Compositions and methods for binding to covalent peptide conjugates

Abstract

Provided are compositions and methods that include binding partners that specifically bind to peptide conjugate / MHC complex, wherein the peptide conjugate / MHC complex comprises a peptide conjugate that is formed by the covalent reaction of a targeted covalent inhibitor with a peptide. The binding partners are provided as antibodies or antibody derivatives that specifically bind to the peptide conjugate / MHC complexes described herein.

Description

[0001] COMPOSITIONS AND METHODS FOR BINDING TO COVALENT PEPTIDE CONJUGATES

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims priority to and benefit of U.S. Provisional Patent Application No. 63 / 509,472, filed on June 21, 2023, and U.S. Provisional Patent Application No. 63 / 637,558, filed on April 23, 2024, each of which is entirely incorporated herein by reference.

[0004] STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

[0005] This invention was made with government support under CAO 16087 and CA267362 awarded by the National Institutes of Health. The government has certain rights in the invention.

[0006] BACKGROUND

[0007] There is an ongoing and unmet need for agents that can bind to targets that include drugs that are covalently bound to proteins or peptides. In particular, there is a need to improve the efficacy of targeted therapy and also to increase tumor immunogenicity and the efficacy of immune therapy against cancer driven by intracellular oncogenes and loss of tumor suppressor genes. The disclosure is pertinent to these needs.

[0008] BRIEF SUMMARY

[0009] The present disclosure provides compositions and methods that include binding partners that bind with specificity to target sites on proteins or peptides that comprise a covalently attached molecule. The disclosure illustrates this approach using binding partners in the form of numerous antibodies and antibody derivatives that specifically bind to proteins and peptides that have been covalently modified by attachment of a molecule, wherein the molecules are illustrated by a variety of drugs. Further, the disclosure demonstrates binding partners that bind with specificity to peptides that have been covalently modified by attachment of a small molecule drug are specific for the described covalently modified peptides when presented in the context of a human leukocyte antigen (HLA), wherein HLA is a representative example of a major histocompatibility complex (MHC). Thus, binding partners that are specific for peptide-drug conjugates in an HLA complex are demonstrated. The disclosure also provides binding partners having specificity to two different drug- peptide / MHC complexes. The disclosure includes polynucleotides encoding the described binding partners and cells that are modified to express the binding partners. The disclosure includes diagnostic, prophylactic and therapeutic approaches using the binding partners.

[0010] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain binds to (i) a first peptide conjugate / MHC complex with a dissociation constant (KD) of at most about 100 nM and (ii) a second peptide conjugate / MHC complex with a KD of at most about 100 nM, wherein the first peptide conjugate / MHC complex comprises: (a) a first peptide conjugate, wherein the first peptide conjugate of the first peptide conjugate / MHC complex is a first peptide covalently linked to a first targeted covalent inhibitor or fragment thereof; and (b) a first MHC; wherein the second peptide conjugate / MHC complex comprises: (a) a second peptide conjugate, wherein the second peptide conjugate of the second peptide conjugate / MHC complex is a second peptide covalently linked to a second targeted covalent inhibitor or fragment thereof; and (b) a second MHC; and wherein the first targeted covalent inhibitor is different from the second targeted covalent inhibitor.

[0011] In some embodiments, the antigen-binding domain binds to (i) the first peptide conjugate / MHC complex with a dissociation constant (KD) of at most about 50 nM and / or (ii) the second peptide conjugate / MHC complex with a KD of at most about 50 nM. In some embodiments, the antigen-binding domain binds to (i) the first peptide conjugate / MHC complex with a dissociation constant (KD) of at most about 10 nM and / or (ii) the second peptide conjugate / MHC complex with a KD of at most about 10 nM. In some embodiments, the antigen-binding domain binds to (i) the first peptide conjugate / MHC complex with a dissociation constant (KD) of at most about 5 nM and / or (ii) the second peptide conjugate / MHC complex with a KD of at most about 5 nM.

[0012] In some embodiments, the first targeted covalent inhibitor is a covalent inhibitor of a RAS protein and the second targeted covalent inhibitor is a covalent inhibitor of a RAS protein. In some embodiments, the first targeted covalent inhibitor is a covalent inhibitor of KRASG12Cand the second targeted covalent inhibitor is a covalent inhibitor of KRASG12C. In some embodiments, (i) the first targeted covalent inhibitor is adagrasib and the second targeted covalent inhibitor is sotorasib, (ii) the first targeted covalent inhibitor is adagrasib and the second targeted covalent inhibitor is divarasib; or (iii) the first targeted covalent inhibitor is divarasib and the second targeted covalent inhibitor is sotorasib.

[0013] In some embodiments, the antigen-binding domain (i) does not bind to a free first targeted covalent inhibitor that is not conjugated to a peptide with a dissociation constant (KD) of less than 200 nM, (ii) does not bind to the first peptide with a KD of less than 200 nM, (iii) does not bind to a free first peptide conjugate that is not complexed with an MHC with a KD of less than 200 nM, or (iv) any combination above.

[0014] In some embodiments, the antigen-binding domain binds to the first peptide conjugate / MHC complex with a greater affinity than to the first peptide, the free first targeted covalent inhibitor, and / or the free first peptide conjugate. In some embodiments, the affinity of the antigen-binding domain for the first peptide conjugate / MHC complex is 100-10,000 times greater than the affinity of the antigen-binding domain for the first peptide or the free first targeted covalent inhibitor. In some embodiments, the antigen-binding domain does not detectably bind to a complex of the first peptide with the first MHC, wherein the first peptide is not covalently bound to the first targeted covalent inhibitor or fragment thereof. In some embodiments, the antigen-binding domain does not detectably bind to the free first targeted covalent inhibitor. In some embodiments, the antigen-binding domain binds to a free first peptide conjugate with a dissociation constant (KD) that is at least 2.5 times more than a KD of the antibody or the antigen-binding fragment to the first peptide conjugate / MHC complex.

[0015] In some embodiments, the antigen-binding domain (i) does not bind to a free second targeted covalent inhibitor that is not conjugated to a peptide with a dissociation constant (KD) of less than 200 nM, (ii) does not bind to the second peptide with a KD of less than 200 nM, (iii) does not bind to a free second peptide conjugate that is not complexed with an MHC with a KD of less than 200 nM, or (iv) any combination above.

[0016] In some embodiments, the antigen-binding domain binds to the second peptide conjugate / MHC complex with a greater affinity than to the second peptide, the free second targeted covalent inhibitor, and / or the free second peptide conjugate.

[0017] In some embodiments, the affinity of the antigen-binding domain for the second peptide conjugate / MHC complex is 100-10,000 times greater than the affinity of the antigenbinding domain for the second peptide or the free second targeted covalent inhibitor. In some embodiments, the antigen-binding domain does not detectably bind to a complex of the second peptide with the second MHC, wherein the second peptide is not covalently bound to the second targeted covalent inhibitor or fragment thereof. In some embodiments, the antigen-binding domain does not detectably bind to the free second targeted covalent inhibitor. In some embodiments, the antigen-binding domain binds to a free second peptide conjugate with a dissociation constant KD that is at least 2.5 times more than a KD of the antibody or the antigen-binding fragment to the second peptide conjugate / MHC complex.

[0018] In some embodiments, the first peptide and the second peptide comprise the same amino acid sequence. In some embodiments, the first peptide and the second peptide consist of the same amino acid sequence. In some embodiments, the first peptide or the second peptide comprises the amino acid sequence of VVVGACGVGK. In some embodiments, the first peptide and second peptide comprise a different amino acid sequence. In some embodiments, the first peptide and the second peptide comprise a shared contiguous amino acid sequence that is at least 3, 4, 5, 6, 7, 8, or 9 amino acids in length. In some embodiments, the first peptide and / or the second peptide comprises an amino acid sequence of VVVGACGVGK, VVGACGVGK, or KLVVVGACGV. In some embodiments, the first MHC or the second MHC is encoded by an HLA, wherein the HLA is HLA-A*02:01, HLA- A*03:01, or HLA-A* 11:01.

[0019] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain binds to a peptide conjugate / MHC complex, wherein the peptide conjugate of the peptide conjugate / MHC complex is a peptide covalently linked to a targeted covalent inhibitor or fragment thereof and a MHC; and wherein the antigen-binding domain binds to the peptide conjugate / MHC complex with a dissociation constant (KD) of at most about 50 nM; wherein the targeted covalent inhibitor is adagrasib.

[0020] In some embodiments, the peptide conjugate / MHC complex is a first peptide conjugate / MHC complex comprising a first peptide conjugate comprising a first peptide and a first targeted covalent inhibitor or fragment thereof; and wherein the antigen-binding domain further binds to a second peptide conjugate / MHC complex comprising (a) a second peptide conjugate, wherein the second peptide conjugate of the second peptide conjugate / MHC complex is a second peptide covalently linked to a second targeted covalent inhibitor or fragment thereof; and (b) a second MHC.

[0021] In some embodiments, the antigen-binding domain binds to the second peptide conjugate / MHC complex with a KD of at most about 50 nM. In some embodiments, the antigen-binding domain binds to (i) the first peptide conjugate / MHC complex with a dissociation constant (KD) of at most about 10 nM and (ii) the second peptide conjugate / MHC complex with a KD of at most about 10 nM. In some embodiments, the antigen-binding domain binds to (i) the first peptide conjugate / MHC complex with a dissociation constant (KD) of at most about 5 nM and (ii) the second peptide conjugate / MHC complex with a KD of at most about 5 nM.

[0022] In some embodiments, the second targeted covalent inhibitor is sotorasib or divarasib. In some embodiments, the antigen-binding domain does not bind to a free first targeted covalent inhibitor with a dissociation constant (KD) of less than 200 nM. In some embodiments, the antigen-binding domain binds to the first peptide conjugate / MHC complex with a greater affinity than to the first peptide or the free first targeted covalent inhibitor. In some embodiments, the affinity of the antigen-binding domain for the first peptide conjugate / MHC complex is 100-10,000 times greater than the affinity of the antigen-binding domain for the first peptide or the free first targeted covalent inhibitor.

[0023] In some embodiments, the antigen-binding domain does not detectably bind to a complex of the first peptide with a first MHC, wherein the first peptide is not covalently bound to the first targeted covalent inhibitor or fragment thereof. In some embodiments, the antigen-binding domain does not detectably bind to the free first targeted covalent inhibitor. In some embodiments, the antigen-binding domain binds to a free first peptide conjugate with a dissociation constant KD) that is at least 2.5 times more than a Ko of the antibody or the antigen-binding fragment to the first peptide conjugate / MHC complex.

[0024] In some embodiments, the antigen-binding domain does not bind to a free second targeted covalent inhibitor with a dissociation constant (KD) of less than 200 nM. In some embodiments, the antigen-binding domain binds to the second peptide conjugate / MHC complex with a greater affinity than to the second peptide or the free second targeted covalent inhibitor. In some embodiments, the affinity of the antigen-binding domain for the second peptide conjugate / MHC complex is 100-10,000 times greater than the affinity of the antigenbinding domain for the second peptide or the free second targeted covalent inhibitor.

