Multispecific molecules binding to TCR and uses thereof

WO2026096770A3PCT designated stage Publication Date: 2026-06-25MARENGO THERAPEUTICS INC
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Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
MARENGO THERAPEUTICS INC
Filing Date
2025-10-30
Publication Date
2026-06-25

AI Technical Summary

Technical Problem

Current molecules targeting the CD3 epsilon subunit of the T cell receptor for cancer immunotherapy can cause T cell dysfunction, immunosuppressive effects, and cytokine storms, leading to neurotoxicity due to non-physiological massive activation of T cells.

Method used

Development of anti-TCRβV27-binding molecules, specifically anti-TCRβV27 antibodies or antigen binding domains with defined heavy and light chain complementarity determining regions, to selectively target T cells for cancer immunotherapy, reducing the risk of cytokine storms and neurotoxicity.

Benefits of technology

The anti-TCRβV27-binding molecules provide targeted T cell activation, minimizing cytokine storms and neurotoxicity, thereby enhancing the safety and efficacy of cancer immunotherapy.

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Abstract

MULTISPECIFIC MOLECULES BINDING TO TCR AND USES THEREOF ABSTRACT Provides herein are multifunctional molecules comprising T cell receptor variable beta-binding moieties, and methods of treating conditions or diseases in a subject using the same.
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Description

MULTISPECIFIC MOLECULES BINDING TO TCR AND USES THEREOFCROSS REFERENCE

[0001] This application claims the benefit of U. S. Provisional Application No. 63 / 713,981, filed on October 30, 2024, which is incorporated herein by reference in its entirety.BACKGROUND

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

[0003] In an aspect, provided herein, inter alia, is a molecule comprising an TCRβV27-binding moiety, wherein the TCRβV27-binding moiety is an anti-TCRβV27 antibody molecule or an anti-TCRβV27 antigen binding domain comprising:(i) a heavy chain variable region (VH) comprises a heavy chain complementarity determining region 1 (HC CDR1), a heavy chain complementarity determining region 2 (HC CDR2), and a heavy chain complementarity determining region 3 (HC CDR3) comprising the sequences of:(a) SEQ ID NO: 1470, SEQ ID NO: 1451, and SEQ ID NO: 1426, respectively;(b) SEQ ID NO: 1470, SEQ ID NO: 1451, and SEQ ID NO: 1513, respectively;(c) SEQ ID NO: 1471, SEQ ID NO: 1451, and SEQ ID NO: 1426, respectively;(d) SEQ ID NO: 1471, SEQ ID NO: 1451, and SEQ ID NO: 1513, respectively;(e) SEQ ID NO: 1472, SEQ ID NO: 1452, and SEQ ID NO: 1426, respectively;(f) SEQ ID NO: 1472, SEQ ID NO: 1452, and SEQ ID NO: 1513, respectively; or(g) SEQ ID NO: 1473, SEQ ID NO: 1453, and SEQ ID NO: 1432, respectively;(ii) a light chain variable region (VL) comprises a light chain complementarity determining region 1 (LC CDR1), a light chain complementarity determining region 2 (LC CDR2), and a light chain complementarity determining region 1 (LC CDR3) comprising the sequences of:(a) SEQ ID NO: 1442, SEQ ID NO: 1434, and SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, and SEQ ID NO: 1438, respectively.

[0004] In some embodiments, the anti-TCR(3V27 antibody molecule or the anti-TCR(3V27 antigen binding domain comprises the VH and the VL respectively comprising a HC CDR1, a HC CDR2, and aHC CDR3, and a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of;(a) SEQ ID NO: 1470, SEQ ID NO: 1451, SEQ ID NO: 1426, SEQ ID NO: 1442, SEQ ID NO: 1434, and SEQ ID NO: 1438, respectively;(b) SEQ ID NO: 1470, SEQ ID NO: 1451, SEQ ID NO: 1513, SEQ ID NO: 1442, SEQ ID NO: 1434, and SEQ ID NO: 1438, respectively;(c) SEQ ID NO: 1471, SEQ ID NO: 1451, SEQ ID NO: 1426, SEQ ID NO: 1442, SEQ ID NO: 1434, and SEQ ID NO: 1438, respectively;(d) SEQ ID NO: 1471, SEQ ID NO: 1451, SEQ ID NO: 1513, SEQ ID NO: 1442, SEQ ID NO: 1434, and SEQ ID NO: 1438, respectively;(e) SEQ ID NO: 1472, SEQ ID NO: 1452, SEQ ID NO: 1426, SEQ ID NO: 1442, SEQ ID NO: 1434, and SEQ ID NO: 1438, respectively; or(f) SEQ ID NO: 1472, SEQ ID NO: 1452, SEQ ID NO: 1513, SEQ ID NO: 1442, SEQ ID NO: 1434, and SEQ ID NO: 1438, respectively; or(g) SEQ ID NO: 1473, SEQ ID NO: 1453, SEQ ID NO: 1432, SEQ ID NO: 1443, SEQ ID NO: 1437, and SEQ ID NO: 1438, respectively.

[0005] In some embodiments, the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1423.

[0006] In some embodiments, the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413.

[0007] In some embodiments, the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1423 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413.

[0008] In some embodiments, the VH comprises the sequence of SEQ ID NO: 1423.

[0009] In some embodiments, the VL comprises the sequence of 1413.

[0010] In some embodiments, the VH comprises the sequence of SEQ ID NO: 1423 and the VL comprises the sequence of 1413.

[0011] In another aspect, provided herein is a molecule comprising an TCRβV27-binding moiety, wherein the TCRβV27-binding moiety is an anti-TCRβV27 antibody molecule or an anti-TCRβV27 antigen binding domain comprising:(i) a heavy chain variable region (VH) comprising:(a) a heavy chain complementarity determining region 1 (HC CDR1) comprising the sequence GFKTEX1X2YMY, wherein X₁ is D or E, and X₂ is T, Y, or A (SEQ ID NO: 1480);(b) a heavy chain complementarity determining region 2 (HC CDR2) comprising the sequence X3IX4PX5X6X7X8TX9YDPKFQD, wherein X₃ is R or D, X₄ is D or Y, X₅ is A, F or Y, X₆ is N or A,X₇ is G or A, X₈ is N or A, and X₉ is K or S (SEQ ID NO: 1481); and(c) a heavy chain complementarity determining region 3 (HC CDR3) comprising the sequence GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513); and(ii) a light chain variable region (VL) comprising:(a) a light chain complementarity determining region 1 (LC CDR1) comprising the sequence RASESVX10SYGX11SFMH, wherein X₁₀ is D or A, and X₁₁ is N or A (SEQ ID NO: 1482);(b) a light chain complementarity determining region 2 (LC CDR2) comprising the sequence RASNLES (SEQ ID NO: 1434); and(c) a light chain complementarity determining region 3 (LC CDR3) comprising the sequence QQSNEDPYT (SEQ ID NO: 1438),with the proviso that:(A) the HC CDR1, the HC CDR2, the HC CDR3, the LC CDR1, the LC CDR2, and the LC CDR3 are not GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), respectively; or(B) the HC CDR1, the HC CDR2, the HC CDR3, the LC CDR1, the LC CDR2, and the LC CDR3 are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), respectively, and the VH comprises a sequence having at least 97.5%, 98%, 98.5%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

[0012] In some embodiments, HC CDR1 is GFKTEDTYMY (SEQ ID NO: 1424), GFKTEDYYMY (SEQ ID NO: 1447), GFKTEDAYMY (SEQ ID NO: 1470), or GFKTEETYMY (SEQ ID NO: 1457).

[0013] In some embodiments, HC CDR2 is RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), RIDPANGATKYDPKFQD (SEQ ID NO: 1439), RIDPYAGATKYDPKFQD (SEQ ID NO: 1444), RIDPYNAATKYDPKFQD (SEQ ID NO: 1451), RIDPFNGNTKYDPKFQD (SEQ ID NO: 1454), DIYPAAGATSYDPKFQD (SEQ ID NO: 1458), RIDPFAGATKYDPKFQD (SEQ ID NO: 1464), or RIDPFNAATKYDPKFQD (SEQ ID NO: 1467).

[0014] In some embodiments, HC CDR3 is GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513).

[0015] In some embodiments, LC CDR1 is RASESVDSYGNSFMH (SEQ ID NO: 1433) or RASESVASYGASFMH (SEQ ID NO: 1442).

[0016] In some embodiments, LC CDR2 is RASNLES (SEQ ID NO: 1434).

[0017] In some embodiments, LC CDR3 is QQSNEDPYT (SEQ ID NO: 1438).

[0018] In another aspect, provided herein is a molecule comprising an TCRβV27-binding moiety, wherein the TCRβV27-binding moiety is an anti-TCRβV27 antibody molecule or an anti-TCRβV27 antigen binding domain comprising:(i) a VH comprising:(a) a HC CDR1, a HC CDR2, and a HC CDR3 comprising the HC CDR1 sequence, a HC CDR2 sequence, and a HC CDR3 sequence as listed in table 16;(b) a HC CDR1, a HC CDR2, and a HC CDR3 comprising the HC CDR1 sequence, a HC CDR2 sequence, and a HC CDR3 sequence according to Kabat numbering as listed in table 16;(c) a HC CDR1, a HC CDR2, and a HC CDR3 comprising the HC CDR1 sequence, a HC CDR2 sequence, and a HC CDR3 sequence according to Chothia numbering as listed in table 16;(d) a HC CDR1, a HC CDR2, and a HC CDR3 comprising the HC CDR1 sequence, a HC CDR2 sequence, and a HC CDR3 sequence according to IMGT numbering as listed in table 16;(ii) a VL comprising:(a) a LC CDR1, a LC CDR2, and a LC CDR3 comprising the LC CDR1 sequence, a LC CDR2 sequence, and a LC CDR3 sequence as listed in table 16;(b) a LC CDR1, a LC CDR2, and a LC CDR3 comprising the LC CDR1 sequence, a LC CDR2 sequence, and a LC CDR3 sequence according to Kabat numbering as listed in table 16;(c) a LC CDR1, a LC CDR2, and a LC CDR3 comprising the LC CDR1 sequence, a LC CDR2 sequence, and a LC CDR3 sequence according to Chothia numbering as listed in table 16;(d) a LC CDR1, a LC CDR2, and a LC CDR3 comprising the LC CDR1 sequence, a LC CDR2 sequence, and a LC CDR3 sequence according to IMGT numbering as listed in table 16; or(iii) any combination thereof,with the proviso that:(A) the HC CDR1, the HC CDR2, the HC CDR3, the LC CDR1, the LC CDR2, and the LC CDR3 are not GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), respectively; or(B) the HC CDR1, the HC CDR2, the HC CDR3, the LC CDR1, the LC CDR2, and the LC CDR3 are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), respectively, and the VH comprises a sequence having at least 97.5%, 98%, 98.5%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

[0019] In some embodiments,(1) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of;(a) SEQ ID NO: 1424, SEQ ID NO: 1425, SEQ ID NO: 1426 or 1513, respectively;(b) SEQ ID NO: 1427, SEQ ID NO: 1425, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1428, SEQ ID NO: 1429, SEQ ID NO: 1426 or 1513, respectively; or(d) SEQ ID NO: 1430, SEQ ID NO: 1431, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of:(a) SEQ ID NO: 1433, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1436, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(2) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of: (a) SEQ ID NO: 1424, SEQ ID NO: 1439, SEQ ID NO: 1426 or 1513, respectively;(b) SEQ ID NO: 1427, SEQ ID NO: 1439, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1428, SEQ ID NO: 1440, SEQ ID NO: 1426 or 1513, respectively; or(d) SEQ ID NO: 1430, SEQ ID NO: 1441, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of: (a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively, or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(3) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of: (a) SEQ ID NO: 1424, SEQ ID NO: 1444, SEQ ID NO: 1426 or 1513, respectively;(b) SEQ ID NO: 1427, SEQ ID NO: 1444, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1428, SEQ ID NO: 1445, SEQ ID NO: 1426 or 1513, respectively; or(d) SEQ ID NO: 1430, SEQ ID NO: 1446, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of: (a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(4) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of: (a) SEQ ID NO: 1447, SEQ ID NO: 1444, SEQ ID NO: 1426 or 1513, respectively;(b) SEQ ID NO: 1448, SEQ ID NO: 1444, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1449, SEQ ID NO: 1445, SEQ ID NO: 1426 or 1513, respectively; or(d) SEQ ID NO: 1450, SEQ ID NO: 1446, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of: (a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(5) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of: (a) SEQ ID NO: 1447, SEQ ID NO: 1451, SEQ ID NO: 1426 or 1513, respectively;(b) SEQ ID NO: 1448, SEQ ID NO: 1451, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1449, SEQ ID NO: 1452, SEQ ID NO: 1426 or 1513, respectively; or(d) SEQ ID NO: 1450, SEQ ID NO: 1453, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of: (a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(6) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of:(a) SEQ ID NO: 1424, SEQ ID NO: 1454, SEQ ID NO: 1426 or 1513, respectively;(b) SEQ ID NO: 1427, SEQ ID NO: 1454, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1428, SEQ ID NO: 1455, SEQ ID NO: 1426 or 1513, respectively; or(d) SEQ ID NO: 1430, SEQ ID NO: 1456, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of: (a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(7) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of: (a) SEQ ID NO: 1457, SEQ ID NO: 1458, SEQ ID NO: 1426 or 1513, respectively;(b) SEQ ID NO: 1459, SEQ ID NO: 1458, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1460, SEQ ID NO: 1461, SEQ ID NO: 1426 or 1513, respectively; or(d) SEQ ID NO: 1462, SEQ ID NO: 1463, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of: (a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(8) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of: (a) SEQ ID NO: 1424, SEQ ID NO: 1464, SEQ ID NO: 1426 or 1513, respectively;(b) SEQ ID NO: 1427, SEQ ID NO: 1464, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1428, SEQ ID NO: 1465, SEQ ID NO: 1426 or 1513, respectively; or(d) SEQ ID NO: 1430, SEQ ID NO: 1466, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of: (a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(9) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of: (a) SEQ ID NO: 1424, SEQ ID NO: 1467, SEQ ID NO: 1426 or 1513, respectively;(b) SEQ ID NO: 1427, SEQ ID NO: 1467, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1428, SEQ ID NO: 1468, SEQ ID NO: 1426 or 1513, respectively; or(d) SEQ ID NO: 1430, SEQ ID NO: 1469, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of: (a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(10) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of: (a) SEQ ID NO: 1424, SEQ ID NO: 1451, SEQ ID NO: 1426 or 1513, respectively;(b) SEQ ID NO: 1427, SEQ ID NO: 1451, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1428, SEQ ID NO: 1452, SEQ ID NO: 1426 or 1513, respectively; or(d) SEQ ID NO: 1430, SEQ ID NO: 1453, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of: (a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(11) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of: (a) SEQ ID NO: 1470, SEQ ID NO: 1464, SEQ ID NO: 1426 or 1513, respectively;(b) SEQ ID NO: 1471, SEQ ID NO: 1464, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1472, SEQ ID NO: 1465, SEQ ID NO: 1426 or 1513, respectively; or(d) SEQ ID NO: 1473, SEQ ID NO: 1466, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of: (a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(12) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of: (a) SEQ ID NO: 1470, SEQ ID NO: 1444, SEQ ID NO: 1426 or 1513, respectively;(b) SEQ ID NO: 1471, SEQ ID NO: 1444, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1472, SEQ ID NO: 1445, SEQ ID NO: 1426 or 1513, respectively; or(d) SEQ ID NO: 1473, SEQ ID NO: 1446, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of: (a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(13) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of: (a) SEQ ID NO: 1470, SEQ ID NO: 1467, SEQ ID NO: 1426 or 1513, respectively;(b) SEQ ID NO: 1471, SEQ ID NO: 1467, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1472, SEQ ID NO: 1468, SEQ ID NO: 1426 or 1513, respectively; or(d) SEQ ID NO: 1473, SEQ ID NO: 1469, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of: (a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof; or(14) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of: (a) SEQ ID NO: 1470, SEQ ID NO: 1451, SEQ ID NO: 1426 or 1513, respectively;(b) SEQ ID NO: 1471, SEQ ID NO: 1451, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1472, SEQ ID NO: 1452, SEQ ID NO: 1426 or 1513, respectively; or(d) SEQ ID NO: 1473, SEQ ID NO: 1453, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of:(a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof,with the proviso that when the HC CDR1, the HC CDR2, the HC CDR3, the LC CDR1, the LC CDR2, and the LC CDR3 are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), respectively, the VH comprises a sequence having at least 97.5%, 98%, 98.5%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

[0020] In some embodiments, the anti-TCRβV27 antibody molecule or the anti-TCRβV27 antigen binding domain comprises the VH and the VL respectively comprising a HC CDR1, a HC CDR2, and a HC CDR3, and a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of;(i) SEQ ID NOs: 1424, 1425, and 1426, and SEQ ID NOs: 1433, 1434, and 1438, respectively;(ii) SEQ ID NOs: 1427, 1425, and 1426, and SEQ ID NOs: 1433, 1434, and 1438, respectively;(iii) SEQ ID NOs: 1428, 1429, and 1426, and SEQ IDNOs: 1433, 1434, and 1438, respectively;(iv) SEQ ID NOs: 1430, 1431, and 1432, and SEQ ID NOs: 1436, 1437, and 1438, respectively;(v) SEQ ID NOs: 1424, 1439, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(vi) SEQ ID NOs: 1427, 1439, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(vii) SEQ ID NOs: 1428, 1440, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(viii) SEQ ID NOs: 1430, 1441, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively;(ix) SEQ ID NOs: 1424, 1444, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(x) SEQ ID NOs: 1427, 1444, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xi) SEQ ID NOs: 1428, 1445, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xii) SEQ ID NOs: 1430, 1446, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively;(xiii) SEQ ID NOs: 1447, 1444, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xiv) SEQ ID NOs: 1448, 1444, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xv) SEQ ID NOs: 1449, 1445, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xvi) SEQ ID NOs: 1450, 1446, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively;(xvii) SEQ ID NOs: 1447, 1451, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xviii) SEQ ID NOs: 1448, 1451, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xix) SEQ ID NOs: 1449, 1452, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xx) SEQ ID NOs: 1450, 1453, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively;(xxi) SEQ ID NOs: 1424, 1454, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xxii) SEQ ID NOs: 1427, 1454, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xxiii) SEQ ID NOs: 1428, 1455, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xxiv) SEQ ID NOs: 1430, 1456, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively;(xxv) SEQ ID NOs: 1457, 1458, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xxvi) SEQ ID NOs: 1459, 1458, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xxvii) SEQ ID NOs: 1460, 1461, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xxviii) SEQ ID NOs: 1462, 1463, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively; (xxix) SEQ ID NOs: 1424, 1464, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xxx) SEQ ID NOs: 1427, 1464, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xxxi) SEQ ID NOs: 1428, 1465, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xxxii) SEQ ID NOs: 1430, 1466, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively; (xxxiii) SEQ ID NOs: 1424, 1467, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xxxiv) SEQ ID NOs: 1427, 1467, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xxxv) SEQ ID NOs: 1428, 1468, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xxxvi) SEQ ID NOs: 1430, 1469, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively; (xxxvii) SEQ ID NOs: 1424, 1451, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xxxviii) SEQ ID NOs: 1427, 1451, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xxxix) SEQ ID NOs: 1428, 1452, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xl) SEQ ID NOs: 1430, 1453, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively;(xli) SEQ ID NOs: 1470, 1464, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xlii) SEQ ID NOs: 1471, 1464, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xliii) SEQ ID NOs: 1472, 1465, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xliv) SEQ ID NOs: 1473, 1466, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively;(xlv) SEQ ID NOs: 1470, 1444, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xlvi) SEQ ID NOs: 1471, 1444, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xlvii) SEQ ID NOs: 1472, 1445, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xlviii) SEQ ID NOs: 1473, 1446, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively; (xlix) SEQ ID NOs: 1470, 1467, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(1) SEQ ID NOs: 1471, 1467, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(li) SEQ ID NOs: 1472, 1468, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(lii) SEQ ID NOs: 1473, 1469, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively;(liii) SEQ ID NOs: 1470, 1451, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(liv) SEQ ID NOs: 1471, 1451, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(lv) SEQ ID NOs: 1472, 1452, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; or (lvi) SEQ ID NOs: 1473, 1453, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively, with the proviso that when the HC CDR1, the HC CDR2, the HC CDR3, the LC CDR1, the LC CDR2, and the LC CDR3 are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), respectively, the VH comprises a sequence having at least 97.5%, 98%, 98.5%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

[0021] In some embodiments, the VH comprise a sequence having at least 70%, 75%, 80%, 85%, 90%,95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VH sequences listed in Table 16,with the proviso that when the VH comprises the HC CDR1, the HC CDR2, and the HC CDR3 that are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), and GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), and the VL comprises the LC CDR1, the LC CDR2, and the LC CDR3 that are RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), the VH sequence has at least 97.5%, 98%, 98.5%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

[0022] In some embodiments, the VL comprise a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VL sequences listed in Table 16,with the proviso that when the VH comprises the HC CDR1, the HC CDR2, and the HC CDR3 that are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), and GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), and the VL comprises the LC CDR1, the LC CDR2, and the LC CDR3 that are RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), the VH sequence has at least 97.5%, 98%, 98.5%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

[0023] In some embodiments, the VH comprise a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VH sequences listed in Table 16 and the VL comprise a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VL sequences listed in Table 16,with the proviso that when the VH comprises the HC CDR1, the HC CDR2, and the HC CDR3 that are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), and GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), and the VL comprises the LC CDR1, the LC CDR2, and the LC CDR3 that are RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), the VH sequence has at least 97.5%, 98%, 98.5%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

[0024] In some embodiments, the VH comprise any one of the VH sequences listed in Table 16.

[0025] In some embodiments, the VL comprise any one of the VL sequences listed in Table 16.

[0026] In some embodiments, the VH comprise any one of the VH sequences listed in Table 16 and the VL comprise any one of the VL sequences listed in Table 16.

[0027] In some embodiments, the VH comprise a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VH sequences selected from the group consisting of SEQ ID NOs: 1401, 1403, 1405, 1407, 1409,1410, 1411, 1412, 1414, 1415, 1416, 1417, 1418, 1419, 1420, 1421, 1422, and 1423, with the proviso that when the VH comprises the HC CDR1, the HC CDR2, and the HC CDR3 that are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), and GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), and the VL comprises the LC CDR1, the LC CDR2, and the LC CDR3 that are RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), the VH sequence has at least 97.5%, 98%, 98.5%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

[0028] In some embodiments, the VL comprise a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VL sequences selected from the group consisting of SEQ ID NOs: 1402, 1404, 1406, 1408, and 1413,with the proviso that when the VH comprises the HC CDR1, the HC CDR2, and the HC CDR3 that are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), and GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), and the VL comprises the LC CDR1, the LC CDR2, and the LC CDR3 that are RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), the VH sequence has at least 97.5%, 98%, 98.5%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

[0029] In some embodiments, the VH comprise any one of the VH sequences selected from the group consisting of SEQ ID NOs: 1423, 1401, 1403, 1405, 1407, 1409, 1410, 1411, 1412, 1414, 1415, 1416, 1417, 1418, 1419, 1420, 1421, and 1422.

[0030] In some embodiments, the VL comprise any one of the VL sequences selected from the group consisting of SEQ ID NOs: 1413, 1402, 1404, 1406, and 1408,with the proviso that when the VH comprises the HC CDR1, the HC CDR2, and the HC CDR3 that are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), and GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), and the VL comprises the LC CDR1, the LC CDR2, and the LC CDR3 that are RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), the VH sequence has at least 97.5%, 98%, 98.5%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

[0031] In some embodiments,(i) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1423 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413;(ii) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401 andthe VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1402;(iii) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1403 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1404;(iv) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1405 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1406;(v) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1407 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1408;(vi) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1409 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1408;(vii) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1410 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1408;(viii) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1411 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1408;(ix) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1412 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413;(x) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1414 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413;(xi) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1415 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413;(xii) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1416 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413;(xiii) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1417 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413;(xiv) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1418 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413;(xv) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1419 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413;(xvi) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1420 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413;(xvii) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1421 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413; or (xviii) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1422 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413, with the proviso that when the VH comprises the HC CDR1, the HC CDR2, and the HC CDR3 that are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), and GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), and the VL comprises the LC CDR1, the LC CDR2, and the LC CDR3 that are RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), the VH sequence has at least 97.5%, 98%, 98.5%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

[0032] In some embodiments,(i) the VH comprises the sequence of SEQ ID NO: 1423 and the VL comprises the sequence of 1413; (ii) the VH comprises the sequence of SEQ ID NO: 1401 and the VL comprises the sequence of 1402;(iii) the VH comprises the sequence of SEQ ID NO: 1403 and the VL comprises the sequence of 1404; (iv) the VH comprises the sequence of SEQ ID NO: 1405 and the VL comprises the sequence of 1406; (v) the VH comprises the sequence of SEQ ID NO: 1407 and the VL comprises the sequence of 1408; (vi) the VH comprises the sequence of SEQ ID NO: 1409 and the VL comprises the sequence of 1408; (vii) the VH comprises the sequence of SEQ ID NO: 1410 and the VL comprises the sequence of 1408; (viii) the VH comprises the sequence of SEQ ID NO: 1411 and the VL comprises the sequence of 1408; (ix) the VH comprises the sequence of SEQ ID NO: 1412 and the VL comprises the sequence of 1413; (x) the VH comprises the sequence of SEQ ID NO: 1414 and the VL comprises the sequence of 1413; (xi) the VH comprises the sequence of SEQ ID NO: 1415 and the VL comprises the sequence of 1413; (xii) the VH comprises the sequence of SEQ ID NO: 1416 and the VL comprises the sequence of 1413; (xiii) the VH comprises the sequence of SEQ ID NO: 1417 and the VL comprises the sequence of 1413; (xiv) the VH comprises the sequence of SEQ ID NO: 1418 and the VL comprises the sequence of 1413; (xv) the VH comprises the sequence of SEQ ID NO: 1419 and the VL comprises the sequence of 1413; (xvi) the VH comprises the sequence of SEQ ID NO: 1420 and the VL comprises the sequence of 1413; (xvii) the VH comprises the sequence of SEQ ID NO: 1421 and the VL comprises the sequence of 1413; or(xviii) the VH comprises the sequence of SEQ ID NO: 1422 and the VL comprises the sequence of 1413.

[0033] In some embodiments, the anti-TCRpV27 antibody molecule or the anti-TCR(3V27 antigen binding domain binds to a TCR V region of TCRPV27.

[0034] In some embodiments, the anti-TCRpV27 antibody molecule or the anti-TCRβV27 antigen binding domain binds to a TCR V region of human TCR V27.

[0035] In some embodiments, the anti-TCR(3V27 antibody molecule or the anti-TCR(3V27 antigen binding domain comprises any one selected from the group consisting of a full-length antibody, a Fab, a F(ab')2, an Fv, a single chain Fv, a camelid antibody, a VHH, a half arm antibody, a diabody, a bivalent antibody, a monovalent antibody, or a bispecific antibody, and any combination thereof.

[0036] In some embodiments, the molecule is a multispecific molecule.

[0037] In some embodiments, the multispecific molecule further comprises one or more molecule that binds to a co-stimulatory receptor of a T cell.

[0038] In some embodiments, the one or more molecule that binds to a co-stimulatory receptor of a T cell activates the co-stimulatory receptor when the one or more molecule that binds to a co-stimulatory receptor of a T cell binds to the co-stimulatory receptor.

[0039] In some embodiments, the one or more molecule that binds to a co-stimulatory receptor of a T cell comprises at least one cytokine molecule or a functional fragment or functional variant thereof.

[0040] In some embodiments, the at least one cytokine molecule or a functional fragment or functional variant thereof is selected from the group consisting of interleukin-2 (IL-2) or a functional fragment or functional variant thereof, interleukin-7 (IL-7) or a functional fragment or functional variant thereof, interleukin- 12 (IL- 12) or a functional fragment or functional variant thereof, interleukin- 15 (IL- 15) or a functional fragment or functional variant thereof, interleukin- 18 (IL- 18) or a functional fragment orfunctional variant thereof, interleukin-21 (IL-21) or a functional fragment or functional variant thereof, or interferon gamma or a functional fragment or functional variant thereof, or any combination thereof.

[0041] In some embodiments, the at least one cytokine molecule or a functional fragment or functional variant thereof comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the cytokine sequences listed in Table 17.

[0042] In some embodiments, the at least one cytokine molecule or a functional fragment or functional variant thereof comprises any one of the cytokine sequences listed in Table 17.

[0043] In some embodiments, the at least one cytokine molecule or a functional fragment or functional variant thereof comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the sequences selected from the group consisting of SEQ ID NOs: 2191, 2270, 2280, 3542, 3543, 3545, 2170, 3799, 3523, 2193, 5000-5036, 5052, 5053, 5054, and 5037.

[0044] In some embodiments, the at least one cytokine molecule or a functional fragment or functional variant thereof comprises any one of the sequences selected from the group consisting of SEQ ID NOs: 2191, 2270, 2280, 3542, 3543, 3545, 2170, 3799, 3523, 2193, 5000-5036, 5052, 5053, 5054, and 5037.

[0045] In some embodiments, the at least one cytokine molecule or a functional fragment or functional variant thereof comprises interleukin-2 (IL-2) or a functional fragment or functional variant thereof.

[0046] In some embodiments, the at least one cytokine molecule or a functional fragment or functional variant thereof is an IL-2 variant comprising a substitution mutation.

[0047] In some embodiments, the at least one cytokine molecule or a functional fragment or functional variant thereof is an IL-2 variant comprising C125A mutation.

[0048] In some embodiments, the at least one cytokine molecule or a functional fragment or functional variant thereof comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 2270.

[0049] In some embodiments, the at least one cytokine molecule or a functional fragment or functional variant thereof comprises the sequence of SEQ ID NO: 2270.

[0050] In some embodiments, the at least one cytokine molecule or a functional fragment or functional variant thereof comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 2191.

[0051] In some embodiments, the at least one cytokine molecule or a functional fragment or functional variant thereof comprises the sequence of SEQ ID NO: 2191.

[0052] In some embodiments, the one or more molecule that binds to a co-stimulatory receptor of a T cell comprises an antibody molecule, an antigen binding domain, a ligand, an extra-cellular domain of a receptor, or any combination thereof.

[0053] In some embodiments, the antibody molecule or the antigen binding domain comprises any oneselected from the group consisting of a full-length antibody, a Fab, a F(ab')2, an Fv, a single chain Fv, a camelid antibody, a VHH, a half arm antibody, a diabody, a bivalent antibody, a monovalent antibody, or a bispecific antibody, and any combination thereof.

[0054] In some embodiments, the one or more molecule that binds to a co-stimulatory receptor of a T cell binds to CD2, 4-1BB, CD27, CD28, or any combination thereof

[0055] In some embodiments, the multispecific molecule further comprises one or more TCR binding moiety.

[0056] In some embodiments, the one or more TCR binding moiety binds to a T cell receptor alpha (TCRa) chain, a T cell receptor beta (TCRP) chain, a T cell receptor gamma (TC Ry) chain, a T cell receptor delta (TCR5) chain, a CD3 gamma (CD3y) chain, a CD3 delta (CD35) chain, a CD3 epsilon (CD3s) chain, a CD3 zeta (CD3Q chain, or any combination thereof.

[0057] In some embodiments, the one or more TCR binding moiety binds to a T cell receptor beta (TCR0) chain.

[0058] In some embodiments, the one or more TCR binding moiety binds to a T cell receptor beta variable (TCRPV) region.

[0059] In some embodiments, the one or more TCR binding moiety binds to a TCRPV region of human TCRPV1, human TCRPV2, human TCRPV3, human TCRPV4, human TCRPV5, human TCRPV6, human TCRpV7, human TCRpV8, human TCRpV9, human TCRpVIO, human TCRpVll, human TCRpV12, human TCRPV19, human TCRPV20, human TCRPV21, hu-man TCRPV23, human TCRPV24, human TCRPV25, human TCRPV26, human TCRPV27, human TCRPV28, human TCRPV29, human TCRPV30, or any combination thereof.

[0060] In some embodiments, the one or more TCR binding moiety binds to a TCRPV region of human TCRpV2, human TCRpV4-l, human TCRpV4-2, human TCRpV5-l, hu-man TCRpV5-5, human TCRpV5-6, human TCRpV6, human TCRpV6-5, human TCRpV6-6, hu-man TCRpV6-9, human TCRPV7-2, human TCRPV7-3, human TCRPV7-8, human TCRPV7-9, human TCRPV9, human TCRpV10-l, human TCRpV10-2, human TCRPV10-3, human TCRpVll-2, human TCRPV12-3, human TCRPV 12-4, human TCRPV 12-5, human TCRPV 19, human TCRPV20-1, human TCRPV21, human TCRPV24-1, human TCRPV25-1, human TCRPV28, or any combination thereof.

[0061] In some embodiments, the one or more TCR binding moiety binds to a TCRPV region of human TCRPV2, human TCRPV3-1, human TCRPV4-1, human TCRPV4-2, hu-man TCRPV5-1, human TCRpV5-4, human TCRPV5-5, human TCRPV5-6, human TCRpV6-l, human TCRPV6-5, human TCRPV6-6, human TCRPV7-3, human TCRPV7-6, human TCRPV7-8, human TCRPV9, human TCRPV 11-2, human TCRPV 19, human TCRPV20-1, human TCRPV24-1, human TCRPV27, human TCRPV28, human TCRPV29-1, human TCRPV30, or any combination thereof.

[0062] In some embodiments, the one or more TCR binding moiety binds to a TCRPV region of human TCRPV5, human TCRPV6, human TCRpVIO, human TCRPV12, human TCRPV20 or any combination thereof.

[0063] In some embodiments, the one or more TCR binding moiety binds to a T cell receptor alpha(TCRa) chain.

[0064] In some embodiments, the one or more TCR binding moiety binds to a T cell receptor alpha variable (TCRaV) region.

[0065] In some embodiments, the one or more TCR binding moiety binds to a TCRaV region of TRAV12-1, TRAV12-2, TRAV12-3, TRAV13-1, TRAV13-2, TRAV19-1, TRAV21-1, TRAV30-1, or any combination thereof.

[0066] In some embodiments, the one or more TCR binding moiety comprises an antibody molecule or an antigen binding domain.

[0067] In some embodiments, the one or more TCR binding moiety comprises an antibody molecule or an antigen binding domain comprising a scFv, a full-length antibody, a Fab, a F(ab')2, an Fv, a single chain Fv, a camelid antibody, a half arm antibody, a diabody, a bivalent antibody, a monovalent antibody, or a bispecific antibody.

[0068] In some embodiments, the one or more TCR binding moiety comprises the antibody molecule or the antigen binding domain comprising a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HC CDR1) sequence comprising any one of the HC CDR1 sequences listed in Tables 1, 2, 12, 13, 14, and 22, a heavy chain complementarity determining region 2 (HC CDR2) sequence comprising any one of the HC CDR2 sequences listed in Tables 1, 2, 12, 13, and 14, and a heavy chain complementarity determining region 3 (HC CDR3) sequence of comprising any one of the HC CDR3 sequences listed in Tables 1, 2, 12, 13, and 14.

[0069] In some embodiments, the one or more TCR binding moiety comprises the antibody molecule or the antigen binding domain comprising a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LC CDR1) sequence comprising any one of the LC CDR1 sequences listed in Tables 1, 2, 12, 13, and 14, a light chain complementarity determining region 2 (LC CDR2) sequence comprising any one of the LC CDR2 sequences listed in Tables 1, 2, 12, 13, and 14, and a light chain complementarity determining region 3 (LC CDR3) sequence of comprising any one of the LC CDR3 sequences listed in Tables 1, 2, 12, 13, and 14.

[0070] In some embodiments, the one or more TCR binding moiety comprises the antibody molecule or the antigen binding domain comprising:(i) a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HC CDR1) sequence comprising any one of the HC CDR1 sequences listed in Tables 1, 2, 12, 13, and 14, a heavy chain complementarity determining region 2 (HC CDR2) sequence comprising any one of the HC CDR2 sequences listed in Tables 1, 2, 12, 13, and 14, and a heavy chain complementarity determining region 3 (HC CDR3) sequence of comprising any one of the HC CDR3 sequences listed in Tables 1, 2, 12, 13, and 14; and(ii) a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LC CDR1) sequence comprising any one of the LC CDR1 sequences listed in Tables 1, 2, 12, 13, and 14, a light chain complementarity determining region 2 (LC CDR2) sequence comprising any one of the LC CDR2 sequences listed in Tables 1, 2, 12, 13, and 14, and a light chain complementarity determining region3 (LC CDR3) sequence of comprising any one of the LC CDR3 sequences listed in Tables 1, 2, 12, 13, and 14.

[0071] In some embodiments, the one or more TCR binding moiety comprises the antibody molecule or the antigen binding domain comprising a VH comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VH sequences listed in Tables 1, 2, 12, 13, and 14.

[0072] In some embodiments, the one or more TCR binding moiety comprises the antibody molecule or the antigen binding domain comprising a VL comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VL sequences listed in Tables 1, 2, 12, 13, and 14.

[0073] In some embodiments, the one or more TCR binding moiety comprises the antibody molecule or the antigen binding domain comprising a VH comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one ofthe VH sequences listed in Tables 1, 2, 12, 13, and 14; and a VL comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one ofthe VL sequences listed in Tables 1, 2, 12, 13, and 14.

[0074] In some embodiments, the one or more TCR binding moiety comprises the antibody molecule or the antigen binding domain comprising a VH comprising any one of the VH sequences listed in Tables 1, 2, 12, 13, and 14.

[0075] In some embodiments, the one or more TCR binding moiety comprises the antibody molecule or the antigen binding domain comprising a VL comprising any one of the VL sequences listed in Tables 1, 2, 12, 13, and 14.

[0076] In some embodiments, the one or more TCR binding moiety comprises the antibody molecule or the antigen binding domain comprising a VH comprising any one of the VH sequences listed in Tables 1, 2, 12, 13, and 14; and a VL comprising any one of the VL sequences listed in Tables 1, 2, 12, 13, and 14.

[0077] In some embodiments, the multispecific molecule comprises a first poly-peptide chain comprising a first portion of a dimerization module, and a second polypeptide chain comprising a second portion of the dimerization module;wherein the first polypeptide chain and the second polypeptide chain are non-contiguous, and wherein the TCRpV27-binding moiety is operatively linked to the first portion ofthe dimerization module.

[0078] In some embodiments, the one or more molecule that binds to a co-stimulatory receptor of a T cell are operatively linked to the first portion of the dimerization module, the second portion of the dimerization module, or a combination thereof.

[0079] In some embodiments, (i) the TCR(3V27-binding moiety is operatively linked to the N-terminus of the first portion of the dimerization module, and the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the N-terminus of the first portion of the dimerization module, the C-terminus of the first portion of the dimerization module, the N-terminus of the second portion of thedimerization module, the C-terminus of the second portion of the dimerization module, or any combination thereof; or(ii) the TCRβV27 is operatively linked to the C-terminus of the first portion of the dimerization module, and the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the N-terminus of the first portion of the dimerization module, the C-terminus of the first portion of the dimerization module, the N-terminus of the second portion of the dimerization module, the C-terminus of the second portion of the dimerization module, or any combination thereof.

[0080] In some embodiments, the TCRβV27-binding moiety and the one or more molecule that binds to a co-stimulatory receptor of a T cell is within a single contiguous polypeptide chain of the first polypeptide chain.

[0081] In some embodiments, the TCRpV27-binding moiety and the one or more molecule that binds to a co-stimulatory receptor of a T cell are operatively linked to the first portion of the dimerization module.

[0082] In some embodiments, the TCRpV27-binding moiety and the one or more molecule that binds to a co-stimulatory receptor of a T cell are operatively linked to the N-terminus of the first portion of the dimerization module.

[0083] In some embodiments,(i) the C-terminus of the TCRpV27-binding moiety is operatively linked to the one or more molecule that binds to a co-stimulatory receptor of a T cell operatively linked to the N-terminus of the first portion of the dimerization module; and / or(ii) the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the N-terminus of the TCRpV27-binding moiety operatively linked to the N-terminus of the first portion of the dimerization module.

[0084] In some embodiments, the TCRpV27-binding moiety and the one or more molecule that binds to a co-stimulatory receptor of a T cell are operatively linked to the C-terminus of the first portion of the dimerization module.

[0085] In some embodiments,(i) the N-terminus of the TCRpV27-binding moiety is operatively linked to the C-terminus of the first portion of the dimerization module and the C-terminus of the TCRβV27-binding moiety is operatively linked to the one or more molecule that binds to a co-stimulatory receptor of a T cell; and / or(ii) the N-terminus of the TCRβV27-binding moiety is operatively linked to the one or more molecule that binds to a co-stimulatory receptor of a T cell operatively linked to the C-terminus of the first portion of the dimerization module.

[0086] In some embodiments, the one or more TCR binding moiety are operatively linked to the first portion of the dimerization module, the second portion of the dimerization module, or a combination thereof.

[0087] In some embodiments,(i) the TCRβV27-binding moiety is operatively linked to the N-terminus of the first portion of the dimerization module, and the one or more TCR binding moiety is operatively linked to the N-terminus ofthe first portion of the dimerization module, the C-terminus of the first portion of the dimerization module, the N-terminus of the second portion of the dimerization module, the C-terminus of the second portion of the dimerization module, or any com-bination thereof; or(ii) the TCRβV27 is operatively linked to the C-terminus of the first portion of the dimerization module, and the one or more TCR binding moiety is operatively linked to the N-terminus of the first portion of the dimerization module, the C-terminus of the first portion of the dimerization module, the N-terminus of the second portion of the dimerization mod-ule, the C-terminus of the second portion of the dimerization module, or any combination thereof.

[0088] In some embodiments, the TCRβV27-binding moiety and the one or more TCR binding moiety is within a single contiguous polypeptide chain of the first polypeptide chain.

[0089] In some embodiments, the TCRβV27-binding moiety and the one or more TCR binding moiety are operatively linked to the first portion of the dimerization module.

[0090] In some embodiments, the TCRβV27-binding moiety and the one or more TCR binding moiety are operatively linked to the N-terminus of the first portion of the dimerization module.

