding fragment thereof has an EC ５０ 191. The isolated nucleic acid of any one of claims 181 to 190, which induces γδ T cell-dependent cytotoxicity of cancer cells in vitro.

192. the bispecific antibody or antigen-binding fragment thereof has an EC ５０ 192. The isolated nucleic acid of claim 191, wherein the isolated nucleic acid induces γδ T cell-dependent cytotoxicity of cancer cells in vitro.

193. the bispecific antibody or antigen-binding fragment thereof has an EC ５０ 192. The isolated nucleic acid of claim 191, wherein the isolated nucleic acid induces γδ T cell-dependent cytotoxicity of cancer cells in vitro.

194. The EC ５０ 194. The isolated nucleic acid of any one of claims 191 to 193, wherein said nucleic acid is assessed in a mixture of γδ T effector cells and Kasumi3 AML target cells.

195. 195. The isolated nucleic acid of claim 194, wherein said effector cell to target cell ratio is from about 0.01:1 to about 5:

1.

196. 196. The isolated nucleic acid of claim 195, wherein said effector cell to target cell ratio is from about 0.1:1 to about 2:

1.

197. 197. The isolated nucleic acid of claim 196, wherein the ratio of effector cells to target cells is about 1:

1.

198. 198. The isolated nucleic acid of any one of claims 181-197, wherein the bispecific antibody or antigen-binding fragment thereof is multivalent.

199. 200. The isolated nucleic acid of claim 198, wherein the bispecific antibody or antigen-binding fragment thereof is capable of binding to at least three antigens.

200. 200. The isolated nucleic acid of claim 198, wherein the bispecific antibody or antigen-binding fragment thereof is capable of binding to at least five antigens.

201. A vector comprising the isolated nucleic acid of any one of claims 181 to 200.

202. A host cell comprising the vector of claim 201.

203. 202. A kit comprising the vector of claim 201 and a package therefor.

204. 1. An isolated TRGV9 bispecific antibody or antigen-binding fragment thereof, comprising: a. HC1, and b. HC2; c. LC1; d. LC2; HC1 is associated with LC1, HC2 is associated with LC2, (A) HC1 is i. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively; ii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31, respectively; iii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32, respectively; or iv. comprising HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:33, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, respectively, to form a binding site for a first antigen; or (B) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:1, SEQ ID NO:76, and SEQ ID NO:3, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:77, SEQ ID NO:5, and SEQ ID NO:6, respectively, and forms a binding site for a first antigen; or (C) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 60, SEQ ID NO: 61, and SEQ ID NO: 62, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:63, SEQ ID NO:64, and SEQ ID NO:6, respectively, and forms a binding site for a first antigen; or (D) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:89, SEQ ID NO:90, and SEQ ID NO:91, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:92, SEQ ID NO:93, and SEQ ID NO:94, respectively, and forms a binding site for a first antigen; or (E) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO:98, SEQ ID NO:99, and SEQ ID NO:100, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 103, respectively, and forms a binding site for a first antigen; or (F) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 109, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO:110, SEQ ID NO:111, and SEQ ID NO:112, respectively, and forms a binding site for a first antigen; or (G) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 119, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 120, SEQ ID NO: 121, and SEQ ID NO: 122, respectively, to form a binding site for a first antigen; or (H) HC1 comprises HCDR1, HCDR2, and HCDR3 comprising the amino acid sequences of SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 129, respectively; LC1 comprises LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 130, SEQ ID NO: 131, and SEQ ID NO: 132, respectively, and forms a binding site for a first antigen; an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein HC2 and LC2 form a binding site for a second antigen; and a pharmaceutically acceptable carrier.

205. (A) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8; or (B) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 65, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 66; or (C) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 67, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 68; or (D) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 95, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 96; or (E) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 104, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 105; or (F) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 113, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 114; or (G) HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 123, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 124; or (H) The pharmaceutical composition of claim 204, wherein HC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 133, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:

134.