[0025] In some embodiments, the antigen-binding domain does not detectably bind to a complex of the second peptide with the second MHC, wherein the second peptide is not covalently bound to the second targeted covalent inhibitor or fragment thereof. In some embodiments, the antigen-binding domain does not detectably bind to the free second targeted covalent inhibitor. In some embodiments, the antigen-binding domain binds to a free second peptide conjugate with a dissociation constant KD) that is at least 2.5 times more than a Ko of the antibody or the antigen-binding fragment to the second peptide conjugate / MHC complex.

[0026] In some embodiments, the first peptide and the second peptide comprise the same amino acid sequence. In some embodiments, the first peptide and the second peptide consist of the same amino acid sequence. In some embodiments, the first peptide or the second peptide comprises the amino acid sequence of VVVGACGVGK. In some embodiments, the first peptide and second peptide comprise a different amino acid sequence. In some embodiments, the first peptide or the second peptide comprises an amino acid sequence of VVVGACGVGK, VVGACGVGK, or KLVVVGACGV. In some embodiments, the MHC or the second MHC is an HL A, and wherein the HL A is HLA-A*02:01, HLA-A*03:01, or HLA-A* 11 :01.

[0027] In some embodiments, the first peptide or the second peptide comprises a nucleophilic or an electrophilic residue, wherein the residue comprises cysteine, aspartic acid, arginine, serine, or tyrosine. In some embodiments, the first peptide or the second peptide comprises a cysteine residue. In some embodiments, the first peptide conjugate is formed by a covalent reaction between the first targeted covalent inhibitor and a cysteine residue in the first peptide. In some embodiments, the second peptide conjugate is formed by a covalent reaction between the second targeted covalent inhibitor and a cysteine residue in the second peptide.

[0028] In some embodiments, the first peptide or the second peptide is a segment of a protein that is associated with a cancer, optionally wherein the protein is encoded by a gene that is mutated in a cancer. In some embodiments, the first peptide or the second peptide is a segment of an enzyme, and wherein the first targeted covalent inhibitor or second targeted covalent inhibitor is an inhibitor of the enzyme. In some embodiments, the enzyme is a kinase or GTPase.

[0029] In some embodiments, the first peptide or the second peptide is or is derived from KRAS. In some embodiments, the first peptide or the second peptide comprises a segment of KRASG12C, KRASG12D, or KRASG12R. In some embodiments, the first targeted covalent inhibitor or the second targeted covalent inhibitor is (i) a tri-complex KRASG12Cinhibitor or a KRASG12Cdegrader, (ii) a tri-complex KRASG12Dinhibitor or a KRASG12Ddegrader, or (iii) a tri-complex KRASG12Rinhibitor or a KRASG12Rdegrader.

[0030] In some embodiments, the first peptide conjugate or the second peptide conjugate comprises a compound selected from the group consisting of compounds (1), (2), and (3):

[0031] wherein the compound is covalently bonded to a cysteine residue in a peptide, wherein the peptide comprises an amino acid sequence of VVVGACGVGK, VVGACGVGK, or KLVVVGACGV. In some embodiments, the peptide comprises the amino acid sequence of VVVGACGVGK or VVGACGVGK and the MHC is HLA-A*03 :01 or HLA-A* 11 :01. In some embodiments, the peptide comprises the amino acid sequence of KLVVVGACGV and the MHC is HLA-A*02:01. In some embodiments, the first peptide conjugate is formed by the covalent reaction of adagrasib with a KRASG12Cpeptide. In some embodiments, the second peptide conjugate is formed by the covalent reaction of sotorasib with a KRASG12Cpeptide. In some embodiments, the second peptide conjugate is formed by the covalent reaction of divarasib with a KRASG12Cpeptide.

[0032] In some embodiments, the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein (a) the VH comprises: (i) a HC CDR1 comprising an amino acid sequence of X1SX3X4SIH, wherein Xi is I, F or V, X3 is S or Y, and XHs S or Y; (ii) a HC CDR2 comprising an amino acid sequence of X1ISX4X5X6X7X8TX10YADSVKG, wherein Xi is S or Y, X4is S or P, X5is S or Y, X6is S or Y, X7 is S or G, Xs is S or Y, and X10 is S or Y, and (iii) a HC CDR3 comprising an amino acid sequence of XNX1X2DY, wherein XN IS an amino acid sequence selected from LWAS, FQWY, GYGW, GWYYL, YWYYM, YWYYL, GYYYPYY, SYYGFWQALW, SSRQYYHSQVEPPM, SGYYSSHWYLQSWYQ, and HYSEKWWGWYTMYID, Xi is G or A, and X2 is L or M; and / or (b) the VL comprises: (i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;

[0033] (ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and (iii) a LC CDR3 comprising the amino acid sequence of QQX3X4X5X6X7X8X9X10T, wherein X3 is W, T, S, A or G, X4is N, W, S, G, Y, D or K, X5is W, Y, S, A or T, X6is G, S, Y, L, W, E or D, X7 is W, S, H, Y, E, F or absent, Xs is P, Q, S, W, E, L, G or absent, X9 is L or P, and X10 is I, L, F, or V.

[0034] In some embodiments, the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises: (i) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (ii) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or

[0035] (iii) a HC CDR3 comprising an amino acid sequence of LWASGLDY; and / or the VL comprises: (i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2is N, W, S, or D, X3is W, S, or Y, X4is G, L, S, E or Y, Xs is W S, Y, E, or F, Xe is P, W, G, E, or Q, and X7 is I, F, or V.

[0036] In some embodiments, the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein (a) the VH comprises: (i) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (ii) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (iii) a HC CDR3 comprising an amino acid sequence of SYYGFWQALWALDY; and / or (b) the VL comprises: (i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V. In some embodiments, the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein (a) the VH comprises: (i) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (ii) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (iii) a HC CDR3 comprising an amino acid sequence of GYYYPYYAMDY; and / or (b) the VL comprises: (i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4YPX5T, wherein Xi is W or S, X2 is K, W, or S, X3 is W, T, or A, X4is S, W, or Y, and X5is I, L, or V.

[0037] In some embodiments, the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein (a) the VH comprises: (i) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (ii) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (iii) a HC CDR3 comprising an amino acid sequence of GYYYPYYAMDY; and / or (b) the VL comprises: (i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2is N, W, S, or D, X3is W, S, or Y, X4is G, L, S, E or Y, Xs is W S, Y, E, or F, Xe is P, W, G, E, or Q, and X7 is I, F, or V.

[0038] In some embodiments, the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein (a) the VH comprises: (i) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (ii) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (iii) a HC CDR3 comprising an amino acid sequence of X1X2X3X4X5MDY, wherein Xi is F or G, X2 is Q or Y, X3 is W or G, X4is Y or W, and X5 is A or G; and / or (b) the VL comprises: (i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2is N, W, S, or D, X3is W, S, or Y, X4is G, L, S, E or Y, Xs is W S, Y, E, or F, Xe is P, W, G, E, or Q, and X7 is I, F, or V.

[0039] In some embodiments, the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein (a) the VH comprises: (i) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (ii) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (iii) a HC CDR3 comprising an amino acid sequence of SGYYSSHWYLQSWYQAMDY; and / or (b) the VL comprises: (i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4YPX5T, wherein Xi is W or S, X2 is K, W, or S, X3 is W, T, or A, X4is S, W, or Y, and X5 is I, L, or V.

[0040] In some embodiments, the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein (a) the VH comprises: (i) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (ii) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (iii) a HC CDR3 comprising an amino acid sequence of SGYYSSHWYLQSWYQAMDY; and / or (b) the VL comprises: (i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (iii) a LC CDR3 comprising the amino acid sequence of QQXIX2X3X4X5X6T, wherein Xi is G or A, X2 is S or Y, X3 is S or Y, X4is G, D, or S, X5is P or L, and Xe is I or L.

[0041] In some embodiments, the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein (a) the VH comprises: (i) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (ii) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (iii) a HC CDR3 comprising an amino acid sequence of HYSEKWWGWYTMYIDAMDY; and / or (b) the VL comprises: (i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

[0042] In some embodiments, the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein (a) the VH comprises: (i) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (ii) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (iii) a HC CDR3 comprising an amino acid sequence of Xi WYYX2GMD Y, wherein Xi is G or Y and X2 is M or L; and / or (b) the VL comprises: (i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;

[0043] (ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (iii) a LC CDR3 comprising the amino acid comprising the amino acid sequence of QQX1X2X3X4YPX5T, wherein Xi is W or S, X2 is K, W, or S, X3is W, T, or A, X4is S, W, or Y, and X5is I, L, or V.

[0044] In some embodiments, the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein (a) the VH comprises: (i) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (ii) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or

[0045] (iii) a HC CDR3 comprising an amino acid sequence of Xi WYYX2GMD Y, wherein Xi is G or Y and X2 is M or L; and / or (b) the VL comprises: (i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;

[0046] (ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6T, wherein Xi is G or A, X2 is S or Y, X3 is S or Y, X4is G, D, or S, X5 is P or L, and Xe is I or L.

[0047] In some embodiments, the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein (a) the VH comprises: (i) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (ii) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or

[0048] (iii) a HC CDR3 comprising an amino acid sequence of Xi WYYX2GMD Y, wherein Xi is G or Y and X2 is M or L; and / or (b) the VL comprises: (i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;

[0049] (ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

[0050] In some embodiments, the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein (a) the VH comprises: (i) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (ii) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or

[0051] (iii) a HC CDR3 comprising an amino acid sequence of SSRQYYHSQVEPPMAMDY; and / or (b) the VL comprises: (i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (iii) a LC CDR3 comprising the amino acid comprising the amino acid sequence of QQX1X2X3X4YPX5T, wherein Xi is W or S, X2 is K, W, or S, X3 is W, T, or A, X4is S, W, or Y, and X5is I, L, or V.

[0052] In some embodiments, the antigen-binding domain comprises the HC CDR1, HC CDR2, and HC CDR3 amino acid sequences of a VH amino acid sequence and / or the LC CDR1, LC CDR2, and LC CDR3 amino acid sequences of a VL amino acid sequence of a polypeptide selected from the group consisting of RM_001, RM_002, RM_003, RM_004, RM_005, RM_006, RM_007, RM_008, RM_009, RM_010, RM_011, RM_012, RM_013, RM_014, RM_015, RM_016, RM_017, RM_018, RM_019, RM_020, RM_021, RM_022, , RM 023, RM_024, RM_025, RM_026, RM_027, RM_028 , RM_029, RM_030, RM_031, and RM 032; or a variant thereof comprising 1-5 amino acid changes in one or more of the CDR amino acid sequences.

[0053] In some embodiments, the antigen-binding domain comprises the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 amino acid sequences of a polypeptide selected from the group consisting of RM_001, RM_002, RM_003, RM_004, RM_005, RM_006, RM_007, RM_008, RM_009, RM_010, RM_011, RM_012, RM_013, RM_014, RM_015, RM_016, RM_017, RM_018, RM_019, RM_020, RM_021, RM_022, , RM 023, RM_024, RM_025, RM_026, RM_027, RM_028 , RM_029, RM_030, RM_031, and RM 032, or a variant thereof comprising 1-5 amino acid changes in one or more of the CDR amino acid sequences.