[0091] In some embodiments,(i) the C-terminus of the TCRβV27-binding moiety is operatively linked to the one or more TCR binding moiety operatively linked to the N-terminus of the first portion of the dimerization module; and / or (ii) the one or more TCR binding moiety is operatively linked to the N-terminus of the TCR(3V27-binding moiety operatively linked to the N-terminus of the first portion of the dimerization module.

[0092] In some embodiments, the TCRβV27-binding moiety and the one or more TCR binding moiety are operatively linked to the C-terminus of the first portion of the dimerization module.

[0093] In some embodiments,(i) the N-terminus of the TCRpV27-binding moiety is operatively linked to the C-terminus of the first portion of the dimerization module and the C-terminus of the TCRβV27-binding moiety is operatively linked to the one or more TCR binding moiety; and / or(ii) the N-terminus of the TCRβV27-binding moiety is operatively linked to the one or more TCR binding moiety operatively linked to the C-terminus of the first portion of the dimerization module.

[0094] In some embodiments,(i) the one or more TCR binding moiety are operatively linked to the first portion of the dimerization module and the one or more TCR binding moiety are operatively linked to the first portion of the dimerization module, the second portion of the dimerization module, or a combination thereof; or (ii) the one or more TCR binding moiety are operatively linked to the second portion of the dimerization module and the one or more TCR binding moiety are operatively linked to the first portion of the dimerization module or the second portion of the dimerization module, or a combination thereof.

[0095] In some embodiments,(i) the TCRβV27-binding moiety is operatively linked to the N-terminus of the first portion of the dimerization module, the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the N-terminus of the first portion of the dimerization module, the C-terminus of thefirst portion of the dimerization module, the N-terminus of the second portion of the dimerization module, the C-terminus of the second portion of the dimerization module, or any combination thereof, and the one or more TCR binding moiety is operatively linked to the N-terminus of the first portion of the dimerization module, the C-terminus of the first portion of the dimerization module, the N-terminus of the second portion of the dimerization module, the C-terminus of the second portion of the dimerization module, or any combination thereof; or(ii) the TCRPV27 is operatively linked to the C-terminus of the first portion of the dimerization module, and the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the N-terminus of the first portion of the dimerization module, the C-terminus of the first portion of the dimerization module, the N-terminus of the second portion of the dimerization module, the C-terminus of the second portion of the dimerization module, or any combination thereof, and the one or more TCR binding moiety is operatively linked to the N-terminus of the first portion of the dimerization module, the C-terminus of the first portion of the dimerization module, the N-terminus of the second portion of the dimerization module, the C-terminus of the second portion of the dimerization module, or any combination thereof.

[0096] In some embodiments, the TCRpV27-binding moiety and the one or more molecule that binds to a co-stimulatory receptor of a T cell, the TCRpV27-binding moiety and the one or more TCR binding moiety, the one or more molecule that binds to a co-stimulatory receptor of a T cell and the one or more TCR binding moiety, or the TCRpV27-binding moiety, the one or more molecule that binds to a co-stimulatory receptor of a T cell and the one or more TCR binding moiety are within a single contiguous polypeptide chain of the first polypeptide chain.

[0097] In some embodiments, the TCRpV27-binding moiety, the one or more molecule that binds to a co-stimulatory receptor of a T cell and the one or more TCR binding moiety are operatively linked to the first portion of the dimerization module.

[0098] In some embodiments, the TCRpV27-binding moiety, the one or more molecule that binds to a co-stimulatory receptor of a T cell and the one or more TCR binding moiety are operatively linked to the N-terminus of the first portion of the dimerization module.

[0099] In some embodiments,(i) the C-terminus of the TCRpV27-binding moiety is operatively linked to the one or more molecule that binds to a co-stimulatory receptor of a T cell operatively linked to the one or more TCR binding moiety operatively linked to the N-terminus of the first portion of the dimerization module;(ii) the C-terminus of the TCRpV27-binding moiety is operatively linked to the one or more TCR binding moiety operatively linked to the one or more molecule that binds to a co-stimulatory receptor of a T cell operatively linked to the N-terminus of the first portion of the dimerization module;(iii) the C-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the TCRβV27-binding moiety operatively linked to the one or more TCR binding moiety operatively linked to the N-terminus of the first portion of the dimerization module;(iv) the C-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell isoperatively linked to the one or more TCR binding moiety operatively linked to the TCRpV27-binding moiety operatively linked to the N-terminus of the first portion of the dimerization module;(v) the C-terminus of the one or more TCR binding moiety is operatively linked to the TCRpV27-binding moiety operatively linked to the one or more molecule that binds to a co-stimulatory receptor of a T cell operatively linked to the N-terminus of the first portion of the dimerization module; and / or(vi) the C-terminus of the one or more TCR binding moiety is operatively linked to the one or more molecule that binds to a co-stimulatory receptor of a T cell operatively linked to the TCRpV27-binding moiety operatively linked to the N-terminus of the first portion of the dimerization module,

[0100] In some embodiments, the TCRpV27-binding moiety, the one or more molecule that binds to a co-stimulatory receptor of a T cell and the one or more TCR binding moiety are operatively linked to the C-terminus of the first portion of the dimerization module.

[0101] In some embodiments,(i) the C-terminus of the first portion of the dimerization module is operatively linked to the N-terminus of the TCRpV27-binding moiety, and the C-terminus of the TCRpV27-binding moiety is operatively linked to the one or more molecule that binds to a co-stimulatory receptor of a T cell operatively linked to the one or more TCR binding moiety;(ii) the C-terminus of the first portion of the dimerization module is operatively linked to the N-terminus of the TCRpV27-binding moiety, and the C-terminus of the TCRpV27-binding moiety is operatively linked to the one or more TCR binding moiety operatively linked to the one or more molecule that binds to a co-stimulatory receptor of a T cell;(iii) the C-terminus of the first portion of the dimerization module is operatively linked to the N-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell, and the C-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the TCRβV27-binding moiety operatively linked to the one or more TCR binding moiety;(iv) the C-terminus of the first portion of the dimerization module is operatively linked to the N-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell, and the C-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the one or more TCR binding moiety operatively linked to the TCR(3V27-binding moiety;(v) the C-terminus of the first portion of the dimerization module is operatively linked to the N-terminus of the one or more TCR binding moiety, and the C-terminus of the one or more TCR binding moiety is operatively linked to the TCRβV27-binding moiety operatively linked to the one or more molecule that binds to a co-stimulatory receptor of a T cell; and / or(vi) the C-terminus of the first portion of the dimerization module is operatively linked to the N-terminus of the one or more TCR binding moiety, and the C-terminus of the one or more TCR binding moiety is operatively linked to the one or more molecule that binds to a co-stimulatory receptor of a T cell operatively linked to the TCRβV27-binding moiety.

[0102] In some embodiments, the one or more molecule that binds to a co-stimulatory receptor of a T cell and the one or more TCR binding moiety is within a single contiguous polypeptide chain of the secondpolypeptide chain.

[0103] In some embodiments, the one or more molecule that binds to a co-stimulatory receptor of a T cell and the one or more TCR binding moiety are operatively linked to the second portion of the dimerization module.

[0104] In some embodiments, the one or more molecule that binds to a co-stimulatory receptor of a T cell and the one or more TCR binding moiety are operatively linked to the N-terminus of the second portion of the dimerization module.

[0105] In some embodiments,(i) the C-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the one or more TCR binding moiety operatively linked to the N-terminus of the second portion of the dimerization module; and / or(ii) the one or more TCR binding moiety is operatively linked to the N-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell operatively linked to the N-terminus of the second portion of the dimerization module.

[0106] In some embodiments, the one or more molecule that binds to a co-stimulatory receptor of a T cell and the one or more TCR binding moiety are operatively linked to the C-terminus of the second portion of the dimerization module.

[0107] In some embodiments,(i) the N-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the C-terminus of the second portion of the dimerization module and the C-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the one or more TCR binding moiety; and / or(ii) the N-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the one or more TCR binding moiety operatively linked to the C-terminus of the second portion of the dimerization module.

[0108] In some embodiments, the one or more molecule that binds to a co-stimulatory receptor of a T cell and the one or more TCR binding moiety is within a single contiguous polypeptide chain of the first polypeptide chain.

[0109] In some embodiments, the one or more molecule that binds to a co-stimulatory receptor of a T cell and the one or more TCR binding moiety are operatively linked to the first portion of the dimerization module.

[0110] In some embodiments, the one or more molecule that binds to a co-stimulatory receptor of a T cell and the one or more TCR binding moiety are operatively linked to the N-terminus of the first portion of the dimerization module.

[0111] In some embodiments,(i) the C-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the one or more TCR binding moiety operatively linked to the N-terminus of the first portion of the dimerization module; and / or(ii) the one or more TCR binding moiety is operatively linked to the N-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell operatively linked to the N-terminus of the first portion of the dimerization module.

[0112] In some embodiments, the one or more molecule that binds to a co-stimulatory receptor of a T cell and the one or more TCR binding moiety are operatively linked to the C-terminus of the first portion of the dimerization module.

[0113] In some embodiments,(i) the N-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the C-terminus of the first portion of the dimerization module and the C-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the one or more TCR binding moiety; and / or(ii) the N-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the one or more TCR binding moiety operatively linked to the C-terminus of the first portion of the dimerization module.

[0114] In some embodiments, the TCRβV27-binding moiety comprises a VH and a VL, or a single domain antibody.

[0115] In some embodiments, the TCRβV27-binding moiety comprises a first portion of TCRβV27-binding moiety, andwherein the multispecific molecule further comprises a third polypeptide chain comprising a second portion of the TCRβV27-binding moiety, wherein the third polypeptide chain is non-contiguous with the first polypeptide chain and the second polypeptide chain.

[0116] In some embodiments, the first portion of the TCRpV27-binding moiety comprises a VH of the TCRpV27-binding moiety and the second portion of the TCRpV27-binding moiety comprises a VL of the TCRpV27-binding moiety, or the first portion of the TCRpV27-binding moiety comprises a VL of the TCRpV27-binding moiety and the second portion of the TCRpV27-binding moiety comprises a VH of the TCRpV27-binding moiety.

[0117] In some embodiments, the first portion of the dimerization module and the second portion of the dimerization module associates to form a dimer.

[0118] In some embodiments, the first portion of the dimerization module comprises a first immunoglobulin constant region and the second portion of the dimerization module comprises a second immunoglobulin constant region.

[0119] In some embodiments, the first immunoglobulin constant region comprises a first Fc region and the second immunoglobulin constant region comprises a second Fc region.

[0120] In some embodiments, the first Fc region, the second Fc region, or a combination there-of is selected from the group consisting of an IgGl Fc region or a fragment thereof, an IgG2 Fc region or a fragment thereof, an IgG3 Fc region or a fragment thereof, an IgGAl Fc region or a fragment thereof, an IgGA2 Fc region or a fragment thereof, an IgG4 Fc region or a fragment thereof, an IgJ Fc region or a fragment thereof, an IgM Fc region or a fragment thereof, an IgD Fc region or a fragment thereof, and anIgE Fc region or a fragment thereof.

[0121] In some embodiments, the first Fc region, the second Fc region, or a combination thereof is selected from the group consisting of a human IgGl Fc region or a fragment thereof, a human IgG2 Fc region or a fragment thereof, and a human IgG4 Fc region or a fragment thereof.

[0122] In some embodiments, the first Fc region, the second Fc region, or a com-bination thereof comprises an Fc interface with one or more of: a paired cavity-protuberance, an electrostatic interaction, or a strand-exchange, wherein the dimerization of the first Fc region and the second Fc region is enhanced as indicated by a greater ratio of heteromultimer:homomultimer forms relative to a dimerization of Fc regions with a non-engineered interface.

[0123] In some embodiments, the first Fc region, the second Fc region, or a com-bination thereof comprises an amino acid substitution listed in Table 3, 4, 5, 15, or 22.

[0124] In some embodiments,(i) the first Fc region comprises a mutation that decreases Fc receptor binding relative to a Fc region without the mutation;(ii) the second Fc region comprise a mutation that decreases Fc receptor binding relative to a Fc region without the mutation; or(iii) a combination thereof.

[0125] In some embodiments, the mutation that decreases Fc receptor binding is an N297A mutation according to EU Numbering in a heavy chain constant region.

[0126] In some embodiments, the first Fc region, the second Fc region, or a com-bination thereof comprises an Asn297Ala (N297A) mutation or a Leu234Ala / Leu235Ala (LALA) mutation according to EU Numbering.

[0127] In some embodiments, the first Fc region and the second Fc region comprise an Fc interface with one or more of: a knob-in-a hole, an electrostatic interaction, or a strand-exchange.

[0128] In some embodiments, the first Fc region is an engineered Fc region comprising a knob and the second Fc region is an engineered Fc region comprising a hole, or the first Fc region is an engineered Fc region comprising a hole and the second Fc region is an engineered Fc region comprising a knob.

[0129] In some embodiments,(A) (i) the first Fc region comprises:(a) Y349C mutation according to EU Numbering,(b) T366S mutation according to EU Numbering,(c) L368A mutation according to EU Numbering, and(d) Y407V mutation according to EU Numbering; and(ii) the second Fc region comprises:(a) S354C mutation according to EU Numbering, and(b) T366W mutation according to EU Numbering; or(B) (i) the first Fc region comprises:(a) S354C mutation according to EU Numbering, and(b) T366W mutation according to EU Numbering; and(ii) the second Fc region comprises:(a) Y349C mutation according to EU Numbering,(b) T366S mutation according to EU Numbering,(c) E368A mutation according to EU Numbering, and(d) Y407V mutation according to EU Numbering.

[0130] In some embodiments, the first Fc region, the second Fc region, or a com-bination thereof comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the Fc region sequences or the heavy chain constant region sequences listed in Tables 3, 15, or 22.

[0131] In some embodiments, the first Fc region, the second Fc region, or a com-bination thereof comprises any one Fc region sequence or heavy chain constant region sequence listed in Tables 3, 15, or 22.

[0132] In some embodiments, the first Fc region, the second Fc region, or a com-bination thereof comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one sequence selected from the group consisting of SEQ ID NOs: 40, 41, 42, 3645, 3646, 3647, 5038, 5108, 5109, 5110, 5111, 5041, 3649, 5044, 5045, 5113, 5048, 5049, 1483, 5039, 5040, 5042, 5043, 5050, 5051, 3648, 5046, 5047, and 5112.

[0133] In some embodiments, the first Fc region and the second Fc region comprise:(i) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 40, 41, 42, 3645, 3646, 3647, 5038, 5108, 5109, 5110, 5111, 5041, 1483, 5039, 5040, 5042, or 5043, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 40, 41, 42, 3645, 3646, 3647, 5108, 5109, 5110, 5111, 5038, 5041, 1483, 5039, 5040, 5042, or 5043, respectively;(ii) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 40, 41, 42, 3645, 3646, 3647, 5038, 5108, 5109, 5110, 5111, or 5041, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 40, 41, 42, 3645, 3646, 3647, 5038, 5108, 5109, 5110, 5111, or 5041, respectively;(iii) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 1483, 5039, 5040, 5042, or 5043, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%.99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 1483, 5039, 5040, 5042, or 5043, respectively; (iv) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 40, 41, 42, 3645, 3646, 3647, 5038,5108, 5109, 5110, 5111, or 5041, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 1483, 5039, 5040, 5042, or 5043, respectively;(v) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 1483, 5039, 5040, 5042, or 5043, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 40, 41, 42, 3645, 3646, 3647, 5038, 5108, 5109, 5110, 5111, or 5041, respectively;(vi) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 3649, 5044, 5045, 5113, 5050, or 5051, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 5048, 5049, 3648, 5046, 5047, or 5112, respectively;(vii) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 5048, 5049, 3648, 5046, 5047, or 5112, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 3649, 5044, 5045, 5113, 5050, or 5051, respectively;(viii) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 3649, 5044, 5045, or 5113, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 5048 or 5049, respectively;(ix) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 5048 or 5049, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 3649, 5044, 5045, or 5113, respectively;(x) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 5050 or 5051, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 3648, 5046, 5047, or 5112, respectively;(xi) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 3648, 5046, 5047, or 5112, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 5050 or 5051, respectively;(xii) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 3649, 5044, 5045, or 5113, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 3648, 5046, 5047, or 5112, respectively;(xiii) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 3648, 5046, 5047, or 5112, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 3649, 5044, 5045, or 5113, respectively; (xiv) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 5048 or 5049, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 5050 or 5051, respectively, or(xv) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 5050 or 5051, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 5048 or 5049, respectively.

[0134] In some embodiments, the first Fc region, the second Fc region, or a com-bination thereof comprises any one sequence selected from the group consisting of SEQ ID NOs: 40, 41, 42, 3645, 3646, 3647, 5038, 5108, 5109, 5110, 5111, 5041, 3649, 5044, 5045, 5113, 5048, 5049, 1483, 5039, 5040, 5042, 5043, 5050, 5051, 3648, 5046, 5047, and 5112.

[0135] In some embodiments, the first Fc region and the second Fc region comprise:(i) any one sequence selected from the group consisting of SEQ ID NOs: 40, 41, 42, 3645, 3646, 3647, 5038, 5108, 5109, 5110, 5111, 5041, 1483, 5039, 5040, 5042, and 5043, and any one sequence selected from the group consisting of SEQ ID NOs: 40, 41, 42, 3645, 3646, 3647, 5108, 5109, 5110, 5111, 5038, 5041, 1483, 5039, 5040, 5042, and 5043, respectively;(ii) any one sequence selected from the group consisting of SEQ ID NOs: 40, 41, 42, 3645, 3646, 3647, 5038, 5108, 5109, 5110, 5111, and 5041, and any one sequence selected from the group consisting of SEQ ID NOs: 40, 41, 42, 3645, 3646, 3647, 5038, 5108, 5109, 5110, 5111, and 5041, respectively;(iii) any one sequence selected from the group consisting of SEQ ID NOs: 1483, 5039, 5040, 5042, and 5043, and any one sequence selected from the group consisting of SEQ ID NOs: 1483, 5039, 5040, 5042, and 5043, respectively;(iv) any one sequence selected from the group consisting of SEQ ID NOs: 40, 41, 42, 3645, 3646, 3647, 5038, 5108, 5109, 5110, 5111, and 5041, and any one sequence selected from the group consisting of SEQ ID NOs: 1483, 5039, 5040, 5042, and 5043, respectively;(v) any one sequence selected from the group consisting of SEQ ID NOs: 1483, 5039, 5040, 5042, and 5043, and any one sequence selected from the group consisting of SEQ ID NOs: 40, 41, 42, 3645, 3646, 3647, 5038, 5108, 5109, 5110, 5111, and 5041, respectively;(vi) any one sequence selected from the group consisting of SEQ ID NOs: 3649, 5044, 5045, 5113, 5050, and 5051, and any one sequence selected from the group consisting of SEQ ID NOs: 5048, 5049, 3648, 5046, 5047, and 5112, respectively;(vii) any one sequence selected from the group consisting of SEQ ID NOs: 5048, 5049, 3648, 5046, 5047, and 5112, and any one sequence selected from the group consisting of any one sequence selected from thegroup consisting of SEQ ID NOs: 3649, 5044, 5045, 5113, 5050, and 5051, respectively;(viii) any one sequence selected from the group consisting of SEQ ID NOs: 3649, 5044, 5045, and 5113, and any one sequence selected from the group consisting of SEQ ID NOs: 5048 and 5049, respectively; (ix) any one sequence selected from the group consisting of SEQ ID NOs: 5048 and 5049, and any one sequence selected from the group consisting of SEQ ID NOs: 3649, 5044, 5045, and 5113, respectively; (x) any one sequence selected from the group consisting of SEQ ID NOs: 5050 and 5051, and any one sequence selected from the group consisting of SEQ ID NOs: 3648, 5046, 5047, and 5112, respectively; (xi) any one sequence selected from the group consisting of SEQ ID NOs: 3648, 5046, 5047, and 5112, and any one sequence selected from the group consisting of SEQ ID NOs: 5050 and 5051, respectively; (xii) any one sequence selected from the group consisting of SEQ ID NOs: 3649, 5044, 5045, and 5113, and any one sequence selected from the group consisting of SEQ ID NOs: 3648, 5046, 5047, and 5112, respectively;(xiii) any one sequence selected from the group consisting of SEQ ID NOs: 3648, 5046, 5047, and 5112, and any one sequence selected from the group consisting of SEQ ID NOs: 3649, 5044, 5045, and 5113, respectively;(xiv) any one sequence selected from the group consisting of SEQ ID NOs: 5048 and 5049, and any one sequence selected from the group consisting of SEQ ID NOs: 5050 and 5051, respectively; or(xv) any one sequence selected from the group consisting of SEQ ID NOs: 5050 and 5051, and any one sequence selected from the group consisting of SEQ ID NOs: 5048 and 5049, respectively.

[0136] In some embodiments, the TCRβV27-binding moiety further comprises a heavy chain constant domain 1 (CH1) operatively linked to the VH of the TCRβV27-binding moiety.

[0137] In some embodiments, the TCRpV27-binding moiety further comprises a light chain constant domain (CL) or a fragment thereof operatively linked to the VL of TCRpV27-binding moiety.

[0138] In some embodiments, the light chain constant region or a fragment thereof comprises a kappa chain constant domain or a fragment thereof or a lambda chain constant domain or a fragment thereof.

[0139] In some embodiments, the light chain constant region or a fragment thereof comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity any one of the light chain constant region sequences listed in Table 3.

[0140] In some embodiments, the light chain constant region or a fragment there-of comprises any one of the light chain constant region sequences listed in Table 3.

[0141] In some embodiments, the light chain constant region or a fragment there-of comprise a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 39 or SEQ ID NO: 3644.

[0142] In some embodiments, the light chain constant region or a fragment there-of comprise the sequence of SEQ ID NO: 39 or SEQ ID NO: 3644

[0143] In some embodiments, the multispecific molecule further comprises:(i) a linker between the first portion of the dimerization module and the TCRpV27-binding moiety or the first portion of the TCRpV27-binding moiety;(ii) a linker between the one or more molecule that binds to a co-stimulatory receptor of a T cell and the first portion of the dimerization module, a linker between the one or more molecule that binds to a costimulatory receptor of a T cell and the second portion of the dimerization module, or a combination thereof;(iii) a linker between the one or more TCR binding moiety and the first portion of the dimerization module, a linker between the one or more TCR binding moiety and the second portion of the dimerization module, or a combination thereof;(iv) a linker between the one or more molecule that binds to a co-stimulatory receptor of a T cell and the TCRpV27-binding moiety, the first portion of the TCRβV27-binding moiety, or the second portion of the TCRβV27-binding moiety;(v) a linker between the one or more TCR binding moiety and the TCRpV27-binding moiety, the first portion of the TCRpV27-binding moiety, or the second portion of the TCRpV27-binding moiety;(vi) a linker between the one or more molecule that binds to a co-stimulatory receptor of a T cell and the one or more TCR binding moiety;(vii) a linker between the VH and the VL of the TCRpV27-binding moiety;(viii) a linker between the CHI and the VH of the TCRpV27-binding moiety;(ix) a linker between the CL and the VL of the TCRpV27-binding moiety; or(x) any combination thereof.

[0144] In some embodiments, the linker is selected from the group consisting of a cleavable linker, a non-cleavable linker, a peptide linker, a flexible linker, a rigid linker, a helical linker, and a non-helical linker.

[0145] In some embodiments, the linker is selected from the group consisting of SEQ ID NOs: 3307-3310, 1474, 1475, 3801, 3309, 3308, 3643, 3437, and 3314-3317.

[0146] In some embodiments, the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are noncontiguous;wherein the first polypeptide chain comprises a first Fc region, and the second polypeptide chain comprises a second Fc region;wherein the first Fc region and the second Fc region comprise an Fc interface with a knob-in-a hole; wherein:(i) the first polypeptide chain comprises the VH of the TCRβV27, wherein the VH is operatively linked to the first Fc region,(ii) the second polypeptide chain comprises one or more molecule that binds to a co-stimulatory receptor of a T cell, wherein the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the second Fc region,(iii) the third polypeptide chain comprises the VL of the TCRβV27, wherein the VL is operatively linked to a light chain constant region; andwherein:(1) the first Fc region and the second Fc region each comprises an Asn297Ala mutation according to EU Numbering; and(2) the first Fc region comprises Y349C, T366S, L368A, and Y407V mutations according to EU Numbering, and the second Fc region comprises S354C and T366W mutations according to EU Numbering, or the first Fc region comprises S354C and T366W mutations according to EU Numbering, and the second Fc region comprises mutations Y349C, T366S, L368A, and Y407V according to EU Numbering.

[0147] In some embodiments, the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are noncontiguous;wherein the first polypeptide chain comprises a first Fc region, and the second polypeptide chain comprises a second Fc region;wherein the first Fc region and the second Fc region comprise an Fc interface with a knob-in-a hole; wherein:(i) the first polypeptide chain comprises the VH of the TCRβV27, wherein the VH is operatively linked to the first Fc region,(ii) the second polypeptide chain comprises one cytokine molecule or a functional fragment or functional variant thereof, wherein the one cytokine molecule or a functional fragment or functional variant thereof is operatively linked to the second Fc region,(lii) the third polypeptide chain comprises the VL of the TCRβV27, wherein the VL is operatively linked to a light chain constant region; andwherein:(1) the first Fc region and the second Fc region each comprises an Asn297Ala mutation according to EU Numbering; and(2) the first Fc region comprises Y349C, T366S, L368A, and Y407V mutations according to EU Numbering, and the second Fc region comprises S354C and T366W mutations according to EU Numbering, or the first Fc region comprises S354C and T366W mutations according to EU Numbering, and the second Fc region comprises mutations Y349C, T366S, L368A, and Y407V according to EU Numbering.

[0148] In some embodiments, the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are noncontiguous;wherein the first polypeptide chain comprises a first Fc region, and the second polypeptide chain comprises a second Fc region;wherein the first Fc region and the second Fc region comprise an Fc interface with a knob-in-a hole; wherein:(i) the first polypeptide chain comprises the VH of the TCRβV27, wherein the VH is operatively linked to the first Fc region,(ii) the second polypeptide chain comprises IL-2 or a functional fragment or functional variant thereof, wherein the IL-2 or a functional fragment or functional variant thereof is operatively linked to the second Fc region,(iii) the third polypeptide chain comprises the VL of the TCRβV27, wherein the VL is operatively linked to a light chain constant region; andwherein:(1) the first Fc region and the second Fc region each comprises an Asn297Ala mutation according to EU Numbering; and(2) the first Fc region comprises Y349C, T366S, L368A, and Y407V mutations according to EU Numbering, and the second Fc region comprises S354C and T366W mutations according to EU Numbering, or the first Fc region comprises S354C and T366W mutations according to EU Numbering, and the second Fc region comprises mutations Y349C, T366S, L368A, and Y407V according to EU Numbering.

[0149] In some embodiments, the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are noncontiguous;wherein the first polypeptide chain comprises a first Fc region, and the second polypeptide chain comprises a second Fc region;wherein the first Fc region and the second Fc region comprise an Fc interface with a knob-in-a hole; wherein:(i) the first polypeptide chain comprises the VH of the TCRβV27, wherein the VH is operatively linked to the first Fc region,(ii) the second polypeptide chain comprises IL-2 or a functional fragment or functional variant thereof, wherein the IL-2 comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 2270, and wherein the IL-2 or a functional fragment or functional variant thereof is operatively linked to the second Fc region,(iii) the third polypeptide chain comprises the VL of the TCRβV27, wherein the VL is operatively linked to a light chain constant region comprising a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 39 or 3644; andwherein the first Fc region comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 5044 or 3649, and the second Fc region comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identityto the sequence of SEQ ID NO: 3648 or 5046,with a proviso that (1) the first Fc region and the second Fc region each comprises an Asn297Ala mutation according to EU Numbering; and (2) the first Fc region comprises Y349C, T366S, L368A, and Y407V mutations according to EU Numbering, and the second Fc region comprises S354C and T366W mutations according to EU Numbering.

[0150] In some embodiments, the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are noncontiguous;wherein the first polypeptide chain comprises a first Fc region, and the second polypeptide chain comprises a second Fc region;wherein the first Fc region and the second Fc region comprise an Fc interface with a knob-in-a hole; wherein:(i) the first polypeptide chain comprises the VH of the TCRβV27, wherein the VH is operatively linked to the first Fc region,(ii) the second polypeptide chain comprises IL-2 or a functional fragment or functional variant thereof, wherein the IL-2 comprises the sequence of SEQ ID NO: 2270, and wherein the IL-2 or a functional fragment or functional variant thereof is operatively linked to the second Fc region,(iii) the third polypeptide chain comprises the VL of the TCRβV27, wherein the VL is operatively linked to a light chain constant region comprising the sequence of SEQ ID NO: 39 or 3644; andwherein the first Fc region comprises the sequence of SEQ ID NO: 5044 or 3649, and the second Fc region comprises the sequence of SEQ ID NO: SEQ ID NO: 3648 or 5046.

[0151] In some embodiments, the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are noncontiguous; andwherein:(i) the first polypeptide chain comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1423 and an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 5050 or the sequence of SEQ ID NO: 5051;(ii) the second polypeptide chain comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 2270 and an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 5046 or the sequence of SEQ ID NO: 5047; and(iii) the third polypeptide chain comprises an amino acid sequence having at least 70%, 75%, 80%, 85%,90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1413 and an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 3644.

[0152] In some embodiments, the first polypeptide chain further comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 549.

[0153] In some embodiments, the second polypeptide chain further comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 3308.

[0154] In some embodiments, the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are noncontiguous; andwherein:(i) the first polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1423 operatively linked to an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 5050 or the sequence of SEQ ID NO: 5051;(ii) the second polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 2270 operatively linked to an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 5046 or the sequence of SEQ ID NO: 5047; and(iii) the third polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1413 operatively linked to an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 3644.

[0155] In some embodiments, the first polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1423 operatively linked to an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to thesequence of SEQ ID NO: 5050 or the sequence of SEQ ID NO: 5051 via an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 549.

[0156] In some embodiments, the second polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 2270 operatively linked to an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 5046 or the sequence of SEQ ID NO: 5047 via an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 3308.

[0157] In some embodiments, the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are noncontiguous; andwherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 1423 and the sequence of SEQ ID NO: 5050 or the sequence of SEQ ID NO: 5051;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 2270 and the sequence of SEQ ID NO: 5046 or the sequence of SEQ ID NO: 5047; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 1413 and the sequence of SEQ ID NO: 3644.

[0158] In some embodiments, the first polypeptide chain further comprises the sequence of SEQ ID NO:549.

[0159] In some embodiments, the second polypeptide chain further comprises the sequence of SEQ ID NO: 3308.

[0160] In some embodiments, the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are noncontiguous; andwherein:(i) the first polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, the sequence of SEQ ID NO: 1423 operatively linked to the sequence of SEQ ID NO: 5050 or the sequence of SEQ ID NO: 5051;(ii) the second polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, the sequence of SEQ ID NO: 2270 operatively linked to the sequence of SEQ ID NO: 5046 or the sequence of SEQ ID NO: 5047; and(iii) the third polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, the sequence of SEQ ID NO: 1413 operatively linked to the sequence of SEQ ID NO: 3644.

[0161] In some embodiments, the first polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, the sequence of SEQ ID NO: 1423 operatively linked to the sequence of SEQ ID NO: 5050 or the sequence of SEQ ID NO: 5051 via the sequence of SEQ ID NO: 549.

[0162] In some embodiments, the second polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, the sequence of SEQ ID NO: 2270 operatively linked to the sequence of SEQ ID NO: 5046 or the sequence of SEQ ID NO: 5047 via the sequence of SEQ ID NO: 3308.

[0163] In some embodiments, the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are noncontiguous; andwherein:(i) the first polypeptide chain comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1501 or 1502;(ii) the second polypeptide chain comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1505 or 1506; and(iii) the third polypeptide chain comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1504.

[0164] In some embodiments, the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are noncontiguous; andwherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 1501 or 1502;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 1505 or 1506; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 1504.

[0165] In some embodiments, the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are noncontiguous; andwherein:(i) the first polypeptide chain comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1423 and an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to thesequence of SEQ ID NO: 5046 or the sequence of SEQ ID NO: 5047;(ii) the second polypeptide chain comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 2270 and an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 5050 or the sequence of SEQ ID NO: 5051; and(iii) the third polypeptide chain comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1413 and an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 3644.

[0166] In some embodiments, the first polypeptide chain further comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 549.

[0167] In some embodiments, the second polypeptide chain further comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 3308.

[0168] In some embodiments, the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are noncontiguous; andwherein:(i) the first polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1423 operatively linked to an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 5046 or the sequence of SEQ ID NO: 5047;(ii) the second polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 2270 operatively linked to an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 5050 or the sequence of SEQ ID NO: 5051; and(iii) the third polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1413 operatively linked to an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%,98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 3644.

[0169] In some embodiments, the first polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1423 operatively linked to an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 5046 or the sequence of SEQ ID NO: 5047 via an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 549.

[0170] In some embodiments, the second polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 2270 operatively linked to an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 5050 or the sequence of SEQ ID NO: 5051 via an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 3308.

[0171] In some embodiments, the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are noncontiguous; andwherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 1423 and the sequence of SEQ ID NO: 5046 or the sequence of SEQ ID NO: 5047;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 2270 and the sequence of SEQ ID NO: 5050 orthe sequence of SEQ ID NO: 5051; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 1413 and the sequence of SEQ ID NO: 3644.

[0172] In some embodiments, the first polypeptide chain further comprises the sequence of SEQ ID NO:549.

[0173] In some embodiments, the second polypeptide chain further comprises the sequence of SEQ ID NO: 3308.

[0174] In some embodiments, the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are noncontiguous; andwherein:(i) the first polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, the sequence of SEQ ID NO: 1423 operatively linked to the sequence of SEQ ID NO: 5046 or the sequence of SEQ ID NO: 5047;(ii) the second polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, the sequence of SEQ ID NO: 2270 operatively linked to the sequence of SEQ ID NO: 5050 or the sequence of SEQ ID NO: 5051; and(iii) the third polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, the sequence of SEQ ID NO: 1413 operatively linked to the sequence of SEQ ID NO: 3644.

[0175] In some embodiments, the first polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, the sequence of SEQ ID NO: 1423 operatively linked to the sequence SEQ ID NO: 5046 or the sequence of SEQ ID NO: 5047 of via the sequence of SEQ ID NO: 549.

[0176] In some embodiments, the second polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, the sequence of SEQ ID NO: 2270 operatively linked to the sequence of SEQ ID NO: 5050 orthe sequence of SEQ ID NO: 5051 via the sequence of SEQ ID NO: 3308.

[0177] In some embodiments, the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are noncontiguous; andwherein:(i) the first polypeptide chain comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1507 or 1508;(ii) the second polypeptide chain comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1509 or 1510; and(iii) the third polypeptide chain comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1504.

[0178] In some embodiments, the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are noncontiguous; andwherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 1507 or 1508;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 1509 or 1510; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 1504.

[0179] In some embodiments, the multispecific molecule is an isolated multi -specific molecule.

[0180] In another aspect, provided herein is a composition comprising the molecule as described herein.

[0181] In some embodiments, the composition further comprises a second molecule that comprises a TCR binding domain,wherein the anti-TCRpV27 antibody molecule or the anti-TCR(3V27 antigen binding domain of the molecule and the TCR binding domain are different, andwherein the molecule and the second molecule are not covalently linked.

[0182] In some embodiments, the TCR binding domain binds to a T cell receptor alpha (TCRa) chain, a T cell receptor beta (TCRP) chain, a T cell receptor gamma (TCRy) chain, a T cell receptor delta (TCR5) chain, a CD3 gamma (CD3y) chain, a CD3 delta (CD38) chain, a CD3 epsilon (CD3E) chain, a CD3 zeta (CD3 chain, or any combination thereof.

[0183] In some embodiments, the TCR binding domain binds to a T cell receptor beta (TCRP) chain.

[0184] In some embodiments, the TCR binding domain binds to a T cell receptor beta variable (TCRPV) region.

[0185] In some embodiments, the TCR binding domain binds to a TCRPV region of human TCRPV 1, human TCRPV2, human TCRPV3, human TCRPV4, human TCRPV5, human TCRPV6, human TCRPV7, human TCRPV8, human TCRPV9, human TCRPVIO, human TCRPVII, human TCRPV12, human TCRpV 19, human TCRpV20, human TCRpV21, human TCRpV23, human TCRpV24, human TCRpV25, human TCRpV26, human TCRPV27, human TCRpV28, human TCRpV29, or human TCRPV30.

[0186] In some embodiments, the TCR binding domain binds to a TCRPV region of human TCRPV2, human TCRPV4-1, human TCRPV4-2, human TCRPV5-1, human TCRPV5-5, human TCRPV5-6, human TCRPV6, human TCRPV6-5, human TCRPV6-6, human TCRPV6-9, human TCRPV7-2, human TCRPV7-3, human TCRPV7-8, human TCRPV7-9, human TCRPV9, human TCRpVIO-l, human TCRPV 10-2, human TCRpV 10-3, human TCRpV 11-2, hu-man TCRpV 12-3, human TCRpV 12-4, human TCRpV12-5, human TCRpV19, human TCRpV20-l, human TCRPV21, human TCRpV24-l, human TCRpV25-l, or human TCRpV28.

[0187] In some embodiments, the TCR binding domain binds to a TCRpV region of human TCRPV2, human TCRPV3-1, human TCRPV4-1, human TCRPV4-2, human TCRPV5-1, human TCRPV5-4, human TCRPV5-5, human TCRPV5-6, human TCRPV6-1, human TCRPV6-5, human TCRPV6-6, human TCRPV7-3, human TCRPV7-6, human TCRPV7-8, human TCRPV9, human TCRpV 11-2, human TCRPV 19, human TCRPV20-1, human TCRPV24-1, human TCRPV27, human TCRPV28, human TCRPV29-1, or human TCRPV30.

[0188] In some embodiments, the TCR binding domain binds to a TCRpV region of human TCRPV5, human TCRPV6, human TCRpVIO, human TCRPV12, or human TCRPV20.

[0189] In some embodiments, the TCR binding domain binds to a T cell receptor alpha (TCRa) chain.

[0190] In some embodiments, the TCR binding domain binds to a T cell receptor alpha variable (TCRaV) region.

[0191] In some embodiments, the TCR binding domain binds to a TCRaV region of TRAV12-1, TRAV12-2, TRAV12-3, TRAV13-1, TRAV13-2, TRAV19-1, TRAV21-1, orTRAV30-l.

[0192] In some embodiments, the TCR binding domain comprises an anti-body molecule or an antigenbinding domain.

[0193] In some embodiments, the TCR binding domain comprises an anti-body molecule or an antigen binding domain comprising a scFv, a full-length antibody, a Fab, a F(ab')2, an Fv, a single chain Fv, a camelid antibody, a half arm antibody, a diabody, a bivalent antibody, a monovalent antibody, or a bispecific antibody.

[0194] In some embodiments, the antibody molecule or the antigen binding domain comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HC CDR1) sequence comprising any one of the HC CDR1 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, a heavy chain complementarity determining region 2 (HC CDR2) sequence comprising any one of the HC CDR2 sequences listed in Tables 1,2, 12, 13, 14, 16, or 22, and a heavy chain complementarity determining region 3 (HC CDR3) sequence of comprising any one of the HC CDR3 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

[0195] In some embodiments, the antibody molecule or the antigen binding domain comprises a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LC CDR1) sequence comprising any one of the LC CDR1 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, a light chain complementarity determining region 2 (LC CDR2) sequence comprising any one of the LC CDR2 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, and a light chain complementarity determining region 3 (LC CDR3) sequence of comprising any one of the LC CDR3 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

[0196] In some embodiments, the antibody molecule or the antigen binding domain comprises:(i) a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HC CDR1) sequence comprising any one of the HC CDR1 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, a heavy chain complementarity determining region 2 (HC CDR2) sequence comprising any one of the HC CDR2 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, and a heavy chain complementarity determining region 3 (HC CDR3) sequence of comprising any one of the HC CDR3 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22; and(ii) a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LC CDR1) sequence comprising any one of the LC CDR1 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, a light chain complementarity determining region 2 (LC CDR2) sequence comprising any one of the LC CDR2 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, and a light chain complementarity determining region 3 (LC CDR3) sequence of comprising any one of the LC CDR3 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

[0197] In some embodiments, the antibody molecule or the antigen binding domain comprises a VH comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VH sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

[0198] In some embodiments, the antibody molecule or the antigen binding domain comprises a VL comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%,99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VL sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

[0199] In some embodiments, the antibody molecule or the antigen binding domain comprises a VH comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VH sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22; and a VL comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VL sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

[0200] In some embodiments, the antibody molecule or the antigen binding domain comprises a VH comprising any one of the VH sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

[0201] In some embodiments, the antibody molecule or the antigen binding domain comprises a VL comprising any one of the VL sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

[0202] In some embodiments, the antibody molecule or the antigen binding domain comprises a VH comprising any one of the VH sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22; and a VL comprising any one of the VL sequences listed Tables 1, 2, 12, 13, 14, 16, or 22.

[0203] In another aspect, provided herein is a polynucleotide comprising a sequence encoding the molecule as described herein.

[0204] In some embodiments, the polynucleotide is an isolated nucleic acid molecule.

[0205] In another aspect, provided herein is a vector comprising one or more of the polynucleotides as described herein.

[0206] In another aspect, provided herein is a cell comprising the polynucleotide as described herein or the vector as described herein.

[0207] In another aspect, provided herein is a method of making the molecule as described herein comprising culturing a host cell comprising a recombinant polynucleotide comprising a sequence encoding the molecule or a vector comprising the recombinant polynucleotide under conditions suitable for gene expression and / or homo- or heterodimerization.

[0208] In another aspect, provided herein is a pharmaceutical composition comprising the molecule as described herein, the composition as described herein, the polynucleotide as described herein, the vector as described herein, or the cell as described herein, and a pharmaceutically acceptable carrier, excipient, or diluent.

[0209] In another aspect, provided herein is a method of treating a condition or disease in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the molecule as described herein, the com-position as described herein, the polynucleotide as described herein, the vector as described herein, the cell as described herein, the pharmaceutical composition as described herein, or any combination thereof,wherein the administering is effective to treat the condition or disease in the subject.

[0210] In another aspect, provided herein is use of the molecule as described herein, the as described herein, the polynucleotide as described herein, the vector as described herein, the cell as described herein,the pharmaceutical composition as described herein, or any combination thereof for treating a condition or disease in a subject in need thereof comprising administering to the subject,wherein the molecule, the composition, the polynucleotide, the vector, the cell, the pharmaceutical composition, or any combination thereof is formulated in a therapeutically effective amount to treat the condition or disease in the subject.