206. (A) HC1 comprises the amino acid sequence of SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36, and LC1 comprises the amino acid sequence of SEQ ID NO:8; or (B) HC1 comprises the amino acid sequence of SEQ ID NO: 65 and LC1 comprises the amino acid sequence of SEQ ID NO: 66; or (C) HC1 comprises the amino acid sequence of SEQ ID NO: 67 and LC1 comprises the amino acid sequence of SEQ ID NO: 68; or (D) HC1 comprises the amino acid sequence of SEQ ID NO: 95 and LC1 comprises the amino acid sequence of SEQ ID NO: 96; or (E) HC1 comprises the amino acid sequence of SEQ ID NO: 104 and LC1 comprises the amino acid sequence of SEQ ID NO: 105; or (F) HC1 comprises the amino acid sequence of SEQ ID NO: 113 and LC1 comprises the amino acid sequence of SEQ ID NO: 114; or (G) HC1 comprises the amino acid sequence of SEQ ID NO: 123 and LC1 comprises the amino acid sequence of SEQ ID NO: 124; or (H) The pharmaceutical composition of claim 205, wherein HC1 comprises the amino acid sequence of SEQ ID NO: 133 and LC1 comprises the amino acid sequence of SEQ ID NO:

134.

207. 207. The pharmaceutical composition of any one of claims 204 to 206, wherein the binding site for a first antigen binds to TRGV9 on γδ T cells.

208. 208. The pharmaceutical composition of any one of claims 204 to 207, wherein the binding site for a second antigen binds to a cancer antigen present on the surface of a cancer cell.

209. 209. The pharmaceutical composition of claim 208, wherein said binding of said bispecific antibody to TRGV9 present on the surface of said γδ T cell and said binding of said cancer antigen present on the surface of said cancer cell results in killing of said cancer cell.

210. The pharmaceutical composition of any one of claims 204 to 209, wherein HC1 and LC1 are humanized.

211. The pharmaceutical composition of any one of claims 204 to 210, wherein HC2 and LC2 bind to CD123.

212. 212. The pharmaceutical composition of any one of claims 204 to 211, wherein the bispecific antibody or antigen-binding fragment thereof is of the IgG1, IgG2, IgG3, or IgG4 isotype.

213. 213. A method of directing Vγ9-expressing γδ T cells to cancer cells, said method comprising contacting Vγ9-expressing γδ T cells with the pharmaceutical composition of any one of claims 204-212, wherein contacting said Vγ9-expressing γδ T cells with said pharmaceutical composition directs said Vγ9-expressing γδ T cells to cancer cells.

214. 213. A method of inhibiting the growth or proliferation of cancer cells that express a cancer antigen on the cell surface, comprising contacting said cancer cells with the pharmaceutical composition of any one of claims 204 to 212, wherein contacting said cancer cells with said pharmaceutical composition inhibits the growth or proliferation of said cancer cells.

215. 215. The method of claim 214, wherein the cancer cells are in the presence of Vγ9-expressing γδ T cells while in contact with the anti-TRGV9 bispecific antibody or antigen-binding fragment thereof.

216. 1. A method for treating cancer in a subject in need thereof, said method comprising: a. identifying a subject in need of cancer treatment; b. Administering the pharmaceutical composition of any one of claims 204 to 212 to the subject in need thereof; The method, wherein administering said pharmaceutical composition to said subject in need thereof treats said cancer in said subject.

217. 213. A method of activating Vγ9-expressing γδ T cells, said method comprising contacting said Vγ9-expressing γδ T cells with the pharmaceutical composition of any one of claims 204-212, wherein contacting said Vγ9-expressing γδ T cells with said pharmaceutical composition results in increased CD69, CD25, and / or Granzyme B expression compared to control Vγ9-expressing γδ T cells.

218. 213. A method of producing the pharmaceutical composition of any one of claims 204 to 212, comprising combining the bispecific antibody or antigen-binding fragment thereof with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition.

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