[0054] In some embodiments, the antigen-binding domain comprises a VH and / or a VL amino acid sequence that is 90%, 95%, or 100% identical to the following VH and VL sequences:

[0055] RM_001

[0056] VL :DIQMTQ SP S SLS AS VGDRVTITCRASQ S VS S AV AW YQQKPGKAPKLLI YS AS SL YSGVPSRFSGSRSGTDFTL

[0057] TISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTV

[0058] VH:EVQLVESGGGL VQPGGSLRLSC AASGFTIS S S SIHWVRQAPGKGLEWVASIS S Y YGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARLWASGLDYWG QGTLVTVSS

[0059] RM_002

[0060] VL :DIQMTQ SP S SLS AS VGDRVTITCRASQ S VS S AV AW YQQKPGKAPKLLI YS AS SL YSGVPSRFSGSRSGTDFTL

[0061] TISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTV

[0062] VH:EVQLVESGGGL VQPGGSLRLSC AASGFTF S S S SIHWVRQAPGKGLEWVASIS SY YGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARLWASGLDYWG QGTLVTVSS

[0063] RM_003

[0064] VL :DIQMTQ SP S SLS AS VGDRVTITCRASQ S VS S AV AW YQQKPGKAPKLLI YS AS SL YSGVPSRFSGSRSGTDFTL

[0065] TISSLQPEDFATYYCQQWWYGSPLFTFGQGTKVEIKRTV

[0066] VH:EVQLVESGGGL VQPGGSLRLSC AASGFTF S S S SIHWVRQAPGKGLEWVASIS S S SGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSYYGFWQALW ALD YWGQGTL VT VS S

[0067] RM_004

[0068] VL :DIQMTQ SP S SLS AS VGDRVTITCRASQ S VS S AV AW YQQKPGKAPKLLI YS AS SL YSGVPSRFSGSRSGTDFTL

[0069] TISSLQPEDFATYYCQQWWYGSPLFTFGQGTKVEIKRTV

[0070] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVASISSS SGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSYYGFWQALW ALD YWGQGTL VT VS S

[0071] RM_005

[0072] VL :DIQMTQ SP S SLS AS VGDRVTITCRASQ S VS S AV AW YQQKPGKAPKLLI YS AS SL YSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISS YYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAM D YWGQGTL VTVSS

[0073] RM_006 VL :DIQMTQ SP S SLS AS VGDRVTITCRASQ S VS S AV AW YQQKPGKAPKLLI YS AS SL YSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISP YYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAM DYWGQGTLVTVSS

[0074] RM_007

[0075] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQTSWYHSLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSY

[0076] YGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDY WGQGTLVTVSS

[0077] RM_008

[0078] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV

[0079] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVASISSY YGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDY WGQGTLVTVSS

[0080] RM_009

[0081] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSY

[0082] YGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDY WGQGTLVTVSS

[0083] RM_010

[0084] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSSWLYWLVTFGQGTKVEIKRTV VH:EVQLVESGGGL VQPGGSLRLSC AASGFTF S S S SIHWVRQAPGKGLEWVASIS S SS GSTSYADSVKGRFTISAD

[0085] TSKNTAYLQMNSLRAEDTAVYYCARFQWYAMDYWGQGTLVTVSS

[0086] RM_011

[0087] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTISSYSIHWVRQAPGKGLEWVAYISSYS GYTSYADSVKGRFTISAD

[0088] TSKNTAYLQMNSLRAEDTAVYYCARGYGWGMDYWGQGTLVTVSS

[0089] RM_012

[0090] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTV

[0091] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTISYSSIHWVRQAPGKGLEWVAYISSSS GYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSGYYSSHWYLQS W YQ AMD YWGQGTL VT VS S RM_013

[0092] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQASYGPITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSY

[0093] YGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSGYYSSHWYLQS W YQ AMD YWGQGTL VT VS S

[0094] RM_014

[0095] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQWWSSSQLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYSSIHWVRQAPGKGLEWVASISSY

[0096] YGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARHYSEKWWGWY TMYID AMD YWGQGTL VT VS S

[0097] RM_015

[0098] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY

[0099] SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV

[0100] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPY

[0101] SGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYW

[0102] GQGTLVTVSS

[0103] RM_016

[0104] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY

[0105] SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV

[0106] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYS

[0107] SYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWG

[0108] QGTLVTVSS

[0109] RM_017

[0110] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY

[0111] SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV

[0112] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPY

[0113] SGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYW

[0114] GQGTLVTVSS

[0115] RM_018

[0116] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY

[0117] SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV

[0118] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVAYISPY

[0119] SGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYW GQGTLVTVSS

[0120] RM_019

[0121] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY

[0122] SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVASISPYS

[0123] SYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWG QGTLVTVSS

[0124] RM_020

[0125] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY

[0126] SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTV

[0127] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPY

[0128] SGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYW

[0129] GQGTLVTVSS

[0130] RM_021

[0131] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY

[0132] SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV

[0133] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYS

[0134] SYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWG

[0135] QGTLVTVSS

[0136] RM_022

[0137] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY

[0138] SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTV

[0139] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYS

[0140] SYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWG

[0141] QGTLVTVSS

[0142] RM_023

[0143] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY

[0144] SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSSYYEELITFGQGTKVEIKRTV

[0145] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYS

[0146] SYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWG

[0147] QGTLVTVSS

[0148] RM_024

[0149] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY

[0150] SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQAYSDPLTFGQGTKVEIKRTV

[0151] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYS

[0152] SYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWG

[0153] QGTLVTVSS

[0154] RM 025

[0155] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY

[0156] SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGSSSLLTFGQGTKVEIKRTV

[0157] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYS

[0158] SYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWG

[0159] QGTLVTVSS

[0160] RM_026 VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSGSYLLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYS SYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWG QGTLVTVSS

[0161] RM_027

[0162] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQADYEFGLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYS SYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWG QGTLVTVSS

[0163] RM_028

[0164] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVAYISSSY GYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPP MAMD YWGQGTL VT VS S

[0165] RM_029

[0166] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVAYISSS YGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEP PMAMD YWGQGTL VT VS S

[0167] RM_030

[0168] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSSSIHWVRQAPGKGLEWVAYISSSY GYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPP MAMD YWGQGTL VT VS S

[0169] RM_031

[0170] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSC AASGFT VS YS SIHWVRQAPGKGLEWVAYIS S S YGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEP PMAMD YWGQGTL VT VS S

[0171] RM_032

[0172] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGSSSLLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVAYISPY SGYTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYLGMDYW GQGTLVTVSS In some embodiments, the polypeptide specifically binds to the first peptide conjugate / MHC complex and a T cell antigen. In some embodiments, the polypeptide specifically binds to the first peptide conjugate / MHC complex and human CD3. In some embodiments, the polypeptide specifically binds to the second peptide conjugate / MHC complex and a T cell antigen. In some embodiments, the polypeptide specifically binds to the second peptide conjugate / MHC complex and human CD3. In some embodiments, the polypeptide comprises a heavy chain constant region selected from the group consisting of human IgM, IgGi, IgG2, IgGs, IgG4, IgAi, and IgA. In some embodiments, the heavy chain constant region comprises one or more amino acid substitutions, deletions, or additions in the Fc region. In some embodiments, the polypeptide is conjugated to a detectable label, a chemotherapeutic agent, a radioisotope, or a toxin.

[0173] In some embodiments, the polypeptide is comprised within a chimeric antigen receptor. In some embodiments, the polypeptide is expressed by a T cell, a killer macrophage, a neutrophil or a natural killer cell.

[0174] In an aspect, the present disclosure provides a polynucleotide encoding the polypeptide described herein.

[0175] In an aspect, the present disclosure provides a polynucleotide encoding a heavy chain variable region and / or a light chain variable region of the polypeptide described herein. In some embodiments, the polynucleotide is a modified polynucleotide.

[0176] In an aspect, the present disclosure provides a vector comprising the polynucleotide described herein. In some embodiments, the vector is a viral vector. In some embodiments, the viral vector is an adenoviral vector, lentiviral vector, retroviral vector, or adeno- associated viral vector.

[0177] In an aspect, the present disclosure provides a recombinant host cell comprising: (a) the polynucleotide described herein; (b) the vector described herein; (c) a first polynucleotide encoding a VH or a heavy chain of the polypeptide described herein, and a second polynucleotide encoding a VL or a light chain of the polypeptide described herein; or (d) a first vector comprising a first polynucleotide encoding a VH or a heavy chain of the polypeptide described herein, and a second vector comprising a second polynucleotide encoding a VL or a light chain of the polypeptide described herein.

[0178] In an aspect, the present disclosure provides a pharmaceutical composition comprising the polypeptide described herein, the polynucleotide described herein, the vector described herein, or the host cell described herein and a pharmaceutically acceptable carrier or excipient. In an aspect, the present disclosure provides a method of producing a polypeptide, the method comprising culturing the host cell described herein under suitable conditions so that the polynucleotide is expressed and the binding partner is produced.

[0179] In an aspect, the present disclosure provides an eukaryotic cell comprising the polynucleotide described herein or the vector described herein, wherein the cell is optionally a totipotent, multipotent, or pluripotent stem cell, wherein optionally the stem cell has an induced stem cell phenotype, or wherein the cell is optionally a leukocyte, optionally a CD4+ T cell, optionally a CD8+ T cell, optionally a y5 T cell, optionally a natural killer cell , a neutrophil or a macrophage.

[0180] In an aspect, the present disclosure provides a method comprising administering to an individual in need thereof the polypeptide described herein, the polynucleotide described herein, the vector described herein, the pharmaceutical composition described herein, or the cell described herein.

[0181] In an aspect, the present disclosure provides a cell free peptide conjugate / MHC complex comprising: (a) an isolated peptide conjugate formed by the covalent reaction of a targeted covalent inhibitor with a peptide; and (b) an MHC, wherein the targeted covalent inhibitor is sotorasib, adagrasib, or divarasib, wherein the MHC is an HLA, and wherein the HL A i s HL A- A* 02 : 01 , HL A- A* 03 : 01 , or HL A- A* 11 :01.

[0182] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein (a) the VH comprises: (i) a HC CDR3 comprising an amino acid sequence of XNX1X2DY, wherein X\ is an amino acid sequence selected from LWAS, FQWY, GYGW, GWYYL, YWYYM, YWYYL, GYYYPYY, SYYGFWQALW, SSRQYYHSQVEPPM, SGYYSSHWYLQSWYQ, and HYSEKWWGWYTMYID, Xi is G or A, and X2 is L or M; and / or (b) the VL comprises: (i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and (iii) a LC CDR3 comprising the amino acid sequence of QQX3X4X5X6X7X8X9X10T, wherein X3 is W, T, S, A or G, X4is N, W, S, G, Y, D or K, X5is W, Y, S, A or T, X6is G, S, Y, L, W, E or D, X7 is W, S, H, Y, E, F or absent, X8is P, Q, S, W, E, L, G or absent, X9 is L or P, and X10 is I, L, F, or V. In some embodiments, the VH comprises a HC CDR1 comprising an amino acid sequence of X1SX3X4SIH, wherein Xi is I, F or V, X3 is S or Y, and X4 is S or Y. In some embodiments, the VH comprises a HC CDR2 comprising an amino acid sequence of X1ISX4X5X6X7X8TX10YADSVKG, wherein Xi is S or Y, X4 is S or P, X5 is S or Y, Xe is S or Y, X7 is S or G, Xs is S or Y, and X10 is S or Y.