[0211] In some embodiments, the condition or disease is cancer.

[0212] In some embodiments, the cancer is a solid tumor, a hematological cancer, a metastatic cancer, a soft tissue tumor, or any combination thereof.

[0213] In some embodiments, the cancer is the solid tumor selected from the group consisting of melanoma, pancreatic cancer, breast cancer, colorectal cancer, lung cancer, skin cancer, ovarian cancer, liver cancer, and any combination thereof.

[0214] In some embodiments, the cancer is the hematological cancer selected from the group consisting of Hodgkin’s lymphoma, Non-Hodgkin’s lymphoma, acute myeloid leukemia (AML), chronic myeloid leukemia, myelodysplastic syndrome, multiple myeloma, T-cell lymphoma, acute lymphocytic leukemia, and any combination thereof.

[0215] In some embodiments, the Non-Hodgkin’s lymphoma is selected from the group consisting of B cell lymphoma, diffuse large B cell lymphoma (DLBCL), follicular lympho-ma, chronic lymphocytic leukemia (B-CLL), mantle cell lymphoma, marginal zone B-cell lympho-ma, Burkitt lymphoma, lymphoplasmacytic lymphoma, hairy cell leukemia, and any combination thereof.

[0216] In some embodiments, the T-cell lymphoma is peripheral T-cell lymphoma.

[0217] In some embodiments, the cancer is characterized by a cancer antigen present on the cancer.

[0218] In some embodiments, the cancer antigen is a tumor antigen, a stromal antigen, or a hematological antigen.

[0219] In some embodiments, the cancer antigen is selected from the group consisting of CD19, CD123, CD22, CD30, CD 171, CS-1, C-type lectin-like molecule- 1, CD33, epi -dermal growth factor receptor variant III (EGFRvIII), ganglioside G2 (GD2), ganglioside GD3, TNF receptor family member B cell maturation (BCMA), Tn antigen ((Tn Ag) or (GalNAca-Ser / Thr)), prostate-specific membrane antigen (PSMA), Receptor tyrosine kinase-like orphan receptor 1 (ROR1), Fms-Like Tyrosine Kinase 3 (FLT3), Tumor-associated glycoprotein 72 (TAG72), CD38, CD44v6, Carcinoembryonic antigen (CEA), Epithelial cell adhesion molecule (EPCAM), B7H3 (CD276), KIT (CD 117), Interleukin- 13 receptor subunit alpha-2, mesothelin, Interleukin 11 receptor alpha (IL-llRa), prostate stem cell antigen (PSCA), Protease Serine 21, vascular endothelial growth factor receptor 2 (VEGFR2), Lewis(Y) antigen, CD24, Platelet-derived growth factor receptor beta (PDGFR-beta), Stage -specific embryonic antigen-4 (SSEA-4), CD20, Folate receptor alpha, Receptor tyrosine-protein kinase ERBB2 (Her2 / neu), Mucin 1, cell surface associated (MUC1), epidermal growth factor receptor (EGFR), neural cell adhesion molecule (NCAM), Prostase, prostatic acid phosphatase (PAP), elongation factor 2 mutated (ELF2M), Ephrin B2, fibroblast activation protein alpha (FAP), insulin-like growth factor 1 receptor (IGF -I receptor), carbonic anhydrase IX (CAIX), Proteasome (Prosome, Macropain) Subunit, Beta Type, 9 (LMP2), glycoprotein 100(gpl00 / pmell7), oncogene fusion protein consisting of breakpoint cluster region (BCR) and Abel-son murine leukemia viral oncogene homolog 1 (Abl) (bcr-abl), tyrosinase, ephrintype-A receptor 2 (EphA2), Fucosyl GM1, sialyl Lewis adhesion molecule (sLe), ganglioside GM3, transglutaminase 5 (TGS5), high molecular weight-melanoma-associated antigen (HMWMAA), o-acetyl-GD2 ganglioside (0AcGD2), Folate receptor beta, tumor endothelial marker 1 (TEM1 / CD248), tumor endothelial marker 7-related (TEM7R), claudin 6 (CLDN6), thyroid stimulating hormone receptor (TSHR), G protein-coupled receptor class C group 5, member D (GPRC5D), chromosome X open reading frame 61 (CXORF61), CD97, CD179a, anaplastic lymphoma kinase (ALK), Polysialic acid, placenta-specific 1 (PLAC1), hexasaccharide portion of globoH glycoceramide (GloboH), mammary gland differentiation antigen (NY-BR-1), uroplakin 2 (UPK2), Hepatitis A virus cellular receptor 1 (HAVCR1), adrenoceptor beta 3 (ADRB3), pannexin 3 (PANX3), G protein-coupled receptor 20 (GPR20), lymphocyte antigen 6 complex, locus K 9 (LY6K), Olfactory receptor 51E2 (OR51E2), TCR Gamma Alternate Reading Frame Protein (TARP), Wilms tumor protein (WT1), Cancer / testis antigen 1 (NY-ESO-l / LAGE-1), Cancer / testis antigen 2 (LAGE- la), Melanoma-associated antigen 1 (MAGE-A1), ETS translocation-variant gene 6, located on chromosome 12p (ETV6-AML), sperm protein 17 (SPA17), X Antigen Family, Member 1A (XAGE1), angiopoietin-binding cell surface receptor 2 (Tie 2), melanoma cancer testis antigen-1 (MAD-CT-1), melanoma cancer testis antigen-2 (MAD-CT-2), Fos-related antigen 1, tumor protein p53 (p53), p53 mutant, prostein, Survivin, telomerase, prostate carcinoma tumor antigen- 1, melanoma antigen recognized by T cells 1, Rat sarcoma (Ras) mutant, human Telomerase reverse transcriptase (hTERT), sarcoma translocation breakpoints, melanoma inhibitor of apoptosis (ML-IAP), ERG (transmembrane protease, senne 2 (TMPRSS2) ETS fusion gene), N-Acetyl glucosaminyl -transferase V (NA 17), paired box protein Pax-3 (PAX3), Androgen receptor, Cyclin Bl, v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN), Ras Homolog Family Member C (RhoC), Tyrosinase-related protein2 (TRP-2), Cytochrome P450 1B1 (CYP1B1), CCCTC-Binding Factor (Zinc Finger Protein) -Like, Squamous Cell Carcinoma Antigen Recognized By T Cells 3 (SART3), Paired box protein Pax-5 (PAX5), proacrosin binding protein sp32 (OY-TES1), lymphocyte -specific protein tyrosine kinase (LCK), A kinase anchor protein 4 (AKAP-4), synovial sarcoma, X breakpoint 2 (SSX2), Receptor for Advanced Glycation Endproducts (RAGE-1), renal ubiquitous 1 (RU1), renal ubiquitous 2 (RU2), legumain, human papilloma virus E6 (HPV E6), human papilloma virus E7 (HPV E7), intestinal carboxyl esterase, heat shock protein 70-2 mutated (mut hsp70-2), CD79a, CD79b, CD72, Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), Fc fragment of IgA receptor (FCAR or CD89), Leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2), CD300 molecule-like family member f (CD300LF), C-type lectin domain family 12 member A (CLEC12A), bone marrow stromal cell antigen 2 (BST2), EGF-like modulecontaining mucin-like hormone receptor-like 2 (EMR2), lymphocyte antigen 75 (LY75), Glypican-3 (GPC3), Fc receptor-like 5 (FCRL5), FcRH5, PDL1, CD47, prostate specific membrane antigen (PMSA), prostate-specific antigen (PSA), Ron Kinase, c-Met, Immature laminin receptor, TAG-72, BING-4, Calcium-activated chloride channel 2, Cyclin-Bl, 9D7, Ep-CAM, EphA3, SAP-1, PRAME, SSX-2, Melan-A / MART-1, TRPl / gp75, MC1R, 0-catemn, BRCA1 / 2, CDK4, CML66, Fibronectin, Ras, TGF-Breceptor, AFP, ETA, MAGE, CA-125, BAGE, GAGE, CDC27, a actinin-4, gangliosides, MART -2, MUC2, MUM1, MUM2, MUM3, NA88-1, NPM, 0A1, OGT, RCC, RUH, RU12, SAGE, TRG, TSTA, Ll-CAM, gpA33, GM2, VEGFR, Integrins, carbohydrates, TRAILR1, TRAILR2, RANKL, TGF-beta, hyaluronic acid, collagen, tenascin C, tenascin W, and immunoglobulin lambda-like polypeptide 1 (IGLL1).

[0220] In some embodiments, the cancer comprises breast cancer, lung cancer, pancreatic cancer, head and neck cancer, bladder cancer, urothelial cancer, ovarian cancer, gallbladder cancer, gastric cancer, esophageal cancer, hepatocellular cancer, epithelial cancer, or any combination thereof.

[0221] In some embodiments, the cancer comprises breast cancer, pancreatic cancer, lung cancer, or any combination thereof.

[0222] In some embodiments, the cancer comprises a solid cancer selected from the group consisting of colon cancer, breast cancer, renal cancer, melanoma, prostate cancer, lung cancer, rectal cancer, colorectal cancer, cervical cancer, and any combination thereof.

[0223] In some embodiments, the cancer comprises an anti-PDl therapy resistant cancer.

[0224] In some embodiments, the cancer comprises an anti-PDl therapy resistant solid cancer.

[0225] In some embodiments, the cancer comprises an HPV-positive cancer.

[0226] In some embodiments, the cancer comprises an HPV-positive solid cancer.

[0227] In some embodiments, the cancer comprises a cancer with a high tumor mutation burden.

[0228] In some embodiments, the method or the use as provided herein further comprises administering a second therapeutic agent or therapy to the subject.

[0229] In some embodiments, the second therapeutic agent or therapy comprises a chemotherapeutic agent, a biologic agent, a hormonal therapy, radiation, or surgery.

[0230] In some embodiments, the second therapeutic agent comprises a second molecule that comprises a TCR binding domain,wherein the anti-TCRpV27 antibody molecule or the anti-TCR(3V27 antigen binding domain of the molecule and the TCR binding domain are different, andwherein the molecule and the second molecule are not covalently linked.

[0231] In some embodiments, the TCR binding domain binds to a T cell receptor alpha (TCRa) chain, a T cell receptor beta (TCRP) chain, a T cell receptor gamma (TCRy) chain, a T cell receptor delta (TCR5) chain, a CD3 gamma (CD3y) chain, a CD3 delta (CD35) chain, a CD3 epsilon (CD3e) chain, a CD3 zeta (CD3 chain, or any combination thereof.

[0232] In some embodiments, the TCR binding domain binds to a T cell receptor beta (TCRP) chain.

[0233] In some embodiments, the TCR binding domain binds to a T cell receptor beta variable (TCRpV) region.

[0234] In some embodiments, the TCR binding domain binds to a TCRpV region of human TCRpV 1, human TCRPV2, human TCRPV3, human TCRPV4, human TCRPV5, human TCRPV6, human TCRPV7, human TCRPV8, human TCRPV9, human TCRpVIO, human TCRpVll, human TCRPV12, human TCRpV 19, human TCRpV20, human TCRpV21, human TCRpV23, human TCRpV24, human TCRpV25,human TCRPV26, human TCRβV27, human TCRPV28, human TCRPV29, or human TCRPV30.

[0235] In some embodiments, the TCR binding domain binds to a TCRpV region of human TCRPV2, human TCRPV4-1, human TCRPV4-2, human TCRPV5-1, hu-man TCRPV5-5, human TCRPV5-6, human TCRPV6, human TCRPV6-5, human TCRPV6-6, hu-man TCRPV6-9, human TCRPV7-2, human TCRPV7-3, human TCRPV7-8, human TCRPV7-9, human TCRPV9, human TCRpV10-l, human TCRPV10-2, human TCRpV10-3, human TCRpVl 1-2, human TCRPV12-3, human TCRPV12-4, human TCRPV12-5, human TCRPV19, human TCRPV20-1, human TCRPV21, human TCRPV24-1, human TCRpV25-l, or human TCRpV28.

[0236] In some embodiments, the TCR binding domain binds to a TCRPV region of human TCRPV2, human TCRPV3-1, human TCRPV4-1, human TCRPV4-2, hu-man TCRPV5-1, human TCRPV5-4, human TCRpV5-5, human TCRPV5-6, human TCRPV6-1, human TCRpV6-5, human TCRPV6-6, human TCRpV7-3, human TCRpV7-6, human TCRPV7-8, human TCRpV9, human TCRpVl 1-2, human TCRpV 19, human TCRpV20-l, human TCRpV24-l, human TCRPV27, human TCR V28, human TCRpV29-l, or human TCRpV30.

[0237] In some embodiments, the TCR binding domain binds to a TCRPV region of human TCRPV5, human TCRPV6, human TCRPVIO, human TCRPV12, or human TCRPV20.

[0238] In some embodiments, the TCR binding domain binds to a T cell receptor alpha (TCRa) chain.

[0239] In some embodiments, the TCR binding domain binds to a T cell receptor alpha variable (TCRaV) region.

[0240] In some embodiments, the TCR binding domain binds to a TCRaV region of TRAV12-1, TRAV12-2, TRAV12-3, TRAV13-1, TRAV13-2, TRAV19-1, TRAV21-1, orTRAV30-l.

[0241] In some embodiments, the TCR binding domain comprises an antibody molecule or an antigen binding domain.

[0242] In some embodiments, the TCR binding domain comprises an antibody molecule or an antigen binding domain comprising a scFv, a full-length antibody, a Fab, a F(ab')2, an Fv, a single chain Fv, a camelid antibody, a half arm antibody, a diabody, a bivalent antibody, a monovalent antibody, or a bispecific antibody.

[0243] In some embodiments, the antibody molecule or the antigen binding domain comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HC CDR1) sequence comprising any one of the HC CDR1 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, a heavy chain complementarity determining region 2 (HC CDR2) sequence comprising any one of the HC CDR2 sequences listed in Tables 1,2, 12, 13, 14, 16, or 22, and a heavy chain complementarity determining region 3 (HC CDR3) sequence of comprising any one of the HC CDR3 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

[0244] In some embodiments, the antibody molecule or the antigen binding domain comprises a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LC CDR1) sequence comprising any one of the LC CDR1 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, a light chain complementarity determining region 2 (LC CDR2) sequence comprising any one of the LC CDR2sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, and a light chain complementarity determining region 3 (LC CDR3) sequence of comprising any one of the LC CDR3 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

[0245] In some embodiments, the antibody molecule or the antigen binding domain comprises:(i) a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HC CDR1) sequence comprising any one of the HC CDR1 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, a heavy chain complementarity determining region 2 (HC CDR2) sequence comprising any one of the HC CDR2 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, and a heavy chain complementarity determining region 3 (HC CDR3) sequence of comprising any one of the HC CDR3 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22; and(ii) a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LC CDR1) sequence comprising any one of the LC CDR1 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, a light chain complementarity determining region 2 (LC CDR2) sequence comprising any one of the LC CDR2 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, and a light chain complementarity determining region 3 (LC CDR3) sequence of comprising any one of the LC CDR3 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

[0246] In some embodiments, the antibody molecule or the antigen binding domain comprises a VH comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VH sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

[0247] In some embodiments, the antibody molecule or the antigen binding domain comprises a VL comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VL sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

[0248] In some embodiments, the antibody molecule or the antigen binding domain comprises a VH comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VH sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22; and a VL comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VL sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

[0249] In some embodiments, the antibody molecule or the antigen binding domain comprises a VH comprising any one of the VH sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

[0250] In some embodiments, the antibody molecule or the antigen binding domain comprises a VL comprising any one of the VL sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

[0251] In some embodiments, the antibody molecule or the antigen binding domain comprises a VH comprising any one of the VH sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22; and a VL comprising any one of the VL sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

[0252] In some embodiments, the antibody molecule or the antigen binding domain comprises a VHcomprising any one of the VH sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22; and a VL comprising any one of the VL sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

[0253] In some embodiments, the second therapeutic agent or therapy is administered in combination with the molecule as described herein, the composition as described herein, the polynucleotide as described herein, the vector as described herein, the cell as described herein, the pharmaceutical composition as described herein, or any combination thereof, sequentially, simultaneously, or concurrently.

[0254] In some embodiments, the second therapeutic agent is not concomitantly administered to the subject with the molecule as described herein, the composition as described herein, the polynucleotide as described herein, the vector as described herein, the cell as described herein, the pharmaceutical composition as described herein, or any combination thereof.

[0255] In some embodiments, the administration of the molecule as described herein, the composition as described herein, the polynucleotide as described herein, the vector as described herein, the cell as described herein, the pharmaceutical composition as described herein, or any combination thereof to the subject is followed by an administration of the second therapeutic agent to the subject.

[0256] In some embodiments, an administration of the second therapeutic agent to the subject is followed by the administration of the molecule as described herein, the composition as described herein, the polynucleotide as described herein, the vector as described herein, the cell as described herein, the pharmaceutical composition as described herein, or any combination thereof to the subject.

[0257] In some embodiments, the administration of the molecule as described herein, the composition as described herein, the pharmaceutical composition as described herein, or any combination thereof to the subject is followed by an administration of the second therapeutic agent to the subject.

[0258] In some embodiments, an administration of the second therapeutic agent to the subject is followed by the administration of the molecule as described herein, the composition as described herein, the pharmaceutical composition as described herein, or any combination thereof to the subject.

[0259] In some embodiments, the method is more effective to treat the disease or condition in the subject relative to a method in which the molecule as described herein, the composition as described herein, the polynucleotide as described herein, the vector as described herein, the cell as described herein, the pharmaceutical composition as described herein, or any combination thereof is administered to the subject but not the second therapeutic agent.INCORPORATION BY REFERENCE

[0260] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.BRIEF DESCRIPTION OF THE DRAWINGS

[0261] The novel features of the disclosure are set forth with particularity in the appended claims A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of thedisclosure are utilized, and the accompanying drawings of which:

[0262] FIGs. 1A-1T depict exemplary embodiments of the multispecific molecules as described herein. For FIGs. 1A-1F, 1I-1P, IS, and IT, the “anti-TCR0V antibody molecule” may represent two TCRβV27-binding moieties as described herein or one the TCRβV27-binding moiety as described herein and one TCR binding moiety as described herein. For FIGs. 1G, 1H, IQ, and 1R, the “anti-TCR0V antibody molecule” represents the TCRβV27-binding moiety as described herein. The “IL2” is an exemplary embodiment of the one or more molecule that binds to a co-stimulatory receptor of a T cell as described herein or the at least one cytokine molecule or a functional fragment or functional variant thereof as described herein. In some embodiments, the “IL-2” is replaced with the one or more molecule that binds to a co-stimulatory receptor of a T cell as described herein. In some embodiments, the “IL-2” is replaced with the at least one cytokine molecule or a functional fragment or functional variant thereof as described herein. FIGs. 1A-1M depict the exemplary embodiments of the multispecific molecules as described herein comprising an exemplary dimerization module, e.g., Fc regions. FIGs. 1N-1T depict the exemplary embodiments of the multispecific molecules as described herein comprising another exemplary dimerization module, e.g., Fc regions comprising aN297A mutation according to EU numbering and knobin-hole mutations.

[0263] FIG. 2 depicts the phylogenetic tree of TCRBV gene family and subfamilies with corresponding antibodies mapped. Subfamily identities are as follows: Subfamily A: TCR0 V6; Subfamily B: TCR0 V10; Subfamily C: TCRp V12; Subfamily D: TCRp V5; Subfamily E: TCRp V7; Subfamily F: TCRp VI 1; Subfamily G: TCR0 V14; Subfamily H: TCRp V16; Subfamily LTCRp V18; Subfamily J: TCRp V9; Subfamily K: TC Rp V13; Subfamily L: TCRP V4; Subfamily M: TCRP V3; Subfamily N: TCR0 V2; Subfamily O: TCR0 V15; Subfamily P: TCR0 V30; Subfamily Q: TCR0 V19; Subfamily R: TCR0 V27; Subfamily S: TCRp V28; Subfamily T: TCRp V24; Subfamily U: TCRp V20; Subfamily V: TCRp V25; and Subfamily W: TCRp V29 subfamily. Subfamily members are described in detail herein in the Section titled “TCR beta V (TCR0V)”.

[0264] FIG. 3 shows a graphical representation of the relation of sequences between different TCRVB clonotype subfamilies.

[0265] FIG. 4 is a schematic of the experimental design for the pharmacokinetic (PK) profile and dosing strategy of the multispecific polypeptide molecule as described herein.

[0266] FIGs. 5A, 5B, and 5C show Table 9, which depict alignment of TCRBV amino acid sequences (SEQ ID NOs: 3457-3516, 3669-3673, 3522, 3674-3675, 3525, 3676-3687, 3538, 3688-3698, 3550-3639 and 3699-3790, respectively, in order of appearance). The alignment of TCRBV amino acid sequences in Table 9 underscores the diversity of TCR sequences. In particular, the TRBV sequences from different subfamilies are considerably different from each other.

[0267] FIG.6 shows the experimental design for the tumor rechallenge study. Cured EMT6 tumor bearing mice were rechallenged with EMT6 tumor cells in one flank and CT26 tumor cells in another flank and monitored for tumor growth for 28 days.

[0268] FIGs. 7A-7BB depict exemplary embodiments of the multispecific molecules as described herein.FIG.7A shows an exemplary embodiment of the multispecific molecules comprising a TCRβV27-binding moiety and an exemplary one or more molecule that binds to a co-stimulatory receptor of a T cell, e.g., IL2-C125A, as described herein. The exemplary embodiment of the multispecific molecules as described herein comprises an exemplary dimerization module, e.g., Fc regions comprising a N297A mutation according to EU numbering and knob-in-hole mutations FIG. 7B shows another exemplary embodiment of the multispecific molecules comprising a TCRβV27-binding moiety and an exemplary one or more molecule that binds to a co-stimulatory receptor of a T cell, e.g., at least one cytokine molecule or a functional fragment or functional variant thereof, as described herein. The exemplary embodiment of the multispecific molecules as described herein comprises an exemplary dimerization module, e.g., Fc regions comprising a N297A mutation according to EU numbering and knob-in-hole mutations. FIGs. 7C-7BB depict exemplary embodiments of the configuration of the multispecific molecules as described herein. For FIGs. 7C-7BB, the pentagon represents the TCRpV27-binding moiety, the circle represents the one or more molecule that binds to a co-stimulatory receptor of a T cell, and the rectangles represent the dimerization module, e.g., the first portion of dimerization module and the second portion of dimerization module. FIGs. 7C-7O depict the exemplary embodiments of the multispecific molecules as described herein comprising an exemplary dimerization module, e.g., Fc regions. FIGs. 7P-7BB depict the exemplary embodiments of the multispecific molecules as described herein comprising another exemplary dimerization module, e.g., Fc regions comprising aN297A mutation according to EU numbering and knobin-hole mutations.

[0269] FIGs. 8A-8B shows that TRBV27 has the highest usage in tumor-infiltrating lymphocytes (TILs) across various cancer types upon a TCRseq data analysis of a database (-41,000; 25 cancers). FIG. 8A shows percentage of all TRBV expression in TILs. FIG.8B shows expression of TRBV27 across multiple tumor types.

[0270] FIG. 9 shows that V0 / TRBV-27 surface binding indicates dominant CD8 bias usage in healthy donor peripheral blood. In particular, FIG. 9 illustrates the flow cytometry data measuring percentage of TCRV027 or TCRV06-5 expressing CD4+ T cells and CD8+ T cells.

[0271] FIG. 10 shows that V0 / TRBV-27 expression indicates dominant CD8 bias usage in healthy donor peripheral blood. In particular, FIG. 10 illustrates the TRBV gene expression in CD8, CD4, and Treg cells, measured via TCR sequencing.

[0272] FIG. 11 shows the TRBV27 usage across T cell subsets in tumor-infiltrating lymphocytes isolated from non-small cell lung cancer (NSCLC) patients by analysis of single cell RNA / TCR sequencing of tumor-infiltrating lymphocytes.

[0273] FIG. 12 shows affinity of various anti-TCRβV27 antibody molecule or anti-TCR(3V27 antigen binding domain constructs with varying VH liability sites, VL liability sites, A54 mutation, NG liability site removal, and / or DT liability site removal. FIG. 12 describes the sequences according to SEQ ID NO: 1130, SEQ ID NO: 1129, SEQ ID NO: 1511, and 1512.

[0274] FIG. 13 shows affinity of various anti-TCRβV27 antibody molecule or anti-TCRβV27 antigen binding domain constructs with varying VH liability sites, VL liability sites, A54 mutation, NG liabilitysite removal, and / or DT liability site removal. FIG. 13 describes the sequences according to SEQ ID NO: 1130, SEQ ID NO: 1511, and 1512.

[0275] FIG. 14 shows characteristics of various anti-TCR(3V27 antibody molecule or anti-TCRpV27 antigen binding domain constructs, with two exemplary embodiments of the molecule comprising an TCRpV27-binding moiety as described herein, BOM0064 and BOM0074, having acceptable biophysical properties.

[0276] FIG. 15 shows that two exemplary embodiments of the molecule comprising an TCRPV27-binding moiety as described herein, BOM0064 and BOM0074, promote potent activation of human T cells and acquisition of cytotoxic phenotype as assessed by expression of CD25, granzyme B, perforin, and CD107a in human T cells treated with BLM0283, BOM0064, BOM0074, or BKM0345 (comparative control construct).

[0277] FIG. 16 shows that an exemplary embodiment of the molecule comprising an TCRpV27-binding moiety as described herein, BOM0074, induces potent in vitro IFN-y release from human T cells, as assessed by the analysis of in vitro IFNy secretion and different cytokine release from human T cells treated with BOM0074 (lOOnM dose, 5-day hPBMC expansion).

[0278] FIG. 17 shows that two exemplary embodiments of the molecule comprising an TCRPV27-binding moiety as described herein, BOM0064 and BOM0074, promote the reprogramming of human T cells to a TCM phenotype upon treatment.

[0279] FIG. 18 shows that an exemplary embodiment of the molecule comprising an TCRβV27-binding moiety as described herein, BOM0074 is highly selective for expansion of T cells expressing TRBV27 TCRs upon treatment with BLM0283 or BOM0074. TRVB27 transcripts were calculated as a percent of all Vb transcripts and here reported as enrichment Day 5 / Day 0 from each of 3 donors. Another exemplary embodiment of the molecule comprising an TCRpV27-binding moiety as described herein, BOM0064 shows similar results in a separate studyDETAILED DESCRIPTION DEFINITION

[0280] Certain specific details of this description are set forth in order to provide a thorough understanding of various embodiments. However, one skilled in the art will understand that the present disclosure may be practiced without these details. In other instances, well-known structures have not been shown or described in detail to avoid unnecessarily obscuring descriptions of the embodiments.

[0281] Unless the context requires otherwise, throughout the specification and claims which follow, the word “comprise” and variations thereof, such as, “comprises” and “comprising” are to be construed in an open, inclusive sense, that is, as “including, but not limited to.” Further, headings provided herein are for convenience only and do not interpret the scope or meaning of the claimed disclosure.

[0282] As used in this specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the content clearly dictates otherwise. The use of the words “a” or “an” when used in conjunction with the term “comprising” herein may mean “one,” but it is also consistent with the meaning of “one or more,” “at least one,” and “one or more than one.”

[0283] It should also be noted that the term “or” is generally employed in its sense including “and / or” unless the content clearly dictates otherwise.

[0284] Unless otherwise defined, 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 disclosure belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, suitable methods and materials are described below

[0285] The term “about” when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass variations of ±20% or in some instances ±10%, or in some instances ±5%, or in some instances ±1%, or in some instances ±0.1% from the specified value, as such variations are appropriate to perform the disclosed methods. As used herein, “about” and “approximately” generally mean an acceptable degree of error for the quantity measured given the nature or precision of the measurements. Exemplary degrees of error are within 20 percent (%), typically, within 10%, and more typically, within 5% of a given range of values.

[0286] The term “acquire” or “acquiring” as the terms are used herein, refer to obtaining possession of a physical entity (e.g.. a sample, a polypeptide, a nucleic acid, or a sequence), or a value, e.g., a numerical value, by “directly acquiring” or “indirectly acquiring” the physical entity or value. “Directly acquiring” means performing a process (e.g., performing a synthetic or analytical method) to obtain the physical entity or value. “Indirectly acquiring” refers to receiving the physical entity or value from another party or source (e g., a third party laboratory that directly acquired the physical entity or value). Directly acquiring a physical entity includes performing a process that includes a physical change in a physical substance, e.g., a starting material. Directly acquiring a value includes performing a process that includes a physical change in a sample or another substance, e.g., performing an analytical process which includes a physical change in a substance, e.g., a sample.

[0287] “Antibody molecule” as used herein refers to a protein, e.g., an immunoglobulin chain or fragment thereof, comprising at least one immunoglobulin variable domain structure and / or sequence. An antibody molecule encompasses antibodies (e.g., full-length antibodies), antibody fragments, and antigen binding domains. In some embodiments, an antibody molecule comprises an antigen binding or functional fragment of a full length antibody, an antigen binding domain, or a full length immunoglobulin chain. For example, a full-length antibody is an immunoglobulin (Ig) molecule (e.g., an IgG antibody) that is naturally occurring or formed by normal immunoglobulin gene fragment recombinatorial processes). In embodiments, an antibody molecule refers to an immunologically active, antigen-binding portion of an immunoglobulin molecule, such as an antibody fragment. An antibody fragment, e g., functional fragment, is a portion of an antibody, e g., Fab, Fab', F(ab')2, F(ab)2, variable fragment (Fv), domain antibody (dAb), or single chain variable fragment (scFv). An antigen binding domain can be Fab, Fab', F(ab')2, F(ab)2, variable fragment (Fv), domain antibody (dAb), or single chain variable fragment (scFv). A functional antibody fragment or antigen binding domain binds to the same antigen as that recognized by the intact (e.g., full-length) antibody. The terms “antibody fragment” or “functional fragment” or “antigen binding domain” also include isolated fragments consisting of the variable regions, such as the “Fv” fragments consisting of thevariable regions of the heavy and light chains or recombinant single chain polypeptide molecules in which light and heavy variable regions are connected by a peptide linker (“scFv proteins”). In some embodiments, an antibody fragment or an antigen binding domain does not include portions of antibodies without antigen binding activity, such as Fc fragments or single amino acid residues. In some embodiments, an antibody fragment or an antigen binding domain includes portions of antibodies without antigen binding activity, such as Fc fragments or single amino acid residues. Exemplary antibody molecules or antigen binding domains include full length antibodies and antibody fragments, e.g., dAb (domain antibody), single chain, Fab, Fab’, and F(ab’)2 fragments, and single chain variable fragments (scFvs). In some embodiments, the antibody molecule or the antigen binding domain is an antibody mimetic. In some embodiments, the antibody molecule or the antigen binding domain is, or comprises, an antibody-like framework or scaffold, such as, fibronectins, ankyrin repeats (e g., designed ankyrin repeat proteins (DARPins)), avimers, affibody affinity ligands, anticalins, or affilin molecules.

[0288] The term “human-like antibody molecule” as used herein refers to a humanized antibody molecule, human antibody molecule or an antibody molecule having at least 95% sequence identity with a nonmurine germline framework region, e.g., FR1, FR2, FR3 and / or FR4. In some embodiments, the humanlike antibody molecule comprises a framework region having at least 95% sequence identity to a human germline framework region, e.g., a FR1, FR2, FR3 and / or FR4 of a human germline framework region. The term “human-like antibody molecule” as used herein refers to a humanized antibody molecule, human antibody molecule or an antibody molecule having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity with a non-murine germline framework region, e.g., FR1, FR2, FR3 and / or FR4. In some embodiments, the human-like antibody molecule comprises a framework region having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to a human germline framework region, e.g., a FR1, FR2, FR3 and / or FR4 of a human germline framework region. In some embodiments, the human-like antibody molecule is a recombinant antibody. In some embodiments, the human-like antibody molecule is a humanized antibody molecule. In some embodiments, the human-like antibody molecule is human antibody molecule. In some embodiments, the human-like antibody molecule is a phage display or a yeast display antibody molecule. In some embodiments, the human-like antibody molecule is a chimeric antibody molecule. In some embodiments, the human-like antibody molecule is a CDR grafted antibody molecule.

[0289] As used herein, an “immunoglobulin variable domain sequence” refers to an amino acid sequence which can form the structure of an immunoglobulin variable domain. For example, the sequence may include all or part of the amino acid sequence of a naturally-occurring variable domain. For example, the sequence may or may not include one, two, or more N- or C-terminal amino acids, or may include other alterations that are compatible with formation of the protein structure.

[0290] In embodiments, an antibody molecule is monospecific, e.g., it comprises binding specificity for a single epitope. In some embodiments, an antibody molecule is multispecific, e.g., it comprises a plurality of immunoglobulin variable domain sequences, where a first immunoglobulin variable domain sequencehas binding specificity for a first epitope and a second immunoglobulin variable domain sequence has binding specificity for a second epitope. In some embodiments, an antibody molecule is a bispecific antibody molecule. “Bispecific antibody molecule” as used herein refers to an antibody molecule that has specificity formore than one (e.g., two, three, four, or more) epitope and / or antigen.

[0291] “Antigen” (Ag) as used herein refers to a molecule that can provoke an immune response, e.g., involving activation of certain immune cells and / or antibody generation. Any macromolecule, including almost all proteins or peptides, can be an antigen. Antigens can also be derived from genomic recombinant or DNA. For example, any DNA comprising a nucleotide sequence or a partial nucleotide sequence that encodes a protein capable of eliciting an immune response encodes an “antigen.” In embodiments, an antigen does not need to be encoded solely by a full length nucleotide sequence of a gene, nor does an antigen need to be encoded by a gene at all. In embodiments, an antigen can be synthesized or can be derived from a biological sample, e.g., a tissue sample, a tumor sample, a cell, or a fluid with other biological components. As used, herein a “tumor antigen” or interchangeably, a “cancer antigen” includes any molecule present on, or associated with, a cancer, e.g., a cancer cell or a tumor microenvironment that can provoke an immune response. As used, herein an “immune cell antigen” includes any molecule present on, or associated with, an immune cell that can provoke an immune response.

[0292] The “antigen-binding site,” or “binding portion” of an antibody molecule refers to the part of an antibody molecule, e.g., an immunoglobulin (Ig) molecule, that participates in antigen binding. In embodiments, the antigen binding site is formed by amino acid residues of the variable (V) regions of the heavy (H) and light (L) chains. Three highly divergent stretches within the variable regions of the heavy and light chains, referred to as hypervanable regions, are disposed between more conserved flanking stretches called “framework regions,” (FRs). FRs are amino acid sequences that are naturally found between, and adjacent to, hypervariable regions in immunoglobulins. In embodiments, in an antibody molecule, the three hypervariable regions of a light chain and the three hypervariable regions of a heavy chain are disposed relative to each other in three dimensional space to form an antigen-binding surface, which is complementary to the three-dimensional surface of a bound antigen. The three hypervariable regions of each of the heavy and light chains are referred to as “complementarity-determining regions,” or “CDRs.” The framework region and CDRs have been defined and described, e.g., in Kabat, E. A., et al. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, U. S. Department of Health and Human Services, NIH Publication No. 91-3242, and Chothia, C. et al. (1987) J. Mol. Biol. 196:901-917. Each variable chain (e.g., variable heavy chain and variable light chain) is typically made up of three CDRs and four FRs, arranged from amino-terminus to carboxy-terminus in the amino acid order: FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4.

[0293] As used herein, an “immune cell” refers to any of various cells that function in the immune system, e.g., to protect against agents of infection and foreign matter In embodiments, this term includes leukocytes, e.g., neutrophils, eosinophils, basophils, lymphocytes, and monocytes. Innate leukocytes include phagocytes (e g., macrophages, neutrophils, and dendritic cells), mast cells, eosinophils, basophils, and natural killer cells. Innate leukocytes identify and eliminate pathogens, either by attacking largerpathogens through contact or by engulfing and then killing microorganisms, and are mediators in the activation of an adaptive immune response. The cells of the adaptive immune system are special types of leukocytes, called lymphocytes. B cells and T cells are important types of lymphocytes and are derived from hematopoietic stem cells in the bone marrow. B cells are involved in the humoral immune response, whereas T cells are involved in cell-mediated immune response. The term “immune cell” includes immune effector cells.

[0294] “Immune effector cell,” as that term is used herein, refers to a cell that is involved in an immune response, e.g., in the promotion of an immune effector response. Examples of immune effector cells include, but are not limited to, T cells, e.g., alpha / beta T cells and gamma / delta T cells, B cells, natural killer (NK) cells, natural killer T (NK T) cells, and mast cells.

[0295] The term “effector function” or “effector response” refers to a specialized function of a cell. Effector function of a T cell, for example, may be cytolytic activity or helper activity including the secretion of cytokines.

[0296] The terms “polypeptide”, “peptide” and “protein” (if single chain) are used interchangeably herein to refer to polymers of amino acids of any length. The polymer may be linear or branched, it may comprise modified amino acids, and it may be interrupted by non-amino acids. The terms also encompass an amino acid polymer that has been modified; for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation, such as conjugation with a labeling component. The polypeptide can be isolated from natural sources, can be a produced by recombinant techniques from a eukaryotic or prokaryotic host, or can be a product of synthetic procedures.

[0297] The terms “nucleic acid,” “nucleic acid sequence,” “nucleotide sequence,” or “polynucleotide sequence,” and “polynucleotide” are used interchangeably. They refer to a polymeric form of nucleotides of any length, either deoxyribonucleotides or ribonucleotides, or analogs thereof. The polynucleotide may be either single-stranded or double-stranded, and if single-stranded may be the coding strand or non-coding (antisense) strand. A polynucleotide may comprise modified nucleotides, such as methylated nucleotides and nucleotide analogs. The sequence of nucleotides may be interrupted by non-nucleotide components. A polynucleotide may be further modified after polymerization, such as by conjugation with a labeling component. The nucleic acid may be a recombinant polynucleotide, or a polynucleotide of genomic, cDNA, semisynthetic, or synthetic origin which either does not occur in nature or is linked to another polynucleotide in a non-natural arrangement.

[0298] The term “isolated,” as used herein, refers to material that is removed from its original or native environment (e.g., the natural environment if it is naturally occurring). For example, a naturally-occurring polynucleotide or polypeptide present in a living animal is not isolated, but the same polynucleotide or polypeptide, separated by human intervention from some or all of the co-existing materials in the natural system, is isolated. Such polynucleotides could be part of a vector and / or such polynucleotides or polypeptides could be part of a composition, and still be isolated in that such vector or composition is not part of the environment in which it is found in nature. An isolated polynucleotide (ribonucleic acid (RNA), deoxyribonucleic acid (DNA)), or polypeptide is free of the genes / nucleic acids or sequences / amino acidsthat flank it in its naturally-occurring state.

[0299] The compositions and methods of the present invention encompass polypeptides and nucleic acids having the sequences specified, or sequences substantially identical or similar thereto, e.g., sequences at least 80%, 85%, 90%, 95% identical or higher to the sequence specified. In the context of an amino acid sequence, the term “substantially identical” is used herein to refer to a first amino acid that contains a sufficient or minimum number of amino acid residues that are i) identical to, or ii) conservative substitutions of aligned amino acid residues in a second amino acid sequence such that the first and second amino acid sequences can have a common structural domain and / or common functional activity. For example, amino acid sequences that contain a common structural domain having at least about 80%, 85%, 90%. 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% 99%, 99.5%, 99.9%, or 100% sequence identity to a reference sequence, e.g., a sequence provided herein. In the context of nucleotide sequence, the term “substantially identical” is used herein to refer to a first nucleic acid sequence that contains a sufficient or minimum number of nucleotides that are identical to aligned nucleotides in a second nucleic acid sequence such that the first and second nucleotide sequences encode a polypeptide having common functional activity, or encode a common structural polypeptide domain or a common functional polypeptide activity. For example, nucleotide sequences having at least about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% 99%, 99.5%, 99.9%, or 100% sequence identity to a reference sequence, e.g., a sequence provided herein.

[0300] The term “variant” refers to a polypeptide that has a substantially identical amino acid sequence to a reference amino acid sequence, or is encoded by a substantially identical nucleotide sequence. In some embodiments, the variant is a functional variant. In some embodiments, a TCR V variant can bind to TCRa and form a TCR a (3 complex.. In some embodiments, a TCRaV variant can bind to TCRa and form a TCR a:p complex

[0301] The term “functional variant” refers to a polypeptide that has a substantially identical amino acid sequence to a reference amino acid sequence, or is encoded by a substantially identical nucleotide sequence, and is capable of having one or more activities of the reference amino acid sequence.

[0302] Calculations of homology or sequence identity between sequences (the terms are used interchangeably herein) are performed as follows. To determine the percent identity of two amino acid sequences, or of two nucleic acid sequences, the sequences are aligned for optimal comparison purposes (e.g., gaps can be introduced in one or both of a first and a second amino acid or nucleic acid sequence for optimal alignment and non-homologous sequences can be disregarded for comparison purposes). In a preferred embodiment, the length of a reference sequence aligned for comparison purposes is at least 30%, preferably at least 40%, more preferably at least 50%, 60%, and even more preferably at least 70%, 80%, 90%, 100% of the length of the reference sequence. The amino acid residues or nucleotides at corresponding amino acid positions or nucleotide positions are then compared. When a position in the first sequence is occupied by the same amino acid residue or nucleotide as the corresponding position in the second sequence, then the molecules are identical at that position (as used herein amino acid or nucleic acid “identity” is equivalent to amino acid or nucleic acid “homology”).

[0303] The percent identity between the two sequences is a function of the number of identical positions shared by the sequences, taking into account the number of gaps, and the length of each gap, which need to be introduced for optimal alignment of the two sequences. The comparison of sequences and determination of percent identity between two sequences can be accomplished using a mathematical algorithm. In a preferred embodiment, the percent identity between two amino acid sequences is determined using the Needleman and Wunsch ((1970) J. Mol. Biol. 48:444-453 ) algorithm which has been incorporated into the GAP program in the GCG software package (available at htp: / / www.gcg.com), using either a Blossum 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5, or 6. In yet another preferred embodiment, the percent identity between two nucleotide sequences is determined using the GAP program in the GCG software package (available at http: / / www.gcg.com), using a NWSgapdna. CMP matrix and a gap weight of 40, 50, 60, 70, or 80 and a length weight of 1, 2, 3, 4, 5, or 6. A particularly preferred set of parameters (and the one that should be used unless otherwise specified) are a Blossum 62 scoring matrix with a gap penalty of 12, a gap extend penalty of 4, and a frameshift gap penalty of 5.