[0183] In some embodiments, the VL comprises a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VL comprises a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes.

[0184] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein (a) the VH comprises: (i) a HC CDR1 comprising an amino acid sequence of X1SX3X4SIH, wherein Xi is I, F or V, X3 is S or Y, and X4 is S or Y; (ii) a HC CDR2 comprising an amino acid sequence of X1ISX4X5X6X7X8TX10YADSVKG, wherein Xi is S or Y, X4is S or P, X5is S or Y, Xe is S or Y, X7 is S or G, Xs is S or Y, and X10 is S or Y, and (iii) a HC CDR3 comprising an amino acid sequence of XNX1X2DY, wherein XN IS an amino acid sequence selected from LWAS, FQWY, GYGW, GWYYL, YWYYM, YWYYL, GYYYPYY, SYYGFWQALW, SSRQYYHSQVEPPM, SGYYSSHWYLQSWYQ, and HYSEKWWGWYTMYID, Xi is G or A, and X2 is L or M; and / or (b) the VL comprises: (i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and (iii) a LC CDR3 comprising the amino acid sequence of QQX3X4X5X6X7X8X9X10T, wherein X3 is W, T, S, A or G, X4is N, W, S, G, Y, D or K, X5is W, Y, S, A or T, X6is G, S, Y, L, W, E or D, X7 is W, S, H, Y, E, F or absent, Xs is P, Q, S, W, E, L, G or absent, X9 is L or P, andXio is I, L, F, or V.

[0185] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of LWASGLDY (SEQ ID NO: 5).

[0186] In some embodiments, the VH comprises a HC CDR2 sequence of SISSYYGSTSYADSVKG (SEQ ID NO: 4). In some embodiments, the VH comprises a HC CDR1 sequence of ISSSSIH (SEQ ID NO: 3). In some embodiments, the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQWNWGWPLIT (SEQ ID NO: 8). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 7). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 6). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of ISSSSIH (SEQ ID NO: 3), a HC CDR2 sequence of SISSYYGSTSYADSVKG (SEQ ID NO: 4), a HC CDR3 sequence of LWASGLDY (SEQ ID NO: 5), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 6), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 7), and a LC CDR3 sequence of QQWNWGWPLIT (SEQ ID NO: 8). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence

[0187] EVQLVESGGGL VQPGGSLRLSC AASGFTIS S S SMWVRQAPGKGLEWVASIS S YYGST SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARLWASGLDYWGQGTLV TVSS (SEQ ID NO: 2). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTV (SEQ ID NO: 1).

[0188] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of LWASGLDY (SEQ ID NO: 13).

[0189] In some embodiments, the VH comprises a HC CDR2 sequence of SISSYYGSTSYADSVKG (SEQ ID NO: 12). In some embodiments, the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 11). In some embodiments, the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQWNWGWPLIT (SEQ ID NO: 16). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 15). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 14). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 11), a HC CDR2 sequence of SISSYYGSTSYADSVKG (SEQ ID NO: 12), a HC CDR3 sequence of LWASGLDY (SEQ ID NO: 13), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 14), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 15), and a LC CDR3 sequence of QQWNWGWPLIT (SEQ ID NO: 16). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGL VQPGGSLRLSC AASGFTF S S S SMWVRQAPGKGLEWVASIS S YYGST SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARLWASGLDYWGQGTLV TVSS (SEQ ID NO: 10). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTV (SEQ ID NO: 9).

[0190] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of SYYGFWQALWALDY (SEQ ID NO: 21).

[0191] In some embodiments, the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 20). In some embodiments, the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 19). In some embodiments, the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQWWYGSPLFT (SEQ ID NO: 24). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 23). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 22). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 19), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 20), a HC CDR3 sequence of SYYGFWQALWALDY (SEQ ID NO: 21), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 22), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 23), and a LC CDR3 sequence of QQWWYGSPLFT (SEQ ID NO: 24). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGL VQPGGSLRLSC AASGFTF S S S SMWVRQAPGKGLEWVASIS S SSGST SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSYYGFWQALWALDYW GQGTLVTVSS (SEQ ID NO: 18). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWWYGSPLFTFGQGTKVEIKRT (SEQ ID NO: 17).

[0192] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of SYYGFWQALWALDY (SEQ ID NO: 29).

[0193] In some embodiments, the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 28). In some embodiments, the VH comprises a HC CDR1 sequence of FSSYSIH (SEQ ID NO: 27). In some embodiments, the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQWWYGSPLFT (SEQ ID NO: 32). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 31). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 30). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSSYSIH (SEQ ID NO: 27), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 28), a HC CDR3 sequence of SYYGFWQALWALDY (SEQ ID NO: 29), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 30), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 31), and a LC CDR3 sequence of QQWWYGSPLFT (SEQ ID NO: 32). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGL VQPGGSLRLSC AASGFTF S S YSIHWVRQAPGKGLEW VASIS S S SGST SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSYYGFWQALWALDYW GQGTLVTVSS (SEQ ID NO: 26). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWWYGSPLFTFGQGTKVEIKRT (SEQ ID NO: 25).

[0194] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of GYYYP YYAMD Y (SEQ ID NO: 37).

[0195] In some embodiments, the VH comprises a HC CDR2 sequence of SISSYYGSTYYADSVKG (SEQ ID NO: 36). In some embodiments, the VH comprises a HC CDR1 sequence of FSYYSIH (SEQ ID NO: 35). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQGKTYYPIT (SEQ ID NO: 40). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 39). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 38). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSYYSIH (SEQ ID NO: 35), a HC CDR2 sequence of SISSYYGSTYYADSVKG (SEQ ID NO: 36), a HC CDR3 sequence of GYYYP YYAMD Y (SEQ ID NO: 37), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 38), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 39), and a LC CDR3 sequence of QQGKTYYPIT (SEQ ID NO: 40). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence

[0196] EVQLVESGGGL VQPGGSLRLSC AASGFTF S YYSIHWVRQAPGKGLEWVASIS S YYGS TYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYP YYAMD YWG QGTLVTVSS (SEQ ID NO: 34). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV (SEQ ID NO: 33).

[0197] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of GYYYP YYAMD Y (SEQ ID NO: 45).

[0198] In some embodiments, the VH comprises a HC CDR2 sequence of SISPYYGSTYYADSVKG (SEQ ID NO: 44). In some embodiments, the VH comprises a HC CDR1 sequence of FSYYSIH (SEQ ID NO: 43). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQGKTYYPIT (SEQ ID NO: 48). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 47). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 46). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSYYSIH (SEQ ID NO: 43), a HC CDR2 sequence of SISPYYGSTYYADSVKG (SEQ ID NO: 44), a HC CDR3 sequence of GYYYP YYAMD Y (SEQ ID NO: 45), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 46), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 47), and a LC CDR3 sequence of QQGKTYYPIT (SEQ ID NO: 48). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGL VQPGGSLRLSC AASGFTF SYYSIHWVRQAPGKGLEWVASISP YYGS TYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYP YYAMD YWG QGTLVTVSS (SEQ ID NO: 42). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV (SEQ ID NO: 41).

[0199] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of GYYYP YYAMD Y (SEQ ID NO: 53).

[0200] In some embodiments, the VH comprises a HC CDR2 sequence of SISSYYGSTYYADSVKG (SEQ ID NO: 52). In some embodiments, the VH comprises a HC CDR1 sequence of FSYYSIH (SEQ ID NO: 51). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQTSWYHSLIT (SEQ ID NO: 56). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 55). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 54). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSYYSIH (SEQ ID NO: 51), a HC CDR2 sequence of SISSYYGSTYYADSVKG (SEQ ID NO: 52), a HC CDR3 sequence of GYYYP YYAMD Y (SEQ ID NO: 53), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 54), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 55), and a LC CDR3 sequence of QQTSWYHSLIT (SEQ ID NO: 56). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGL VQPGGSLRLSC AASGFTF S YYSIHWVRQAPGKGLEWVASIS S YYGS TYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYP YYAMD YWG QGTLVTVSS (SEQ ID NO: 50). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQTSWYHSLITFGQGTKVEIKRTV (SEQ ID NO: 49).

[0201] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of GYYYP YYAMD Y (SEQ ID NO: 61). In some embodiments, the VH comprises a HC CDR2 sequence of SISSYYGSTYYADSVKG (SEQ ID NO: 60). In some embodiments, the VH comprises a HC CDR1 sequence of VSYYSIH (SEQ ID NO: 59). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQGKTYYPIT (SEQ ID NO: 64). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 63). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 62). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of VSYYSIH (SEQ ID NO: 59), a HC CDR2 sequence of SISSYYGSTYYADSVKG (SEQ ID NO: 60), a HC CDR3 sequence of GYYYP YYAMD Y (SEQ ID NO: 61), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 62), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 63), and a LC CDR3 sequence of QQGKTYYPIT (SEQ ID NO: 64). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVASISSYYGS TYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYP YYAMD YWG QGTLVTVSS (SEQ ID NO: 58). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV (SEQ ID NO: 57).

[0202] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of GYYYP YYAMD Y (SEQ ID NO: 69).

[0203] In some embodiments, the VH comprises a HC CDR2 sequence of SISSYYGSTYYADSVKG (SEQ ID NO: 68). In some embodiments, the VH comprises a HC CDR1 sequence of FSYYSIH (SEQ ID NO: 67). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSWWSYPLT (SEQ ID NO: 72). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 71). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 70). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSYYSIH (SEQ ID NO: 67), a HC CDR2 sequence of SISSYYGSTYYADSVKG (SEQ ID NO: 68), a HC CDR3 sequence of GYYYP YYAMD Y (SEQ ID NO: 69), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 70), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 71), and a LC CDR3 sequence of QQSWWSYPLT (SEQ ID NO: 72). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence

[0204] EVQLVESGGGL VQPGGSLRLSC AASGFTF S YYSIHWVRQAPGKGLEWVASIS S YYGS TYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYP YYAMD YWG QGTLVTVSS (SEQ ID NO: 66). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence

[0205] DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV (SEQ ID NO: 65).

[0206] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of FQWYAMDY (SEQ ID NO: 77).

[0207] In some embodiments, the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 76). In some embodiments, the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 75). In some embodiments, the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSSWLYWLVT (SEQ ID NO: 80). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 79). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 78). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 75), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 76), a HC CDR3 sequence of FQWYAMDY (SEQ ID NO: 77), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 78), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 79), and a LC CDR3 sequence of QQSSWLYWLVT (SEQ ID NO: 80). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGL VQPGGSLRLSC AASGFTF S S S SMWVRQAPGKGLEWVASIS S SSGST SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFQWYAMDYWGQGTL VTVSS (SEQ ID NO: 74). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWLVTFGQGTKVEIKRTV (SEQ ID NO: 73).

[0208] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of GYGWGMDY (SEQ ID NO: 85).

[0209] In some embodiments, the VH comprises a HC CDR2 sequence of YISSYSGYTSYADSVKG (SEQ ID NO: 84). In some embodiments, the VH comprises a HC CDR1 sequence of ISSYSIH (SEQ ID NO: 83). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQWNWGWPLIT (SEQ ID NO: 88). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 87). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 86). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of ISSYSIH (SEQ ID NO: 83), a HC CDR2 sequence of YISSYSGYTSYADSVKG (SEQ ID NO: 84), a HC CDR3 sequence of GYGWGMDY (SEQ ID NO: 85), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 86), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 87), and a LC CDR3 sequence of QQWNWGWPLIT (SEQ ID NO: 88). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGL VQPGGSLRLSC AASGFTIS S YSMWVRQAPGKGLEWVAYIS S YSGY TSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYGWGMDYWGQGT LVTVSS (SEQ ID NO: 82). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTV (SEQ ID NO: 81).

[0210] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of SGYYSSHWYLQSWYQAMDY (SEQ ID NO: 93).

[0211] In some embodiments, the VH comprises a HC CDR2 sequence of YISSSSGYTSYADSVKG (SEQ ID NO: 92). In some embodiments, the VH comprises a HC CDR1 sequence of ISYSSIH (SEQ ID NO: 91). In some embodiments, the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSSAWYPVT (SEQ ID NO: 96). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 95). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 94). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of ISYSSIH (SEQ ID NO: 91), a HC CDR2 sequence of YISSSSGYTSYADSVKG (SEQ ID NO: 92), a HC CDR3 sequence of SGYYSSHWYLQSWYQAMDY (SEQ ID NO: 93), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 94), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 95), and a LC CDR3 sequence of QQSSAWYPVT (SEQ ID NO: 96). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTISYSSIHWVRQAPGKGLEWVAYISSSSGYT SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSGYYSSHWYLQSWYQ AMDYWGQGTLVTVSS (SEQ ID NO: 90). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence

[0212] DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTV (SEQ ID NO: 89).

[0213] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of SGYYSSHWYLQSWYQAMDY (SEQ ID NO: 101).

[0214] In some embodiments, the VH comprises a HC CDR2 sequence of SISSYYGSTYYADSVKG (SEQ ID NO: 100). In some embodiments, the VH comprises a HC CDR1 sequence of FSYYSIH (SEQ ID NO: 99). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQASYGPIT (SEQ ID NO: 104). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 103). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 102). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSYYSIH (SEQ ID NO: 99), a HC CDR2 sequence of SISSYYGSTYYADSVKG (SEQ ID NO: 100), a HC CDR3 sequence of SGYYSSHWYLQSWYQAMDY (SEQ ID NO: 101), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 102), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 103), and a LC CDR3 sequence of QQASYGPIT (SEQ ID NO: 104). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGL VQPGGSLRLSC AASGFTF S YYSIHWVRQAPGKGLEWVASIS S YYGS TYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSGYYSSHWYLQSWY QAMDYWGQGTLVTVSS (SEQ ID NO: 98). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASYGPITFGQGTKVEIKRTV (SEQ ID NO: 97).

[0215] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of HYSEKWWGWYTMYIDAMDY (SEQ ID NO: 109).

[0216] In some embodiments, the VH comprises a HC CDR2 sequence of SISSYYGSTYYADSVKG (SEQ ID NO: 108). In some embodiments, the VH comprises a HC CDR1 sequence of VSYSSIH (SEQ ID NO: 107). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQWWSSSQLIT (SEQ ID NO: 112). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 111). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 110). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of VSYSSIH (SEQ ID NO: 107), a HC CDR2 sequence of SISSYYGSTYYADSVKG (SEQ ID NO: 108), a HC CDR3 sequence of HYSEKWWGWYTMYIDAMDY (SEQ ID NO: 109), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 110), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 111), and a LC CDR3 sequence of QQWWSSSQLIT (SEQ ID NO: 112). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGL VQPGGSLRLSC AASGFT VS YSSIHWVRQAPGKGLEWVASISS YYGS TYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARHYSEKWWGWYTMYI DAMDYWGQGTLVTVSS (SEQ ID NO: 106). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWWSSSQLITFGQGTKVEIKRTV (SEQ ID NO: 105).

[0217] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of GWYYLGMDY (SEQ ID NO: 117).

[0218] In some embodiments, the VH comprises a HC CDR2 sequence of YISPYSGYTSYADSVKG (SEQ ID NO: 116). In some embodiments, the VH comprises a HC CDR1 sequence of VSYYSIH (SEQ ID NO: 115). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQGKTYYPIT (SEQ ID NO: 120). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 119). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 118). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of VSYYSIH (SEQ ID NO: 115), a HC CDR2 sequence of YISPYSGYTSYADSVKG (SEQ ID NO: 116), a HC CDR3 sequence of GWYYLGMDY (SEQ ID NO: 117), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 118), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 119), and a LC CDR3 sequence of QQGKTYYPIT (SEQ ID NO: 120). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSG YTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQ GTLVTVSS (SEQ ID NO: 114). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV (SEQ ID NO: 113).

[0219] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of GWYYLGMDY (SEQ ID NO: 125).

[0220] In some embodiments, the VH comprises a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 124). In some embodiments, the VH comprises a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 123). In some embodiments, the antigen- binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQGKTYYPIT (SEQ ID NO: 128). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 127). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 126). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 123), a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 124), a HC CDR3 sequence of GWYYLGMDY (SEQ ID NO: 125), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 126), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 127), and a LC CDR3 sequence of QQGKTYYPIT (SEQ ID NO: 128). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSY TSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQG TLVTVSS (SEQ ID NO: 122). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV (SEQ ID NO: 121).

[0221] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of GWYYLGMDY (SEQ ID NO: 133).

[0222] In some embodiments, the VH comprises a HC CDR2 sequence of YISPYSGYTSYADSVKG (SEQ ID NO: 132). In some embodiments, the VH comprises a HC CDR1 sequence of VSYYSIH (SEQ ID NO: 131). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSWWSYPLT (SEQ ID NO: 136). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 135). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 134). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of VSYYSIH (SEQ ID NO: 131), a HC CDR2 sequence of YISPYSGYTSYADSVKG (SEQ ID NO: 132), a HC CDR3 sequence of GWYYLGMDY (SEQ ID NO: 133), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 134), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 135), and a LC CDR3 sequence of QQSWWSYPLT (SEQ ID NO: 136). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSG YTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQ GTLVTVSS (SEQ ID NO: 130). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV (SEQ ID NO: 129).

[0223] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of GWYYLGMDY (SEQ ID NO: 141).

[0224] In some embodiments, the VH comprises a HC CDR2 sequence of YISPYSGYTSYADSVKG (SEQ ID NO: 140). In some embodiments, the VH comprises a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 139). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSWWSYPLT (SEQ ID NO: 144). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 143). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 142). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 139), a HC CDR2 sequence of YISPYSGYTSYADSVKG (SEQ ID NO: 140), a HC CDR3 sequence of GWYYLGMDY (SEQ ID NO: 141), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 142), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 143), and a LC CDR3 sequence of QQSWWSYPLT (SEQ ID NO: 144). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVAYISPYSGY TSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQG TLVTVSS (SEQ ID NO: 138). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV (SEQ ID NO: 137). In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of GWYYLGMDY (SEQ ID NO: 149).

[0225] In some embodiments, the VH comprises a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 148). In some embodiments, the VH comprises a HC CDR1 sequence of FSSYSIH (SEQ ID NO: 147). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSWWSYPLT (SEQ ID NO: 152). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 151). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 150). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSSYSIH (SEQ ID NO: 147), a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 148), a HC CDR3 sequence of GWYYLGMDY (SEQ ID NO: 149), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 150), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 151), and a LC CDR3 sequence of QQSWWSYPLT (SEQ ID NO: 152). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVASISPYSSYT SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGT LVTVSS (SEQ ID NO: 146). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV (SEQ ID NO: 145).

[0226] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of GWYYLGMDY (SEQ ID NO: 157).

[0227] In some embodiments, the VH comprises a HC CDR2 sequence of YISPYSGYTSYADSVKG (SEQ ID NO: 156). In some embodiments, the VH comprises a HC CDR1 sequence of VSYYSIH (SEQ ID NO: 155). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSSAWYPVT (SEQ ID NO: 160). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 159). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 158). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of VSYYSIH (SEQ ID NO: 155), a HC CDR2 sequence of YISPYSGYTSYADSVKG (SEQ ID NO: 156), a HC CDR3 sequence of GWYYLGMDY (SEQ ID NO: 157), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 158), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 159), and a LC CDR3 sequence of QQSSAWYPVT (SEQ ID NO: 160). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSG YTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQ GTLVTVSS (SEQ ID NO: 154). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTV (SEQ ID NO: 153).

[0228] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of YWYYMGMDY (SEQ ID NO: 165).

[0229] In some embodiments, the VH comprises a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 164). In some embodiments, the VH comprises a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 163). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSWWSYPLT (SEQ ID NO: 168). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 167). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 166). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 163), a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 164), a HC CDR3 sequence of YWYYMGMDY (SEQ ID NO: 165), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 166), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 167), and a LC CDR3 sequence of QQSWWSYPLT (SEQ ID NO: 168). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSY TSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQG TLVTVSS (SEQ ID NO: 162). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV (SEQ ID NO: 161).

[0230] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of YWYYMGMDY (SEQ ID NO: 173).

[0231] In some embodiments, the VH comprises a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 172). In some embodiments, the VH comprises a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 171). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSSAWYPVT (SEQ ID NO: 176). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 175). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 174). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 171), a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 172), a HC CDR3 sequence of YWYYMGMDY (SEQ ID NO: 173), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 174), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 175), and a LC CDR3 sequence of QQSSAWYPVT (SEQ ID NO: 176). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSY TSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQG TLVTVSS (SEQ ID NO: 170). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTV (SEQ ID NO: 169).

[0232] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of YWYYMGMDY (SEQ ID NO: 181).

[0233] In some embodiments, the VH comprises a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 180). In some embodiments, the VH comprises a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 179). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSSYYEELIT (SEQ ID NO: 184). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 183). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 182). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 179), a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 180), a HC CDR3 sequence of YWYYMGMDY (SEQ ID NO: 181), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 182), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 183), and a LC CDR3 sequence of QQSSYYEELIT (SEQ ID NO: 184). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSY TSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQG TLVTVSS (SEQ ID NO: 178). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSYYEELITFGQGTKVEIKRTV (SEQ ID NO: 177).

[0234] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of YWYYMGMDY (SEQ ID NO: 189).

[0235] In some embodiments, the VH comprises a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 188). In some embodiments, the VH comprises a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 187). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQAYSDPLT (SEQ ID NO: 192). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 191). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 190). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 187), a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 188), a HC CDR3 sequence of YWYYMGMDY (SEQ ID NO: 189), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 190), a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 191), and a LC CDR3 sequence of QQAYSDPLT (SEQ ID NO: 192). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSY TSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQG TLVTVSS (SEQ ID NO: 186). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQAYSDPLTFGQGTKVEIKRTV (SEQ ID NO: 185).

[0236] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of YWYYMGMDY (SEQ ID NO: 197).