[0304] The percent identity between two amino acid or nucleotide sequences can be determined using the algorithm of E. Meyers and W. Miller ((1989) CABIOS, 4:11-17) which has been incorporated into the ALIGN program (version 2.0), using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4. The nucleic acid and protein sequences described herein can be used as a “query sequence” to perform a search against public databases to, for example, identify other family members or related sequences. Such searches can be performed using the NBLAST and XBLAST programs (version 2.0) of Altschul, et al. (1990) J. Mol. Biol. 215:403-10. BLAST nucleotide searches can be performed with the NBLAST program, score = 100, wordlength = 12 to obtain nucleotide sequences homologous to a nucleic acid molecule of the invention. BLAST protein searches can be performed with the XBLAST program, score = 50, wordlength = 3 to obtain amino acid sequences homologous to protein molecules of the invention. To obtain gapped alignments for comparison purposes, Gapped BLAST can be utilized as described in Altschul etal., (1997) Nucleic Acids Res. 25:3389-3402. When utilizing BLAST and Gapped BLAST programs, the default parameters of the respective programs (e.g., XBLAST and NBLAST) can be used.

[0305] It is understood that the molecules of the present invention may have additional conservative or non-essential amino acid substitutions, which do not have a substantial effect on their functions.

[0306] The term “amino acid” is intended to embrace all molecules, whether natural or synthetic, which include both an amino functionality and an acid functionality and capable of being included in a polymer of naturally-occurring amino acids. Exemplary amino acids include naturally-occurring amino acids; analogs, derivatives and congeners thereof; amino acid analogs having variant side chains; and all stereoisomers of any of any of the foregoing. As used herein the term “amino acid” includes both the D-or L- optical isomers and peptidomimetics.

[0307] A “conservative amino acid substitution” is one in which the amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar sidechains have been defined in the art. These families include amino acids with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine)

[0308] As used herein, the term “molecule” as used in, e.g., antibody molecule, cytokine molecule, receptor molecule, includes full-length, naturally-occurring molecules, as well as variants, e.g., functional variants (e g., truncations, fragments, mutated (e.g., substantially similar sequences) or derivatized form thereof), so long as at least one function and / or activity of the unmodified (e g., naturally-occurring) molecule remains.

[0309] As used herein, the term “mutation” refers to an alteration in the nucleotide sequence of the genome of an organism, virus, or extrachromosomal DNA. In some embodiments, the mutation may be a large-scale mutation, such as amplifications (or gene duplications) or repetitions of a chromosomal segment, deletions of large chromosomal regions, chromosomal rearrangements (e.g., chromosomal translocations, chromosomal inversions, non-homologous chromosomal crossover, and interstitial deletions), and loss of heterozygosity. In some embodiments, the mutation may be a small-scale mutation, such as insertions, deletions, and substitution mutations. As used herein, the term “substitution mutation” refers to the transition that exchange a single nucleotide for another.

[0310] “Interleukin-2” also known as IL2, IL-2, IL 2, TCGF, lymphokine, and interleukin 2, as referred to herein, includes any of the recombinant or naturally-occurring forms of IL-2 or variants or homologs thereof that have or maintain IL-2 activity (e.g., at least 40% 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity). In some aspects, the variants or homologs have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g., a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring IL-2. In some embodiments, IL-2 is substantially identical to the protein identified by the UniProt reference number P60568 or a variant or homolog having substantial identity thereto.

[0311] The term “co-stimulatory receptor,” as used herein, refers to the cell surface molecules that can positively induce a secondary signal to fully activate T cells with TCR signaling and cytokine stimulation. In some embodiments, exemplary co-stimulatory receptors include, but are not limited to, CD2, CD27, CD28, ICOS (CD278), 4-1BB (CD137), 0X40 (CD134), CD40, CD40L, Toll-like receptors (TLRs), or any combination thereof.

[0312] The tern “Cancer” as used herein can encompass all types of oncogenic processes and / or cancerous growths. In embodiments, cancer includes primary tumors as well as metastatic tissues or malignantly transformed cells, tissues, or organs. In embodiments, cancer encompasses all histopathologies and stages, e.g., stages of invasiveness / severity, of a cancer. In embodiments, cancer includes relapsed and / or resistant cancer. The terms “cancer” and “tumor” can be used interchangeably. For example, both terms encompasssolid and liquid tumors. As used herein, the term “cancer” or “tumor” includes premalignant, as well as malignant cancers and tumors. As used herein, the terms “tumor antigen”, “tumor-associated antigen”, and “tumor associate antigen” can be used interchangeably.Anti-TCRBV antibodiesHuman T cell receptor (TCR) complex

[0313] TCR is a disulfide-linked membrane -anchored heterodimeric protein normally consisting of the highly variable alpha (a) and beta ((3) chains expressed as part of a complex with the invariant CD3 chain molecules. TCR on a[ T cells is formed by a heterodimer of one alpha chain and one beta chain. Each alpha or beta chain consists of a constant domain and a highly variable domain classified as the Immunoglobulin superfamily (IgSF) fold. The TCR0V chains can be further classified into 30 subfamilies (TRBV1-30). Despite their high structural and functional homology, the amino acid sequence homology in the TRBV genes is very low. Only 4 amino acids out of approximately 95 are identical while 10 additional amino acids are conserved among all subfamilies (see, an alignment of TCRBV amino acid sequences in Table 9). Nevertheless, TCRs formed between alpha and beta chains of highly diverse sequences show a remarkable structural homology and elicit a similar function, e.g., activation of T cells.

[0314] T cell receptors (TCR) can be found on the surface of T cells. TCRs recognize antigens, e.g., peptides, presented on, e.g., bound to, major histocompatibility complex (MHC) molecules on the surface of cells, e.g., antigen-presenting cells. TCRs are heterodimeric molecules and can comprise an alpha chain, a beta chain, a gamma chain or a delta chain. TCRs comprising an alpha chain and a beta chain are also referred to as TCRa0. The TCR beta chain consists of the following regions (also known as segments): variable (V), diversity (D), joining (J) and constant (C) (see Mayer G. and Nyland J. (2010) Chapter 10: Major Histocompatibility Complex and T-cell Receptors-Role in Immune Responses. In: Microbiology and Immunology on-line, University of South Carolina School of Medicine). The TCR alpha chain consists of V, J and C regions. The rearrangement of the T-cell receptor (TCR) through somatic recombination of V (variable), D (diversity), J (joining), and C (constant) regions is a defining event in the development and maturation of a T cell. TCR gene rearrangement takes place in the thymus.

[0315] TCRs can comprise a receptor complex, known as the TCR complex, which comprises a TCR heterodimer comprising of an alpha chain and a beta chain, and dimeric signaling molecules, e.g., CD3 coreceptors, e.g., CD35 / e, and / or CD3y / e.

[0316] As used herein, the term “T cell receptor beta variable chain” or “TCR0V,” refers to an extracellular region of the T cell receptor beta chain which comprises the antigen recognition domain of the T cell receptor. The term TCR0V includes isoforms, mammalian, e.g., human TCR0V, species homologs of human and analogs comprising at least one common epitope with TCR0V. Human TCR0V comprises a gene family comprising subfamilies including, but not limited to: a TCR0 V6 subfamily, a TCR0 V10 subfamily, aTCR0 V12 subfamily, aTCR0 V5 subfamily, aTCR0 V7 subfamily, a TCR0 VI 1 subfamily, a TCR0 V 14 subfamily, a TC Rp V 16 subfamily, a TCR0 V 18 subfamily, a TCR0 V 9 subfamily, a TCR0 V13 subfamily, a TCR0 V4 subfamily, a TCR0 V3 subfamily, a TCR0 V2 subfamily, a TCR0V15 subfamily, a TCRp V30 subfamily, a TCRp V19 subfamily, a TCRp V27 subfamily, a TCRp V28 subfamily, a TCRp V24 subfamily, a TCRp V20 subfamily, TCRp V25 subfamily, a TCRp V29 subfamily, a TCRp V 1 subfamily, a TCRp V 17 subfamily, a TCRp V21 subfamily, a TCRp V23 subfamily, or a TCRp V26 subfamily, as well as family members of said subfamilies, and variants thereof (e.g., a structural or functional variant thereof). In some embodiments, the TCRp V6 subfamily comprises: TCRp V6-4*01, TCRP V6-4* 02, TCRP V6-9* 01, TCRp V6-8 * 01, TCRp V6-5 * 01, TCRp V6-6* 02, TCRp V6-6* 01, TCRp V6-2*01, TCRp V6-3*01 or TCRp V6-l*01. In some embodiments, TCRpV comprises TCRp V6-5*01, or a variant thereof, e.g., a variant having 85%, 90%, 95%, 99% or more identity the naturally-occurring sequence. TCRp ¥6-5*01 is also known as TRBV65; TCRBV6S5; TCRBV13S1, or TCRp V13.1. The amino acid sequence of TCRP ¥6-5*01, e.g., human TCRP ¥6-5*01, is known in that art, e.g., as provided by IMGT ID L36092. In some embodiments, TCRP V6-5*01 comprises the amino acid sequence of SEQ ID NO: 44, or a sequence having 85%, 90%, 95%, 99% or more identity thereof.

[0317] SEQ ID NO: 43 ATGAGCATCGGCCTCCTGTGCTGTGCAGCCTTGTCTCTCCTGTGGGCAGGTCCAGTGAATGC TGGTGTCACTCAGACCCCAAAATTCCAGGTCCTGAAGACAGGACAGAGCATGACACTGCAG TGTGCCCAGGATATGAACCATGAATACATGTCCTGGTATCGACAAGACCCAGGCATGGGGC TGAGGCTGATTCATTACTCAGTTGGTGCTGGTATCACTGACCAAGGAGAAGTCCCCAATGGC TACAATGTCTCCAGATCAACCACAGAGGATTTCCCGCTCAGGCTGCTGTCGGCTGCTCCCTC CCAGACATCTGTGTACTTCTGTGCCAGCAGTTACTC

[0318] SEQ ID NO: 44 MSIGLLCCAALSLLWAGPVNAGVTQTPKFQVLKTGQSMTLQCAQDMNHEYMSWYRQDPGMG LRLIHY-SVGAGITDQGEVPNGYNVSRSTTEDFPLRLLSAAPSQTSVYFCASSYTCR beta V (TCRRV)

[0319] Diversity in the immune system enables protection against a huge array of pathogens. Since the germline genome is limited in size, diversity is achieved not only by the process of V(D)J recombination but also by junctional (junctions between V-D and D-J segments) deletion of nucleotides and addition of pseudo-random, non-templated nucleotides. The TCR beta gene undergoes gene arrangement to generate diversity.

[0320] The TCR V beta repertoire varies between individuals and populations because of, e.g., 7 frequently occurring inactivating polymorphisms in functional gene segments and a large insertion / deletion-related polymorphism encompassing 2 V beta gene segments.

[0321] Provided herein are, inter alia, antibody molecules and fragments thereof, that bind, e.g., specifically bind, to a human TCR beta V chain (TCRpV), e.g., a TCRpV gene family (also referred to as a group), e.g., a TCRpV subfamily (also referred to as a subgroup), e.g., as described herein. TCR beta V families and subfamilies are known in the art, e.g., as described in Yassai et al., (2009) Immunogenetics 61(7)pp:493-502; Wei S. and Concannon P. ( 1994) Human Immunology 41(3) pp: 201-206. The antibodies described herein can be recombinant antibodies, e.g., recombinant non-murine antibodies, e.g.,recombinant human or humanized antibodies.

[0322] The terms TCRBV, TCRVB, TRBV, TCR0V, TCRV0 or TRpV are used interchangeably herein and refer to a TCR beta V chain, e.g., as described herein.

[0323] In some embodiments, provided herein is an anti-TCRpV antibody molecule that binds to human TCRpV, e.g., a TCR0V family, e.g., gene family or a variant thereof. In some embodiments a TCRBV gene family comprises one or more subfamilies, e.g., as described herein, e.g., in FIG. 2, Table 10 or Table 11. In some embodiments, the TCR0V gene family comprises: a TCR0 V6 subfamily, a TCR0 V10 subfamily, a TCR0 V12 subfamily, a TCR0 V5 subfamily, a TCR0 V7 subfamily, a TCR0 VI 1 subfamily, a TCR0 V14 subfamily, a TCRP V 16 subfamily, a TCR0 VI 8 subfamily, a TCR0 V9 subfamily, a TCR0 V13 subfamily, a TCR0 V4 subfamily, a TCR0 V3 subfamily, a TCR0 V2 subfamily, a TCR0 V15 subfamily, a TCR0 V30 subfamily, a TCRP V19 subfamily, a TCR0 V27 subfamily, a TCRP V28 subfamily, a TCRp V24 subfamily, a TCR0 V20 subfamily, TCR0 V25 subfamily, a TCR0 V29 subfamily, a TCR0 V 1 subfamily, a TCR0 V 17 subfamily, a TCR0 V21 subfamily, a TCR0 V23 subfamily, or a TCR0 V26 subfamily.

[0324] In some embodiments, TCRp V6 subfamily is also known as TCR0 VI 3.1. In some embodiments, the TCRP V6 subfamily comprises: TCR V6-4*01, TCRp V6-4*02, TCRp V6-9*01, TCRp V6-8*01, TCRp V6-5*01, TCRP V6-6*02, TCRp V6-6*01, TCRP V6-2*01, TCRp V6-3*01 or TCRP V6-l*01, or a variant thereof. In some embodiments, TCR0 V6 comprises TCR0 V6-4*01, or a variant thereof. In some embodiments, TCR0 V6 comprises TCRP V6-4*02, or a variant thereof. In some embodiments, TCR0 V6 comprises TCR0 V6-9*01, or a variant thereof. In some embodiments, TCR0 V6 comprises TCR0 V6-8 * 01, or a variant thereof. In some embodiments, TCR0 V 6 comprises TCR0 V6-5 * 01, or a variant thereof. In some embodiments, TCR0 V6 comprises TCR0 V6-6*02, or a variant thereof. In some embodiments, TCRp V6 comprises TCRp V6-6*01, or a variant thereof. In some embodiments, TCRp V6 comprises TCRp V6-2*01, or a variant thereof. In some embodiments, TCRp V6 comprises TCRp V6-3*01, or a variant thereof. In some embodiments, TCR0 V6 comprises TCR0 V6-l*01, or a variant thereof.

[0325] In some embodiments, TCR0 V6 comprises TCRp V6-5*01, or a variant thereof. In some embodiments, TCR0 V6, e.g., TCR0 V6-5*01, is recognized, e.g., bound, by SEQ ID NO: 1 and / or SEQ ID NO: 2. In some embodiments, TCR0 V6, e.g, TCR0 V6-5*01, is recognized, e.g., bound, by SEQ ID NO: 9 and / or SEQ ID NO: 10. In some embodiments, TCR0 V6 is recognized, e.g., bound, by SEQ ID NO: 9 and / or SEQ ID NO: 11.

[0326] In some embodiments, TCR0 V10 subfamily is also known as TCRp V12. In some embodiments, the TCR0 V10 subfamily comprises: TCRp V10- 01, TCRp V10-l*02, TCRp V10-3*01 or TCRp V10-2* 01, or a variant thereof.

[0327] In some embodiments, TCRp V12 subfamily is also known as TCR0 V8.1. In some embodiments, the TCR0 V12 subfamily composes: TCR0 V12-4*01, TCR0 V12-3*01, or TCR0 V12-5*01, or a variant thereof. In some embodiments, TCR0 V12 is recognized, e.g., bound, by SEQ ID NO: 15 and / or SEQ ID NO: 16. In some embodiments, TCRp V12 is recognized, e.g., bound, by any one of SEQ ID NOs 23-25, and / or any one of SEQ ID NO: 26-30:

[0328] In some embodiments, the TCR0 V5 subfamily is chosen from: TCR(3 V5-5*01, TCR V5-6*01, TCR0 V5-4*01, TCR0 V5-8*01, TCR0 V5-l*01, or a variant thereof.

[0329] In some embodiments, the TCR0 V7 subfamily comprises TCR0 V7-7*01, TCR0 V7-6*01, TCR0 V7 -8*02, TCR0 V7 -4*01, TCR0 V7-2*02, TCR0 V7-2*03, TCR0 V7-2*01, TCR0 V7-3*01, TCR0 V7-9*03, or TCR0 V7-9*01, or a variant thereof

[0330] In some embodiments, the TCR0 V 11 subfamily comprises: TCR0 Vll-l*01, TCRpVll-2*01 or TCR0 Vll-3*01, or a variant thereof. In some embodiments, the TCR0 V14 subfamily comprises TCR0 VI 4* 01, or a variant thereof. In some embodiments, the TCR0 V16 subfamily comprises TCR VI 6*01, or a variant thereof. In some embodiments, the TCR V 18 subfamily comprises TCR0 V18*01, ora variant thereof. In some embodiments, the TCR V9 subfamily comprises TCR0 V9*01 or TCR V9*02, or a variant thereof. In some embodiments, the TCR0 V13 subfamily comprises TCR0 V13*01, or a variant thereof. In some embodiments, the TCR. V4 subfamily comprises TCR0 V4-2*01, TCR0 V4-3*01, or TCR V4-l*01, or a variant thereof. In some embodiments, the TCR0 V3 subfamily comprises TCR0 V3- 1*01, or a variant thereof. In some embodiments, the TCR V2 subfamily comprises TCR V2*01, or a variant thereof. In some embodiments, the TCR0 V15 subfamily comprises TCR0 V15*01, or a variant thereof. In some embodiments, the TCR V30 subfamily comprises TCR V30*01, or TCR0 V30*02, or a variant thereof. In some embodiments, the TCR V19 subfamily comprises TCR VI 9*01, or TCR V19*02, or a variant thereof. In some embodiments, the TCR0 V27 subfamily comprises TCR V27*01, or a variant thereof. In some embodiments, the TCR V28 subfamily comprises TCR0 V28*01, or a variant thereof. In some embodiments, the TCRp V24 subfamily comprises TCR V24-l*01, or a variant thereof. In some embodiments, the TCR0 V20 subfamily comprises TCR V20-l*01, or TCR0 V20-l*02, or a variant thereof. In some embodiments, the TCR0 V25 subfamily comprises TCR0 V25-l*01, or a vanant thereof. In some embodiments, the TCR0 V29 subfamily comprises TCRp V29-l*01, or a variant thereof.

[0331] Exemplary amino acid sequences for TCR0V subfamily members can be found on the ImMunoGeneTics Information System website: http: / / www.imgt.org / , or in a similar resource.

[0332] Current bispecific constructs designed to redirect T cells to promote tumor cell lysis for cancer immunotherapy typically utilize antibody fragments (Fab, scFv, VH, single domain antibody, etc.) that are derived from monoclonal antibodies (mAb) directed against the CD3e subunit of the T cell receptor (TCR). However, there are limitations to this approach which may prevent the full realization of the therapeutic potential for such bispecific constructs. Previous studies have shown that even low “activating” doses of anti-CD3e mAb can cause long-term T cell dysfunction and exert immunosuppressive effects. In addition, anti-CD3e mAbs have been associated with side effects that result from massive T cell activation. The large number of activated T cells secrete substantial amounts of cytokines, the most important of which is Interferon gamma (IFNy). This excess amount of IFNy in turn activates macrophages which then overproduce proinflammatory cytokines such as IL-lbeta, IL-6, IL-10 and TNF-alpha, causing a “cytokine storm” known as the cytokine release syndrome (CRS) (Shimabukuro-Vomhagen et al., J ImmunotherCancer. 2018 Jun 15;6(1):56, herein incorporated by reference in its entirety). Thus, the need exists for developing antibodies that are capable of binding and activating only a subset of effector T cells, e.g., to re-duce the CRS and / or neurotoxicity (NT).

[0333] Described herein are molecules targeting the TCR0V chain of TCR and methods thereof. Without wishing to be bound by theory, such molecules are capable of binding, activating, and / or expanding only a subset of T cells, avoiding or reducing CRS and / or NT and minimizing potential immunosuppressive effects of anti-CD3 mAbs.

[0334] Described herein is a class of antibodies, i.e., anti-TCR0V antibody molecules as described herein, which despite having low sequence similarity (e.g., low sequence identity among the different antibody molecules that recognize different TCR0V subfamilies), recognize a structurally conserved, yet sequencewise variable, region, e.g., domain, on the TCR0V protein and have a similar function (e.g., activation of T cells and a similar cytokine profile as described herein). Thus, the anti-TCR0V antibody molecules as described herein share a structure-function relationship.

[0335] Without wishing to be bound by theory, in some embodiments, the anti-TCR0Y antibody molecules as described herein bind to an outward facing epitope of a TCR0V protein when it is in a complex with a TCRalpha protein. In some embodiments, the anti-TCR0V antibody molecules as described herein recognize (e.g., bind to), a domain (e.g., an epitope) on the TCR0V protein that is: (1) structurally conserved among different TCR0V subfamilies; and (2) has minimal sequence identity among the different TCR0V subfamilies. As shown in Table 9, TCR0V proteins from the different TCRBV subfamilies share minimal sequence similarity. However, TCR0V proteins which have minimal sequence similarity, share a similar 3D conformation and structure.

[0336] The alignment of TCRBV amino acid sequences in Table 9 underscores the diversity of TCR sequences. In particular, the TRBV sequences from different subfamilies are considerably different from each other.

[0337] In some embodiments, the anti-TCR0V antibody molecules as described herein do not recognize, e.g., bind to, an interface of a TCR0V: TCRalpha complex. In some embodiments, the anti-TCR0V antibody molecules as described herein do not recognize, e.g., bind to, a constant region of a TCR0V protein. An exemplary antibody that binds to a constant region of a TCRBV region is JOVI.1 as de-scribed in Viney et al., (Hybridoma. 1992 Dec;ll(6):701-13). In some embodiments, the anti-TCR0V antibody molecules as described herein do not recognize, e.g., bind to, one or more (e.g., all) of a complementarity determining region (e.g., CDR1, CDR2 and / or CDR3) of a TCR0V protein.

[0338] Provided herein are, inter alia, antibody molecules directed to the variable chain of the beta subunit of TCR (TCR0V) which bind and, e.g., activate a subset of T cells. The anti-TCR0V antibody molecules as described herein result in lesser or no production of cytokines associated with CRS, e.g., IL-6, IL-lbeta, IL- 10 and TNF alpha; and enhanced and / or delayed production of IL-2 and IFNy. In some embodiments, the anti-TCR0V antibodies as described herein have a cytokine profile, e g., as described herein, which differs from a cytokine profile of a T cell engager that binds to a receptor or molecule other than a TCR0V region (“a non-TCR0V-binding T cell engager”). In some embodiments, the non-TCRpV-binding T cellengager comprises an antibody that binds to a CD3 molecule (e.g., CD3 epsilon (CD3e) molecule). In some embodiments, the non-TCR0V-binding T cell engager is an 0KT3 antibody or an SP34-2 antibody.

[0339] In some embodiments, the anti-TCR0V antibodies as described herein result in expansion of TCR0V+T cells, e.g., a subset of memory effector T cells known as TEMRA. Without wishing to be bound by theory, it is believed that in some embodiments, TEMRA cells can promote tumor cell lysis but not CRS. Accordingly, provided herein are methods of making said anti-TCR(3V antibody molecules and uses thereof. Also described herein are multispecific molecules, e.g., bispecific molecules comprising said anti-TCR0V antibody molecules. In some embodiments, compositions comprising anti-TCR0V antibody molecules of the present disclosure, can be used, e.g., to: (1) activate and redirect T cells to promote tumor cell lysis for cancer immuno-therapy; and / or (2) expand TCR0V+ T cells. In some embodiments, compositions comprising anti-TCR0V antibody molecules as described herein limit the harmful sideeffects of CRS and / or NT, e g., CRS and / or NT associated with anti-CD3e targeting.

[0340] In some embodiments, the anti-TCR0V antibody molecule binds to one or more of TRBV2, TRBV3-1, TRBV4-1, TRBV4-2, TRBV4-3, TRBV5-1, TRBV5-4, TRBV5-5, TRBV5-6, TRBV5-8, TRBV6-1, TRBV6-2, TRBV6-3, TRBV6-4, TRBV6-5, TRBV6-6, TRBV6-8, TRBV6-9, TRBV7-2, TRBV7-3, TRBV7-4, TRBV7-6, TRBV7-7, TRBV7-8, TRBV7-9, TRBV9, TRBV10-1, TRBV10-2, TRBV10-3, TRBV11-1, TRBV11-2, TRBV11-3, TRBV12-3, TRBV12-4, TRBV12-5, TRBV13, TRBV14, TRBV15, TRBV16, TRBV18, TRBV19, TRBV20-1, TRBV24-1, TRBV25-1, TRBV27, TRBV28, TRBV29-1 and TRBV30. In some embodiments, the anti-TCR0V antibody molecule binds to one or more of TRBV6-1, TRBV6-2, TRBV6-3, TRBV6-4, TRBV6-5, TRBV6-6, TRBV6-8 and TRBV6-9. In some embodiments, the anti-TCR0V antibody molecule is an anti-TRBV2, anti-TRBV3-l, anti-TRBV4-1, anti-TRBV4-2, anti-TRBV4-3, anti-TRBV5-l, anti-TRBV5-4, anti-TRBV5-5, anti-TRBV5-6, anti-TRBV5-8, anti-TRBV6-l, anti-TRBV6-2, anti-TRBV6-3, anti-TRBV6-4, anti-TRBV6-5, anti-TRBV6-6, anti-TRBV6-8, anti-TRBV6-9, anti-TRBV7-2, anti-TRBV7-3, anti-TRBV7-4, anti-TRBV7-6, anti-TRBV7-7, anti-TRBV7-8, anti-TRBV7-9, anti-TRBV9, anti-TRBV10-l, anti-TRBV10-2, anti-TRBV10-3, anti-TRBVl 1-1, anti-TRBVl 1-2, anti-TRBVl 1-3, anti-TRBV12-3, anti-TRBV12-4, anti-TRBVl 2-5, anti-TRBVl 3, anti-TRBVl 4, anti-TRBVl 5, anti-TRBVl 6, anti-TRBVl 8, anti-TRBV19, anti-TRBV20-l, anti-TRBV24-l, anti-TRBV25-l, anti-TRBV27, anti-TRBV28, anti-TRBV29-l, or anti-TRBV30.

[0341] In some embodiments, the anti-TCR0V antibody molecule binds specifically to TRBV2, TRBV3-1, TRBV4-1, TRBV4-2, TRBV4-3, TRBV5-1, TRBV5-4, TRBV5-5, TRBV5-6, TRBV5-8, TRBV6-1, TRBV6-2, TRBV6-3, TRBV6-4, TRBV6-5, TRBV6-6, TRBV6-8, TRBV6-9, TRBV7-2, TRBV7-3, TRBV7-4, TRBV7-6, TRBV7-7, TRBV7-8, TRBV7-9, TRBV9, TRBV10-1, TRBV10-2, TRBV10-3, TRBV11-1, TRBV11-2, TRBV11-3, TRBV12-3, TRBV12-4, TRBV12-5, TRBV13, TRBV14, TRBV15, TRBV16, TRBV18, TRBV19, TRBV20-1, TRBV24-1, TRBV25-1, TRBV27, TRBV28, TRBV29-1 or TRBV30. In some embodiments, the anti-TCR0V antibody molecule binds specifically to TRBV6-1. In some embodiments, the anti-TCR0V antibody molecule binds specifically to TRBV6-2. In some embodiments, the anti-TCR0V antibody molecule binds specifically to TRBV6-3. In some embodiments,the anti-TCRpV antibody molecule binds specifically to TRBV6-4. In some embodiments, the anti-TCRpV antibody molecule binds specifically to TRBV6-5. In some embodiments, the anti-TCRpV antibody molecule binds specifically to TRBV6-6. In some embodiments, the anti-TCRpV antibody molecule binds specifically to TRBV6-8. In some embodiments, the anti-TCRpV antibody molecule binds specifically to TRBV6-9.Anti-TCRBV27 antibodies

[0342] In some embodiments, the heavy or light chain variable domain, or both, of the anti-TCRpV27 antibody molecule includes an amino acid sequence, which is substantially identical to an amino acid as described herein, e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical to a variable region of an antibody described herein, e.g., an antibody chosen from any one as described in Table 16 or 22; or which differs at least 1 or 5 residues, but less than 40, 30, 20, or 10 residues, from a variable region of an antibody described herein.

[0343] In some embodiments, the anti-TCRpV27 antibody molecule comprises at least one, two, three, or four antigen-binding regions, e.g., variable regions, having an amino acid sequence as set forth in Table 16 or 22, or a sequence substantially identical thereto (e.g, a sequence at least about 85%, 90%, 95%, 99% or more identical thereto, or which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the sequences shown in Table 16 or 22. In another embodiment, the anti-TCRpV27 antibody molecule includes a VH and / or VL domain encoded by a nucleic acid having a nucleotide sequence as set forth in Table 16 or 22, or a sequence substantially identical thereto (e.g, a sequence at least about 85%, 90%, 95%, 99% or more identical thereto, or which differs by no more than 3, 6, 15, 30, or 45 nucleotides from the sequences shown in Table 16 or 22.

[0344] In some embodiments, the anti-TCRpV27 antibody molecule is a full antibody or fragment thereof (e.g., a Fab, F(ab')2, Fv, single domain antibody, or a single chain Fv fragment (scFv)). In embodiments, the anti-TCRpV27 antibody molecule is a monoclonal antibody or an antibody with single specificity. In some embodiments, the anti-TCRpV27 antibody molecule, can also be a humanized, chimeric, camelid, shark, or an in vifro-generated antibody molecule. In some embodiments, the anti-TCRpV27 antibody molecule, is a humanized antibody molecule. The heavy and light chains of the anti-TCRpV27 antibody molecule, can be full-length (e.g., an antibody can include at least one, and preferably two, complete heavy chains, and at least one, and preferably two, complete light chains) or can include an antigen-binding fragment (e.g., a Fab, F(ab')2, Fv, a single chain Fv fragment, a single domain antibody, a diabody (dAb), a bivalent antibody, or bispecific antibody or fragment thereof, a single domain variant thereof, a VHH, or a camelid antibody).

[0345] In some embodiments, the anti-TCRpV27 antibody molecule, is in the form of a multispecific molecule, e.g., a bispecific molecule, e.g., as described herein

[0346] In some embodiments, the anti-TCRpV27 antibody molecule, has a heavy chain constant region (Fc) chosen from, e.g., the heavy chain constant regions of IgGl, IgG2, IgG3, IgG4, IgM, IgAl, IgA2, IgD, and IgE. In some embodiments, the Fc region is chosen from the heavy chain constant regions ofIgGl, IgG2, IgG3, and IgG4. In some embodiments, the Fc region is chosen from the heavy chain constant region of IgGl or IgG2 (e.g., human IgGl, or IgG2). In some embodiments, the heavy chain constant region is human IgGl. In some embodiments, the Fc region comprises a Fc region variant, e.g., as described herein.

[0347] In some embodiments, the anti-TCRpV27 antibody molecule, has a light chain constant region chosen from, e.g., the light chain constant regions of kappa or lambda, preferably kappa (e.g., human kappa). In some embodiments, the constant region is altered, e.g, mutated, to modify the properties of the anti-TCRpV27 antibody molecule (e g., to increase or decrease one or more of: Fc receptor binding, antibody glycosylation, the number of cysteine residues, effector cell function, or complement function). For example, the constant region is mutated at positions 296 (M to Y), 298 (S to T), 300 (T to E), 477 (H to K) and 478 (N to F) to alter Fc receptor binding (e.g., the mutated positions correspond to positions 132 (Mto Y), 134 (S to T), 136 (Tto E), 313 (Hto K) and 314 (N to F) of SEQ IDNOs: 212 or 214; or positions 135 (Mto Y), 137 (S to T), 139 (Tto E), 316 (Hto K) and 317 (N to F) of SEQ ID NOs: 215, 216, 217 or 218), e.g., relative to human IgGl.

[0348] Additional exemplary humanized anti-TCRB V27 antibodies are provided in Table 16 or 22. In some embodiments, the anti-TCR V27 antibody molecule is a humanized antibody as provided in Table 16 or 22. In some embodiments, the anti-TCRpV27 antibody molecule comprises one or more (e.g., all three) of a LC CDR1, LC CDR2, and LC CDR3 provided in Table 16 or 22; and / or one or more (e.g., all three) of a HC CDR1, HC CDR2, and HC CDR3 provided in Table 16 or 22, or a sequence with at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, or 100% sequence identity thereto. In some embodiments, the anti-TCRpV27 antibody molecule comprises a variable heavy chain (VH) and / or a variable light chain (VL) provided in Table 16 or 22, or a sequence with at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, or 100% sequence identity thereto.

[0349] In some embodiments, the anti-TCRpV27 antibody molecule includes at least one, two, or three CDRs (or collectively all of the CDRs) from a heavy chain variable region comprising an amino acid sequence shown in Table 16 or 22. In some embodiments, one or more of the CDRs (or collectively all of the CDRs) have one, two, three, four, five, six or more changes, e.g., amino acid substitutions or deletions, relative to the amino acid sequence shown in Table 2.

[0350] In some embodiments, the anti-TCRpV antibody molecule, e.g., anti-TCRp V12 antibody molecule, includes at least one, two, or three complementarity determining regions (CDRs) from a light chain variable region of an antibody described herein, e.g., an antibody as described in Table 2, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences.

[0351] In an aspect, provided herein, inter alia, is a molecule comprising an TCRPV27 -binding moiety, wherein the TCRpV27-binding moiety is an anti-TCRpV27 antibody molecule or an anti-TCRpV27 antigen binding domain comprising:(i) a heavy chain variable region (VH) comprising:(a) a heavy chain complementarity determining region 1 (HC CDR1) comprising the sequenceGFKTEX1X2YMY, wherein Xi is D or E, and X2is T, Y, or A (SEQ ID NO: 1480);(b) a heavy chain complementarity determining region 2 (HC CDR2) comprising the sequence X3IX4PX5X6X7X8TX9YDPKFQD, wherein X3is R or D, X4is D or Y, X5is A, F or Y, X6is N or A, X7is G or A, X8is N or A, and X9is K or S (SEQ ID NO: 1481); and(c) a heavy chain complementarity determining region 3 (HC CDR3) comprising the sequence GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513); and(ii) a light chain variable region (VL) comprising:(a) a light chain complementarity determining region 1 (LC CDR1) comprising the sequence RASESVX10SYGX11SFMH, wherein X10 is D or A, and Xu is N or A (SEQ ID NO: 1482);(b) a light chain complementarity determining region 2 (LC CDR2) comprising the sequence RASNLES (SEQ ID NO: 1434); and(c) a light chain complementarity determining region 3 (LC CDR3) comprising the sequence QQSNEDPYT (SEQ ID NO: 1438),with the proviso that:(A) the HC CDR1, the HC CDR2, the HC CDR3, the LC CDR1, the LC CDR2, and the LC CDR3 are not GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), respectively; or(B) the HC CDR1, the HC CDR2, the HC CDR3, the LC CDR1, the LC CDR2, and the LC CDR3 are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), respectively, and the VH comprises a sequence having at least 90%, 90.5%, 91%, 91.5%, 92%, 92.5%, 93%, 93.5%, 94%, 94,5%, 95%, 95.5%, 96%, 96.5%, 97%, 97.1%, 97.2%, 97.3%, 97.4%, 97.5%, 97.6%, 97.7%, 97.8%, 97.9%, 98%, 98.1%, 98.2%, 98.3%, 98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

[0352] In some embodiments, HC CDR1 is GFKTEDTYMY (SEQ ID NO: 1424), GFKTEDYYMY (SEQ ID NO: 1447), GFKTEDAYMY (SEQ ID NO: 1470), or GFKTEETYMY (SEQ ID NO: 1457).

[0353] In some embodiments, HC CDR2 is RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), RIDPANGATKYDPKFQD (SEQ ID NO: 1439), RIDPYAGATKYDPKFQD (SEQ ID NO: 1444), RIDPYNAATKYDPKFQD (SEQ ID NO: 1451), RIDPFNGNTKYDPKFQD (SEQ ID NO: 1454), DIYPAAGATSYDPKFQD (SEQ ID NO: 1458), RIDPFAGATKYDPKFQD (SEQ ID NO: 1464), or RIDPFNAATKYDPKFQD (SEQ ID NO: 1467).

[0354] In some embodiments, HC CDR3 is GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513).

[0355] In some embodiments, LC CDR1 is RASESVDSYGNSFMH (SEQ ID NO: 1433) or RASESVASYGASFMH (SEQ ID NO: 1442).

[0356] In some embodiments, LC CDR2 is RASNLES (SEQ ID NO: 1434).

[0357] In some embodiments, LC CDR3 is QQSNEDPYT (SEQ ID NO: 1438).

[0358] In another aspect, provided herein is a molecule comprising an TCRβV27-binding moiety, wherein the TCR(3V27-binding moiety is an anti-TCRβV27 antibody molecule or an anti-TCRβV27 antigen binding domain comprising:(i) a VH comprising:(a) a HC CDR1, a HC CDR2, and a HC CDR3 comprising the HC CDR1 sequence, a HC CDR2 sequence, and a HC CDR3 sequence as listed in Table 16 or 22;(b) a HC CDR1, a HC CDR2, and a HC CDR3 comprising the HC CDR1 sequence, a HC CDR2 sequence, and a HC CDR3 sequence according to Kabat numbering as listed in Table 16 or 22;(c) a HC CDR1, a HC CDR2, and a HC CDR3 comprising the HC CDR1 sequence, a HC CDR2 sequence, and a HC CDR3 sequence according to Chothia numbering as listed in Table 16 or 22;(d) a HC CDR1, a HC CDR2, and a HC CDR3 comprising the HC CDR1 sequence, a HC CDR2 sequence, and a HC CDR3 sequence according to IMGT numbering as listed in Table 16 or 22;(ii) a VL comprising:(a) a LC CDR1, a LC CDR2, and a LC CDR3 comprising the LC CDR1 sequence, a LC CDR2 sequence, and a LC CDR3 sequence as listed in Table 16 or 22;(b) a LC CDR1, a LC CDR2, and a LC CDR3 comprising the LC CDR1 sequence, a LC CDR2 sequence, and a LC CDR3 sequence according to Kabat numbering as listed in Table 16 or 22;(c) a LC CDR1, a LC CDR2, and a LC CDR3 comprising the LC CDR1 sequence, a LC CDR2 sequence, and a LC CDR3 sequence according to Chothia numbering as listed in Table 16 or 22;(d) a LC CDR1, a LC CDR2, and a LC CDR3 comprising the LC CDR1 sequence, a LC CDR2 sequence, and a LC CDR3 sequence according to IMGT numbering as listed in Table 16 or 22; or(iii) any combination thereof,with the proviso that:(A) the HC CDR1, the HC CDR2, the HC CDR3, the LC CDR1, the LC CDR2, and the LC CDR3 are not GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), respectively; or(B) the HC CDR1, the HC CDR2, the HC CDR3, the LC CDR1, the LC CDR2, and the LC CDR3 are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), respectively, and the VH comprises a sequence having at least 90%, 90.5%, 91%, 91.5%, 92%, 92.5%, 93%, 93.5%, 94%, 94,5%, 95%, 95.5%, 96%, 96.5%, 97%, 97.1%, 97.2%, 97.3%, 97.4%, 97.5%, 97.6%, 97.7%, 97.8%, 97.9%, 98%, 98.1%, 98.2%, 98.3%, 98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

[0359] In some embodiments,(l)(i) the VH comprises aHC CDR1, aHC CDR2, and a HC CDR3 comprising the sequences of;(a) SEQ ID NO: 1424, SEQ ID NO: 1425, SEQ ID NO: 1426 or 1513, respectively;(b) SEQ ID NO: 1427, SEQ ID NO: 1425, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1428, SEQ ID NO: 1429, SEQ ID NO: 1426 or 1513, respectively; or(d) SEQ ID NO: 1430, SEQ ID NO: 1431, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of: (a) SEQ ID NO: 1433, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1436, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(2) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of: (a) SEQ ID NO: 1424, SEQ ID NO: 1439, SEQ ID NO: 1426 or 1513, respectively;(b) SEQ ID NO: 1427, SEQ ID NO: 1439, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1428, SEQ ID NO: 1440, SEQ ID NO: 1426 or 1513, respectively; or(d) SEQ ID NO: 1430, SEQ ID NO: 1441, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of: (a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(3) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of: (a) SEQ ID NO: 1424, SEQ ID NO: 1444, SEQ ID NO: 1426 or 1513, respectively;(b) SEQ ID NO: 1427, SEQ ID NO: 1444, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1428, SEQ ID NO: 1445, SEQ ID NO: 1426 or 1513, respectively; or(d) SEQ ID NO: 1430, SEQ ID NO: 1446, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of: (a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(4) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of: (a) SEQ ID NO: 1447, SEQ ID NO: 1444, SEQ ID NO: 1426 or 1513, respectively;(b) SEQ ID NO: 1448, SEQ ID NO: 1444, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1449, SEQ ID NO: 1445, SEQ ID NO: 1426 or 1513, respectively; or(d) SEQ ID NO: 1450, SEQ ID NO: 1446, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of: (a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(5) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of: (a) SEQ ID NO: 1447, SEQ ID NO: 1451, SEQ ID NO: 1426 or 1513, respectively;(b) SEQ ID NO: 1448, SEQ ID NO: 1451, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1449, SEQ ID NO: 1452, SEQ ID NO: 1426 or 1513, respectively; or(d) SEQ ID NO: 1450, SEQ ID NO: 1453, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of: (a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(6) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of: (a) SEQ ID NO: 1424, SEQ ID NO: 1454, SEQ ID NO: 1426 or 1513, respectively;(b) SEQ ID NO: 1427, SEQ ID NO: 1454, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1428, SEQ ID NO: 1455, SEQ ID NO: 1426 or 1513, respectively; or(d) SEQ ID NO: 1430, SEQ ID NO: 1456, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of: (a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(7) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of: (a) SEQ ID NO: 1457, SEQ ID NO: 1458, SEQ ID NO: 1426 or 1513, respectively;(b) SEQ ID NO: 1459, SEQ ID NO: 1458, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1460, SEQ ID NO: 1461, SEQ ID NO: 1426 or 1513, respectively; or(d) SEQ ID NO: 1462, SEQ ID NO: 1463, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of: (a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(8) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of: (a) SEQ ID NO: 1424, SEQ ID NO: 1464, SEQ ID NO: 1426 or 1513, respectively;(b) SEQ ID NO: 1427, SEQ ID NO: 1464, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1428, SEQ ID NO: 1465, SEQ ID NO: 1426 or 1513, respectively; or(d) SEQ ID NO: 1430, SEQ ID NO: 1466, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of: (a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(9) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of: (a) SEQ ID NO: 1424, SEQ ID NO: 1467, SEQ ID NO: 1426 or 1513, respectively;(b) SEQ ID NO: 1427, SEQ ID NO: 1467, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1428, SEQ ID NO: 1468, SEQ ID NO: 1426 or 1513, respectively; or(d) SEQ ID NO: 1430, SEQ ID NO: 1469, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of: (a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(10) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of: (a) SEQ ID NO: 1424, SEQ ID NO: 1451, SEQ ID NO: 1426 or 1513, respectively;(b) SEQ ID NO: 1427, SEQ ID NO: 1451, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1428, SEQ ID NO: 1452, SEQ ID NO: 1426 or 1513, respectively; or(d) SEQ ID NO: 1430, SEQ ID NO: 1453, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of: (a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(11) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of: (a) SEQ ID NO: 1470, SEQ ID NO: 1464, SEQ ID NO: 1426 or 1513, respectively;(b) SEQ ID NO: 1471, SEQ ID NO: 1464, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1472, SEQ ID NO: 1465, SEQ ID NO: 1426 or 1513, respectively; or(d) SEQ ID NO: 1473, SEQ ID NO: 1466, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of: (a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(12) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of: (a) SEQ ID NO: 1470, SEQ ID NO: 1444, SEQ ID NO: 1426 or 1513, respectively;(b) SEQ ID NO: 1471, SEQ ID NO: 1444, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1472, SEQ ID NO: 1445, SEQ ID NO: 1426 or 1513, respectively; or(d) SEQ ID NO: 1473, SEQ ID NO: 1446, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of: (a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(13) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of: (a) SEQ ID NO: 1470, SEQ ID NO: 1467, SEQ ID NO: 1426 or 1513, respectively;(b) SEQ ID NO: 1471, SEQ ID NO: 1467, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1472, SEQ ID NO: 1468, SEQ ID NO: 1426 or 1513, respectively; or(d) SEQ ID NO: 1473, SEQ ID NO: 1469, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of: (a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively, or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof; or(14) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of: (a) SEQ ID NO: 1470, SEQ ID NO: 1451, SEQ ID NO: 1426 or 1513, respectively;(b) SEQ ID NO: 1471, SEQ ID NO: 1451, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1472, SEQ ID NO: 1452, SEQ ID NO: 1426 or 1513, respectively; or(d) SEQ ID NO: 1473, SEQ ID NO: 1453, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of:(a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof,with the proviso that when the HC CDR1, the HC CDR2, the HC CDR3, the LC CDR1, the LC CDR2, and the LC CDR3 are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), respectively, the VH comprises a sequence having at least 90%, 90.5%, 91%, 91.5%, 92%, 92.5%, 93%, 93.5%, 94%, 94,5%, 95%, 95.5%, 96%, 96.5%, 97%, 97.1%, 97.2%, 97.3%, 97.4%, 97.5%, 97.6%, 97.7%, 97.8%, 97.9%, 98%, 98.1%, 98.2%, 98.3%, 98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

[0360] In some embodiments, the anti-TCRβV27 antibody molecule or the anti-TCRβV27 antigen binding domain comprises the VH and the VL respectively comprising a HC CDR1, a HC CDR2, and a HC CDR3, and a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of;(i) SEQ ID NOs: 1424, 1425, and 1426, and SEQ ID NOs: 1433, 1434, and 1438, respectively;(ii) SEQ ID NOs: 1427, 1425, and 1426, and SEQ ID NOs: 1433, 1434, and 1438, respectively;(iii) SEQ ID NOs: 1428, 1429, and 1426, and SEQ IDNOs: 1433, 1434, and 1438, respectively;(iv) SEQ ID NOs: 1430, 1431, and 1432, and SEQ ID NOs: 1436, 1437, and 1438, respectively;(v) SEQ ID NOs: 1424, 1439, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(vi) SEQ ID NOs: 1427, 1439, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(vii) SEQ ID NOs: 1428, 1440, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(viii) SEQ ID NOs: 1430, 1441, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively;(ix) SEQ ID NOs: 1424, 1444, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(x) SEQ ID NOs: 1427, 1444, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xi) SEQ ID NOs: 1428, 1445, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xii) SEQ ID NOs: 1430, 1446, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively;(xiii) SEQ ID NOs: 1447, 1444, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xiv) SEQ ID NOs: 1448, 1444, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xv) SEQ ID NOs: 1449, 1445, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xvi) SEQ ID NOs: 1450, 1446, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively; (xvii) SEQ ID NOs: 1447, 1451, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xviii) SEQ ID NOs: 1448, 1451, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xix) SEQ ID NOs: 1449, 1452, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xx) SEQ ID NOs: 1450, 1453, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively; (xxi) SEQ ID NOs: 1424, 1454, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xxii) SEQ ID NOs: 1427, 1454, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xxiii) SEQ ID NOs: 1428, 1455, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xxiv) SEQ ID NOs: 1430, 1456, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively; (xxv) SEQ ID NOs: 1457, 1458, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xxvi) SEQ ID NOs: 1459, 1458, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xxvii) SEQ ID NOs: 1460, 1461, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xxviii) SEQ ID NOs: 1462, 1463, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively; (xxix) SEQ ID NOs: 1424, 1464, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xxx) SEQ ID NOs: 1427, 1464, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xxxi) SEQ ID NOs: 1428, 1465, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xxxii) SEQ ID NOs: 1430, 1466, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively; (xxxiii) SEQ ID NOs: 1424, 1467, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xxxiv) SEQ ID NOs: 1427, 1467, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xxxv) SEQ ID NOs: 1428, 1468, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xxxvi) SEQ ID NOs: 1430, 1469, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively; (xxxvii) SEQ ID NOs: 1424, 1451, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xxxviii) SEQ ID NOs: 1427, 1451, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xxxix) SEQ ID NOs: 1428, 1452, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xl) SEQ ID NOs: 1430, 1453, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively; (xli) SEQ ID NOs: 1470, 1464, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xlii) SEQ ID NOs: 1471, 1464, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xliii) SEQ ID NOs: 1472, 1465, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xliv) SEQ ID NOs: 1473, 1466, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively; (xlv) SEQ ID NOs: 1470, 1444, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xlvi) SEQ ID NOs: 1471, 1444, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xlvii) SEQ ID NOs: 1472, 1445, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xlviii) SEQ ID NOs: 1473, 1446, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively; (xlix) SEQ ID NOs: 1470, 1467, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (1) SEQ ID NOs: 1471, 1467, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (li) SEQ ID NOs: 1472, 1468, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (lii) SEQ ID NOs: 1473, 1469, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively; (liii) SEQ ID NOs: 1470, 1451, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(liv) SEQ ID NOs: 1471, 1451, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(lv) SEQ ID NOs: 1472, 1452, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; or (lvi) SEQ ID NOs: 1473, 1453, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively, with the proviso that when the HC CDR1, the HC CDR2, the HC CDR3, the LC CDR1, the LC CDR2, and the LC CDR3 are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), respectively, the VH comprises a sequence having at least 90%, 90.5%, 91%, 91.5%, 92%, 92.5%, 93%, 93.5%, 94%, 94,5%, 95%, 95.5%, 96%, 96.5%, 97%, 97.1%, 97.2%, 97.3%, 97.4%, 97.5%, 97.6%, 97.7%, 97.8%, 97.9%, 98%, 98.1%, 98.2%, 98.3%, 98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

[0361] In some embodiments, the VH comprise a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VH sequences listed in Table 16 or 22,with the proviso that when the VH comprises the HC CDR1, the HC CDR2, and the HC CDR3 that are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), and GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), and the VL comprises the LC CDR1, the LC CDR2, and the LC CDR3 that are RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), the VH sequence has at least 90%, 90.5%, 91%, 91.5%, 92%, 92.5%, 93%, 93.5%, 94%, 94,5%, 95%, 95.5%, 96%, 96.5%, 97%, 97.1%, 97.2%, 97.3%, 97.4%, 97.5%, 97.6%, 97.7%, 97.8%, 97.9%, 98%, 98.1%, 98.2%, 98.3%, 98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

[0362] In some embodiments, the VL comprise a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VL sequences listed in Table 16 or 22,with the proviso that when the VH comprises the HC CDR1, the HC CDR2, and the HC CDR3 that are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), and GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), and the VL comprises the LC CDR1, the LC CDR2, and the LC CDR3 that are RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), the VH sequence has at least 90%, 90.5%, 91%, 91.5%, 92%, 92.5%, 93%, 93.5%, 94%, 94,5%, 95%, 95.5%, 96%, 96.5%, 97%, 97.1%, 97.2%, 97.3%, 97.4%, 97.5%, 97.6%, 97.7%, 97.8%, 97.9%, 98%, 98.1%, 98.2%, 98.3%, 98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

[0363] In some embodiments, the VH comprise a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%,99.9%, or 100% sequence identity to any one of the VH sequences listed in Table 16 or 22 and the VL comprise a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VL sequences listed in Table 16 or 22,with the proviso that when the VH comprises the HC CDR1, the HC CDR2, and the HC CDR3 that are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), and GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), and the VL comprises the LC CDR1, the LC CDR2, and the LC CDR3 that are RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), the VH sequence has at least 90%, 90.5%, 91%, 91.5%, 92%, 92.5%, 93%, 93.5%, 94%, 94,5%, 95%, 95.5%, 96%, 96.5%, 97%, 97.1%, 97.2%, 97.3%, 97.4%, 97.5%, 97.6%, 97.7%, 97.8%, 97.9%, 98%, 98.1%, 98.2%, 98.3%, 98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

[0364] In some embodiments, the VH comprise any one of the VH sequences listed in Table 16 or 22.

[0365] In some embodiments, the VL comprise any one of the VL sequences listed in Table 16 or 22.

[0366] In some embodiments, the VH comprise any one of the VH sequences listed in Table 16 or 22 and the VL comprise any one of the VL sequences listed in Table 16 or 22.

[0367] In some embodiments, the VH comprise a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VH sequences selected from the group consisting of SEQ ID NOs: 1401, 1403, 1405, 1407, 1409, 1410, 1411, 1412, 1414, 1415, 1416, 1417, 1418, 1419, 1420, 1421, 1422, and 1423,with the proviso that when the VH comprises the HC CDR1, the HC CDR2, and the HC CDR3 that are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), and GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), and the VL comprises the LC CDR1, the LC CDR2, and the LC CDR3 that are RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), the VH sequence has at least 90%, 90.5%, 91%, 91.5%, 92%, 92.5%, 93%, 93.5%, 94%, 94,5%, 95%, 95.5%, 96%, 96.5%, 97%, 97.1%, 97.2%, 97.3%, 97.4%, 97.5%, 97.6%, 97.7%, 97.8%, 97.9%, 98%, 98.1%, 98.2%, 98.3%, 98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

[0368] In some embodiments, the VL comprise a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VL sequences selected from the group consisting of SEQ ID NOs: 1402, 1404, 1406, 1408, and 1413,with the proviso that when the VH comprises the HC CDR1, the HC CDR2, and the HC CDR3 that are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), and GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), and the VL comprises the LCCDR1, the LC CDR2, and the LC CDR3 that are RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), the VH sequence has at least 90%, 90.5%, 91%, 91.5%, 92%, 92.5%, 93%, 93.5%, 94%, 94,5%, 95%, 95.5%, 96%, 96.5%, 97%, 97.1%, 97.2%, 97.3%, 97.4%, 97.5%, 97.6%, 97.7%, 97.8%, 97.9%, 98%, 98.1%, 98.2%, 98.3%, 98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

[0369] In some embodiments, the VH comprise any one of the VH sequences selected from the group consisting of SEQ ID NOs: 1401, 1403, 1405, 1407, 1409, 1410, 1411, 1412, 1414, 1415, 1416, 1417, 1418, 1419, 1420, 1421, 1422, and 1423.

[0370] In some embodiments, the VL comprise any one of the VL sequences selected from the group consisting of SEQ ID NOs: 1402, 1404, 1406, 1408, and 1413,with the proviso that when the VH comprises the HC CDR1, the HC CDR2, and the HC CDR3 that are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), and GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), and the VL comprises the LC CDR1, the LC CDR2, and the LC CDR3 that are RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), the VH sequence has at least 90%, 90.5%, 91%, 91.5%, 92%, 92.5%, 93%, 93.5%, 94%, 94,5%, 95%, 95.5%, 96%, 96.5%, 97%, 97.1%, 97.2%, 97.3%, 97.4%, 97.5%, 97.6%, 97.7%, 97.8%, 97.9%, 98%, 98.1%, 98.2%, 98.3%, 98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

[0371] In some embodiments,(i) the VH comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401 and the VL comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1402;(ii) the VH comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1403 and the VL comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1404;(iii) the VH comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1405 and the VL comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1406;(iv) the VH comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequenceidentity to the sequence of SEQ ID NO: 1407 and the VL comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1408;(v) the VH comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1409 and the VL comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1408;(vi) the VH comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1410 and the VL comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1408;(vii) the VH comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1411 and the VL comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1408;(viii) the VH comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1412 and the VL comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413;(ix) the VH comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1414 and the VL comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413;(x) the VH comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1415 and the VL comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413;(xi) the VH comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1416 and the VL comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413;(xii) the VH comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1417 and the VL comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413;(xiii) the VH comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1418 and the VL comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413;(xiv) the VH comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1419 and the VL comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413;(xv) the VH comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1420 and the VL comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413;(xvi) the VH comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1421 and the VL comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413;(xvii) the VH comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1422 and the VL comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413; or(xviii) the VH comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1423 and the VL comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413,with the proviso that when the VH comprises the HC CDR1, the HC CDR2, and the HC CDR3 that are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), and GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), and the VL comprises the LCCDR1, the LC CDR2, and the LC CDR3 that are RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), the VH sequence has at least 90%, 90.5%, 91%, 91.5%, 92%, 92.5%, 93%, 93.5%, 94%, 94,5%, 95%, 95.5%, 96%, 96.5%, 97%, 97.1%, 97.2%, 97.3%, 97.4%, 97.5%, 97.6%, 97.7%, 97.8%, 97.9%, 98%, 98.1%, 98.2%, 98.3%, 98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

[0372] In some embodiments,(i) the VH comprises the sequence of SEQ ID NO: 1401 and the VL comprises the sequence of 1402; (ii) the VH comprises the sequence of SEQ ID NO: 1403 and the VL comprises the sequence of 1404; (iii) the VH comprises the sequence of SEQ ID NO: 1405 and the VL comprises the sequence of 1406; (iv) the VH comprises the sequence of SEQ ID NO: 1407 and the VL comprises the sequence of 1408; (v) the VH comprises the sequence of SEQ ID NO: 1409 and the VL comprises the sequence of 1408; (vi) the VH comprises the sequence of SEQ ID NO: 1410 and the VL comprises the sequence of 1408; (vii) the VH comprises the sequence of SEQ ID NO: 1411 and the VL comprises the sequence of 1408; (viii) the VH comprises the sequence of SEQ ID NO: 1412 and the VL comprises the sequence of 1413; (ix) the VH comprises the sequence of SEQ ID NO: 1414 and the VL comprises the sequence of 1413; (x) the VH comprises the sequence of SEQ ID NO: 1415 and the VL comprises the sequence of 1413; (xi) the VH comprises the sequence of SEQ ID NO: 1416 and the VL comprises the sequence of 1413; (xii) the VH comprises the sequence of SEQ ID NO: 1417 and the VL comprises the sequence of 1413; (xiii) the VH comprises the sequence of SEQ ID NO: 1418 and the VL comprises the sequence of 1413; (xiv) the VH comprises the sequence of SEQ ID NO: 1419 and the VL comprises the sequence of 1413; (xv) the VH comprises the sequence of SEQ ID NO: 1420 and the VL comprises the sequence of 1413; (xvi) the VH comprises the sequence of SEQ ID NO: 1421 and the VL comprises the sequence of 1413; (xvii) the VH comprises the sequence of SEQ ID NO: 1422 and the VL comprises the sequence of 1413; (xviii) the VH comprises the sequence of SEQ ID NO: 1423 and the VL comprises the sequence of 1413.

[0373] In some embodiments, the anti-TCR(3V27 antibody molecule or the anti-TCR(3V27 antigen binding domain comprises any one selected from the group consisting of a full-length antibody, a Fab, a F(ab')2, an Fv, a single chain Fv, a camelid antibody, a VHH, a half arm antibody, a diabody, a bivalent antibody, a monovalent antibody, or a bispecific antibody, and any combination thereof.

[0374] In some embodiments, the anti-TCRβV27 antibody molecule or the anti-TCRpV27 antigen binding domain comprises a VH comprising a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1511. In some embodiments, some embodiments, the anti-TCRpV27 antibody molecule or the anti-TCRpV27 antigen binding domain comprises a VH comprising a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1512. In some embodiments, the anti-TCRpV27 antibody molecule or the anti-TCRpV27 antigen binding domain comprises a VH comprising a sequencehaving at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1511 and a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1512 In some embodiments, the anti-TCRpV27 antibody molecule or the anti-TCRpV27 antigen binding domain comprises a VH comprising a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1511, a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1512, and a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the HC CDR3 sequences as listed in table 16. In some embodiments, the anti-TCRpV27 antibody molecule or the anti-TCRpV27 antigen binding domain comprises a VH comprising a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1511, a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1512, and a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1426, the sequence of SEQ ID NO: 1513, or the sequence of SEQ ID NO: 1432.

[0375] In some embodiments, the anti-TCRpV27 antibody molecule or the anti-TCRpV27 antigen binding domain comprises a VH comprising the sequence of SEQ ID NO: 1511. In some embodiments, some embodiments, the anti-TCRpV27 antibody molecule orthe anti-TCRpV27 antigen binding domain comprises a VH comprising the sequence of SEQ ID NO: 1512. In some embodiments, the anti-TCRβV27 antibody molecule or the anti-TCRβV27 antigen binding domain comprises a VH comprising the sequence of SEQ ID NO: 1511 and the sequence of SEQ ID NO: 1512. In some embodiments, the anti-TCRβV27 antibody molecule or the anti-TCRβV27 antigen binding domain comprises a VH comprising the sequence of SEQ ID NO: 1511, the sequence of SEQ ID NO: 1512, and any one of the HC CDR3 sequences as listed in table 16. In some embodiments, the anti-TCRpV27 antibody molecule orthe anti-TCRpV27 antigen binding domain comprises a VH comprising the sequence of SEQ ID NO: 1511, the sequence of SEQ ID NO: 1512, and the sequence of SEQ ID NO: 1426, the sequence of SEQ ID NO: 1513, or the sequence of SEQ ID NO: 1432.

[0376] In an aspect, provided herein is, inter alia, an TCRβV27-binding moiety as described herein.

[0377] In an aspect, provided herein is, inter alia, an TCRβV27-binding moiety as described herein, wherein the TCRβV27-binding moiety is an anti-TCRβV27 antibody molecule or an anti-TCRβV27 antigen binding domain as described herein.

[0378] In an aspect, provided herein is, inter alia, an anti-TCRpV27 antibody molecule or an anti-TCRPV27 antigen binding domain as described hereinTCR binding moiety or TCR binding domain

[0379] In some embodiments, the multispecific molecule further comprises one or more TCR binding moiety.

[0380] In some embodiments, the one or more TCR binding moiety or TCR binding domain binds to a TCRpV region of TCRpV5, TCRpV6, TCRPV10, TCRPV12, TCRPV20 or any combination thereof. In some embodiments, the one or more TCR binding moiety or TCR binding domain comprises an anti-TCRPV5 antibody molecule or an anti-TCRpV5 antigen binding domain, an anti-TCRpV6 antibody molecule or an anti-TCRpV6 antigen binding domain, an anti -TCRPV 10 antibody molecule or an anti-TCRPV10 antigen binding domain, an anti-TCRpV12 antibody molecule or an anti-TCRpV12 antigen binding domain, an anti-TCRpV20 antibody molecule or an anti-TCRpV20 antigen binding domain, or any combination thereof. In some embodiments, the one or more TCR binding moiety or TCR binding domain are multispecific or multifunctional molecules as described herein comprising an anti-TCRpV5 antibody molecule or an anti-TCRpV5 antigen binding domain, an anti-TCRpV6 antibody molecule or an anti-TCRpV6 antigen binding domain, an anti -TCRPV 10 antibody molecule or an anti -TCRPV 10 antigen binding domain, an anti-TCRpV12 antibody molecule or an anti-TCRpV12 antigen binding domain, an anti-TCRpV20 antibody molecule or an anti-TCRpV20 antigen binding domain, or any combination thereof. In some embodiments, the one or more TCR binding moiety or TCR binding domain are multispecific or multifunctional molecules as described herein.

[0381] In some embodiments, the one or more TCR binding moiety binds to a T cell receptor alpha (TCRa) chain, a T cell receptor beta (TCRp) chain, a T cell receptor gamma (TCRy) chain, a T cell receptor delta (TCR5) chain, a CD3 gamma (CD3y) chain, a CD3 delta (CD35) chain, a CD3 epsilon (CD3s) chain, a CD3 zeta (CD3Q chain, or any combination thereof.

[0382] In some embodiments, the one or more TCR binding moiety binds to a T cell receptor beta (TCRP) chain.

[0383] In some embodiments, the one or more TCR binding moiety binds to a T cell receptor beta variable (TCRpV) region.

[0384] In some embodiments, the one or more TCR binding moiety binds to a TCRpV region ofTCRpVl, TCRPV2, TCRPV3, TCRPV4, TCRPV5, TCRPV6, TCRPV7, TCRPV8, TCRPV, TCRpV 10, TCRpV 11, TCRPV12, TCRPV19, TCRPV20, TCRPV21, TCRPV23, TCRPV24, TCRPV25, TCRPV26, TCRPV27, TCRPV28, TCRPV29, TCRPV30, or any combination thereof.

[0385] In some embodiments, the one ormore TCR binding moiety binds to a TCRpV region of TCRPV2, TCRPV4-1, TCRPV4-2, TCRPV5-1, TCRPV5-5, TCRPV5-6, TCRPV6, TCRPV6-5, TCRPV6-6, TCRpV6-9, TCRPV7-2, TCRpV7-3, TCRpV7-8, TCRpV7-9, TCRPV9, TCRpVIO-l, TCRpV10-2, TCRpV10-3, TCRPV11-2, TCRpV12-3, TCRpV12-4, TCRpV12-5, TCRPV19, TCRpV20-l, TCRpV21, TCRPV24-1, TCRPV25-1, TCRPV28, or any combination thereof.

[0386] In some embodiments, the one ormore TCR binding moiety binds to a TCR0V region of TCR0V2, TCR0V3-1, TCR0V4-1, TCR0V4-2, TCR0V5-1, TCR0V5-4, TCR0V5-5, TCR0V5-6, TCR0V6-1, TCR0V6-5, TCR0V6-6, TCR0V7-3, TCR0V7-6, TCR0V7-8, TCR0V9, TCR0V11-2, TCR0V19, TCR0V2O-1, TCR0V24-1, TCRβV27, TCR0V28, TCR0V29-1, TCR0V3O, or any combination thereof.

[0387] In some embodiments, the one ormore TCR binding moiety binds to a TCR0V region of TCR0V5, TCR0V6, TCR0V1O, TCR0V12, TCR0V2O or any combination thereof

[0388] In some embodiments, the one or more TCR binding moiety binds to a T cell receptor alpha (TCRa) chain.

[0389] In some embodiments, the one or more TCR binding moiety binds to a T cell receptor alpha variable (TCRaV) region.

[0390] In some embodiments, the one ormore TCR binding moiety binds to a TCRaV region of TRAV12-1, TRAV12-2, TRAV12-3, TRAV13-1, TRAV13-2, TRAV19-1, TRAV21-1, TRAV30-1, or any combination thereof.

[0391] In some embodiments, the one or more TCR binding moiety comprises an antibody molecule or an antigen binding domain.

[0392] In some embodiments, the one or more TCR binding moiety comprises an antibody molecule or an antigen binding domain comprising a scFv, a full-length antibody, a Fab, a F(ab')2, an Fv, a single chain Fv, a camelid antibody, a half arm antibody, a diabody, a bivalent antibody, a monovalent antibody, or a bispecific antibody.

[0393] In some embodiments, the one or more TCR binding moiety comprises the antibody molecule or the antigen binding domain comprising a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HC CDR1) sequence comprising any one of the HC CDR1 sequences listed in Tables 1, 2, 12, 13, 14, 16 or 22, or a sequence with at least one, two, three, four, five, six, seven, eight, nine, or ten amino acid substitutions, deletions, and / or additions therein, a heavy chain complementarity determining region 2 (HC CDR2) sequence comprising any one of the HC CDR2 sequences listed in Tables 1, 2, 12, 13, 14, 16 or 22, or a sequence with at least one, two, three, four, five, six, seven, eight, nine, or ten amino acid substitutions, deletions, and / or additions therein, and a heavy chain complementarity determining region 3 (HC CDR3) sequence of comprising any one of the HC CDR3 sequences listed in Tables 1, 2, 12, 13, 14, 16 or 22, or a sequence with at least one, two, three, four, five, six, seven, eight, nine, or ten amino acid substitutions, deletions, and / or additions therein. In some embodiments, the one or more TCR binding moiety comprises: (i) a HC CDR1, a HC CDR2 and a HC CDR3 comprising amino acid sequences having at least 70%, 75%, 80%, 85%, 90%, 95%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to CDR1, CDR2, and CDR3 sequences of a VH disclosed in Tables 1, 2, 12, 13, 14, 16 or 22, respectively; (ii) a LC CDR1, a LC CDR2, and a LC CDR3 comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to CDR1, CDR2, and CDR3 sequences of a VL disclosed in Tables 1, 2, 12, 13, 14, 16 or 22, respectively; or (iii) a combination thereof

[0394] In some embodiments, the one or more TCR binding moiety comprises a light chain comprising aFR1 comprising: (i) an Aspartic Acid at position 1 according to Kabat numbering; (ii) an Asparagine at position 2 according to Kabat numbering; (iii) a Leucine at position 4 according to Kabat numbering; or (iv) a combination thereof.

[0395] In some embodiments, the one or more TCR binding moiety comprises a light chain comprising a FR3 comprising: (i) a Glycine at position 66 according to Kabat numbering; (ii) an Asparagine at position 69 according to Kabat numbering; (iii) a Tyrosine at position 71 according to Kabat numbering; or (iv) a combination thereof.

[0396] In some embodiments, the one or more TCR binding moiety binds to an outward facing region on a TCR|3V protein. In some embodiments, the outward facing region on the TCRPV protein comprises a structurally conserved region of TCRPV having a similar structure across one or more TCRPV subfamilies.

[0397] In some embodiments, the one or more TCR binding moiety comprises the antibody molecule or the antigen binding domain comprising a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LC CDR1) sequence comprising any one of the LC CDR1 sequences listed in Tables 1, 2, 12, 13, 14, 16 or 22, or a sequence with at least one, two, three, four, five, six, seven, eight, nine, or ten amino acid substitutions, deletions, and / or additions therein, a light chain complementarity determining region 2 (LC CDR2) sequence comprising any one of the LC CDR2 sequences listed in Tables 1, 2, 12, 13, 14, 16 or 22, or a sequence with at least one, two, three, four, five, six, seven, eight, nine, or ten amino acid substitutions, deletions, and / or additions therein, and a light chain complementarity determining region 3 (LC CDR3) sequence of comprising any one of the LC CDR3 sequences listed in Tables 1, 2, 12, 13, 14, 16 or 22, or a sequence with at least one, two, three, four, five, six, seven, eight, nine, or ten ammo acid substitutions, deletions, and / or additions therein.

[0398] In some embodiments, the one or more TCR binding moiety comprises the antibody molecule or the antigen binding domain comprising:(i) a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HC CDR1) sequence comprising any one of the HC CDR1 sequences listed in Tables 1, 2, 12, 13, 14, 16 or 22, or a sequence with at least one, two, three, four, five, six, seven, eight, nine, or ten amino acid substitutions, deletions, and / or additions therein, a heavy chain complementarity determining region 2 (HC CDR2) sequence comprising any one of the HC CDR2 sequences listed in Tables 1, 2, 12, 13, 14, 16 or 22, or a sequence with at least one, two, three, four, five, six, seven, eight, nine, or ten amino acid substitutions, deletions, and / or additions therein, and a heavy chain complementarity determining region 3 (HC CDR3) sequence of comprising any one of the HC CDR3 sequences listed in Tables 1, 2, 12, 13, 14, 16 or 22, or a sequence with at least one, two, three, four, five, six, seven, eight, nine, or ten amino acid substitutions, deletions, and / or additions therein; and(ii) a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LC CDR1) sequence comprising any one of the LC CDR1 sequences listed in Tables 1, 2, 12, 13, 14, 16 or 22, or a sequence with at least one, two, three, four, five, six, seven, eight, nine, or ten amino acid substitutions, deletions, and / or additions therein, a light chain complementarity determining region 2 (LC CDR2) sequence comprising any one of the LC CDR2 sequences listed in Tables 1, 2, 12, 13, 14, 16 or 22, or asequence with at least one, two, three, four, five, six, seven, eight, nine, or ten amino acid substitutions, deletions, and / or additions therein, and a light chain complementarity determining region 3 (LC CDR3) sequence of comprising any one of the LC CDR3 sequences listed in Tables 1, 2, 12, 13, 14, 16 or 22, or a sequence with at least one, two, three, four, five, six, seven, eight, nine, or ten amino acid substitutions, deletions, and / or additions therein.

[0399] In some embodiments, the one or more TCR binding moiety comprises a VH comprising a HC CDR1 sequence, aHC CDR2 sequence, and aHC CDR3 sequences of any set of a HC CDR1, aHC CDR2, and a HC CDR3 listed in Tables 1, 2, 12, 13, 14, 16 or 22. In some embodiments, the one or more TCR binding moiety comprises a VL comprising a LC CDR1 sequence, a LC CDR2 sequence, and a LC CDR3 sequences of any set of a LC CDR1, a LC CDR2, and a LC CDR3 listed in Tables 1, 2, 12, 13, 14, 16 or 22.

[0400] In some embodiments, the one or more TCR binding moiety comprises the antibody molecule or the antigen binding domain comprising a VH comprising an amino acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VH sequences listed in Tables 1, 2, 12, 13, 14, 16 or 22.

[0401] In some embodiments, the one or more TCR binding moiety comprises the antibody molecule or the antigen binding domain comprising a VL comprising an amino acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VL sequences listed in Tables 1, 2, 12, 13, 14, 16 or 22.

[0402] In some embodiments, the one or more TCR binding moiety comprises the antibody molecule or the antigen binding domain comprising a VH comprising an amino acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VH sequences listed in Tables 1, 2, 12, 13, 14, 16 or 22; and a VL comprising an amino acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VL sequences listed in Tables 1, 2, 12, 13, 14, 16 or 22.

[0403] In some embodiments, the one or more TCR binding moiety comprises the antibody molecule or the antigen binding domain comprising a VH comprising any one of the VH sequences listed in Tables 1, 2, 12, 13, 14, 16 or 22.

[0404] In some embodiments, the one or more TCR binding moiety comprises the antibody molecule or the antigen binding domain comprising a VL comprising any one of the VL sequences listed in Tables 1, 2, 12, 13, 14, 16 or 22.

[0405] In some embodiments, the one or more TCR binding moiety comprises the antibody molecule or the antigen binding domain comprising a VH comprising any one of the VH sequences listed in Tables 1, 2, 12, 13, 14, 16 or 22; and a VL comprising any one of the VL sequences listed in Tables 1, 2, 12, 13, 14,16 or 22.

[0406] In some embodiments, the one or more TCR binding moiety comprises: (i) a HC CDR1, a HC CDR2 and a HC CDR3 of an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the CDR1, CDR2, and CDR3 sequences listed in Table 1, 2, 12, or 13.; (ii) aLC CDR1, aLC CDR2, and a LC CDR3 of an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the CDR1, CDR2, and CDR3 the sequences listed in Table 1, 2, 12, or 13; or (iii) a combination thereof. In some embodiments, the one or more TCR binding moiety comprises: (i) a HC CDR1, a HC CDR2 and a HC CDR3 having any one of the CDR1, CDR2, and CDR3 sequences listed in Table 1, 2, 12, or 13; (ii) a LC CDR1, a LC CDR2, and a LC CDR3 having any one of the CDR1, CDR2, and CDR3 the sequences listed in Table 1, 2, 12, or 13; or (iii) a combination thereof.

[0407] In some embodiments, the one or more TCR binding moiety comprises: (i) a HC CDR1, a HC CDR2 and a HC CDR3 of an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the CDR1, CDR2, and CDR3 sequences listed in Table 1, 2, 12, or 13, respectively; (ii) a LC CDR1, a LC CDR2, and a LC CDR3 of an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the CDR1, CDR2, and CDR3 the sequences listed in Table 1, 2, 12, or 13, respectively; or (iii) a combination thereof. In some embodiments, the one or more TCR binding moiety comprises: (i) a HC CDR1, a HC CDR2 and a HC CDR3 having any one of the CDR1, CDR2, and CDR3 sequences listed in Table 1, 2, 12, or 13, respectively; (ii) a LC CDR1, a LC CDR2, and a LC CDR3 having any one of the CDR1, CDR2, and CDR3 the sequences listed in Table 1, 2, 12, or 13, respectively; or (iii) a combination thereof.

[0408] In some embodiments, the one or more TCR binding moiety comprises: (i) a VH comprising a framework region (FR) comprising a framework 1 (FR1), a framework region 2 (FR2), a framework region 3 (FR3), and a framework region 4 (FR4) that have at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity with a non-murine germline FR1, a non-murine germline FR2, a non-murine germline FR3, and a non-murine germline FR4; (ii) a VL comprising a FR comprising a FR1, a FR2, a FR3, and a FR4 that have at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity with anon-murine germline FR1, a non-murine germline FR2, a non-murine germline FR3, and a non-murine germline FR4; or (iii) a combination thereof. In some embodiments, the one or more TCR binding moiety comprises: (i) a VH comprising a FR comprising a FR1, a FR2, a FR3, and a FR4 having the sequences of a non-murine germline FR1, a non-murine germline FR2, a non-murine germline FR3, and a non-murine germline FR4; (ii) a VL comprising a FR comprising a FR1, a FR2, a FR3, and a FR4 having the sequences of a non-murine germline FR1, anon-murine germline FR2, anon-murine germline FR3, and a non-murine germline FR4; or (iii) a combination thereof.

[0409] In some embodiments, the one or more TCR binding moiety comprises: (i) a VH comprising aFR1, a FR2, a FR3, and a FR4 that have at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity with a non-murine germline FR1, a nonmurine germline FR2, a non-murine germline FR3, and a non-murine germline FR4, respectively; (ii) a VL comprising a FR comprising a FR1, a FR2, a FR3, and a FR4 that have at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity with a non-murine germline FR1, a non-murine germline FR2, a non-murine germline FR3, and a non-murine germline FR4, respectively; or (iii) a combination thereof. In some embodiments, the one or more TCR binding moiety comprises: (i) a VH comprising a FR comprising a FR1, a FR2, a FR3, and a FR4 having the sequences of a non-murine germline FR1, a non-murine germline FR2, a non-murine germline FR3, and a non-murine germline FR4, respectively; (ii) a VL comprising a FR comprising a FR1, a FR2, a FR3, and a FR4 having the sequences of a non-murine germline FR1, a non-murine germline FR2, a non-murine germline FR3, and a non-murine germline FR4, respectively; or (iii) a combination thereof.

[0410] In some embodiments, the VH comprises the FR3 comprising (i) a Threonine at position 73 according to Kabat numbering; (ii) a Glycine a position 94 according to Kabat numbering; or (iii) a combination thereof. In some embodiments, the VL comprises the FR1 comprising a Phenylalanine at position 10 according to Kabat numbering. In some embodiments, the VL comprises the FR2 comprising (i) a Histidine at position 36 according to Kabat numbering; (ii) an Alanine at position 46 according to Kabat numbering; or (iii) a combination thereof. In some embodiments, the VL comprises the FR3 comprising a Phenylalanine at position 87 according to Kabat numbering.TCR binding moiety or TCR binding domain - Anti-TCRR V6 antibodies

[0411] In one aspect, provided herein is an anti-TCRpV antibody molecule that binds to human TCRp V6, e.g., a TCRp V6 subfamily comprising: TCRp V6-4*01, TCRp V6-4*02, TCRp V6-9*01, TCRp V6-8*01, TCRp V6-5*01, TCRp V6-6*02, TCRp V6-6*01, TCRp V6-2*01, TCRp V6-3*01 or TCRp V6-1*01. In some embodiments the TCRp V6 subfamily comprises TCRp V6-5*01 or a variant thereof. In some embodiments, TCRp V6 comprises TCRp V6-4*01, or a variant thereof. In some embodiments, TCRp V6 comprises TCRp V6-4*02, or a variant thereof. In some embodiments, TCRp V6 comprises TCRp V6-9*01, or a variant thereof. In some embodiments, TCRp V6 comprises TCRp V6-8*01, or a variant thereof. In some embodiments, TCRp V6 comprises TCRp V6-5*01, or a variant thereof. In some embodiments, TCRp V6 comprises TCRp V6-6*02, or a variant thereof. In some embodiments, TCRp V6 comprises TCRp V6-6*01, or a variant thereof. In some embodiments, TCRp V6 comprises TCRp V6-2*01, ora variant thereof. In some embodiments, TCRp V6 comprises TCRp V6-3*01, or a variant thereof. In some embodiments, TCRp V6 comprises TCRp V6-l*01, or a variant thereof.

[0412] In some embodiments, the one or more TCR binding moiety or TCR binding domain binds to a TCRpV region of TCRPV6, TCRpVIO. In some embodiments, the one or more TCR binding moiety or TCR binding domain comprises an anti-TCRpV5 antibody molecule or an anti-TCRpV5 antigen binding domain.

[0413] In some embodiments, the anti -TCRPV antibody molecule, e.g., anti -TCRP V6 (e.g., anti -TCRV6-5*01) antibody molecule, is a non-murine antibody molecule, e.g, a human or humanized antibody molecule. In some embodiments, the anti-TCRpV antibody molecule, e.g., anti-TCRp V6 (e g., anti-TCRp V6-5*01) antibody molecule is a human antibody molecule. In some embodiments, the anti-TCRpV antibody molecule, e.g., anti-TCRp V6 (e.g., anti-TCRp V6-5*01) antibody molecule is a humanized antibody molecule.

[0414] In some embodiments, the anti-TCRpV antibody molecule, e.g., anti-TCRp V6 (e.g., anti-TCRp V6-5*01) antibody molecule, is isolated or recombinant.

[0415] In some embodiments, the anti-TCRpV antibody molecule, e.g., anti-TCRp V6 (e.g., anti-TCR V6-5*01) antibody molecule, comprises at least one antigen-binding region, e.g., a variable region or an antigen-binding fragment thereof, from an antibody described herein, e.g., an antibody described in Table 1, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences.

[0416] In some embodiments, the anti-TCR V antibody molecule, e.g., anti-TCRp V6 (e.g., anti-TCRp V6-5*01) antibody molecule, comprises at least one, two, three or four variable regions from an antibody described herein, e.g., an antibody described in Table 1, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences.

[0417] In some embodiments, the anti-TCR V antibody molecule, e.g., anti-TCRp V6 (e.g., anti-TCR V6-5*01) antibody molecule, comprises at least one or two heavy chain variable regions from an antibody described herein, e.g., an antibody molecule described in Table 1, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences.

[0418] In some embodiments, the anti-TCRpV antibody molecule, e.g., anti-TCRp V6 (e.g., anti-TCR V6-5*01) antibody molecule, compnses at least one or two light chain variable regions from an antibody described herein, e.g., an antibody described in Table 1, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences.

[0419] In some embodiments, the anti-TCRpV antibody molecule, e.g., anti-TCRp V6 (e.g., anti-TCRp V6-5*01) antibody molecule, comprises a heavy chain constant region for an IgG4, e.g., a human IgG4. In still another embodiment, the anti-TCRpV antibody molecule, e g., anti-TCRp V6 (e.g., anti-TCRp V6-5*01) antibody molecule includes a heavy chain constant region for an IgGl, e.g., a human IgGl. In some embodiments, the heavy chain constant region comprises an amino sequence set forth in Tables 3, 15, or 22, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) thereto.

[0420] In some embodiments, the anti-TCRpV antibody molecule, e.g, anti-TCRp V6 (e.g., anti-TCRp V6-5*01) antibody molecule, includes a kappa light chain constant region, e.g., a human kappa light chain constant region. In some embodiments, the light chain constant region comprises an amino sequence set forth in Tables 3, 15, or 22, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) thereto.

[0421] In some embodiments, the anti-TCRpV antibody molecule, e.g., anti-TCRp V6 (e.g., anti-TCRV6-5*01) antibody molecule, includes at least one, two, or three complementarity determining regions (CDRs) from a heavy chain variable region (VH) of an antibody described herein, e.g., an antibody described in Table 1, ora sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences.

[0422] In some embodiments, the anti-TCR(3V antibody molecule, e.g., anti-TCR0 V6 (e.g., anti-TCR0 V6-5*01) antibody molecule, includes at least one, two, or three CDRs (or collectively all of the CDRs) from a heavy chain variable region comprising an amino acid sequence shown in Table 1. In some embodiments, one or more of the CDRs (or collectively all of the CDRs) have one, two, three, four, five, six or more changes, e.g., amino acid substitutions or deletions, relative to the amino acid sequence shown in Table 1.

[0423] In some embodiments, the anti-TCR0V antibody molecule, e.g., anti-TCR0 V6 (e.g., anti-TCR0 V6-5*01) antibody molecule, includes at least one, two, or three complementarity determining regions (CDRs) from a light chain variable region of an antibody described herein, e.g., an antibody described in Table 1, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences.