[0237] In some embodiments, the VH comprises a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 196). In some embodiments, the VH comprises a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 195). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQGSSSLLT (SEQ ID NO: 200). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 199). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 198). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 195), a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 196), a HC CDR3 sequence of YWYYMGMDY (SEQ ID NO: 197), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 198), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 199), and a LC CDR3 sequence of QQGSSSLLT (SEQ ID NO: 200). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSY TSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQG TLVTVSS (SEQ ID NO: 194). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGSSSLLTFGQGTKVEIKRTV (SEQ ID NO: 193).

[0238] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of YWYYMGMDY (SEQ ID NO: 205).

[0239] In some embodiments, the VH comprises a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 204). In some embodiments, the VH comprises a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 203). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSGSYLLIT (SEQ ID NO: 208). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 207). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 206). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 203), a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 204), a HC CDR3 sequence of YWYYMGMDY (SEQ ID NO: 205), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 206), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 207), and a LC CDR3 sequence of QQSGSYLLIT (SEQ ID NO: 208). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSY TSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQG TLVTVSS (SEQ ID NO: 202). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSGSYLLITFGQGTKVEIKRTV (SEQ ID NO: 201).

[0240] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of YWYYMGMDY (SEQ ID NO: 213). In some embodiments, the VH comprises a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 212). In some embodiments, the VH comprises a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 211). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQADYEFGLIT (SEQ ID NO: 216). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 215). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 214). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 211), a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 212), a HC CDR3 sequence of YWYYMGMDY (SEQ ID NO: 213), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 214), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 215), and a LC CDR3 sequence of QQADYEFGLIT (SEQ ID NO: 216). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSY TSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQG TLVTVSS (SEQ ID NO: 210). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQADYEFGLITFGQGTKVEIKRTV (SEQ ID NO: 209).

[0241] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of SSRQYYHSQVEPPMAMDY (SEQ ID NO: 221).

[0242] In some embodiments, the VH comprises a HC CDR2 sequence of YISSSYGYTSYADSVKG (SEQ ID NO: 220). In some embodiments, the VH comprises a HC CDR1 sequence of FSSYSIH (SEQ ID NO: 219). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSWWSYPLT (SEQ ID NO: 224). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 223). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 222). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSSYSIH (SEQ ID NO: 219), a HC CDR2 sequence of YISSSYGYTSYADSVKG (SEQ ID NO: 220), a HC CDR3 sequence of SSRQYYHSQVEPPMAMDY (SEQ ID NO: 221), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 222), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 223), and a LC CDR3 sequence of QQSWWSYPLT (SEQ ID NO: 224). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVAYISSSYGY TSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMA MDYWGQGTLVTVSS (SEQ ID NO: 218). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV (SEQ ID NO: 217).

[0243] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of SSRQYYHSQVEPPMAMDY (SEQ ID NO: 229).

[0244] In some embodiments, the VH comprises a HC CDR2 sequence of YISSSYGYTSYADSVKG (SEQ ID NO: 228). In some embodiments, the VH comprises a HC CDR1 sequence of FSYYSIH (SEQ ID NO: 227). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSWWSYPLT (SEQ ID NO: 232). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 231). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 230). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSYYSIH (SEQ ID NO: 227), a HC CDR2 sequence of YISSSYGYTSYADSVKG (SEQ ID NO: 228), a HC CDR3 sequence of SSRQYYHSQVEPPMAMDY (SEQ ID NO: 229), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 230), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 231), and a LC CDR3 sequence of QQSWWSYPLT (SEQ ID NO: 232). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVAYISSSYGY TSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMA MDYWGQGTLVTVSS (SEQ ID NO: 226). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV (SEQ ID NO: 225).

[0245] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of SSRQYYHSQVEPPMAMDY (SEQ ID NO: 237).

[0246] In some embodiments, the VH comprises a HC CDR2 sequence of YISSSYGYTSYADSVKG (SEQ ID NO: 236). In some embodiments, the VH comprises a HC CDR1 sequence of VSSSSIH (SEQ ID NO: 235). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSWWSYPLT (SEQ ID NO: 240). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 239). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 238). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of VSSSSIH (SEQ ID NO: 235), a HC CDR2 sequence of YISSSYGYTSYADSVKG (SEQ ID NO: 236), a HC CDR3 sequence of SSRQYYHSQVEPPMAMDY (SEQ ID NO: 237), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 238), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 239), and a LC CDR3 sequence of QQSWWSYPLT (SEQ ID NO: 240). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSSSIHWVRQAPGKGLEWVAYISSSYGY TSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMA MDYWGQGTLVTVSS (SEQ ID NO: 234). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV (SEQ ID NO: 233).

[0247] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of SSRQYYHSQVEPPMAMDY (SEQ ID NO: 245).

[0248] In some embodiments, the VH comprises a HC CDR2 sequence of YISSSYGYTSYADSVKG (SEQ ID NO: 244). In some embodiments, the VH comprises a HC CDR1 sequence of VSYSSIH (SEQ ID NO: 243). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSWWSYPLT (SEQ ID NO: 248). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 247). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 246). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of VSYSSIH (SEQ ID NO: 243), a HC CDR2 sequence of YISSSYGYTSYADSVKG (SEQ ID NO: 244), a HC CDR3 sequence of SSRQYYHSQVEPPMAMDY (SEQ ID NO: 245), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 246), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 247), and a LC CDR3 sequence of QQSWWSYPLT (SEQ ID NO: 248). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSYSSIHWVRQAPGKGLEWVAYISSSYGY TSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMA MDYWGQGTLVTVSS (SEQ ID NO: 242). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV (SEQ ID NO: 241).

[0249] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of YWYYLGMDY (SEQ ID NO: 253).

[0250] In some embodiments, the VH comprises a HC CDR2 sequence of YISPYSGYTYYADSVKG (SEQ ID NO: 252). In some embodiments, the VH comprises a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 251). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQGSSSLLT (SEQ ID NO: 256). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 255). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 254). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 251), a HC CDR2 sequence of YISPYSGYTYYADSVKG (SEQ ID NO: 252), a HC CDR3 sequence of YWYYLGMDY (SEQ ID NO: 253), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 254), a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 255), and a LC CDR3 sequence of QQGSSSLLT (SEQ ID NO: 256). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVAYISPYSGY TYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYLGMDYWGQG TLVTVSS (SEQ ID NO: 250). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence

[0251] DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGSSSLLTFGQGTKVEIKRTV (SEQ ID NO: 249).

[0252] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein (a) the VH comprises: (i) a HC CDR3 comprising the amino acid sequence of LWASGLDY; and / or (b) the VL comprises: (i) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

[0253] In some embodiments, the VH comprises a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes. In some embodiments, the VH comprises a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VL comprises a LC CDR1 comprising an amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VL comprises a LC CDR2 comprising an amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VH comprises: (a) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (b) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (c) a HC CDR3 comprising an amino acid sequence of LWASGLDY. In some embodiments, the VL comprises: (a) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (b) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (c) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

[0254] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein (a) the VH comprises: (i) a HC CDR3 comprising the amino acid sequence of SYYGFWQALWALDY; and / or (b) the VL comprises: (i) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V. In some embodiments, the VH comprises a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes. In some embodiments, the VH comprises a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VL comprises a LC CDR1 comprising an amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VL comprises a LC CDR2 comprising an amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VH comprises: (a) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (b) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (c) a HC CDR3 comprising an amino acid sequence of SYYGFWQALWALDY. In some embodiments, the VL comprises: (a) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1- 5 amino acid changes; (b) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (c) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7is I, F, or V.

[0255] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein (a) the VH comprises: (i) a HC CDR3 comprising the amino acid sequence of GYYYPYYAMDY; and / or (b) the VL comprises: (i) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4YPX5T, wherein Xi is W or S, X2 is K, W, or S, X3 is W, T, or A, X4is S, W, or Y, and X5 is I, L, or V. In some embodiments, the VH comprises a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes. In some embodiments, the VH comprises a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VL comprises a LC CDR1 comprising an amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VL comprises a LC CDR2 comprising an amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VH comprises: (a) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (b) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (c) a HC CDR3 comprising an amino acid sequence of GYYYPYYAMDY. In some embodiments, the VL comprises: (a) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (b) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (c) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4YPX5T, wherein Xi is W or S, X2 is K, W, or S, X3 is W, T, or A, X4is S, W, or Y, and X5 is I, L, or V.

[0256] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein (a) the VH comprises: (i) a HC CDR3 comprising the amino acid sequence of GYYYPYYAMDY; and / or (b) the VL comprises: (i) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V. In some embodiments, the VH comprises a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes. In some embodiments, the VH comprises a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VL comprises a LC CDR1 comprising an amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VL comprises a LC CDR2 comprising an amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VH comprises: (a) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (b) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (c) a HC CDR3 comprising an amino acid sequence of GYYYPYYAMDY. In some embodiments, the VL comprises: (a) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (b) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (c) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

[0257] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein (a) the VH comprises: (i) a HC CDR3 comprising the amino acid sequence of X1X2X3X4X5MDY, wherein Xi is F or G, X2 is Q or Y, X3 is W or G, X4is Y or W, and X5 is A or G; and / or (b) the VL comprises: (i) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V. In some embodiments, the VH comprises a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes. In some embodiments, the VH comprises a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VL comprises a LC CDR1 comprising an amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VL comprises a LC CDR2 comprising an amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VH comprises: (a) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (b) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (c) a HC CDR3 comprising an amino acid sequence of X1X2X3X4X5MDY, wherein Xi is F or G, X2 is Q or Y, X3 is W or G, X4is Y or W, and X5 is A or G. In some embodiments, the VL comprises: (a) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (b) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (c) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

[0258] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein (a) the VH comprises: (i) a HC CDR3 comprising the amino acid sequence of SGYYSSHWYLQSWYQAMDY; and / or (b) the VL comprises: (i) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4YPX5T, wherein Xi is W or S, X2 is K, W, or S, X3 is W, T, or A, X4is S, W, or Y, and X5 is I, L, or V. In some embodiments, the VH comprises a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes. In some embodiments, the VH comprises a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VL comprises a LC CDR1 comprising an amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VL comprises a LC CDR2 comprising an amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VH comprises: (a) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (b) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (c) a HC CDR3 comprising an amino acid sequence of SGYYSSHWYLQSWYQAMDY. In some embodiments, the VL comprises: (a) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (b) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (c) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4YPX5T, wherein Xi is W or S, X2 is K, W, or S, X3is W, T, or A, X4is S, W, or Y, and X5is I, L, or V.

[0259] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein (a) the VH comprises: (i) a HC CDR3 comprising the amino acid sequence of SGYYSSHWYLQSWYQAMDY; and / or (b) the VL comprises: (i) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6T, wherein Xi is G or A, X2 is S or Y, X3 is S or Y, X4 is G, D, or S, X5 is P or L, and Xe is I or L. In some embodiments, the VH comprises a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes. In some embodiments, the VH comprises a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VL comprises a LC CDR1 comprising an amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VL comprises a LC CDR2 comprising an amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VH comprises: (a) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (b) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (c) a HC CDR3 comprising an amino acid sequence of SGYYSSHWYLQSWYQAMDY. In some embodiments, the VL comprises: (a) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (b) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (c) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6T, wherein Xi is G or A, X2 is S or Y, X3 is S or Y, X4 is G, D, or S, X5 is P or L, and Xe is I or L.

[0260] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein (a) the VH comprises: (i) a HC CDR3 comprising the amino acid sequence of HYSEKWWGWYTMYIDAMDY; and / or (b) the VL comprises: (i) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V. In some embodiments, the VH comprises a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes. In some embodiments, the VH comprises a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VL comprises a LC CDR1 comprising an amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VL comprises a LC CDR2 comprising an amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VH comprises: (a) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (b) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (c) a HC CDR3 comprising an amino acid sequence of HYSEKWWGWYTMYIDAMDY. In some embodiments, the VL comprises: (a) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1- 5 amino acid changes; (b) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (c) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7is I, F, or V.

[0261] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein (a) the VH comprises: (i) a HC CDR3 comprising the amino acid sequence of Xi WYYX2GMD Y, wherein Xi is G or Y and X2 is M or L; and / or (b) the VL comprises: (i) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4YPX5T, wherein Xi is W or S, X2 is K, W, or S, X3 is W, T, or A, X4is S, W, or Y, and X5 is I, L, or V. In some embodiments, the VH comprises a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes. In some embodiments, the VH comprises a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VL comprises a LC CDR1 comprising an amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VL comprises a LC CDR2 comprising an amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VH comprises: (a) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (b) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (c) a HC CDR3 comprising an amino acid sequence of Xi WYYX2GMD Y, wherein Xi is G or Y and X2 is M or L. In some embodiments, the VL comprises: (a) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (b) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (c) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4YPX5T, wherein Xi is W or S, X2 is K, W, or S, X3 is W, T, or A, X4is S, W, or Y, and X5 is I, L, or V.

[0262] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein (a) the VH comprises: (i) a HC CDR3 comprising the amino acid sequence of Xi WYYX2GMD Y, wherein Xi is G or Y and X2 is M or L; and / or (b) the VL comprises: (i) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6T, wherein Xi is G or A, X2 is S or Y, X3 is S or Y, X4is G, D, or S, X5 is P or L, and Xe is I or L. In some embodiments, the VH comprises a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes. In some embodiments, the VH comprises a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VL comprises a LC CDR1 comprising an amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VL comprises a LC CDR2 comprising an amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VH comprises: (a) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (b) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (c) a HC CDR3 comprising an amino acid sequence of Xi WYYX2GMD Y, wherein Xi is G or Y and X2 is M or L. In some embodiments, the VL comprises: (a) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (b) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (c) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6T, wherein Xi is G or A, X2 is S or Y, X3 is S or Y, X4is G, D, or S, X5is P or L, and Xe is I or L.

[0263] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein (a) the VH comprises: (i) a HC CDR3 comprising the amino acid sequence of Xi WYYX2GMD Y, wherein Xi is G or Y and X2 is M or L; and / or (b) the VL comprises: (i) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2is N, W, S, or D, X3is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V. In some embodiments, the VH comprises a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes. In some embodiments, the VH comprises a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VL comprises a LC CDR1 comprising an amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VL comprises a LC CDR2 comprising an amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VH comprises: (a) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (b) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (c) a HC CDR3 comprising an amino acid sequence of Xi WYYX2GMD Y, wherein Xi is G or Y and X2 is M or L. In some embodiments, the VL comprises: (a) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (b) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (c) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

[0264] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein (a) the VH comprises: (i) a HC CDR3 comprising the amino acid sequence of SSRQYYHSQVEPPMAMDY; and / or (b) the VL comprises: (i) a LC CDR3 comprising the amino acid sequence of QQXIX2X3X4YPX5T, wherein Xi is W or S, X2 is K, W, or S, X3 is W, T, or A, X4is S, W, or Y, and X5 is I, L, or V. In some embodiments, the VH comprises a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes. In some embodiments, the VH comprises a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VL comprises a LC CDR1 comprising an amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VL comprises a LC CDR2 comprising an amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VH comprises: (a) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (b) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (c) a HC CDR3 comprising an amino acid sequence of SSRQYYHSQVEPPMAMDY. In some embodiments, the VL comprises: (a) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (b) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (c) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4YPX5T, wherein Xi is W or S, X2 is K, W, or S, X3is W, T, or A, X4is S, W, or Y, and X5is I, L, or V.

[0265] In some embodiments, the antigen-binding domain binds to a peptide conjugate / MHC complex, wherein the peptide conjugate of the peptide conjugate / MHC complex is a peptide covalently linked to a targeted covalent inhibitor or fragment thereof and a MHC. In some embodiments, the targeted covalent inhibitor is adagrasib, sotorasib, or divarasib. In some embodiments, the peptide conjugate / MHC complex is a first peptide conjugate / MHC complex comprising a first peptide conjugate comprising a first peptide and a first targeted covalent inhibitor or fragment thereof; and wherein the antigen-binding domain further binds to a second peptide conjugate / MHC complex comprising (a) a second peptide conjugate, wherein the second peptide conjugate of the second peptide conjugate / MHC complex is a second peptide covalently linked to a second targeted covalent inhibitor or fragment thereof; and (b) a second MHC.

[0266] In some embodiments, the antigen-binding domain binds to (i) the first peptide conjugate / MHC complex with a dissociation constant (KD) of at most about 50 nM and (ii) the second peptide conjugate / MHC complex with a KD of at most about 50 nM. In some embodiments, the antigen-binding domain binds to (i) the first peptide conjugate / MHC complex with a dissociation constant (KD) of at most about 10 nM and (ii) the second peptide conjugate / MHC complex with a KD of at most about 10 nM. In some embodiments, the antigen-binding domain binds to (i) the first peptide conjugate / MHC complex with a dissociation constant (KD) of at most about 5 nM and (ii) the second peptide conjugate / MHC complex with a KD of at most about 5 nM.

[0267] In some embodiments, (i) the first targeted covalent inhibitor is adagrasib and the second targeted covalent inhibitor is sotorasib, (ii) the first targeted covalent inhibitor is adagrasib and the second targeted covalent inhibitor is divarasib; or (iii) the first targeted covalent inhibitor is divarasib and the second targeted covalent inhibitor is sotorasib. In some embodiments, the antigen-binding domain does not bind to a free first targeted covalent inhibitor with a dissociation constant (KD) of less than 200 nM. In some embodiments, the antigen-binding domain binds to the first peptide conjugate / MHC complex with a greater affinity than to the first peptide or the free first targeted covalent inhibitor. In some embodiments, the affinity of the antigen-binding domain for the first peptide conjugate / MHC complex is 100-10,000 times greater than the affinity of the antigen-binding domain for the first peptide or the free first targeted covalent inhibitor. In some embodiments, the antigen-binding domain does not detectably bind to a complex of the first peptide with a MHC, wherein the first peptide is not covalently bound to the first targeted covalent inhibitor or fragment thereof. In some embodiments, the antigen-binding domain does not detectably bind to the free first targeted covalent inhibitor. In some embodiments, the antigen-binding domain binds to a free first peptide conjugate with a dissociation constant (KD) that is at least 2.5 times more than a KD of the antibody or the antigen-binding fragment to the first peptide conjugate / MHC complex. In some embodiments, the antigen-binding domain does not bind to a free second targeted covalent inhibitor with a dissociation constant (KD) of less than 200 nM.

[0268] In some embodiments, the antigen-binding domain binds to the second peptide conjugate / MHC complex with a greater affinity than to the second peptide or the free second targeted covalent inhibitor. In some embodiments, the affinity of the antigen-binding domain for the second peptide conjugate / MHC complex is 100-10,000 times greater than the affinity of the antigen-binding domain for the second peptide or the free second targeted covalent inhibitor. In some embodiments, the antigen-binding domain does not detectably bind to a complex of the second peptide with the second MHC, wherein the second peptide is not covalently bound to the second targeted covalent inhibitor or fragment thereof. In some embodiments, the antigen-binding domain does not detectably bind to the free second targeted covalent inhibitor. In some embodiments, the antigen-binding domain binds to a free second peptide conjugate with a dissociation constant KD that is at least 2.5 times more than a KD of the antibody or the antigen-binding fragment to the second peptide conjugate / MHC complex.

[0269] In some embodiments, the first peptide and the second peptide comprise the same amino acid sequence. In some embodiments, the first peptide and the second peptide consist of the same amino acid sequence. In some embodiments, the first peptide or the second peptide comprises the amino acid sequence of VVVGACGVGK. In some embodiments, the first peptide and second peptide comprise a different amino acid sequence. In some embodiments, the first peptide or the second peptide comprises an amino acid sequence of VVVGACGVGK, VVGACGVGK, or KLVVVGACGV. In some embodiments, the MHC is an HL A, and wherein the HL A i s HL A- A* 02 : 01 , HL A- A* 03 : 01 , or HL A- A* 11 :01.

[0270] In some embodiments, the first peptide or the second peptide is or is derived from KRAS. In some embodiments, the first peptide or the second peptide comprises a segment of KRASG12C, KRASG12D, or KRASG12R. In some embodiments, the first peptide conjugate is formed by the covalent reaction of a free first targeted covalent inhibitor with a KRASG12Cpeptide, a KRASG12Dpeptide, or a KRASG12Rpeptide. In some embodiments, the second peptide conjugate is formed by the covalent reaction of a second free targeted covalent inhibitor with a KRASG12Cpeptide, a KRASG12Dpeptide, or a KRASG12Rpeptide. In some embodiments, the free first targeted covalent inhibitor or the second free targeted covalent inhibitor is sotorasib, adagrasib, or divarasib. In some embodiments, the first peptide or the second peptide comprises the amino acid sequence of VVVGACGVGK, VVGACGVGK, or KLVVVGACGV.

[0271] In some embodiments, the antigen-binding domain binds to (a) a first peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 and a second peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01; (b) a first peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 and a second peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01; or (c) a first peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01 and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01.

[0272] In some embodiments, the antigen-binding domain binds to (a) a first peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 and a second peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01; (b) a first peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01; or (c) a first peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01.

[0273] In some embodiments, the antigen-binding domain binds to (a) a first peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 and a second peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A* 11:01; (b) a first peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 and a second peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A* 11 :01; or (c) a first peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01 and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01.

[0274] In some embodiments, the antigen-binding domain binds to (a) a first peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 and a second peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A* 11 :01; (b) a first peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01; or (c) a first peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01.

[0275] In some embodiments, the antigen-binding domain binds to (a) a first peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 and a second peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A* 11:01; (b) a first peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 and a second peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A* 11 :01; or (c) a first peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01 and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01.

[0276] In some embodiments, the antigen-binding domain binds to (a) a first peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 and a second peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A* 11 :01; (b) a first peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01; or (c) a first peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01.

[0277] In some embodiments, the antigen-binding domain binds to (a) a first peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A* 11 :01 and a second peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01; (b) a first peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A* 11 :01 and a second peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01; or (c) a first peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01 and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01.

[0278] In some embodiments, the antigen-binding domain binds to (a) a first peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A* 11 :01 and a second peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01; (b) a first peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A* 11 :01 and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01; or (c) a first peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A* 11 :01 and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01.