[0424] In some embodiments, the anti-TCR0V antibody molecule, e.g., anti-TCR0 V6 (e.g., anti-TCR0 V6-5*01) antibody molecule, includes at least one, two, or three CDRs (or collectively all of the CDRs) from a light chain variable region comprising an amino acid sequence shown in Table 1. In some embodiments, one or more of the CDRs (or collectively all of the CDRs) have one, two, three, four, five, six or more changes, e.g., ammo acid substitutions or deletions, relative to the amino acid sequence shown in Table 1.

[0425] In some embodiments, the anti-TCR(3V antibody molecule, e.g., anti-TCR0 V6 (e.g., anti-TCR(3 V6-5*01) antibody molecule, includes at least one, two, three, four, five or six CDRs (or collectively all of the CDRs) from a heavy and light chain variable region comprising an amino acid sequence shown in Table 1. In some embodiments, one or more of the CDRs (or collectively all of the CDRs) have one, two, three, four, five, six or more changes, e.g., amino acid substitutions or deletions, relative to the amino acid sequence shown in Table 1.

[0426] In some embodiments, the anti-TCR0V antibody molecule, e.g., anti-TCR0 V6 (e.g., anti-TCR0 V6-5*01) antibody molecule, molecule includes all six CDRs from an antibody described herein, e.g., an antibody described in Table 1, or closely related CDRs, e.g., CDRs which are identical or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions). In some embodiments, the anti-TCR0V antibody molecule, e.g., anti-TCR0 V6 (e.g., anti-TCR0 V6-5*01) antibody molecule, may include any CDR described herein.

[0427] In some embodiments, the anti-TCR(3V antibody molecule, e.g, anti-TCR0 V6 (e.g., anti-TCR0 V6-5*01) antibody molecule includes at least one, two, or three CDRs according to Kabat et al. (e.g., at least one, two, or three CDRs according to the Kabat definition as set out in Table 1) from a heavy chain variable region of an antibody described herein, e.g, an antibody described in Table 1, or a sequencesubstantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences; or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to one, two, or three CDRs according to Kabat et al. shown in Table 1.

[0428] In some embodiments, the anti-TCR(3V antibody molecule, e.g., anti-TCR0 V6 (e.g., anti-TCR0 V6-5*01) antibody molecule includes at least one, two, or three CDRs according to Kabat et al. (e.g., at least one, two, or three CDRs according to the Kabat definition as set out in Table 1) from a light chain variable region of an antibody described herein, e.g., an antibody described in Table 1, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences; or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to one, two, or three CDRs according to Kabat et al. shown in Table 1.

[0429] In some embodiments, the anti-TCR0V antibody molecule, e.g., anti-TCR0 V6 (e.g., anti-TCR0 V6-5*01) antibody molecule, includes at least one, two, three, four, five, or six CDRs according to Kabat et al. e.g., at least one, two, three, four, five, or six CDRs according to the Kabat definition as set out in Table 1) from the heavy and light chain variable regions of an antibody described herein, e.g., an antibody described in Table 1; or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences; or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to one, two, three, four, five, or six CDRs according to Kabat et al. shown in Table 1.

[0430] In some embodiments, the anti-TCR(3V antibody molecule, e.g, anti-TCR0 V6 (e.g., anti-TCR(3 V6-5*01) antibody molecule, includes all six CDRs according to Kabat et al. (e.g., all six CDRs according to the Kabat definition as set out in Table 1) from the heavy and light chain variable regions of an antibody described herein, e.g., an antibody described in Table 1; or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences; or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to all six CDRs according to Kabat et al. shown in Table 1. In some embodiments, the anti-TCR0V antibody molecule, e.g., anti-TCR0 V6 (e.g., anti-TCR0 V6-5*01) antibody molecule, may include any CDR described herein.

[0431] In some embodiments, the anti-TCR0V antibody molecule, e.g, anti-TCR0 V6 (e.g., anti-TCR0 V6-5*01) antibody molecule, includes at least one, two, or three hypervariable loops that have the same canonical structures as the corresponding hypervariable loop of an antibody described herein, e.g., the same canonical structures as at least loop 1 and / or loop 2 of the heavy and / or light chain variable domains of an antibody described herein. See, e.g., Chothia et al., (1992) J. Mol. Biol. 227:799-817; Tomlinson et al., (1992) J. Mol. Biol. 227:776-798 for descriptions of hypervariable loop canonical structures. These structures can be determined by inspection of the tables described in these references.

[0432] In some embodiments, the anti-TCR0V antibody molecule, e.g., anti-TCR0 V6 (e.g., anti-TCR0V6-5*01) antibody molecule includes at least one, two, or three CDRs according to Chothia et al. (e.g., at least one, two, or three CDRs according to the Chothia definition as set out in Table 1) from a heavy chain variable region of an antibody described herein, e.g., an antibody as described in Table 1, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences; or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to one, two, or three CDRs according to Chothia et al. shown in Table 1.

[0433] In some embodiments, the anti-TCRpV antibody molecule, e.g., anti-TCRP V6 (e.g., anti-TCR[3 V6-5*01) antibody molecule includes at least one, two, or three CDRs according to Chothia et al. (e.g., at least one, two, or three CDRs according to the Chothia definition as set out in Table 1) from a light chain variable region of an antibody described herein, e.g., an antibody described in Table 1, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences; or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to one, two, or three CDRs according to Chothia et al. shown in Table 1.

[0434] In some embodiments, the anti-TCRpV antibody molecule, e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*01) antibody molecule, includes at least one, two, three, four, five, or six CDRs according to Chothia et al. (e.g., at least one, two, three, four, five, or six CDRs according to the Chothia definition as set out in Table 1) from the heavy and light chain variable regions of an antibody described herein, e.g., an antibody described in Table 1; or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences; or which have at least one ammo acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to one, two, three, four, five, or six CDRs according to Chothia et al. shown in Table 1.

[0435] In some embodiments, the anti-TCRpV antibody molecule, e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*01) antibody molecule, includes all six CDRs according to Chothia et al. (e.g., all six CDRs according to the Chothia definition as set out in Table 1) from the heavy and light chain variable regions of an antibody described herein, e.g., an antibody described in Table 1; or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences; or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to all six CDRs according to Chothia et al. shown in Table 1. In some embodiments, the anti-TCRpV antibody molecule, e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*01) antibody molecule, may include any CDR described herein.

[0436] In some embodiments, the anti-TCRpV antibody molecule, e.g., anti-TCRP V6 (e.g., anti-TCR V6-5*01) antibody molecule, molecule includes a combination of CDRs or hypervariable loops defined according to Kabat et al., Chothia et al., by ImMunoGeneTics (IMGT) numbering system or as described in Table 1.

[0437] In some embodiments, the anti-TCRpV antibody molecule, e.g., anti-TCRP V6 (e.g., anti-TCRV6-5*01) antibody molecule, can contain any combination of CDRs or hypervariable loops according to the Kabat and Chothia definitions, or by ImMunoGeneTics (IMGT) numbering system.

[0438] In some embodiments, a combined CDR as set out in Table 1 is a CDR that comprises a Kabat CDR and a Chothia CDR.

[0439] In some embodiments, the anti-TCR(3V antibody molecule, e.g., anti-TCR0 V6 (e.g., anti-TCR0 V6-5*01) antibody molecule, molecule includes a combination of CDRs or hypervariable loops identified as combined CDRs in Table 1. In some embodiments, the anti-TCR0V antibody molecule, eg., anti-TCR0 V6 (e.g., anti-TCR0 V6-5*01) antibody molecule, can contain any combination of CDRs or hypervariable loops according the “combined” CDRs are described in Table 1.

[0440] In some embodiments, e.g., an embodiment comprising a variable region, a CDR (e.g., a combined CDR, Chothia CDR or Kabat CDR, or by ImMunoGeneTics (IMGT) numbering system), or other sequence referred to herein, e g., in Table 1, the antibody molecule is a monospecific antibody molecule, a bispecific antibody molecule, a bivalent antibody molecule, a biparatopic antibody molecule, or an antibody molecule that comprises an antigen binding fragment of an antibody, e.g., a half antibody or antigen binding fragment of a half antibody. In certain embodiments the antibody molecule comprises a multispecific molecule, e.g., a bispecific molecule, e.g., as described herein.

[0441] In some embodiments, the light or the heavy chain variable framework (e.g., the region encompassing at least FR1, FR2, FR3, and optionally FR4) of the anti-TCR0V antibody molecule, e.g., anti-TCRP V6 antibody molecule can be chosen from: (a) a light or heavy chain variable framework including at least 80%, 85%, 87% 90%, 92%, 93%, 95%, 97%, 98%, or 100% of the amino acid residues from a human light or heavy chain variable framework, e.g., a light or heavy chain variable framework residue from a human mature antibody, a human germline sequence, or a human consensus sequence; (b) a light or heavy chain variable framework including from 20% to 80%, 40% to 60%, 60% to 90%, or 70% to 95% of the amino acid residues from a human light or heavy chain variable framework, e.g., a light or heavy chain variable framework residue from a human mature antibody, a human germline sequence, or a human consensus sequence; (c) a non-human framework (e.g., a rodent framework); or (d) a non-human framework that has been modified, e.g., to remove antigenic or cytotoxic determinants, e.g., deimmunized, or partially humanized. In some embodiments, the light or heavy chain variable framework region (particularly FR1, FR2 and / or FR3) includes a light or heavy chain variable framework sequence at least 70, 75, 80, 85, 87, 88, 90, 92, 94, 95, 96, 97, 98, 99% identical or identical to the frameworks of a VL or VH segment of a human germline gene.

[0442] In some embodiments, the light or the heavy chain variable framework (e.g., the region encompassing at least FR1, FR2, FR3, and optionally FR4) of the anti-TCR0V antibody molecule, e.g., anti-TCRp V6 antibody molecule can be chosen from: (a) a light or heavy chain variable framework including at least 80%, 85%, 87% 90%, 92%, 93%, 95%, 97%, 98%, or 100% of the amino acid residues from a human light or heavy chain variable framework, e.g., a light or heavy chain variable framework residue from a human mature antibody, a human germline sequence, or a human consensus sequence; (b) a light or heavy chain variable framework including from 20% to 80%, 40% to 60%, 60% to 90%, or 70%to 95% of the amino acid residues from a human light or heavy chain variable framework, e.g., a light or heavy chain variable framework residue from a human mature antibody, a human germline sequence, or a human consensus sequence; (c) a non-human framework (e.g., a rodent framework); or (d) a non-human framework that has been modified, e.g., to remove antigenic or cytotoxic determinants, e g., deimmunized, or partially humanized. In some embodiments, the light or heavy chain variable framework region (particularly FR1, FR2 and / or FR3) includes a light or heavy chain variable framework sequence at least 70, 75, 80, 85, 87, 88, 90, 92, 94, 95, 96, 97, 98, 99% identical or identical to the frameworks of a VL or VH segment of a human germline gene.

[0443] In some embodiments, the anti-TCRpV antibody molecule, e.g, anti-TCRP V6 (e.g, anti-TCRP V6-5*01) antibody molecule comprises a VH and / or a VL of an antibody described in Table 1, or a sequence with at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more identity thereto.

[0444] In some embodiments, the anti-TCRpV antibody molecule, e.g, anti-TCRP V6 (e.g, anti-TCRP V6-5*01) antibody molecule comprises a VH and a VL of an antibody described in Table 1, or a sequence with at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more identity thereto.

[0445] In some embodiments, the heavy or light chain variable domain, or both, of the anti-TCRpV antibody molecule, e.g, anti-TCRP V6 (e.g, anti-TCRP V6-5*01) antibody molecule, includes an amino acid sequence, which is substantially identical to an amino acid as described herein, e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical to a variable region of an antibody described herein, e.g., an antibody chosen from any one as described in Table 1; or which differs at least 1 or 5 residues, but less than 40, 30, 20, or 10 residues, from a variable region of an antibody descnbed herein.

[0446] In some embodiments, the anti-TCRpV antibody molecule, e.g, anti-TCRP V6 (e.g, anti-TCRP V6-5*01) antibody molecule, comprises at least one, two, three, or four antigen-binding regions, e.g., variable regions, having an amino acid sequence as set forth in Table 1, or a sequence substantially identical thereto (e.g., a sequence at least about 85%, 90%, 95%, 99% or more identical thereto, or which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the sequences shown in Table 1.

[0447] In some embodiments, the anti-TCRpV antibody molecule, e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*01) antibody molecule is a full antibody or fragment thereof (e.g., a Fab, F(ab')2, Fv, single domain antibody, or a single chain Fv fragment (scFv)). In embodiments, the anti-TCRpV antibody molecule, e.g., anti-TCRP V6 (e.g., anti-TCRP V6-5*01) antibody molecule is a monoclonal antibody or an antibody with single specificity. In some embodiments, the anti-TCRpV antibody molecule, e.g, anti-TCRP V6 (e.g., anti-TCRP V6-5*01) antibody molecule, can also be a humanized, chimeric, camelid, shark, or an in vitro-generated antibody molecule. In some embodiments, the anti-TCRpV antibody molecule, e g., anti-TCRP V6 (e.g., anti-TCRP V6-5*01) antibody molecule, is a humanized antibody molecule. The heavy and light chains of the anti-TCRpV antibody molecule, e.g, anti-TCRP V6 (e g., anti-TCRP V6-5*01) antibody molecule, can be full-length (e.g., an antibody can include at least one, and preferably two, complete heavy chains, and at least one, and preferably two, complete light chains) or can include an antigen-binding fragment (e.g, a Fab, F(ab')2, Fv, a single chain Fv fragment, a single domain antibody, a diabody (dAb), a bivalent antibody, or bispecific antibody or fragment thereof, a single domain variant thereof, a VHH, ora camelid antibody).

[0448] In some embodiments, the anti-TCR0V antibody molecule, e.g., anti-TCR0 V6 (e.g., anti-TCR0 V6-5*01) antibody molecule, is in the form of a multispecific molecule, e.g., a bispecific molecule, e.g., as described herein.

[0449] In some embodiments, the anti-TCR0V antibody molecule, e.g., anti-TCR0 V6 (e.g., anti-TCR0 V6-5*01) antibody molecule, has a heavy chain constant region (Fc) chosen from, e.g., the heavy chain constant regions of IgGl, IgG2, IgG3, IgG4, IgM, IgAl, IgA2, IgD, and IgE. In some embodiments, the Fc region is chosen from the heavy chain constant regions of IgGl, IgG2, IgG3, and IgG4. In some embodiments, the Fc region is chosen from the heavy chain constant region of IgGl or IgG2 (e.g., human IgGl, or IgG2). In some embodiments, the heavy chain constant region is human IgGl. In some embodiments, the Fc region comprises a Fc region variant, e.g., as described herein.

[0450] In some embodiments, the anti-TCR0V antibody molecule, e.g., anti-TCR0 V6 (e.g., anti-TCR[3 V6-5*01) antibody molecule, has a light chain constant region chosen from, e.g., the light chain constant regions of kappa or lambda, preferably kappa (e.g., human kappa). In some embodiments, the constant region is altered, e.g., mutated, to modify the properties of the anti-TCR V antibody molecule, e.g., anti-TCR0 V6 (e.g, anti-TCRp V6-5*01) antibody molecule (e.g., to increase or decrease one or more of: Fc receptor binding, antibody glycosylation, the number of cysteine residues, effector cell function, or complement function). For example, the constant region is mutated at positions 296 (M to Y), 298 (S to T), 300 (T to E), 477 (H to K) and 478 (N to F) to alter Fc receptor binding (e.g., the mutated positions correspond to positions 132 (M to Y), 134 (S to T), 136 (T to E), 313 (H to K) and 314 (N to F) of SEQ ID NOs: 212 or 214; or positions 135 (Mto Y), 137 (S to T), 139 (T to E), 316 (H to K) and 317 (N to F) of SEQ ID NOs: 215, 216, 217 or 218), e.g, relative to human IgGl.

[0451] Additional exemplary humanized anti-TCRB V6 antibodies are provided in Table 1. In some embodiments, the anti-TCRp V6 is antibody A, e.g, humanized antibody A (antibody A-H), as provided in Table 1. In some embodiments, the anti-TCRpV antibody comprises one or more (e.g., all three) of a LC CDR1, LC CDR2, and LC CDR3 provided in Table 1; and / or one or more (e.g, all three) of a HC CDR1, HC CDR2, and HC CDR3 provided in Table 1, or a sequence with at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity sequence identity thereto. In some embodiments, antibody A comprises a variable heavy chain (VH) and / or a variable light chain (VL) provided in Table 1, or a sequence with at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity thereto.TCR binding moiety or TCR binding domain - Anti-TCRB VI 2 antibodies

[0452] In one aspect, provided herein is an anti-TCR0V antibody molecule that binds to human TCR0 V12, e.g., a TCR0 V 12 subfamily comprising: TCR0 V12-4*01, TCR(3 V12-3*01 or TCR0 V12-5*01. In some embodiments the TCR0 V12 subfamily comprises TCR0 V12-4*01. In some embodiments the TCR0 V12 subfamily comprises TCR0 VI2-3*01.

[0453] In some embodiments, the one or more TCR binding moiety or TCR binding domain binds to aTCRpV region of TCRpV 12. In some embodiments, the one or more TCR binding moiety or TCR binding domain comprises an anti-TCRpV12 antibody molecule or an anti-TCRpV12 antigen binding domain.

[0454] In some embodiments, the anti-TCRpV antibody molecule, e.g., anti-TCRp V12 antibody molecule, is a non-murine antibody molecule, e.g., a human or humanized antibody molecule. In some embodiments, the anti-TCRpV antibody molecule, e.g., anti-TCRp V12 antibody molecule is a human antibody molecule. In some embodiments, the anti-TCRpV antibody molecule, e.g., anti-TCRp V12 antibody molecule is a humanized antibody molecule.

[0455] In some embodiments, the anti-TCRpV antibody molecule, e.g., anti-TCRp V12 antibody molecule, is isolated or recombinant.

[0456] In some embodiments, the a...

Claims

CLAIMSWhat is claimed is:

1. A molecule comprising an TCRβV27-binding moiety, wherein the TCRβV27-binding moiety is an anti-TCRβV27 antibody molecule or an anti-TCRβV27 antigen binding domain comprising:(i) a heavy chain variable region (VH) comprises a heavy chain complementarity determining region 1 (HC CDR1), a heavy chain complementarity determining region 2 (HC CDR2), and a heavy chain complementarity determining region 3 (HC CDR3) comprising the sequences of:(a) SEQ ID NO: 1470, SEQ ID NO: 1451, and SEQ ID NO: 1426, respectively;(b) SEQ ID NO: 1470, SEQ ID NO: 1451, and SEQ ID NO: 1513, respectively;(c) SEQ ID NO: 1471, SEQ ID NO: 1451, and SEQ ID NO: 1426, respectively;(d) SEQ ID NO: 1471, SEQ ID NO: 1451, and SEQ ID NO: 1513, respectively;(e) SEQ ID NO: 1472, SEQ ID NO: 1452, and SEQ ID NO: 1426, respectively;(f) SEQ ID NO: 1472, SEQ ID NO: 1452, and SEQ ID NO: 1513, respectively; or (g) SEQ ID NO: 1473, SEQ ID NO: 1453, and SEQ ID NO: 1432, respectively;(ii) a light chain variable region (VL) comprises a light chain complementarity determining region 1 (LC CDR1), a light chain complementarity determining region 2 (LC CDR2), and a light chain complementarity determining region 1 (LC CDR3) comprising the sequences of:(a) SEQ ID NO: 1442, SEQ ID NO: 1434, and SEQ ID NO: 1438, respectively; or (b) SEQ ID NO: 1443, SEQ ID NO: 1437, and SEQ ID NO: 1438, respectively.

2. The molecule of claim 1, wherein the anti-TCRpV27 antibody molecule or the anti-TCRpV27 antigen binding domain comprises the VH and the VL respectively comprising a HC CDR1, a HC CDR2, and a HC CDR3, and a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of;(a) SEQ ID NO: 1470, SEQ ID NO: 1451, SEQ ID NO: 1426, SEQ ID NO: 1442, SEQ ID NO:1434, and SEQ ID NO: 1438, respectively;(b) SEQ ID NO: 1470, SEQ ID NO: 1451, SEQ ID NO: 1513, SEQ ID NO: 1442, SEQ ID NO:1434, and SEQ ID NO: 1438, respectively;(c) SEQ ID NO: 1471, SEQ ID NO: 1451, SEQ ID NO: 1426, SEQ ID NO: 1442, SEQ ID NO:1434, and SEQ ID NO: 1438, respectively;(d) SEQ ID NO: 1471, SEQ ID NO: 1451, SEQ ID NO: 1513, SEQ ID NO: 1442, SEQ ID NO:1434, and SEQ ID NO: 1438, respectively;(e) SEQ ID NO: 1472, SEQ ID NO: 1452, SEQ ID NO: 1426, SEQ ID NO: 1442, SEQ ID NO:1434, and SEQ ID NO: 1438, respectively; or(f) SEQ ID NO: 1472, SEQ ID NO: 1452, SEQ ID NO: 1513, SEQ ID NO: 1442, SEQ ID NO:1434, and SEQ ID NO: 1438, respectively; or(g) SEQ ID NO: 1473, SEQ ID NO: 1453, SEQ ID NO: 1432, SEQ ID NO: 1443, SEQ ID NO:1437, and SEQ ID NO: 1438, respectively.

3. The molecule of claim 1 or 2, wherein the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1423.

4. The molecule of any one of claims 1-3, wherein the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413.

5. The molecule of any one of claims 1-4, wherein the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1423 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413.

6. The molecule of any one of claims 1-5, wherein the VH comprises the sequence of SEQ ID NO: 1423.

7. The molecule of any one of claims 1-6, wherein the VL comprises the sequence of 1413.

8. The molecule of any one of claims 1-7, wherein the VH comprises the sequence of SEQ ID NO: 1423 and the VL comprises the sequence of 1413.

9. A molecule comprising an TCRβV27-binding moiety, wherein the TCRβV27-binding moiety is an anti-TCRβV27 antibody molecule or an anti-TCRβV27 antigen binding domain comprising:(i) a heavy chain variable region (VH) comprising:(a) a heavy chain complementarity determining region 1 (HC CDR1) comprising the sequence GFKTEX1X2YMY, wherein Xi is D or E, and X2is T, Y, or A (SEQ ID NO: 1480);(b) a heavy chain complementarity determining region 2 (HC CDR2) comprising the sequence X3IX4PX5X6X7X8TX9YDPKFQD, wherein X3is R or D, X4 is D or Y, X5is A, F or Y, X6is N or A, X7 is G or A, Xg is N or A, and Xg is K or S (SEQ ID NO: 1481); and (c) a heavy chain complementarity determining region 3 (HC CDR3) comprising the sequence GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513); and(ii) a light chain variable region (VL) comprising:(a) a light chain complementarity determining region 1 (LC CDR1) comprising the sequence RASESVX10SYGX11SFMH, wherein Xw is D or A, and Xu is N or A (SEQ ID NO: 1482); (b) a light chain complementarity determining region 2 (LC CDR2) comprising the sequence RASNLES (SEQ ID NO: 1434); and(c) a light chain complementarity determining region 3 (LC CDR3) comprising the sequence QQSNEDPYT (SEQ ID NO: 1438),with the proviso that:(A) the HC CDR1, the HC CDR2, the HC CDR3, the LC CDR1, the LC CDR2, and the LC CDR3 are not GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513),RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), respectively; or(B) the HC CDR1, the HC CDR2, the HC CDR3, the LC CDR1, the LC CDR2, and the LC CDR3 are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), respectively, and the VH comprises a sequence having at least 97.5%, 98%, 98.5%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

10. The molecule of claim 9, wherein HC CDR1 is GFKTEDTYMY (SEQ ID NO: 1424), GFKTEDYYMY (SEQ ID NO: 1447), GFKTEDAYMY (SEQ ID NO: 1470), or GFKTEETYMY (SEQ ID NO: 1457).

11. The molecule of claim 9 or 10, wherein HC CDR2 is RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), RIDPANGATKYDPKFQD (SEQ ID NO: 1439), RIDPYAGATKYDPKFQD (SEQ ID NO: 1444), RIDPYNAATKYDPKFQD (SEQ ID NO: 1451), RIDPFNGNTKYDPKFQD (SEQ ID NO: 1454), DIYPAAGATSYDPKFQD (SEQ ID NO: 1458), RIDPFAGATKYDPKFQD (SEQ ID NO: 1464), or RIDPFNAATKYDPKFQD (SEQ ID NO: 1467).

12. The molecule of any one of claims 9-11, wherein HC CDR3 is GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513).

13. The molecule of any one of claims 9-12, wherein LC CDR1 is RASESVDSYGNSFMH (SEQ ID NO: 1433) or RASESVASYGASFMH (SEQ ID NO: 1442).

14. The molecule of any one of claims 9-13, wherein LC CDR2 is RASNLES (SEQ ID NO: 1434).

15. The molecule of any one of claims 9-14, wherein LC CDR3 is QQSNEDPYT (SEQ ID NO: 1438).

16. A molecule comprising an TCRβV27-binding moiety, wherein the TCRβV27-binding moiety is an anti-TCRβV27 antibody molecule or an anti-TCRβV27 antigen binding domain comprising:(i) a VH comprising:(a) a HC CDR1, a HC CDR2, and a HC CDR3 comprising the HC CDR1 sequence, a HC CDR2 sequence, and a HC CDR3 sequence as listed in table 16;(b) a HC CDR1, a HC CDR2, and a HC CDR3 comprising the HC CDR1 sequence, a HC CDR2 sequence, and a HC CDR3 sequence according to Kabat numbering as listed in table 16;(c) a HC CDR1, a HC CDR2, and a HC CDR3 comprising the HC CDR1 sequence, a HC CDR2 sequence, and a HC CDR3 sequence according to Chothia numbering as listed in table 16;(d) a HC CDR1, a HC CDR2, and a HC CDR3 comprising the HC CDR1 sequence, a HC CDR2 sequence, and a HC CDR3 sequence according to IMGT numbering as listed in table 16;(ii) a VL comprising:(a) a LC CDR1, a LC CDR2, and a LC CDR3 comprising the LC CDR1 sequence, a LC CDR2 sequence, and a LC CDR3 sequence as listed in table 16;(b) a LC CDR1, a LC CDR2, and a LC CDR3 comprising the LC CDR1 sequence, a LC CDR2 sequence, and a LC CDR3 sequence according to Kabat numbering as listed in table 16; (c) a LC CDR1, a LC CDR2, and a LC CDR3 comprising the LC CDR1 sequence, a LC CDR2 sequence, and a LC CDR3 sequence according to Chothia numbering as listed in table 16; (d) a LC CDR1, a LC CDR2, and a LC CDR3 comprising the LC CDR1 sequence, a LC CDR2 sequence, and a LC CDR3 sequence according to IMGT numbering as listed in table 16; or(iii) any combination thereof,with the proviso that:(A) the HC CDR1, the HC CDR2, the HC CDR3, the LC CDR1, the LC CDR2, and the LC CDR3 are not GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), respectively; or(B) the HC CDR1, the HC CDR2, the HC CDR3, the LC CDR1, the LC CDR2, and the LC CDR3 are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), respectively, and the VH comprises a sequence having at least 97.5%, 98%, 98.5%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

17. The molecule of claim 16, wherein:(1) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of;(a) SEQ ID NO: 1424, SEQ ID NO: 1425, SEQ ID NO: 1426 or 1513, respectively; (b) SEQ ID NO: 1427, SEQ ID NO: 1425, SEQ ID NO: 1426 or 1513, respectively; (c) SEQ ID NO: 1428, SEQ ID NO: 1429, SEQ ID NO: 1426 or 1513, respectively; or (d) SEQ ID NO: 1430, SEQ ID NO: 1431, SEQ ID NO: 1432, respectively; (ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of:(a) SEQ ID NO: 1433, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1436, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively; (iii) any combination thereof;(2) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of:(a) SEQ ID NO: 1424, SEQ ID NO: 1439, SEQ ID NO: 1426 or 1513, respectively; (b) SEQ ID NO: 1427, SEQ ID NO: 1439, SEQ ID NO: 1426 or 1513, respectively;(c) SEQ ID NO: 1428, SEQ ID NO: 1440, SEQ ID NO: 1426 or 1513, respectively; or (d) SEQ ID NO: 1430, SEQ ID NO: 1441, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of:(a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(3) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of:(a) SEQ ID NO: 1424, SEQ ID NO: 1444, SEQ ID NO: 1426 or 1513, respectively; (b) SEQ ID NO: 1427, SEQ ID NO: 1444, SEQ ID NO: 1426 or 1513, respectively; (c) SEQ ID NO: 1428, SEQ ID NO: 1445, SEQ ID NO: 1426 or 1513, respectively; or (d) SEQ ID NO: 1430, SEQ ID NO: 1446, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of:(a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(4) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of:(a) SEQ ID NO: 1447, SEQ ID NO: 1444, SEQ ID NO: 1426 or 1513, respectively; (b) SEQ ID NO: 1448, SEQ ID NO: 1444, SEQ ID NO: 1426 or 1513, respectively; (c) SEQ ID NO: 1449, SEQ ID NO: 1445, SEQ ID NO: 1426 or 1513, respectively; or (d) SEQ ID NO: 1450, SEQ ID NO: 1446, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of:(a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(5) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of:(a) SEQ ID NO: 1447, SEQ ID NO: 1451, SEQ ID NO: 1426 or 1513, respectively; (b) SEQ ID NO: 1448, SEQ ID NO: 1451, SEQ ID NO: 1426 or 1513, respectively; (c) SEQ ID NO: 1449, SEQ ID NO: 1452, SEQ ID NO: 1426 or 1513, respectively; or (d) SEQ ID NO: 1450, SEQ ID NO: 1453, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of:(a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(6) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of:(a) SEQ ID NO: 1424, SEQ ID NO: 1454, SEQ ID NO: 1426 or 1513, respectively; (b) SEQ ID NO: 1427, SEQ ID NO: 1454, SEQ ID NO: 1426 or 1513, respectively; (c) SEQ ID NO: 1428, SEQ ID NO: 1455, SEQ ID NO: 1426 or 1513, respectively; or (d) SEQ ID NO: 1430, SEQ ID NO: 1456, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of:(a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof,(7) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of:(a) SEQ ID NO: 1457, SEQ ID NO: 1458, SEQ ID NO: 1426 or 1513, respectively; (b) SEQ ID NO: 1459, SEQ ID NO: 1458, SEQ ID NO: 1426 or 1513, respectively; (c) SEQ ID NO: 1460, SEQ ID NO: 1461, SEQ ID NO: 1426 or 1513, respectively; or (d) SEQ ID NO: 1462, SEQ ID NO: 1463, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of:(a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(8) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of:(a) SEQ ID NO: 1424, SEQ ID NO: 1464, SEQ ID NO: 1426 or 1513, respectively; (b) SEQ ID NO: 1427, SEQ ID NO: 1464, SEQ ID NO: 1426 or 1513, respectively; (c) SEQ ID NO: 1428, SEQ ID NO: 1465, SEQ ID NO: 1426 or 1513, respectively; or (d) SEQ ID NO: 1430, SEQ ID NO: 1466, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of:(a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(9) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of:(a) SEQ ID NO: 1424, SEQ ID NO: 1467, SEQ ID NO: 1426 or 1513, respectively; (b) SEQ ID NO: 1427, SEQ ID NO: 1467, SEQ ID NO: 1426 or 1513, respectively; (c) SEQ ID NO: 1428, SEQ ID NO: 1468, SEQ ID NO: 1426 or 1513, respectively; or (d) SEQ ID NO: 1430, SEQ ID NO: 1469, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of:(a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof,-271-(10) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences(a) SEQ ID NO: 1424, SEQ ID NO: 1451, SEQ ID NO: 1426 or 1513, respectively; (b) SEQ ID NO: 1427, SEQ ID NO: 1451, SEQ ID NO: 1426 or 1513, respectively; (c) SEQ ID NO: 1428, SEQ ID NO: 1452, SEQ ID NO: 1426 or 1513, respectively; or (d) SEQ ID NO: 1430, SEQ ID NO: 1453, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of:(a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(11) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of:(a) SEQ ID NO: 1470, SEQ ID NO: 1464, SEQ ID NO: 1426 or 1513, respectively; (b) SEQ ID NO: 1471, SEQ ID NO: 1464, SEQ ID NO: 1426 or 1513, respectively; (c) SEQ ID NO: 1472, SEQ ID NO: 1465, SEQ ID NO: 1426 or 1513, respectively; or (d) SEQ ID NO: 1473, SEQ ID NO: 1466, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of:(a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(12) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of:(a) SEQ ID NO: 1470, SEQ ID NO: 1444, SEQ ID NO: 1426 or 1513, respectively; (b) SEQ ID NO: 1471, SEQ ID NO: 1444, SEQ ID NO: 1426 or 1513, respectively; (c) SEQ ID NO: 1472, SEQ ID NO: 1445, SEQ ID NO: 1426 or 1513, respectively; or (d) SEQ ID NO: 1473, SEQ ID NO: 1446, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of:(a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof;(13) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of:(a) SEQ ID NO: 1470, SEQ ID NO: 1467, SEQ ID NO: 1426 or 1513, respectively; (b) SEQ ID NO: 1471, SEQ ID NO: 1467, SEQ ID NO: 1426 or 1513, respectively; (c) SEQ ID NO: 1472, SEQ ID NO: 1468, SEQ ID NO: 1426 or 1513, respectively; or (d) SEQ ID NO: 1473, SEQ ID NO: 1469, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of:(a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof; or(14) (i) the VH comprises a HC CDR1, a HC CDR2, and a HC CDR3 comprising the sequences of:(a) SEQ ID NO: 1470, SEQ ID NO: 1451, SEQ ID NO: 1426 or 1513, respectively; (b) SEQ ID NO: 1471, SEQ ID NO: 1451, SEQ ID NO: 1426 or 1513, respectively; (c) SEQ ID NO: 1472, SEQ ID NO: 1452, SEQ ID NO: 1426 or 1513, respectively; or (d) SEQ ID NO: 1473, SEQ ID NO: 1453, SEQ ID NO: 1432, respectively;(ii) the VL comprises a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of:(a) SEQ ID NO: 1442, SEQ ID NO: 1434, SEQ ID NO: 1438, respectively; or(b) SEQ ID NO: 1443, SEQ ID NO: 1437, SEQ ID NO: 1438, respectively;(iii) any combination thereof,with the proviso that when the HC CDR1, the HC CDR2, the HC CDR3, the LC CDR1, the LC CDR2, and the LC CDR3 are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), respectively, the VH comprises a sequence having at least 97.5%, 98%, 98.5%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

18. The molecule of claim 16 or 17, wherein the anti-TCR(3V27 antibody molecule or the anti-TCRPV27 antigen binding domain comprises the VH and the VL respectively comprising a HC CDR1, a HC CDR2, and a HC CDR3, and a LC CDR1, a LC CDR2, and a LC CDR3 comprising the sequences of;(i) SEQ ID NOs: 1424, 1425, and 1426, and SEQ ID NOs: 1433, 1434, and 1438, respectively; (ii) SEQ ID NOs: 1427, 1425, and 1426, and SEQ ID NOs: 1433, 1434, and 1438, respectively; (iii) SEQ ID NOs: 1428, 1429, and 1426, and SEQ ID NOs: 1433, 1434, and 1438, respectively; (iv) SEQ ID NOs: 1430, 1431, and 1432, and SEQ ID NOs: 1436, 1437, and 1438, respectively; (v) SEQ ID NOs: 1424, 1439, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (vi) SEQ ID NOs: 1427, 1439, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (vii) SEQ ID NOs: 1428, 1440, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (viii)SEQ ID NOs: 1430, 1441, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively; (ix) SEQ ID NOs: 1424, 1444, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (x) SEQ ID NOs: 1427, 1444, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xi) SEQ ID NOs: 1428, 1445, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xii) SEQ ID NOs: 1430, 1446, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively; (xiii)SEQ ID NOs: 1447, 1444, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xiv)SEQ ID NOs: 1448, 1444, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xv) SEQ ID NOs: 1449, 1445, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xvi)SEQ ID NOs: 1450, 1446, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively;(xvii) SEQ ID NOs: 1447, 1451, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xviii) SEQ ID NOs: 1448, 1451, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xix)SEQ ID NOs: 1449, 1452, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xx) SEQ ID NOs: 1450, 1453, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively; (xxi)SEQ ID NOs: 1424, 1454, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xxii) SEQ ID NOs: 1427, 1454, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xxiii) SEQ ID NOs: 1428, 1455, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xxiv) SEQ ID NOs: 1430, 1456, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively;(xxv) SEQ ID NOs: 1457, 1458, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xxvi) SEQ ID NOs: 1459, 1458, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xxvii) SEQ ID NOs: 1460, 1461, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xxviii) SEQ ID NOs: 1462, 1463, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively;(xxix) SEQ ID NOs: 1424, 1464, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xxx) SEQ ID NOs: 1427, 1464, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xxxi) SEQ ID NOs: 1428, 1465, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xxxii) SEQ ID NOs: 1430, 1466, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively;(xxxiii) SEQ ID NOs: 1424, 1467, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xxxiv) SEQ ID NOs: 1427, 1467, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xxxv) SEQ ID NOs: 1428, 1468, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xxxvi) SEQ ID NOs: 1430, 1469, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively;(xxxvii)SEQ ID NOs: 1424, 1451, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xxxviii) SEQ ID NOs: 1427, 1451, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xxxix) SEQ ID NOs: 1428, 1452, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xl) SEQ ID NOs: 1430, 1453, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively; (xli) SEQ ID NOs: 1470, 1464, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xlii)SEQ ID NOs: 1471, 1464, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xliii) SEQ ID NOs: 1472, 1465, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xliv) SEQ ID NOs: 1473, 1466, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively;(xlv)SEQ ID NOs: 1470, 1444, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (xlvi) SEQ ID NOs: 1471, 1444, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xlvii) SEQ ID NOs: 1472, 1445, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(xlviii) SEQ ID NOs: 1473, 1446, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively;(xlix) SEQ ID NOs: 1470, 1467, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively;(1) SEQ ID NOs: 1471, 1467, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (li) SEQ ID NOs: 1472, 1468, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (lii) SEQ ID NOs: 1473, 1469, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively; (liii) SEQ ID NOs: 1470, 1451, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (liv) SEQ ID NOs: 1471, 1451, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively; (Iv) SEQ ID NOs: 1472, 1452, and 1426, and SEQ ID NOs: 1442, 1434, and 1438, respectively:or(lvi) SEQ ID NOs: 1473, 1453, and 1432, and SEQ ID NOs: 1443, 1437, and 1438, respectively, with the proviso that when the HC CDR1, the HC CDR2, the HC CDR3, the LC CDR1, the LC CDR2, and the LC CDR3 are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), respectively, the VH comprises a sequence having at least 97.5%, 98%, 98.5%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

19. The molecule of any one of claims 9- 18, wherein the VH comprise a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VH sequences listed in Table 16,with the proviso that when the VH comprises the HC CDR1, the HC CDR2, and the HC CDR3 that are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), and GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), and the VL comprises the LC CDR1, the LC CDR2, and the LC CDR3 that are RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), the VH sequence has at least 97.5%, 98%, 98.5%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

20. The molecule of any one of claims 9-19, wherein the VL comprise a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VL sequences listed in Table 16,with the proviso that when the VH comprises the HC CDR1, the HC CDR2, and the HC CDR3 that are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), and GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), and the VL comprises the LC CDR1, the LC CDR2, and the LC CDR3 that are RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), the VH sequence has at least 97.5%, 98%, 98.5%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

21. The molecule of any one of claims 9-20, wherein the VH comprise a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VH sequences listed in Table 16 and the VL comprise a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VL sequences listed in Table 16,with the proviso that when the VH comprises the HC CDR1, the HC CDR2, and the HC CDR3 that are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), and GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), and the VL comprises the LC CDR1, the LC CDR2, and the LC CDR3 that are RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), the VH sequence has at least 97.5%, 98%, 98.5%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

22. The molecule of any one of claims 9-21, wherein the VH comprise any one of the VH sequences listed in Table 16.

23. The molecule of any one of claims 9-22, wherein the VL comprise any one of the VL sequences listed in Table 16.

24. The molecule of any one of claims 9-23, wherein the VH comprise any one of the VH sequences listed in Table 16 and the VL comprise any one of the VL sequences listed in Table 16.

25. The molecule of any one of claims 9-21, wherein the VH comprise a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VH sequences selected from the group consisting of SEQ ID NOs: 1401, 1403, 1405, 1407, 1409, 1410, 1411, 1412, 1414, 1415, 1416, 1417, 1418, 1419, 1420, 1421, 1422, and 1423,with the proviso that when the VH comprises the HC CDR1, the HC CDR2, and the HC CDR3 that are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), and GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), and the VL comprises the LC CDR1, the LC CDR2, and the LC CDR3 that are RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), the VH sequence has at least 97.5%, 98%, 98.5%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

26. The molecule of any one of claims 9-21 and 25, wherein the VL comprise a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VL sequences selected from the group consisting of SEQ ID NOs: 1402, 1404, 1406, 1408, and 1413,with the proviso that when the VH comprises the HC CDR1, the HC CDR2, and the HC CDR3 that are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), and GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), and the VL comprises the LC CDR1, the LC CDR2, and the LC CDR3 that are RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), the VH sequence has at least 97.5%, 98%, 98.5%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

27. The molecule of any one of claims 9-26, wherein the VH comprise any one of the VH sequences selected from the group consisting of SEQ ID NOs: 1423, 1401, 1403, 1405, 1407, 1409, 1410, 1411, 1412, 1414, 1415, 1416, 1417, 1418, 1419, 1420, 1421, and 1422.

28. The molecule of any one of claims 9-27, wherein the VL comprise any one of the VL sequences selected from the group consisting of SEQ ID NOs: 1413, 1402, 1404, 1406, and 1408,with the proviso that when the VH comprises the HC CDR1, the HC CDR2, and the HC CDR3 that are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), and GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), and the VL comprises the LC CDR1, the LC CDR2, and the LC CDR3 that are RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), the VH sequence has at least 97.5%, 98%, 98.5%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

29. The molecule of any one of claims 9-21, 25, and 26, wherein:(i) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to thesequence of SEQ ID NO: 1423 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413;(ii) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1402;(iii) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1403 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1404;(iv) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1405 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1406;(v) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1407 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1408;(vi) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1409 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1408;(vii) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1410 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1408;(viii) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1411 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1408;(ix) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1412 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413;(x) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1414 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413;(xi) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1415 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413;(xii) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1416 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413;(xiii) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1417 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413;(xiv) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1418 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413;(xv) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1419 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413;(xvi) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1420 and the VL comprises a sequence having at least 70%, 75%,80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413;(xvii) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1421 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413; or(xviii) the VH comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1422 and the VL comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of 1413,with the proviso that when the VH comprises the HC CDR1, the HC CDR2, and the HC CDR3 that are GFKTEDTYMY (SEQ ID NO: 1424), RIDPANGNTKYDPKFQD (SEQ ID NO: 1425), and GSYYYAMDY (SEQ ID NO: 1426) or GSYYYAMD (SEQ ID NO: 1513), and the VL comprises the LC CDR1, the LC CDR2, and the LC CDR3 that are RASESVDSYGNSFMH (SEQ ID NO: 1433), RASNLES (SEQ ID NO: 1434), and QQSNEDPYT (SEQ ID NO: 1438), the VH sequence has at least 97.5%, 98%, 98.5%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1401.

30. The molecule of any one of claims 9-29, wherein:(i) the VH comprises the sequence of SEQ ID NO: 1423 and the VL comprises the sequence of 1413;(ii) the VH comprises the sequence of SEQ ID NO: 1401 and the VL comprises the sequence of 1402;(iii) the VH comprises the sequence of SEQ ID NO: 1403 and the VL comprises the sequence of 1404;(iv) the VH comprises the sequence of SEQ ID NO: 1405 and the VL comprises the sequence of 1406;(v) the VH comprises the sequence of SEQ ID NO: 1407 and the VL comprises the sequence of 1408;(vi) the VH comprises the sequence of SEQ ID NO: 1409 and the VL comprises the sequence of 1408;(vii) the VH comprises the sequence of SEQ ID NO: 1410 and the VL comprises the sequence of 1408;(viii) the VH comprises the sequence of SEQ ID NO: 1411 and the VL comprises the sequence of 1408;(ix) the VH comprises the sequence of SEQ ID NO: 1412 and the VL comprises the sequence of 1413;(x) the VH comprises the sequence of SEQ ID NO: 1414 and the VL comprises the sequence of 1413;(xi) the VH comprises the sequence of SEQ ID NO: 1415 and the VL comprises the sequence of 1413;(xii) the VH comprises the sequence of SEQ ID NO: 1416 and the VL comprises the sequence of 1413;(xiii) the VH comprises the sequence of SEQ ID NO: 1417 and the VL comprises the sequence of 1413;(xiv) the VH comprises the sequence of SEQ ID NO: 1418 and the VL comprises the sequence of 1413;(xv) the VH comprises the sequence of SEQ ID NO: 1419 and the VL comprises the sequence of 1413;(xvi) the VH comprises the sequence of SEQ ID NO: 1420 and the VL comprises the sequence of 1413;(xvii) the VH comprises the sequence of SEQ ID NO: 1421 and the VL comprises the sequence of 1413; or(xviii) the VH comprises the sequence of SEQ ID NO: 1422 and the VL comprises the sequence of 1413.

31. The molecule of any one of claims 1-30, wherein the anti-TCRpV27 antibody molecule or the anti -TCRPV27 antigen binding domain binds to a TCRpV region of TCRPV27.

32. The molecule of any one of claims 1-31, wherein the anti-TCRpV27 antibody molecule or the anti -TCRPV27 antigen binding domain binds to a TCRpV region of human TCRPV27.

33. The molecule of any one of claims 1 -32, wherein the anti-TCRpV27 antibody molecule or the anti-TCRpV27 antigen binding domain comprises any one selected from the group consisting of a full-length antibody, a Fab, a F(ab')2, an Fv, a single chain Fv, a camelid antibody, a VHH, a half arm antibody, a diabody, a bivalent antibody, a monovalent antibody, or a bispecific antibody, and any combination thereof.

34. The molecule of any one of claims 1-33, wherein the molecule is a multispecific molecule.

35. The molecule of claim 34, wherein the multispecific molecule further comprises one or more molecule that binds to a co-stimulatory receptor of a T cell.

36. The molecule of claim 35, wherein the one or more molecule that binds to a co-stimulatory receptor of a T cell activates the co-stimulatory receptor when the one or more molecule that binds to a co-stimulatory receptor of a T cell binds to the co-stimulatory receptor.

37. The molecule of claim 35 or 36, wherein the one or more molecule that binds to a co-stimulatory receptor of a T cell comprises at least one cytokine molecule or a functional fragment or functional variant thereof.

38. The molecule of claim 37, wherein the at least one cytokine molecule or a functional fragment or functional variant thereof is selected from the group consisting of interleukin-2 (IL-2) or a functional fragment or functional variant thereof, interleukin-7 (IL-7) or a functional fragment or functional variantthereof, interleukin- 12 (IL- 12) or a functional fragment or functional variant thereof, interleukin- 15 (IL-15) or a functional fragment or functional variant thereof, interleukin- 18 (IL-18) or a functional fragment or functional variant thereof, interleukin-21 (IL-21) or a functional fragment or functional variant thereof, or interferon gamma or a functional fragment or functional variant thereof, or any combination thereof.

39. The molecule of claim 37 or 38, wherein the at least one cytokine molecule or a functional fragment or functional variant thereof comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the cytokine sequences listed in Table 17.

40. The molecule of any one of claims 37-39, wherein the at least one cytokine molecule or a functional fragment or functional variant thereof comprises any one of the cytokine sequences listed in Table 17.

41. The molecule of claim 37 or 38, wherein the at least one cytokine molecule or a functional fragment or functional variant thereof comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the sequences selected from the group consisting of SEQ ID NOs: 2191, 2270, 2280, 3542, 3543, 3545, 2170, 3799, 3523, 2193, 5000-5036, 5052, 5053, 5054, and 5037.

42. The molecule of any one of claims 37-39, wherein the at least one cytokine molecule or a functional fragment or functional variant thereof comprises any one of the sequences selected from the group consisting of SEQ ID NOs: 2191, 2270, 2280, 3542, 3543, 3545, 2170, 3799, 3523, 2193, 5000-5036, 5052, 5053, 5054, and 5037.

43. The molecule of any one of claims 37-42, wherein the at least one cytokine molecule or a functional fragment or functional variant thereof comprises interleukm-2 (IL-2) or a functional fragment or functional variant thereof.

44. The molecule of any one of claims 37-43, wherein the at least one cytokine molecule or a functional fragment or functional variant thereof is an IL-2 variant comprising a substitution mutation.

45. The molecule of any one of claims 37-44, wherein the at least one cytokine molecule or a functional fragment or functional variant thereof is an IL-2 variant comprising C125A mutation.

46. The molecule of any one of claims 37-45, wherein the at least one cytokine molecule or a functional fragment or functional variant thereof comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 2270.

47. The molecule of any one of claims 37-46, wherein the at least one cytokine molecule or a functional fragment or functional variant thereof comprises the sequence of SEQ ID NO: 2270.

48. The molecule of any one of claims 37-43, wherein the at least one cytokine molecule ora functional fragment or functional variant thereof comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 2191.

49. The molecule of any one of claims 37-43 and 48, wherein the at least one cytokine molecule or a functional fragment or functional variant thereof comprises the sequence of SEQ ID NO: 2191.

50. The molecule of claim 35 or 36, wherein the one or more molecule that binds to a co-stimulatory receptor of a T cell comprises an antibody molecule, an antigen binding domain, a ligand, an extracellular domain of a receptor, or any combination thereof.

51. The molecule of claim 50, wherein the antibody molecule or the antigen binding domain comprises any one selected from the group consisting of a full-length antibody, a Fab, a F(ab')2, an Fv, a single chain Fv, a camelid antibody, a VHH, a half arm antibody, a diabody, a bivalent antibody, a monovalent antibody, or a bispecific antibody, and any combination thereof.

52. The molecule of claim 50 or 51, wherein the one or more molecule that binds to a co-stimulatory receptor of a T cell binds to CD2, 4-1BB, CD27, CD28, or any combination thereof.

53. The molecule of any one of claims 34-52, wherein the multispecific molecule further comprises one or more TCR binding moiety’.

54. The molecule of claim 53, wherein the one or more TCR binding moiety binds to a T cell receptor alpha (TCRa) chain, a T cell receptor beta (TCRP) chain, a T cell receptor gamma (TCRy) chain, a T cell receptor delta (TCR5) chain, a CD3 gamma (CD3y) chain, a CD3 delta (CD38) chain, a CD3 epsilon (CD3e) chain, a CD3 zeta (CD3Q chain, or any combination thereof.

55. The molecule of claim 53 or 54, wherein the one or more TCR binding moiety binds to a T cell receptor beta (TCR ) chain.

56. The molecule of any one of claims 53-55, wherein the one or more TCR binding moiety binds to a T cell receptor beta variable (TCRPV) region.

57. The molecule of any one of claims 53-56, wherein the one or more TCR binding moiety binds to a TCRPV region of human TCR VI, human TCRPV2, human TCRPV3, human TCRPV4, human TCRPV5, human TCRPV6, human TCRPV7, human TCR[3V8, human TCRPV9, human TCRPV 10, human TCRpVl 1, human TCRpV12, human TCRpV19, human TCR V20, human TCRpV21, human TCRpV23, human TCRpV24, human TCRpV25, human TCR V26, human TCRpV27, human TCR V28, human TCRPV29, human TCRPV30, or any combination thereof.

58. The molecule of any one of claims 53-56, wherein the one or more TCR binding moiety binds to a TCRPV region of human TCRpV2, human TCRpV4-l, human TCRPV4-2, human TCRPV5-1, human TCRPV5-5, human TCRPV5-6, human TC V6, human TCRPV6-5, human TCRPV6-6, human TCRPV6-9, human TCRPV7-2, human TCRPV7-3, human TCRPV7-8, human TCRPV7-9, human TCR V9, human TCRpVIO-l, human TCRpVlO-2, human TCRpV10-3, human TCRpVl 1- 2, human TCRPV 12-3, human TCRPV 12-4, human TCRPV 12-5, human TCRPV 19, human TCR V20-1, human TCRpV21, human TCR V24-1, human TCRPV25-1, human TCRPV28, or any combination thereof.

59. The molecule of any one of claims 53-56, wherein the one or more TCR binding moiety binds to a TCRPV region of human TCRpV2, human TCRPV3-1, human TCRPV4-1, human TCRPV4-2, human TCR V5-1, human TCRPV5-4, human TCRPV5-5, human TCRPV5-6, human TCRpV6-l, human TCRPV6-5, human TCRPV6-6, human TCRPV7-3, human TCRPV7-6, human TCRPV7-8, human TCR V9, human TCRpVl 1-2, human TCRpVl 9, human TCRPV20-1, human TCRPV24-1,human TCRβV27, human TCRPV28, human TCR[3V29-1, human TCRpV30, or any combination thereof.

60. The molecule of any one of claims 53-56, wherein the one or more TCR binding moiety binds to a TCRpV region of human TCRPV5, human TCRPV6, human TCRpVIO, human TCRPV12, human TCRPV20 or any combination thereof.

61. The molecule of claim 53 or 54, wherein the one or more TCR binding moiety binds to a T cell receptor alpha (TCRa) chain.

62. The molecule of any one of claims 53, 54, and 61, wherein the one or more TCR binding moiety binds to a T cell receptor alpha variable (TCRaV) region.

63. The molecule of any one of claims 53, 54, 61, and 62, wherein the one or more TCR binding moiety binds to a TCRaV region of TRAV12-1, TRAV12-2, TRAV12-3, TRAV13-1, TRAV13-2, TRAV19-1, TRAV21-1, TRAV30-1, or any combination thereof.

64. Hie molecule of any one of claims 53-63, wherein the one or more TCR binding moiety comprises an antibody molecule or an antigen binding domain.

65. The molecule of any one of claims 53-64, wherein the one or more TCR binding moiety comprises an antibody molecule or an antigen binding domain comprising a scFv, a full-length antibody, a Fab, a F(ab')2, an Fv, a single chain Fv, a camelid antibody, a half arm antibody, a diabody, a bivalent antibody, a monovalent antibody, or a bispecific antibody.

66. The molecule of any one of claims 53-65, wherein the one or more TCR binding moiety comprises the antibody molecule or the antigen binding domain comprising a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HC CDR1) sequence comprising any one of the HC CDR1 sequences listed in Tables 1, 2, 12, 13, 14, and 22, a heavy chain complementarity determining region 2 (HC CDR2) sequence comprising any one of the HC CDR2 sequences listed in Tables 1, 2, 12, 13, and 14, and a heavy chain complementarity determining region 3 (HC CDR3) sequence of comprising any one of the HC CDR3 sequences listed in Tables 1, 2, 12, 13, and 14.

67. The molecule of any one of claims 53-66, wherein the one or more TCR binding moiety comprises the antibody molecule or the antigen binding domain comprising a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LC CDR1) sequence comprising any one of the LC CDR1 sequences listed in Tables 1, 2, 12, 13, and 14, a light chain complementarity determining region 2 (LC CDR2) sequence comprising any one of the LC CDR2 sequences listed in Tables 1, 2, 12, 13, and 14, and a light chain complementarity determining region 3 (LC CDR3) sequence of comprising any one of the LC CDR3 sequences listed in Tables 1, 2, 12, 13, and 14.

68. The molecule of any one of claims 53-67, wherein the one or more TCR binding moiety comprises the antibody molecule or the antigen binding domain comprising:(i) a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HC CDR1) sequence comprising any one of the HC CDR1 sequences listed in Tables1, 2, 12, 13, and 14, a heavy chain complementarity determining region 2 (HC CDR2) sequence comprising any one of the HC CDR2 sequences listed in Tables 1, 2, 12, 13, and 14, and a heavy chain complementarity determining region 3 (HC CDR3) sequence of comprising any one of the HC CDR3 sequences listed in Tables 1, 2, 12, 13, and 14; and(ii) a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LC CDR1) sequence comprising any one of the LC CDR1 sequences listed in Tables 1, 2, 12, 13, and 14, alight chain complementarity determining region 2 (LC CDR2) sequence comprising any one of the LC CDR2 sequences listed in Tables 1, 2, 12, 13, and 14, and a light chain complementarity determining region 3 (LC CDR3) sequence of comprising any one of the LC CDR3 sequences listed in Tables 1, 2, 12, 13, and 14.

69. The molecule of any one of claims 53-68, wherein the one or more TCR binding moiety comprises the antibody molecule or the antigen binding domain comprising a VH comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VH sequences listed in Tables 1, 2, 12, 13, and 14.

70. The molecule of any one of claims 53-69, wherein the one or more TCR binding moiety compri ses the antibody molecule or the antigen binding domain comprising a VL comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VL sequences listed in Tables 1, 2, 12, 13, and 14.

71. The molecule of any one of claims 53-70, wherein the one or more TCR binding moiety comprises the antibody molecule or the antigen binding domain comprising a VH comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VH sequences listed in Tables 1, 2, 12, 13, and 14; and a VL comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VL sequences listed in Tables 1, 2, 12, 13, and 14.

72. The molecule of any one of claims 53-71, wherein the one or more TCR binding moiety comprises the antibody molecule or the antigen binding domain comprising a VH comprising any one of the VH sequences listed in Tables 1, 2, 12, 13, and 14.

73. The molecule of any one of claims 53-72, wherein the one or more TCR binding moiety' comprises the antibody molecule or the antigen binding domain comprising a VL comprising any one of the VL sequences listed in Tables 1, 2, 12, 13, and 14.

74. The molecule of any one of claims 53-73, wherein the one or more TCR binding moiety comprises the antibody molecule or the antigen binding domain comprising a VH comprising any one of the VH sequences listed in Tables 1, 2, 12, 13, and 14; and a VL comprising any one ofthe VL sequences listed in Tables 1, 2, 12, 13, and 14.

75. The molecule of any one of claims 34-74, wherein the multispecific molecule comprises a first polypeptide chain comprising a first portion of a dimerization module, and a second polypeptide chain comprising a second portion of the dimerization module;wherein the first polypeptide chain and the second polypeptide chain are non-contiguous, and wherein the TCRpV27-binding moiety is operatively linked to the first portion of the dimerization module.

76. The molecule of claim 75, wherein the one or more molecule that binds to a co-stimulatory receptor of a T cell are operatively linked to the first portion of the dimerization module, the second portion of the dimerization module, or a combination thereof.

77. The molecule of claim 75 or 76, wherein:(i) the TCRpV27-binding moiety is operatively linked to the N-terminus of the first portion of the dimerization module, and the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the N-terminus of the first portion of the dimerization module, the C- terminus of the first portion of the dimerization module, the N-terminus of the second portion of the dimerization module, the C-terminus of the second portion of the dimerization module, or any combination thereof; or(ii) the TCRPV27 is operatively linked to the C-terminus of the first portion of the dimerization module, and the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the N-terminus of the first portion of the dimerization module, the C-terminus of the first portion of the dimenzation module, the N-terminus of the second portion of the dimerization module, the C-terminus of the second portion of the dimerization module, or any combination thereof.

78. The molecule of any one of claims 75-77, wherein the TCRpV27-binding moiety and the one or more molecule that binds to a co-stimulatory receptor of a T cell is within a single contiguous polypeptide chain of the first polypeptide chain.

79. The molecule of any one of claims 75-78, wherein the TCRpV27-binding moiety and the one or more molecule that binds to a co-stimulatory receptor of a T cell are operatively linked to the first portion of the dimerization module.

80. The molecule of any one of claims 75-79, wherein the TCRpV27-binding moiety and the one or more molecule that binds to a co-stimulatory receptor of a T cell are operatively linked to the N-terminus of the first portion of the dimerization module.

81. The molecule of any one of claims 75-80, wherein:(i) the C-terminus of the TCRpV27-binding moiety is operatively linked to the one or more molecule that binds to a co-stimulatory receptor of a T cell operatively linked to the N-terminus of the first portion of the dimerization module; and / or(ii) the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the N-terminus of the TCRpV27-binding moiety operatively linked to the N-terminus of the first portion of the dimerization module.

82. The molecule of any one of claims 75-81, wherein the TCRpV27-binding moiety and the one or more molecule that binds to a co-stimulatory receptor of a T cell are operatively linked to the C-terminus of the first portion of the dimerization module.

83. The molecule of any one of claims 75-82, wherein:(i) the N-terminus of the TCRpV27-binding moiety is operatively linked to the C-terminus of the first portion of the dimerization module and the C-terminus of the TCRpV27-binding moiety is operatively linked to the one or more molecule that binds to a co-stimulatory receptor of a T cell; and / or(ii) the N-terminus of the TCRpV27-binding moiety is operatively linked to the one or more molecule that binds to a co-stimulatory receptor of a T cell operatively linked to the C-terminus of the first portion of the dimerization module.

84. The molecule of any one of claims 75-83, wherein the one or more TCR binding moiety are operatively linked to the first portion of the dimerization module, the second portion of the dimerization module, or a combination thereof.

85. The molecule of any one of claims 75-84, wherein:(i) the TCRpV27-binding moiety is operatively linked to the N-terminus of the first portion of the dimerization module, and the one or more TCR binding moiety is operatively linked to the N- terminus of the first portion of the dimerization module, the C-terminus of the first portion of the dimerization module, the N-terminus of the second portion of the dimerization module, the C- termmus of the second portion of the dimerization module, or any combination thereof; or (ii) the TCRPV27 is operatively linked to the C-terminus of the first portion of the dimerization module, and the one or more TCR binding moiety is operatively linked to the N-terminus of the first portion of the dimerization module, the C-terminus of the first portion of the dimerization module, the N-terminus of the second portion of the dimerization module, the C-terminus of the second portion of the dimerization module, or any combination thereof.

86. The molecule of any one of claims 75-85, wherein the TCRpV27-binding moiety and the one or more TCR binding moiety is within a single contiguous polypeptide chain of the first polypeptide chain.

87. The molecule of any one of claims 75-86, wherein the TCRpV27-binding moiety and the one or more TCR binding moiety are operatively linked to the first portion of the dimerization module.

88. The molecule of any one of claims 75-87, wherein the TCRpV27-binding moiety and the one or more TCR binding moiety are operatively linked to the N-terminus of the first portion of the dimerization module.

89. The molecule of any one of claims 75-88, wherein:(i) the C-terminus of the TCRpV27-binding moiety is operatively linked to the one or more TCR binding moiety operatively linked to the N-terminus ofthe first portion ofthe dimerization module; and / or(ii) the one or more TCR binding moiety is operatively linked to the N-terminus of the TCRPV27- binding moiety operatively linked to the N-terminus ofthe first portion ofthe dimerization module.

90. The molecule of any one of claims 75-89, wherein the TCRpV27-binding moiety and the one or more TCR binding moiety are operatively linked to the C-terminus of the first portion of the dimerization module.

91. The molecule of any one of claims 75-90, wherein:(i) the N-terminus of the TCRpV27-binding moiety is operatively linked to the C-terminus of the first portion of the dimerization module and the C-terminus of the TCRpV27-binding moiety is operatively linked to the one or more TCR binding moiety; and / or(ii) the N-terminus of the TCRpV27-binding moiety is operatively linked to the one or more TCR binding moiety operatively linked to the C-terminus of the first portion of the dimerization module.

92. The molecule of any one of claims 75-91, wherein:(i) the one or more TCR binding moiety are operatively linked to the first portion of the dimerization module and the one or more TCR binding moiety are operatively linked to the first portion of the dimerization module, the second portion of the dimerization module, or a combination thereof; or(ii) the one or more TCR binding moiety are operatively linked to the second portion of the dimerization module and the one or more TCR binding moiety are operatively linked to the first portion of the dimerization module or the second portion of the dimerization module, or a combination thereof.

93. The molecule of any one of claims 75-92, wherein:(i) the TCRpV27-binding moiety is operatively linked to the N-terminus of the first portion of the dimerization module, the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the N-termmus of the first portion of the dimerization module, the C- termmus of the first portion of the dimerization module, the N-terminus of the second portion of the dimerization module, the C-terminus of the second portion of the dimerization module, or any combination thereof, and the one or more TCR binding moiety is operatively linked to the N- terminus of the first portion of the dimerization module, the C-terminus of the first portion of the dimerization module, the N-terminus of the second portion of the dimerization module, the C- terminus of the second portion of the dimerization module, or any combination thereof; or (ii) the TCR V27 is operatively linked to the C-terminus of the first portion of the dimerization module, and the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the N-terminus of the first portion of the dimerization module, the C-terminus of the first portion of the dimerization module, the N-terminus of the second portion of the dimerization module, the C-terminus of the second portion of the dimerization module, or any combination thereof, and the one or more TCR binding moiety is operatively linked to the N- terminus of the first portion of the dimerization module, the C-terminus of the first portion of the dimerization module, the N-terminus of the second portion of the dimerization module, the C- terminus of the second portion of the dimerization module, or any combination thereof.

94. The molecule of any one of claims 75-93, wherein the TCRpV27-binding moiety and the one or more molecule that binds to a co-stimulatory receptor of a T cell, the TCRpV27-binding moiety and the one or more TCR binding moiety, the one or more molecule that binds to a co-stimulatory receptor of a T cell and the one or more TCR binding moiety, or the TCRpV27-binding moiety, the one or more molecule that binds to a co-stimulatory receptor of a T cell and the one or more TCR binding moiety are within a single contiguous polypeptide chain of the first polypeptide chain.

95. The molecule of any one of claims 75-94, wherein the TCRpV27-binding moiety, the one or more molecule that binds to a co-stimulatory receptor of a T cell and the one or more TCR binding moiety are operatively linked to the first portion of the dimerization module.

96. The molecule of any one of claims 75-95, wherein the TCRpV27-binding moiety, the one or more molecule that binds to a co-stimulatory receptor of a T cell and the one or more TCR binding moiety are operatively linked to the N-terminus of the first portion of the dimerization module.

97. The molecule of any one of claims 75-96, wherein:(i) the C-terminus of the TCRpV27-binding moiety is operatively linked to the one or more molecule that binds to a co-stimulatory receptor of a T cell operatively linked to the one or more TCR binding moiety operatively linked to the N-terminus of the first portion of the dimerization module;(ii) the C-terminus of the TCRpV27-binding moiety is operatively linked to the one or more TCR binding moiety operatively linked to the one or more molecule that binds to a co-stimulatory receptor of a T cell operatively linked to the N-termmus of the first portion of the dimerization module;(iii) the C-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the TCRpV27-binding moiety operatively linked to the one or more TCR binding moiety operatively linked to the N-terminus ofthe first portion ofthe dimerization module; (iv) the C-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the one or more TCR binding moiety operatively linked to the TCRPV27- binding moiety operatively linked to the N-terminus ofthe first portion ofthe dimerization module; (v) the C-terminus of the one or more TCR binding moiety is operatively linked to the TCRPV27- binding moiety operatively linked to the one or more molecule that binds to a co-stimulatory receptor of a T cell operatively linked to the N-terminus of the first portion of the dimerization module; and / or(vi) the C-terminus of the one or more TCR binding moiety is operatively linked to the one or more molecule that binds to a co-stimulatory receptor of a T cell operatively linked to the TCRPV27- binding moiety operatively linked to the N-terminus ofthe first portion ofthe dimerization module, 98. The molecule of any one of claims 75-97, wherein the TCRpV27-binding moiety, the one or more molecule that binds to a co-stimulatory receptor of a T cell and the one or more TCR binding moiety are operatively linked to the C-terminus of the first portion of the dimerization module.

99. The molecule of any one of claims 75-98, wherein:(i) the C-terminus of the first portion of the dimerization module is operatively linked to the N- terminus of the TCRpV27-binding moiety, and the C-terminus of the TCRpV27-binding moiety is operatively linked to the one or more molecule that binds to a co-stimulatory receptor of a T cell operatively linked to the one or more TCR binding moiety;(ii) the C-terminus of the first portion of the dimerization module is operatively linked to the N- terminus of the TCRpV27-binding moiety, and the C-terminus of the TCRpV27-binding moiety is operatively linked to the one or more TCR binding moiety operatively linked to the one or more molecule that binds to a co-stimulatory receptor of a T cell;(iii) the C-terminus of the first portion of the dimerization module is operatively linked to the N- terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell, and the C-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the TCRpV27-binding moiety operatively linked to the one or more TCR binding moiety;(iv) the C-terminus of the first portion of the dimerization module is operatively linked to the N- terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell, and the C-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the one or more TCR binding moiety operatively linked to the TCRPV27- binding moiety;(v) the C-terminus of the first portion of the dimerization module is operatively linked to the N- terminus of the one or more TCR binding moiety, and the C-terminus of the one or more TCR binding moiety is operatively linked to the TCRpV27-binding moiety operatively linked to the one or more molecule that binds to a co-stimulatory receptor of a T cell; and / or(vi) the C-terminus of the first portion of the dimerization module is operatively linked to the N- terminus of the one or more TCR binding moiety, and the C-terminus of the one or more TCR binding moiety is operatively linked to the one or more molecule that binds to a co-stimulatory receptor of a T cell operatively linked to the TCRβV27-binding moiety.

100. The molecule of any one of claims 75-99, wherein the one or more molecule that binds to a co-stimulatory receptor of a T cell and the one or more TCR binding moiety is within a single contiguous polypeptide chain of the second polypeptide chain.

101. The molecule of any one of claims 75-100, wherein the one or more molecule that binds to a co-stimulatory receptor of a T cell and the one or more TCR binding moiety are operatively linked to the second portion of the dimerization module.

102. The molecule of any one of claims 75-101, wherein the one or more molecule that binds to a co-stimulatory receptor of a T cell and the one or more TCR binding moiety are operatively linked to the N-terminus of the second portion of the dimerization module.

103. The molecule of any one of claims 75-102, wherein:(i) the C-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the one or more TCR binding moiety operatively linked to the N-terminus of the second portion of the dimerization module; and / or(ii) the one or more TCR binding moiety is operatively linked to the N-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell operatively linked to the N-terminus of the second portion of the dimerization module.

104. The molecule of any one of claims 75-103, wherein the one or more molecule that binds to a co-stimulatory receptor of a T cell and the one or more TCR binding moiety are operatively linked to the C-terminus of the second portion of the dimerization module.

105. The molecule of any one of claims 75-104, wherein:(i) the N-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the C-terminus of the second portion of the dimerization module and the C-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the one or more TCR binding moiety; and / or(ii) the N-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the one or more TCR binding moiety operatively linked to the C-terminus of the second portion of the dimerization module.

106. The molecule of any one of claims 75-105, wherein the one or more molecule that binds to a co-stimulatory receptor of a T cell and the one or more TCR binding moiety is within a single contiguous polypeptide chain of the first polypeptide chain.

107. The molecule of any one of claims 75-106, wherein the one or more molecule that binds to a co-stimulatory receptor of a T cell and the one or more TCR binding moiety are operatively linked to the first portion of the dimerization module.

108. The molecule of any one of claims 75-107, wherein the one or more molecule that binds to a co-stimulatory receptor of a T cell and the one or more TCR binding moiety are operatively linked to the N-terminus of the first portion of the dimerization module.

109. The molecule of any one of claims 75-108, wherein:(i) the C-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the one or more TCR binding moiety operatively linked to the N-terminus of the first portion of the dimerization module; and / or(ii) the one or more TCR binding moiety is operatively linked to the N-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell operatively linked to the N-terminus of the first portion of the dimerization module.

110. The molecule of any one of claims 75-109, wherein the one or more molecule that binds to a co-stimulatory receptor of a T cell and the one or more TCR binding moiety are operatively linked to the C-terminus of the first portion of the dimerization module.

111. The molecule of any one of claims 75-110, wherein:(i) the N-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the C-terminus of the first portion of the dimerization module and the C- terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the one or more TCR binding moiety; and / or(ii) the N-terminus of the one or more molecule that binds to a co-stimulatory receptor of a T cell is operatively linked to the one or more TCR binding moiety operatively linked to the C-terminus of the first portion of the dimerization module.

112. The molecule of any one of claims 75-111, wherein the TCRpV27-binding moiety comprises a VH and a VL, or a single domain antibody.

113. The molecule of any one of claims 75-112, wherein the TCRpV27-binding moiety comprises a first portion of TCRpV27-binding moiety, andwherein the multispecific molecule further comprises a third polypeptide chain comprising a second portion of the TCRpV27-binding moiety, wherein the third polypeptide chain is noncontiguous with the first polypeptide chain and the second polypeptide chain.

114. The molecule of claim 112, wherein the first portion of the TCRpV27-binding moiety comprises a VH of the TCRpV27-binding moiety and the second portion of the TCRpV27-binding moiety comprises a VL of the TCRpV27-binding moiety, or the first portion of the TCRpV27-binding moiety comprises a VL of the TCRpV27-binding moiety and the second portion of the TCRpV27-binding moiety comprises a VH of the TCRpV27-binding moiety.

115. The molecule of any one of claims 75-114, wherein the first portion of the dimerization module and the second portion of the dimenzation module associates to form a dimer.

116. The molecule of any one of claims 75-115, wherein the first portion of the dimerization module comprises a first immunoglobulin constant region and the second portion of the dimerization module comprises a second immunoglobulin constant region.

117. The molecule of any one of claims 75-116, wherein the first immunoglobulin constant region comprises a first Fc region and the second immunoglobulin constant region comprises a second Fc region.

118. The molecule of claim 117, wherein the first Fc region, the second Fc region, or a combination thereof is selected from the group consisting of an IgGl Fc region or a fragment thereof, an IgG2 Fc region or a fragment thereof, an IgG3 Fc region or a fragment thereof, an IgGAl Fc region or a fragment thereof, an IgGA2 Fc region or a fragment thereof, an IgG4 Fc region or a fragment thereof, an IgJ Fc region or a fragment thereof, an IgM Fc region or a fragment thereof, an IgD Fc region or a fragment thereof, and an IgE Fc region or a fragment thereof.

119. The molecule of claim 117 or 118, wherein the first Fc region, the second Fc region, or a combination thereof is selected from the group consisting of a human IgGl Fc region or a fragment thereof, a human IgG2 Fc region or a fragment thereof, and a human IgG4 Fc region or a fragment thereof.

120. The molecule of any one of claims 117-119, wherein the first Fc region, the second Fc region, or a combination thereof comprises an Fc interface with one or more of: a paired cavity -protuberance, an electrostatic interaction, or a strand-exchange, wherein the dimerization of the first Fc region and thesecond Fc region is enhanced as indicated by a greater ratio of heteromultimer:homomultimer forms relative to a dimerization of Fc regions with a non-engineered interface.

121. The molecule of any one of claims 117-120, wherein the first Fc region, the second Fc region, or a combination thereof comprises an amino acid substitution listed in Table 3, 4, 5, 15, or 22.

122. The molecule of any one of claims 117-121, wherein:(i) the first Fc region comprises a mutation that decreases Fc receptor binding relative to a Fc region without the mutation;(ii) the second Fc region comprise a mutation that decreases Fc receptor binding relative to a Fc region without the mutation; or(iii) a combination thereof.

123. The molecule of claim 122, wherein the mutation that decreases Fc receptor binding is an N297A mutation according to EU Numbering in a heavy chain constant region.

124. The molecule of any one of claims 117-122, wherein the first Fc region, the second Fc region, or a combination thereof comprises an Asn297Ala (N297A) mutation or a Leu234Ala / Leu235Ala (LALA) mutation according to EU Numbering.

125. The molecule of any one of claims 117-124, wherein the first Fc region and the second Fc region comprise an Fc interface with one or more of: a knob-in-a hole, an electrostatic interaction, or a strandexchange.

126. lire molecule of any one of claims 117-125, wherein the first Fc region is an engineered Fc region comprising a knob and the second Fc region is an engineered Fc region comprising a hole, or the first Fc region is an engineered Fc region comprising a hole and the second Fc region is an engineered Fc region comprising a knob.

127. The molecule of any one of claims 117-126, wherein:(A) (i) the first Fc region comprises:(a) Y349C mutation according to EU Numbering,(b) T366S mutation according to EU Numbering,(c) L368A mutation according to EU Numbering, and(d) Y407V mutation according to EU Numbering; and(ii) the second Fc region comprises:(a) S354C mutation according to EU Numbering, and(b) T366W mutation according to EU Numbering; or(B) (i) the first Fc region comprises:(a) S354C mutation according to EU Numbering, and(b) T366W mutation according to EU Numbering; and(ii) the second Fc region comprises:(a) Y349C mutation according to EU Numbering,(b) T366S mutation according to EU Numbering,(c) L368A mutation according to EU Numbering, and(d) Y407V mutation according to EU Numbering.

128. The molecule of any one of claims 117-127, wherein the first Fc region, the second Fc region, or a combination thereof comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the Fc region sequences orthe heavy chain constant region sequences listed in Tables 3, 15, or 22.

129. The molecule of any one of claims 117-128, wherein the first Fc region, the second Fc region, or a combination thereof comprises any one Fc region sequence or heavy chain constant region sequence listed in Tables 3, 15, or 22.

130. The molecule of any one of claims 117-128, wherein the first Fc region, the second Fc region, or a combination thereof comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one sequence selected from the group consisting of SEQ ID NOs: 40, 41, 42, 3645, 3646, 3647, 5038, 5108, 5109, 5110, 5111, 5041, 3649, 5044, 5045, 5113, 5048, 5049, 1483, 5039, 5040, 5042, 5043, 5050, 5051, 3648, 5046, 5047, and 5112.

131. The molecule of any one of claims 117-128 and 130, wherein the first Fc region and the second Fc region comprise:(i) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 40, 41, 42, 3645, 3646, 3647, 5038, 5108, 5109, 5110, 5111, 5041, 1483, 5039, 5040, 5042, or 5043, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 40, 41, 42, 3645, 3646, 3647, 5108, 5109, 5110, 5111, 5038, 5041, 1483, 5039, 5040, 5042, or 5043, respectively;(n) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 40, 41, 42, 3645, 3646, 3647, 5038, 5108, 5109, 5110, 5111, or 5041, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 40, 41, 42, 3645, 3646, 3647, 5038, 5108, 5109, 5110, 5111, or 5041, respectively;(iii) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 1483, 5039, 5040, 5042, or 5043, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 1483, 5039, 5040, 5042, or 5043, respectively;(iv) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 40, 41, 42, 3645, 3646, 3647, 5038, 5108, 5109, 5110, 5111, or 5041, and a sequence having at least 70%, 75%, 80%,85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 1483, 5039, 5040, 5042, or 5043, respectively;(v) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 1483, 5039, 5040, 5042, or 5043, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 40, 41, 42, 3645, 3646, 3647, 5038, 5108, 5109, 5110, 5111, or 5041, respectively;(vi) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 3649, 5044, 5045, 5113, 5050, or 5051, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 5048, 5049, 3648, 5046, 5047, or 5112, respectively;(vii) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 5048, 5049, 3648, 5046, 5047, or 5112, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 3649, 5044, 5045, 5113, 5050, or 5051, respectively;(viii) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 3649, 5044, 5045, or 5113, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 5048 or 5049, respectively;(ix) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 5048 or 5049, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 3649, 5044, 5045, or 5113, respectively;(x) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 5050 or 5051, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 3648, 5046, 5047, or 5112, respectively;(xi) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 3648, 5046, 5047, or 5112, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 5050 or 5051, respectively;(xii) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 3649, 5044, 5045, or 5113, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 3648, 5046, 5047, or 5112, respectively;(xiii) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 3648, 5046, 5047, or 5112, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 3649, 5044, 5045, or 5113, respectively;(xiv) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 5048 or 5049, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 5050 or 5051, respectively; or (xv) a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 5050 or 5051, and a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to SEQ ID NO: 5048 or 5049, respectively.

132. The molecule of any one of claims 117-130, wherein the first Fc region, the second Fc region, or a combination thereof comprises any one sequence selected from the group consisting of SEQ ID NOs: 40, 41, 42, 3645, 3646, 3647, 5038, 5108, 5109, 5110, 5111, 5041, 3649, 5044, 5045, 5113, 5048, 5049, 1483, 5039, 5040, 5042, 5043, 5050, 5051, 3648, 5046, 5047, and 5112.

133. The molecule of any one of claims 117-132, wherein the first Fc region and the second Fc region comprise:(i) any one sequence selected from the group consisting of SEQ ID NOs: 40, 41, 42, 3645, 3646, 3647, 5038, 5108, 5109, 5110, 5111, 5041, 1483, 5039, 5040, 5042, and 5043, and any one sequence selected from the group consisting of SEQ ID NOs: 40, 41, 42, 3645, 3646, 3647, 5108, 5109, 5110, 5111, 5038, 5041, 1483, 5039, 5040, 5042, and 5043, respectively;(ii) any one sequence selected from the group consisting of SEQ ID NOs: 40, 41, 42, 3645, 3646, 3647, 5038, 5108, 5109, 5110, 5111, and 5041, and any one sequence selected from the group consisting of SEQ ID NOs: 40, 41, 42, 3645, 3646, 3647, 5038, 5108, 5109, 5110, 5111, and 5041, respectively;(iii) any one sequence selected from the group consisting of SEQ ID NOs: 1483, 5039, 5040, 5042, and 5043, and any one sequence selected from the group consisting of SEQ ID NOs: 1483, 5039, 5040, 5042, and 5043, respectively;(iv) any one sequence selected from the group consisting of SEQ ID NOs: 40, 41, 42, 3645, 3646, 3647, 5038, 5108, 5109, 5110, 5111, and 5041, and any one sequence selected from the group consisting of SEQ ID NOs: 1483, 5039, 5040, 5042, and 5043, respectively;(v) any one sequence selected from the group consisting of SEQ ID NOs: 1483, 5039, 5040, 5042, and 5043, and any one sequence selected from the group consisting of SEQ ID NOs: 40, 41, 42, 3645, 3646, 3647, 5038, 5108, 5109, 5110, 5111, and 5041, respectively;(vi) any one sequence selected from the group consisting of SEQ ID NOs: 3649, 5044, 5045, 5113, 5050, and 5051, and any one sequence selected from the group consisting of SEQ ID NOs: 5048, 5049, 3648, 5046, 5047, and 5112, respectively;(vii) any one sequence selected from the group consisting of SEQ ID NOs: 5048, 5049, 3648, 5046, 5047, and 5112, and any one sequence selected from the group consisting of any one sequence selected from the group consisting of SEQ ID NOs: 3649, 5044, 5045, 5113, 5050, and 5051, respectively;(viii) any one sequence selected from the group consisting of SEQ ID NOs: 3649, 5044, 5045, and 5113, and any one sequence selected from the group consisting of SEQ ID NOs: 5048 and 5049, respectively;(ix) any one sequence selected from the group consisting of SEQ ID NOs: 5048 and 5049, and any one sequence selected from the group consisting of SEQ ID NOs: 3649, 5044, 5045, and 5113, respectively;(x) any one sequence selected from the group consisting of SEQ ID NOs: 5050 and 5051, and any one sequence selected from the group consisting of SEQ ID NOs: 3648, 5046, 5047, and 5112, respectively;(xi) any one sequence selected from the group consisting of SEQ ID NOs: 3648, 5046, 5047, and 5112, and any one sequence selected from the group consisting of SEQ ID NOs: 5050 and 5051, respectively;(xii) any one sequence selected from the group consisting of SEQ ID NOs: 3649, 5044, 5045, and 5113, and any one sequence selected from the group consisting of SEQ ID NOs: 3648, 5046, 5047, and 5112, respectively;(xiii) any one sequence selected from the group consisting of SEQ ID NOs: 3648, 5046, 5047, and 5112, and any one sequence selected from the group consisting of SEQ ID NOs: 3649, 5044, 5045, and 5113, respectively;(xiv) any one sequence selected from the group consisting of SEQ ID NOs: 5048 and 5049, and any one sequence selected from the group consisting of SEQ ID NOs: 5050 and 5051, respectively; or(xv) any one sequence selected from the group consisting of SEQ ID NOs: 5050 and 5051, and any one sequence selected from the group consisting of SEQ ID NOs: 5048 and 5049, respectively.

134. The molecule of any one of claims 1-133, wherein the TCRpV27-binding moiety further comprises a heavy chain constant domain 1 (CHI) operatively linked to the VH of the TCRpV27-binding moiety.

135. The molecule of any one of claims 1-134, wherein the TCRpV27-binding moiety further comprises a light chain constant domain (CL) or a fragment thereof operatively linked to the VL of TCRpV27-binding moiety.

136. The molecule of claim 135, wherein the light chain constant region or a fragment thereof comprises a kappa chain constant domain or a fragment thereof or a lambda chain constant domain or a fragment thereof.

137. The molecule of claim 135 or 136, wherein the light chain constant region or a fragment thereof comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity any one of the light chain constant region sequences listed in Table 3.

138. The molecule of any one of claims 135-137, wherein the light chain constant region or a fragment thereof comprises any one of the light chain constant region sequences listed in Table 3.

139. The molecule of any one of claims 135-138, wherein the light chain constant region or a fragment thereof comprise a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 39 or SEQ ID NO: 3644.

140. The molecule of any one of claims 135-139, wherein the light chain constant region or a fragment thereof comprise the sequence of SEQ ID NO: 39 or SEQ ID NO: 3644.

141. The molecule of any one of claims 34-140, wherein the multispecific molecule further comprises:(i) a linker between the first portion of the dimerization module and the TCRpV27-binding moiety or the first portion of the TCR(3V27-binding moiety;(ii) a linker between the one or more molecule that binds to a co-stimulatory receptor of a T cell and the first portion of the dimerization module, a linker between the one or more molecule that binds to a co-stimulatory receptor of a T cell and the second portion of the dimerization module, or a combination thereof;(iii) a linker between the one or more TCR binding moiety and the first portion of the dimerization module, a linker between the one or more TCR binding moiety and the second portion of the dimerization module, or a combination thereof;(iv) a linker between the one or more molecule that binds to a co-stimulatory receptor of a T cell and the TCRpV27-binding moiety, the first portion of the TCRpV27-binding moiety, or the second portion of the TCRpV27-binding moiety;(v) a linker between the one or more TCR binding moiety and the TCRpV27-binding moiety, the first portion of the TCRpV27-binding moiety, or the second portion of the TCRpV27-binding moiety;(vi) a linker between the one or more molecule that binds to a co-stimulatory receptor of a T cell and the one or more TCR binding moiety;(vii) a linker between the VH and the VL of the TCRpV27-binding moiety;(viii) a linker between the CHI and the VH of the TCRpV27-binding moiety;(ix) a linker between the CL and the VL of the TCRpV27-binding moiety; or(x) any combination thereof.

142. The molecule of claim 141, wherein the linker is selected from the group consisting of a cleavable linker, a non-cleavable linker, a peptide linker, a flexible linker, a rigid linker, a helical linker, and a nonhelical linker.

143. The molecule of claim 141 or 142, wherein the linker is selected from the group consisting of SEQ ID NOs: 3307-3310, 1474, 1475, 3801, 3309, 3308, 3643, 3437, and 3314-3317.

144. The molecule of any one of claims 1-143, wherein the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous;wherein the first polypeptide chain comprises a first Fc region, and the second polypeptide chain comprises a second Fc region;wherein the first Fc region and the second Fc region comprise an Fc interface with a knob-in-a hole;wherein:(i) the first polypeptide chain comprises the VH of the TCRPV27, wherein the VH is operatively linked to the first Fc region,(ii) the second polypeptide chain comprises one or more molecule that binds to a costimulatory receptor of a T cell, wherein the one or more molecule that binds to a costimulatory receptor of a T cell is operatively linked to the second Fc region,(iii) the third polypeptide chain comprises the VL of the TCRPV27, wherein the VL is operatively linked to a light chain constant region; andwherein:(1) the first Fc region and the second Fc region each comprises an Asn297Ala mutation according to EU Numbering; and(2) the first Fc region comprises Y349C, T366S, L368A, and Y407V mutations according to EU Numbering, and the second Fc region comprises S354C and T366W mutations according to EU Numbering, or the first Fc region comprises S354C and T366W mutations according to EU Numbering, and the second Fc region comprises mutations Y349C, T366S, L368A, and Y407V according to EU Numbering.

145. The molecule of any one of claims 1-144, wherein the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous;wherein the first polypeptide chain comprises a first Fc region, and the second polypeptide chain comprises a second Fc region;wherein the first Fc region and the second Fc region comprise an Fc interface with a knob-in-a hole;wherein:(i) the first polypeptide chain comprises the VH of the TCRPV27, wherein the VH is operatively linked to the first Fc region,(ii) the second polypeptide chain comprises one cytokine molecule or a functional fragment or functional variant thereof, wherein the one cytokine molecule or a functional fragment or functional variant thereof is operatively linked to the second Fc region,(iii) the third polypeptide chain comprises the VL of the TCRPV27, wherein the VL is operatively linked to a light chain constant region; andwherein:(1) the first Fc region and the second Fc region each comprises an Asn297Ala mutation according to EU Numbering; and(2) the first Fc region comprises Y349C, T366S, L368A, and Y407V mutations according to EU Numbering, and the second Fc region comprises S354C and T366W mutations according to EU Numbering, or the first Fc region comprises S354C and T366W mutations according to EU Numbering, and the second Fc region comprises mutations Y349C, T366S, L368A, and Y407V according to EU Numbering.

146. The molecule of any one of claims 1-145, wherein the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous;wherein the first polypeptide chain comprises a first Fc region, and the second polypeptide chain comprises a second Fc region;wherein the first Fc region and the second Fc region comprise an Fc interface with a knob-in-a hole;wherein:(i) the first polypeptide chain comprises the VH of the TCRPV27, wherein the VH is operatively linked to the first Fc region,(ii) the second polypeptide chain comprises IL-2 or a functional fragment or functional variant thereof, wherein the IL-2 or a functional fragment or functional variant thereof is operatively linked to the second Fc region,(iii) the third polypeptide chain comprises the VL of the TCRPV27, wherein the VL is operatively linked to a light chain constant region; andwherein:(1) the first Fc region and the second Fc region each comprises an Asn297Ala mutation according to EU Numbering; and(2) the first Fc region comprises Y349C, T366S, L368A, and Y407V mutations according to EU Numbering, and the second Fc region comprises S354C and T366W mutations according to EU Numbering, or the first Fc region comprises S354C and T366W mutations according to EUNumbering, and the second Fc region comprises mutations Y349C, T366S, L368A, and Y407V according to EU Numbering.

147. The molecule of any one of claims 1-146, wherein the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous;wherein the first polypeptide chain comprises a first Fc region, and the second polypeptide chain comprises a second Fc region,wherein the first Fc region and the second Fc region comprise an Fc interface with a knob-in-a hole;wherein:(i) the first polypeptide chain comprises the VH of the TCRPV27, wherein the VH is operatively linked to the first Fc region,(ii) the second polypeptide chain comprises IL-2 or a functional fragment or functional variant thereof, wherein the IL-2 comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 2270, and wherein the IL-2 or a functional fragment or functional variant thereof is operatively linked to the second Fc region,(iii) the third polypeptide chain comprises the VL of the TCRPV27, wherein the VL is operatively linked to a light chain constant region comprising a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 39 or 3644; andwherein the first Fc region comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 5044 or 3649, and the second Fc region comprises a sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 00.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 3648 or 5046, with a proviso that (1) the first Fc region and the second Fc region each comprises an Asn297Ala mutation according to EU Numbering; and (2) the first Fc region comprises Y349C, T366S, L368A, and Y407V mutations according to EU Numbering, and the second Fc region comprises S354C and T366W mutations according to EU Numbering.

148. The molecule of any one of claims 1-147, wherein the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous;wherein the first polypeptide chain comprises a first Fc region, and the second polypeptide chain comprises a second Fc region;wherein the first Fc region and the second Fc region comprise an Fc interface with a knob-in-a hole;wherein:(i) the first polypeptide chain comprises the VH of the TCRPV27, wherein the VH is operatively linked to the first Fc region,(ii) the second polypeptide chain comprises IL-2 or a functional fragment or functional variant thereof, wherein the IL-2 comprises the sequence of SEQ ID NO: 2270, and wherein the IL-2 or a functional fragment or functional variant thereof is operatively linked to the second Fc region,(iii) the third polypeptide chain comprises the VL of the TCRPV27, wherein the VL is operatively linked to a light chain constant region comprising the sequence of SEQ ID NO: 39 or 3644; andwherein the first Fc region comprises the sequence of SEQ ID NO: 5044 or 3649, and the second Fc region comprises the sequence of SEQ ID NO: SEQ ID NO: 3648 or 5046.

149. The molecule of any one of claims 1-148, wherein the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous; andwherein:(i) the first polypeptide chain comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1423 and an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 5050 or the sequence of SEQ ID NO: 5051; (ii) the second polypeptide chain comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 2270 and an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 5046 or the sequence of SEQ ID NO: 5047; and(iii) the third polypeptide chain comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1413 and an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 3644.

150. The molecule of claim 149, wherein the first polypeptide chain further comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 549.

151. The molecule of claim 149 or 150, wherein the second polypeptide chain further comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 3308.

152. The molecule of any one of claims 1-151, wherein the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non -contiguous; andwherein:(i) the first polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N- terminus, an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1423 operatively linked to an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 5050 or the sequence of SEQ ID NO: 5051;(ii) the second polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus- to N-terminus, an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 2270 operatively linked to an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 5046 or the sequence of SEQ ID NO: 5047; and (iii) the third polypeptide chain comprises, from N-terminus to C-terminus or from C-termmus-to N-terminus, an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1413 operatively linked to an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 3644.

153. The molecule of claim 152, wherein the first polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1423 operatively linked to an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 5050 or the sequence of SEQ ID NO: 5051 via an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 549.

154. The molecule of claim 152 or 153, wherein the second polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 2270 operatively linked to an amino acid sequencehaving at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 5046 or the sequence of SEQ ID NO: 5047 via an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 3308.

155. The molecule of any one of claims 1-154, wherein the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous; andwherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 1423 and the sequence of SEQ ID NO: 5050 or the sequence of SEQ ID NO: 5051;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 2270 and the sequence of SEQ ID NO: 5046 or the sequence of SEQ ID NO: 5047; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 1413 and the sequence of SEQ ID NO: 3644.

156. The molecule of claim 155, wherein the first polypeptide chain further comprises the sequence of SEQ ID NO: 549.

157. The molecule of claim 155 or 156, wherein the second polypeptide chain further comprises the sequence of SEQ ID NO: 3308.

158. The molecule of any one of claims 1-157, wherein the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous; andwherein:(i) the first polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N- terminus, the sequence of SEQ ID NO: 1423 operatively linked to the sequence of SEQ ID NO: 5050 or the sequence of SEQ ID NO: 5051;(ii) the second polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus- to N-terminus, the sequence of SEQ ID NO: 2270 operatively linked to the sequence of SEQ ID NO: 5046 or the sequence of SEQ ID NO: 5047; and(iii) the third polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, the sequence of SEQ ID NO: 1413 operatively linked to the sequence of SEQ ID NO: 3644.

159. The molecule of claim 158, wherein the first polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, the sequence of SEQ ID NO: 1423 operatively linked to the sequence of SEQ ID NO: 5050 or the sequence of SEQ ID NO: 5051 via the sequence of SEQ ID NO: 549.

160. The molecule of claim 158 or 159, wherein the second polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, the sequence of SEQ ID NO: 2270 operativelylinked to the sequence of SEQ ID NO: 5046 orthe sequence of SEQ ID NO: 5047 via the sequence of SEQ ID NO: 3308.

161. The molecule of any one of claims 1-160, wherein the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous; andwherein:(i) the first polypeptide chain comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1501 or 1502;(ii) the second polypeptide chain comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1505 or 1506; and(iii) the third polypeptide chain comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1504.

162. The molecule of any one of claims 1-161, wherein the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous; andwherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 1501 or 1502;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 1505 or 1506; and (iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 1504.

163. The molecule of any one of claims 1-148, wherein the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous; andwherein:(i) the first polypeptide chain comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1423 and an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 5046 or the sequence of SEQ ID NO: 5047; (ii) the second polypeptide chain comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 2270 and an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%,or 100% sequence identity to the sequence of SEQ ID NO: 5050 or the sequence of SEQ ID NO: 5051; and(iii) the third polypeptide chain comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1413 and an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 3644.

164. The molecule of claim 163, wherein the first polypeptide chain further comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 549.

165. The molecule of claim 163 or 164, wherein the second polypeptide chain further comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 3308.

166. The molecule of any one of claims 1-148 and 163-165, wherein the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous; andwherein:(i) the first polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1423 operatively linked to an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 5046 or the sequence of SEQ ID NO: 5047;(ii) the second polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus- to N-terminus, an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 2270 operatively linked to an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 5050 or the sequence of SEQ ID NO: 5051; and (iii) the third polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1413 operatively linked to an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 3644.

167. The molecule of claim 166, wherein the first polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, an amino acid sequence having at least 70%, 75%, 80%, 85%,90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1423 operatively linked to an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 5046 or the sequence of SEQ ID NO: 5047 via an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 549.

168. The molecule of claim 166 or 167, wherein the second polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 2270 operatively linked to an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 5050 or the sequence of SEQ ID NO: 5051 via an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 3308.

169. The molecule of any one of claims 1-148 and 163-168, wherein the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous; andwherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 1423 and the sequence of SEQ ID NO: 5046 or the sequence of SEQ ID NO: 5047;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 2270 and the sequence of SEQ ID NO: 5050 or the sequence of SEQ ID NO: 5051; and(iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 1413 and the sequence of SEQ ID NO: 3644.

170. The molecule of claim 169, wherein the first polypeptide chain further comprises the sequence of SEQ ID NO: 549.

171. The molecule of claim 169 or 170, wherein the second polypeptide chain further comprises the sequence of SEQ ID NO: 3308.

172. The molecule of any one of claims 1-148 and 163-171, wherein the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous; andwherein:(i) the first polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N- terminus, the sequence of SEQ ID NO: 1423 operatively linked to the sequence of SEQ ID NO: 5046 or the sequence of SEQ ID NO: 5047;(ii) the second polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus- to N-terminus, the sequence of SEQ ID NO: 2270 operatively linked to the sequence of SEQ ID NO: 5050 or the sequence of SEQ ID NO: 5051; and(iii) the third polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, the sequence of SEQ ID NO: 1413 operatively linked to the sequence of SEQ ID NO: 3644.

173. The molecule of claim 172, wherein the first polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, the sequence of SEQ ID NO: 1423 operatively linked to the sequence SEQ ID NO: 5046 or the sequence ofSEQ ID NO: 5047 of via the sequence ofSEQ ID NO: 549.

174. The molecule of claim 172 or 173, wherein the second polypeptide chain comprises, from N-terminus to C-terminus or from C-terminus-to N-terminus, the sequence of SEQ ID NO: 2270 operatively linked to the sequence ofSEQ ID NO: 5050 orthe sequence ofSEQ ID NO: 5051 via the sequence ofSEQ ID NO: 3308.

175. The molecule of any one of claims 1-148 and 163-174, wherein the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous; andwherein:(i) the first polypeptide chain comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence ofSEQ ID NO: 1507 or 1508;(ii) the second polypeptide chain comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 1509 or 1510; and(iii) the third polypeptide chain comprises an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence ofSEQ ID NO: 1504.

176. The molecule of any one of claims 1-148 and 163-175, wherein the molecule comprises a first polypeptide chain, a second polypeptide chain, and a third polypeptide chain;wherein the first polypeptide chain, the second polypeptide chain, and the third polypeptide chain are non-contiguous; andwherein:(i) the first polypeptide chain comprises the sequence of SEQ ID NO: 1507 or 1508;(ii) the second polypeptide chain comprises the sequence of SEQ ID NO: 1509 or 1510; and (iii) the third polypeptide chain comprises the sequence of SEQ ID NO: 1504.

177. The molecule of any one of claims 34-176, wherein the multispecific molecule is an isolated multispecific molecule.

178. A composition comprising the molecule of any one of claims 1-177.

179. The composition of claim 178, wherein the composition further comprises a second molecule that comprises a TCR binding domain,wherein the anti-TCRpV27 antibody molecule or the anti-TCRpV27 antigen binding domain of the molecule and the TCR binding domain are different, andwherein the molecule and the second molecule are not covalently linked.

180. The composition of claim 179, wherein the TCR binding domain binds to a T cell receptor alpha (TCRa) chain, a T cell receptor beta (TCR ) chain, a T cell receptor gamma (TCRy) chain, a T cell receptor delta (TCR5) chain, a CD3 gamma (CD3y) chain, a CD3 delta (CD35) chain, a CD3 epsilon (CD3E) chain, a CD3 zeta (CD3Q chain, or any combination thereof.

181. The composition of claim 179 or 180, wherein the TCR binding domain binds to a T cell receptor beta (TCR ) chain.

182. The composition of any one of claims 179-181, wherein the TCR binding domain binds to a T cell receptor beta variable (TCRPV) region.

183. The composition of any one of claims 179-182, wherein the TCR binding domain binds to a TCR V region of human TCRpVl, human TCRpV2, human TCR V3, human TCRpV4, human TCR V5, human TCR V6, human TCR V7, human TCRpV8, human TCR V9, human TCRPVIO, human TCR V11, human TCRpV12, human TCRPV19, human TCRpV20, human TCRpV21, human TCRpV23, human TCRpV24, human TCRPV25, human TCR V26, human TCR V27, human TCRpV28, human TCRpV29, or human TCRpV30.

184. The composition of any one of claims 179-182, wherein the TCR binding domain binds to a TCRPV region of human TCR V2, human TCR V4-1, human TCRPV4-2, human TCR V5-1, human TCR V5-5, human TCRPV5-6, human TCRPV6, human TCRpV6-5, human TCR[5V6-6, human TCRpV6-9, human TCR V7-2, human TCRpV7-3, human TCRpV7-8, human TCRpV7-9, human TCRpV9, human TCRpVl 0-1, human TCRpV10-2, human TCR V10-3, human TCRpVl 1-2, human TCRPV12-3, human TCR V12-4, human TCRpV12-5, human TCRPV19, human TCRpV20-l, human TCRPV21, human TCRpV24-l, human TCRPV25-1, or human TCRPV28.

185. The composition of any one of claims 179-182, wherein the TCR binding domain binds to a TCRPV region of human TCR V2, human TCRpV3-l, human TCRPV4-1, human TCRPV4-2, human TCRPV5-1, human TCR V5-4, human TCRPV5-5, human TCRPV5-6, human TCR V6-1, human TCRPV6-5, human TCRPV6-6, human TCRPV7-3, human TCRPV7-6, human TCR V7-8, human TCRPV9, human TCRPV 11-2, human TCRpV 19, human TCRpV20-l, human TCRPV24-1, human TCRPV27, human TCRPV28, human TCRpV29-l, or human TCRPV30.

186. The composition of any one of claims 179-182, wherein the TCR binding domain binds to a TCRpV region of human TCRPV5, human TCRPV6, human TCRpVIO, human TCRPV12, or human TCRPV20.

187. The composition of claim 179 or 180, wherein the TCR binding domain binds to a T cell receptor alpha (TCRa) chain.

188. The composition of any one of claims 179, 180, and 187, wherein the TCR binding domain binds to a T cell receptor alpha variable (TCRaV) region.

189. The composition of any one of claims 179, 180, 187, and 188, wherein the TCR binding domain binds to a TCRaV region of TRAV12-1, TRAV12-2, TRAV12-3, TRAV13-1, TRAV13-2, TRAV19-1, TRAV21-1, orTRAV30-l.

190. The composition of any one of claims 179-189, wherein the TCR binding domain comprises an antibody molecule or an antigen binding domain.

191. The composition of any one of claims 179-190, wherein the TCR binding domain comprises an antibody molecule or an antigen binding domain comprising a scFv, a full-length antibody, a Fab, a F(ab')2, an Fv, a single chain Fv, a camelid antibody, a half arm antibody, a diabody, a bivalent antibody, a monovalent antibody, or a bispecific antibody.

192. The composition of any one of claims 179-191, wherein the antibody molecule or the antigen binding domain comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HC CDR1) sequence comprising any one ofthe HC CDR1 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, a heavy chain complementarity determining region 2 (HC CDR2) sequence comprising any one of the HC CDR2 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, and a heavy chain complementarity determining region 3 (HC CDR3) sequence of comprising any one ofthe HC CDR3 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

193. The composition of any one of claims 179-192, wherein the antibody molecule or the antigen binding domain comprises a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LC CDR1) sequence comprising any one ofthe LC CDR1 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, a light chain complementarity determining region 2 (LC CDR2) sequence comprising any one of the LC CDR2 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, and a light chain complementarity determining region 3 (LC CDR3) sequence of comprising any one of the LC CDR3 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

194. The composition of any one of claims 179-193, wherein the antibody molecule or the antigen binding domain comprises:(i) a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HC CDR1) sequence comprising any one ofthe HC CDR1 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, a heavy chain complementarity determining region 2 (HC CDR2) sequence comprising any one of the HC CDR2 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, and a heavy chain complementarity determining region 3 (HC CDR3) sequence of comprising any one of the HC CDR3 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22; and(ii) a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LC CDR1) sequence comprising any one of the LC CDR1 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, a light chain complementarity determining region 2 (LC CDR2) sequence comprising any one of the LC CDR2 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, and alight chain complementarity determining region 3 (LC CDR3) sequence of comprising any one of the LC CDR3 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

195. The composition of any one of claims 179-194, wherein the antibody molecule or the antigen binding domain comprises a VH comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VH sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

196. The composition of any one of claims 179-195, wherein the antibody molecule or the antigen binding domain comprises a VL comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VL sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

197. The composition of any one of claims 179-196, wherein the antibody molecule or the antigen binding domain comprises a VH comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VH sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22; and a VL comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VL sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

198. The composition of any one of claims 179-197, wherein the antibody molecule or the antigen binding domain comprises a VH comprising any one of the VH sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

199. The composition of any one of claims 179-198, wherein the antibody molecule or the antigen binding domain comprises a VL comprising any one of the VL sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

200. The composition of any one of claims 179-199, wherein the antibody molecule or the antigen binding domain comprises a VH comprising any one of the VH sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22; and a VL comprising any one of the VL sequences listed Tables 1, 2, 12, 13, 14, 16, or 22.

201. A polynucleotide comprising a sequence encoding the molecule of any one of claims 1-177.

202. The polynucleotide of claim 201, wherein the polynucleotide is an isolated nucleic acid molecule.

203. A vector comprising one or more of the polynucleotides of claim 201 or 202.

204. A cell comprising the polynucleotide of claim 201 or 202 or the vector of claim 203.

205. A method of making the molecule of any one of claims 1-177 comprising culturing a host cell comprising a recombinant polynucleotide comprising a sequence encoding the molecule or a vector comprising the recombinant polynucleotide under conditions suitable for gene expression and / or homo- or heterodimerization.

206. A pharmaceutical composition comprising the molecule of any one of claims 1-177, the composition of any one of claims 178-200, the polynucleotide of claim 201 or 202, the vector of claim 203, or the cell of claim 204, and a pharmaceutically acceptable carrier, excipient, or diluent.

207. A method of treating a condition or disease in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the molecule of any one of claims 1-177, the composition of any one of claims 178-200, the polynucleotide of claim 201 or 202, the vector of claim 203, the cell of claim 204, the pharmaceutical composition of claim 206, or any combination thereof, wherein the administering is effective to treat the condition or disease in the subject.

208. Use of the molecule of any one of claims 1-177, the composition of any one of claims 178-200, the polynucleotide of claim 201 or 202, the vector of claim 203, the cell of claim 204, the pharmaceutical composition of claim 206, or any combination thereof for treating a condition or disease in a subject in need thereof comprising administering to the subject,wherein the molecule, the composition, the polynucleotide, the vector, the cell, the pharmaceutical composition, or any combination thereof is formulated in a therapeutically effective amount to treat the condition or disease in the subject.

209. The method of claim 207 or the use of claim 208, wherein the condition or disease is cancer.

210. The method or the use of claim 209, wherein the cancer is a solid tumor, a hematological cancer, a metastatic cancer, a soft tissue tumor, or any combination thereof.

211. The method or the use of claim 209 or 210, wherein the cancer is the solid tumor selected from the group consisting of melanoma, pancreatic cancer, breast cancer, colorectal cancer, lung cancer, skin cancer, ovarian cancer, liver cancer, and any combination thereof.

212. The method or the use of any one of claims 209-211, wherein the cancer is the hematological cancer selected from the group consisting of Hodgkin’s lymphoma, Non-Hodgkin’s lymphoma, acute myeloid leukemia (AML), chronic myeloid leukemia, myelodysplastic syndrome, multiple myeloma, T-cell lymphoma, acute lymphocytic leukemia, and any combination thereof.

213. The method or the use of claim 212, wherein the Non-Hodgkin’s lymphoma is selected from the group consisting of B cell lymphoma, diffuse large B cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukemia (B-CLL), mantle cell lymphoma, marginal zone B-cell lymphoma, Burkitt lymphoma, lymphoplasmacytic lymphoma, hairy cell leukemia, and any combination thereof.

214. The method or the use of claim 213, wherein the T-cell lymphoma is peripheral T-cell lymphoma.

215. The method or the use of any one of claims 209-214, wherein the cancer is characterized by a cancer antigen present on the cancer.

216. The method or the use of claim 215, wherein the cancer antigen is a tumor antigen, a stromal antigen, or a hematological antigen.

217. The method or the use of claim 215 or 216, wherein the cancer antigen is selected from the group consisting of CD19, CD123, CD22, CD30, CD171, CS-1, C-type lectin-like molecule-1, CD33, epidermal growth factor receptor variant III (EGFRvIII), ganglioside G2 (GD2), ganglioside GD3, TNF receptor family member B cell maturation (BCMA), Tn antigen ((Tn Ag) or (GalNAca-Ser / Thr)), prostate-specific membrane antigen (PSMA), Receptor tyrosine kinase-like orphan receptor 1 (ROR1), Fms-Like Tyrosine Kinase 3 (FLT3), Tumor-associated glycoprotein 72 (TAG72), CD38, CD44v6, Carcinoembryonic antigen (CEA), Epithelial cell adhesion molecule (EPCAM), B7H3 (CD276), KIT (CD117), Interleukin- 13receptor subunit alpha-2, mesothelin, Interleukin 11 receptor alpha (IL-HRa), prostate stem cell antigen (PSCA), Protease Serine 21, vascular endothelial growth factor receptor 2 (VEGFR2), Lewis(Y) antigen, CD24, Platelet-derived growth factor receptor beta (PDGFR-beta), Stage-specific embryonic antigen-4 (SSEA-4), CD20, Folate receptor alpha, Receptor tyrosine-protein kinase ERBB2 (Her2 / neu), Mucin 1, cell surface associated (MUC1), epidermal growth factor receptor (EGFR), neural cell adhesion molecule (NCAM), Prostase, prostatic acid phosphatase (PAP), elongation factor 2 mutated (ELF2M), Ephrin B2, fibroblast activation protein alpha (FAP), insulin-like growth factor 1 receptor (IGF -I receptor), carbonic anhydrase IX (CAIX), Proteasome (Prosome, Macropain) Subunit, Beta Type, 9 (LMP2), glycoprotein 100 (gpl00 / pmel!7), oncogene fusion protein consisting of breakpoint cluster region (BCR) and Abelson murine leukemia viral oncogene homolog 1 (Abl) (bcr-abl), tyrosinase, ephrin type-A receptor 2 (EphA2), Fucosyl GM1, sialyl Lewis adhesion molecule (sLe), ganglioside GM3, transglutaminase 5 (TGS5), high molecular weight-melanoma-associated antigen (HMWMAA), o-acetyl-GD2 ganglioside (OAcGD2), Folate receptor beta, tumor endothelial marker 1 (TEM1 / CD248), tumor endothelial marker 7-related (TEM7R), claudin 6 (CLDN6), thyroid stimulating hormone receptor (TSHR), G protein-coupled receptor class C group 5, member D (GPRC5D), chromosome X open reading frame 61 (CXORF61), CD97, CD179a, anaplastic lymphoma kinase (ALK), Polysialic acid, placenta-specific 1 (PLAC1), hexasaccharide portion of globoH glycoceramide (GloboH), mammary gland differentiation antigen (NY-BR-1), uroplakin 2 (UPK2), Hepatitis A virus cellular receptor 1 (HAVCR1), adrenoceptor beta 3 (ADRB3), pannexin 3 (PANX3), G protein-coupled receptor 20 (GPR20), lymphocyte antigen 6 complex, locus K 9 (LY6K), Olfactory receptor 51E2 (OR51E2), TCR Gamma Alternate Reading Frame Protein (TARP), Wilms tumor protein (WT1), Cancer / testis antigen 1 (NY-ESO-l / LAGE-1), Cancer / testis antigen 2 (LAGE- la), Melanoma-associated antigen 1 (MAGE-A1), ETS translocation-variant gene 6, located on chromosome 12p (ETV6-AML), sperm protein 17 (SPA17), X Antigen Family, Member 1A (XAGE1), angiopoietin-binding cell surface receptor 2 (Tie 2), melanoma cancer testis antigen-1 (MAD-CT-1), melanoma cancer testis antigen-2 (MAD-CT-2), Fos-related antigen 1, tumor protein p53 (p53), p53 mutant, prostein, Survivin, telomerase, prostate carcinoma tumor antigen- 1, melanoma antigen recognized by T cells 1, Rat sarcoma (Ras) mutant, human Telomerase reverse transcriptase (hTERT), sarcoma translocation breakpoints, melanoma inhibitor of apoptosis (ML-IAP), ERG (transmembrane protease, serine 2 (TMPRSS2) ETS fusion gene), N-Acetyl glucosaminyl-transferase V (NA17), paired box protein Pax-3 (PAX3), Androgen receptor, Cyclin Bl, v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN), Ras Homolog Family Member C (RhoC), Tyrosinase-related protein2 (TRP-2), Cytochrome P450 1B1 (CYP1B1), CCCTC-Binding Factor (Zinc Finger Protein) -Like, Squamous Cell Carcinoma Antigen Recognized By T Cells 3 (SART3), Paired box protein Pax-5 (PAX5), proacrosin binding protein sp32 (OY-TES1), lymphocyte -specific protein tyrosine kinase (LCK), A kinase anchor protein 4 (AKAP-4), synovial sarcoma, X breakpoint 2 (SSX2), Receptor for Advanced Glycation Endproducts (RAGE-1), renal ubiquitous 1 (RU1), renal ubiquitous 2 (RU2), legumain, human papilloma virus E6 (HPV E6), human papilloma virus E7 (HPV E7), intestinal carboxyl esterase, heat shock protein 70-2 mutated (mut hsp70-2), CD79a, CD79b, CD72, Leukocyte-associated immunoglobulin-like receptor1 (LAIR1), Fc fragment of IgA receptor (FCAR or CD89), Leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2), CD300 molecule-like family member f (CD300LF), C-type lectin domain family 12 member A (CLEC12A), bone marrow stromal cell antigen 2 (BST2), EGF-like modulecontaining mucin-like hormone receptor-like 2 (EMR2), lymphocyte antigen 75 (LY75), Glypican-3 (GPC3), Fc receptor-like 5 (FCRL5), FcRH5, PDL1, CD47, prostate specific membrane antigen (PMSA), prostate-specific antigen (PSA), Ron Kinase, c-Met, Immature laminin receptor, TAG-72, BING-4, Calcium-activated chloride channel 2, Cyclin-Bl, 9D7, Ep-CAM, EphA3, SAP-1, PRAME, SSX-2, Melan-A / MART-1, TRPl / gp75, MC1R, 0-catenm, BRCA1 / 2, CDK4, CML66, Fibronectin, Ras, TGF-B receptor, AFP, ETA, MAGE, CA-125, BAGE, GAGE, CDC27, a actinin-4, gangliosides, MART -2, MUC2, MUM1, MUM2, MUM3, NA88-1, NPM, OA1, OGT, RCC, RUH, RU12, SAGE, TRG, TSTA, Ll-CAM, gpA33, GM2, VEGFR, Integrins, carbohydrates, TRAILR1, TRAILR2, RANKL, TGF-beta, hyaluronic acid, collagen, tenascin C, tenascin W, and immunoglobulin lambda-like polypeptide 1 (IGLL1).

218. The method or the use of any one of claims 209-211 and 215-217, wherein the cancer comprises breast cancer, lung cancer, pancreatic cancer, head and neck cancer, bladder cancer, urothelial cancer, ovarian cancer, gallbladder cancer, gastric cancer, esophageal cancer, hepatocellular cancer, epithelial cancer, or any combination thereof.

219. The method or the use of any one of claims 209-211 and 215-218, wherein the cancer comprises breast cancer, pancreatic cancer, lung cancer, or any combination thereof.

220. The method or the use of any one of claims 209-211 and 215-219, wherein the cancer comprises a solid cancer selected from the group consisting of colon cancer, breast cancer, renal cancer, melanoma, prostate cancer, lung cancer, rectal cancer, colorectal cancer, cervical cancer, and any combination thereof.

221. The method of any one of claims 207, and 209-220 or the use of any one of claims 208-220, wherein the cancer comprises an anti-PDl therapy resistant cancer.

222. The method or the use of claim 221, wherein the cancer comprises an anti-PDl therapy resistant solid cancer.

223. The method of any one of claims 207, and 209-222 or the use of any one of claims 208-222, wherein the cancer comprises an HPV-positive cancer.

224. The method or the use of claim 223, wherein the cancer comprises an HPV-positive solid cancer.

225. The method of any one of claims 207, and 209-224 or the use of any one of claims 208-224, wherein the cancer comprises a cancer with a high tumor mutation burden.

226. The method of any one of claims 207, and 209-225 or the use of any one of claims 208-225, further comprising administering a second therapeutic agent or therapy to the subject.

227. The method or the use of claim 226, wherein the second therapeutic agent or therapy comprises a chemotherapeutic agent, a biologic agent, a hormonal therapy, radiation, or surgery.

228. The method or the use of claim 226, wherein the second therapeutic agent comprises a second molecule that comprises a TCR binding domain.wherein the anti-TCR V27 antibody molecule or the anti-TCRpV27 antigen binding domain of the molecule and the TCR binding domain are different, andwherein the molecule and the second molecule are not covalently linked.

229. The method or the use of claim 228, wherein the TCR binding domain binds to a T cell receptor alpha (TCRa) chain, a T cell receptor beta (TCRfl) chain, a T cell receptor gamma (TCRy) chain, a T cell receptor delta (TCR8) chain, a CD3 gamma (CD3y) chain, a CD3 delta (CD38) chain, a CD3 epsilon (CD3E) chain, a CD3 zeta (CD3Q chain, or any combination thereof.

230. The method or the use of claim 228 or 229, wherein the TCR binding domain binds to a T cell receptor beta (TCR ) chain.

231. The method or the use of any one of claims 228-230, wherein the TCR binding domain binds to a T cell receptor beta variable (TCRPV) region.

232. The method or the use of any one of claims 228-231, wherein the TCR binding domain binds to a TCRPV region of human TC V1, human TCRpV2, human TCRPV3, human TCRPV4, human TCRPV5, human TCR V6, human TCR V7, human TCRpVS, human TCRpV9, human TCRPV 10, human TCRpV 11, human TCRpV 12, human TCRpV 19, human TCRpV20, human TCRpV21, human TCRpV23, human TCRPV24, human TCRPV25, human TCRpV26, human TCR V27, human TCRPV28, human TCRPV29, or human TCRPV30.

233. The method or the use of any one of claims 228-231, wherein the TCR binding domain binds to a TCRPV region of human TCR V2, human TCR V4-1, human TCR3V4-2, human TCRPV5-1, human TCRPV5-5, human TCRPV5-6, human TCRPV6, human TCRPV6-5, human TCRpV6-6, human TCRPV6-9, human TCRPV7-2, human TCRPV7-3, human TCRPV7-8, human TCRPV7-9, human TCRPV9, human TCRpVIO-l, human TCRpV10-2, human TCRpV10-3, human TCRpVll-2, human TCRpV 12-3, human TCRpV 12-4, human TCRpV 12-5, human TCRpV 19, human TCRpV20-l, human TCRpV21, human TCRPV24-1, human TCRpV25-l, or human TCRpV28.

234. The method or the use of any one of claims 228-231, wherein the TCR binding domain binds to a TCRpV region of human TCRpV2, human TCRPV3-1, human TCRPV4-1, human TCRPV4-2, human TCRpV5-l, human TCRpV5-4, human TCRPV5-5, human TCRPV5-6, human TCRPV6-1, human TCRPV6-5, human TCRpV6-6, human TCRPV7-3, human TCRPV7-6, human TCRPV7-8, human TCRPV9, human TCRpVll-2, human TCRPV19, human TCRPV20-1, human TCRPV24-1, human TCRpV27, human TCRPV28, human TCRpV29-l, or human TCRpV30.

235. The method or the use of any one of claims 228-231, wherein the TCR binding domain binds to a TCRpV region of human TCRPV, human TCRPV6, human TCRpVIO, human TCRPV12, or human TCRPV20.

236. The method or the use of claim 228 or 229, wherein the TCR binding domain binds to a T cell receptor alpha (TCRa) chain.

237. The method or the use of any one of claims 228, 229, and 236, wherein the TCR binding domain binds to a T cell receptor alpha variable (TCRaV) region.

238. The method or the use of any one of claims 228, 229, 236, and 237, wherein the TCR binding domain binds to a TCRaV region of TRAV12-1, TRAV12-2, TRAV12-3, TRAV13-1, TRAV13-2, TRAV19-1, TRAV21-1, or TRAV30-1.

239. The method or the use of any one of claims 228-238, wherein tire TCR binding domain comprises an antibody molecule or an antigen binding domain.

240. The method or the use of any one of claims 228-239, wherein the TCR binding domain comprises an antibody molecule or an antigen binding domain comprising a scFv, a full-length antibody, a Fab, a F(ab')2, an Fv, a single chain Fv, a camelid antibody, a half arm antibody, a diabody, a bivalent antibody, a monovalent antibody, or a bispecific antibody.

241. The method or the use of any one of claims 228-240, wherein the antibody molecule or the antigen binding domain comprises a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HC CDR1) sequence comprising any one ofthe HC CDR1 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, a heavy chain complementarity determining region 2 (HC CDR2) sequence comprising any one of the HC CDR2 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, and a heavy chain complementarity determining region 3 (HC CDR3) sequence of comprising any one ofthe HC CDR3 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

242. The method or the use of any one of claims 228-241, wherein the antibody molecule or the antigen binding domain comprises a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LC CDR1) sequence comprising any one ofthe LC CDR1 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, a light chain complementarity determining region 2 (LC CDR2) sequence comprising any one of the LC CDR2 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, and a light chain complementarity determining region 3 (LC CDR3) sequence of comprising any one of the LC CDR3 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

243. The method or the use of any one of claims 228-242, wherein the antibody molecule or the antigen binding domain comprises:(i) a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HC CDR1) sequence comprising any one ofthe HC CDR1 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, a heavy chain complementarity determining region 2 (HC CDR2) sequence comprising any one of the HC CDR2 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, and a heavy chain complementarity determining region 3 (HC CDR3) sequence of comprising any one of the HC CDR3 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22; and(ii) a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LC CDR1) sequence comprising any one of the LC CDR1 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, a light chain complementarity determining region 2 (LC CDR2) sequence comprising any one of the LC CDR2 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22, and a light chain complementarity determining region 3 (LC CDR3) sequence of comprising any one of the LC CDR3 sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

244. The method or the use of any one of claims 228-243, wherein the antibody molecule or the antigen binding domain comprises a VH comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VH sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

245. The method or the use of any one of claims 228-244, wherein the antibody molecule or the antigen binding domain comprises a VL comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VL sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

246. The method or the use of any one of claims 228-245, wherein the antibody molecule or the antigen binding domain comprises a VH comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VH sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22; and a VL comprising an amino acid sequence having at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to any one of the VL sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

247. The method or the use of any one of claims 228-246, wherein the antibody molecule or the antigen binding domain comprises a VH comprising any one of the VH sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

248. The method or the use of any one of claims 228-247, wherein the antibody molecule or the antigen binding domain comprises a VL comprising any one of the VL sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

249. The method or the use of any one of claims 228-248, wherein the antibody molecule or the antigen binding domain comprises a VH comprising any one of the VH sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22; and a VL comprising any one of the VL sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

250. The method or the use of any one of claims 228-249, wherein the antibody molecule or the antigen binding domain comprises a VH comprising any one of the VH sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22; and a VL comprising any one of the VL sequences listed in Tables 1, 2, 12, 13, 14, 16, or 22.

251. The method or the use of any one of claims 226-250, wherein the second therapeutic agent or therapy is administered in combination with the molecule of any one of claims 1-177, the composition of any one of claims 178-200, the polynucleotide of claim 201 or 202, the vector of claim 203, the cell of claim 204, the pharmaceutical composition of claim 206, or any combination thereof, sequentially, simultaneously, or concurrently.

252. The method or the use of any one of claims 226-250, wherein the second therapeutic agent is not concomitantly administered to the subject with the molecule of any one of claims 1-177, the composition of any one of claims 178-200, the polynucleotide of claim 201 or 202, the vector of claim 203, the cell of claim 204, the pharmaceutical composition of claim 206, or any combination thereof.

253. The method or the use of any one of claims 226-250, wherein the administration of the molecule of any one of claims 1-177, the composition of any one of claims 178-200, the polynucleotide of claim 201or 202, the vector of claim 203, the cell of claim 204, the pharmaceutical composition of claim 206, or any combination thereof to the subject is followed by an administration of the second therapeutic agent to the subject.

254. The method or the use of any one of claims 226-250, wherein an administration of the second therapeutic agent to the subject is followed by the administration of the molecule of any one of claims 1-177, the composition of any one of claims 178-200, the polynucleotide of claim 201 or 202, the vector of claim 203, the cell of claim 204, the pharmaceutical composition of claim 206, or any combination thereof to the subject.

255. The method or the use of any one of claims 226-250, wherein the administration of the molecule of any one of claims 1-177, the composition of any one of claims 178-200, the pharmaceutical composition of claim 206, or any combination thereof to the subject is followed by an administration of the second therapeutic agent to the subject.

256. The method or the use of any one of claims 226-250, wherein an administration of the second therapeutic agent to the subject is followed by the administration of the molecule of any one of claims 1-177, the composition of any one of claims 178-200, the pharmaceutical composition of claim 206, or any combination thereof to the subject.

257. The method or the use of any one of claims 226-256, wherein the method is more effective to treat the disease or condition in the subject relative to a method in which the molecule of any one of claims 1-177, the composition of any one of claims 178-200, the polynucleotide of claim 201 or 202, the vector of claim 203, the cell of claim 204, the pharmaceutical composition of claim 206, or any combination thereof is administered to the subject but not the second therapeutic agent.