[0279] In some embodiments, the first targeted covalent inhibitor or the second targeted covalent inhibitor is sotorasib, adagrasib, or divarasib.

[0280] In some embodiments, the VH is linked to the VL via a linker sequence. In some embodiments, the linker sequence comprises (G4S)n or (S4G)n, wherein n is any integer from 1 to 10. In some embodiments, the linker comprises the glycine-serine-alanine linker G4SA3 or a glycine-serine linker (G4S In some embodiments, the polypeptide is an intact antibody, a bispecific antibody, a multispecific antibody, an antigen-binding (Fab) fragment, an Fab’ fragment, an (Fab’)2 fragment, an Fd, an Fv, a dAb, a single domain fragment or single monomeric variable antibody domain, a single-chain Diabody (scDb), a diabody (Db), a dualaffinity retargeting (DART) molecule, a single-chain variable fragment (scFv), a Bi-specific T-cell engager (BiTE), bispecific killer cell engager (BiKE), CrossMab, a tri-specific binding partner, a chimeric antigen receptor (CAR), a camelid antibody, a monobody (e.g., adnectin), a DARPin, an anticalin, an affibody, or an affimer. In some embodiments, the polypeptide comprises a monobody (e.g., adnectin), a DARPin, an anticalin, an affibody, or an affimer. In some embodiments, the polypeptide comprises a polypeptide chain comprising the antigenbinding domain. In some embodiments, the polypeptide chain further comprises a cytokine or fragment thereof. In some embodiments, cytokine comprises IL-2, IL-7, IL-15, IL-12, IL-18, IL-21, or an interferon (IFN). In some embodiments, the cytokine comprises a modified or mutated IL-2, IL-7, IL-15, IL-12, IL-18, IL-21, or IFN. In some embodiments, the polypeptide chain further comprises an agonist molecule. In some embodiments, the agonist molecule is a CD28 agonist or a 4-1BB agonist.

[0281] In an aspect, the present disclosure provides a pharmaceutical composition comprising a polypeptide described herein, and a pharmaceutically acceptable carrier, excipient, adjuvant or diluent.

[0282] In an aspect, the present disclosure provides a method of treating cancer in a subject in need thereof wherein the subject has been treated with a free targeted covalent inhibitor, the method comprising administering to the subject the polypeptide described herein or the pharmaceutical composition described herein. In some embodiments, the free targeted covalent inhibitor is sotorasib, adagrasib, or divarasib. In some embodiments, the subject is refractory to a treatment with the free targeted covalent inhibitor.

[0283] In an aspect, the present disclosure provides a method of treating a cancer in a subject in need thereof, the method comprising administering to the subject the polypeptide described herein or the pharmaceutical composition described herein. In some embodiments, the method further comprises administering simultaneously a small molecule drug.

[0284] In an aspect, the present disclosure provides a method of administering to the subject in need thereof the polypeptide described herein or the pharmaceutical composition described herein, and a free targeted covalent inhibitor, wherein the free targeted covalent inhibitor is optionally sotorasib, adagrasib, or divarasib. In some embodiments, the polypeptide described herein or the pharmaceutical composition described herein is administered after administration of the free targeted covalent inhibitor or simultaneously with the free targeted covalent inhibitor.

[0285] In an aspect, the present disclosure provides a method of manufacturing a T-cell receptor (TCR) that recognizes the first peptide conjugate / MHC complex or the second peptide conjugate / MHC complex described herein, the method comprising: (a) a plurality of candidate TCRs with the first peptide conjugate / MHC complex or the second peptide conjugate / MHC complex, and (b) identifying at least one TCR that binds to the first peptide conjugate / MHC complex or the second peptide conjugate / MHC complex. In some embodiments, identifying in (b) further comprises selecting or isolating the at least one TCR.

[0286] In some embodiments, the plurality of candidate TCRs is a plurality of soluble TCRs or a plurality of TCRs expressed on cell surface of a plurality of cells. In some embodiments, the plurality of candidate TCRs is the plurality of TCRs expressed on cell surface of the plurality of cells, and identifying in (b) comprises isolating or selecting a cell comprising the at least one TCR based on an activation marker of the cell. In some embodiments, the activation marker is a T cell activation marker. In some embodiments, the T cell activation marker is CD26, CD27, CD28, CD30, CD154, CD40L, CD134. CD25, CD44, CD69, CD 137, PD-1 or KLRGl.

[0287] In an aspect, the present disclosure provides a T-cell receptor (TCR) comprising the at least one TCR of (b) of a method described herein. In some embodiments, the TCR is a soluble TCR. In some embodiments, the TCR is a bispecific TCR.

[0288] In some embodiments, the first peptide conjugate / MHC complex is different from the second peptide conjugate / MHC complex, wherein each of the first and second peptide conjugate / MHC complexes independently comprises: a different peptide selected from the group consisting of peptides comprising the formula X#X#+iX#+2X#+3X#+4(X#+5)X#+6X#+7X#+sX#+9, and X#X#+ 1 X#+2X#+3 (X#+4)X#+sX#+eX#+7X#+8X#+9, and X#X#+iX#+2(X#+3)X#+4X#+sX#+6X#+7X#+8X#+9, and X#X#+i(X#+2)X#+3X#+4X#+sX#+6X#+7X#+8X#+9, and X#-iX#X#+iX#+2X#+3X#+4(X#+s)X#+6X#+7X#+8X#+9, and X#+iX#+2X#+3X#+4(X#+s)X#+6X#+7X#+8X#+9, wherein the peptide conjugate of the first and second peptide conjugate / MHC complex is formed by the covalent reaction of the first targeted covalent inhibitor, second targeted covalent inhibitor or fragment thereof with the residue in parenthesis; and (b) the same MHC; wherein the polypeptide binds to the first peptide conjugate / MHC complex with a KD that is at most 100 nM and binds to the second peptide conjugate / MHC complex with an KD that is at most 100 nM, or wherein when the polypeptide is contacted to the first peptide conjugate / MHC complex a maximum wavelength shift of at least 0.1 nm is observed according to a background-subtracted biolayer interferometry analysis and wherein when the polypeptide is contacted to the second peptide conjugate / MHC complex a maximum wavelength shift of at least 0.1 nm is observed according to the biolayer interferometry analysis, or wherein when the polypeptide is contacted to the first peptide conjugate / MHC complex a maximum binding signal of at least 0.1-fold of a reference binding signal is observed according to a background-subtracted biolayer interferometry analysis and wherein when the polypeptide is contacted to the second peptide conjugate / MHC complex a maximum binding signal of at least 0.1-fold of a reference binding signal is observed according to the background-subtracted biolayer interferometry analysis, and wherein the reference binding signal is the maximum binding signal of the polypeptide binding to X#X#+ 1 X#+2X#+3X#+4(X#+5)X#+6X#+7X#+8X#+9.

[0289] In some embodiments, the formula X#X#+iX#+2X#+3X#+4(X#+s)X#+6X#+7X#+8X#+9 is the formula X7X8X9X10X11X12X13X14X15X16, and wherein X12 is covalently linked to the first targeted covalent inhibitor, second targeted covalent inhibitor or fragment thereof.

[0290] In some embodiments, the polypeptide binds to the first peptide conjugate / MHC complex and the second peptide conjugate / MHC complex, wherein each of the first and the second peptide conjugate / MHC complex comprises: a peptide comprising the formula X7X8X9X10X11X12X13X14X15X16; and the same MHC; wherein the first peptide conjugate of the first peptide conjugate / MHC complex is formed by the covalent reaction of the first targeted covalent inhibitor or fragment thereof with X12 of the peptide, and wherein the second peptide conjugate of the second peptide conjugate / MHC complex is formed by the covalent reaction of the second targeted covalent inhibitor or fragment thereof with X13 of the peptide, wherein the second targeted covalent inhibitor is the same as the first targeted covalent inhibitor; and wherein the polypeptide binds to the second peptide conjugate / MHC complex with a KD that is at most 100,000-fold higher than the KD of the polypeptide to the first peptide conjugate / MHC complex, or wherein a maximum wavelength shift of the polypeptide binding to the second peptide conjugate / MHC complex is at least 10-fold less than a maximum wavelength shift of the polypeptide binding to the first peptide conjugate / MHC complex, or wherein a maximum binding signal of the polypeptide binding to the second peptide conjugate / MHC complex is at least 10-fold less than a maximum binding signal of the polypeptide binding to the first peptide conjugate / MHC complex.

[0291] In some embodiments, the polypeptide binds to the first peptide conjugate / MHC complex and the second peptide conjugate / MHC complex, wherein each of the first and the second peptide conjugate / MHC complex comprises: a peptide comprising the formula X7X8X9X10X11X12X13X14X15X16; and the same MHC; wherein the first peptide conjugate of the first peptide conjugate / MHC complex is formed by the covalent reaction of the first targeted covalent inhibitor or fragment thereof with a residue selected from the group consisting of X9, X10, X11, and X12, and wherein the second peptide conjugate of the second peptide conjugate / MHC complex is formed by the covalent reaction of the second targeted covalent inhibitor or fragment thereof with a residue selected from the group consisting of X13, X14, and X15, wherein the second targeted covalent inhibitor is the same as the first targeted covalent inhibitor; wherein the polypeptide binds to the second peptide conjugate / MHC complex with a KD that is at most 100,000 fold higher that the KD of the polypeptide to the first peptide conjugate / MHC complex, or wherein a maximum wavelength shift of the polypeptide binding to the second peptide conjugate / MHC complex is at least 10- fold less than a maximum wavelength shift of the polypeptide binding to the first peptide conjugate / MHC complex, or wherein a maximum binding signal of the polypeptide binding to the second peptide conjugate / MHC complex is at least 10-fold less than a maximum binding signal of the polypeptide binding to the first peptide conjugate / MHC complex.

[0292] In some embodiments, the polypeptide binds to the first peptide conjugate / MHC complex and the second peptide conjugate / MHC complex, wherein each of the first and the second peptide conjugate / MHC complex comprises: a peptide comprising the formula A-B- C, where A comprises no more than three residues having an N-terminal anchor residue, B comprises at least four but no more than seven residues having a residue covalently linked to the first targeted covalent inhibitor or fragment thereof or the second targeted covalent inhibitor or fragment thereof, and C comprises no more than three residues having a C- terminal anchor residue, wherein the N-terminal anchor residues and the C-terminal anchor residue bind to an MHC; and the same MHC; wherein the residue covalently linked to the first targeted covalent inhibitor or fragment thereof of the peptide of the first peptide conjugate / MHC complex is different from the residue covalently linked to the second targeted covalent inhibitor or fragment thereof of the peptide of the second peptide conjugate / MHC complex; and wherein the polypeptide binds to the first peptide conjugate / MHC complex with a KD that is at most 100 nM and binds to the second peptide conjugate / MHC complex with a KD that is at most 100 nM, or wherein when the polypeptide is contacted to the first peptide conjugate / MHC complex a maximum wavelength shift of at least 0.1 nm is observed according to a background- subtracted biolayer interferometry analysis and wherein when the polypeptide is contacted to the second peptide conjugate / MHC complex a maximum wavelength shift of at least 0.1 nm is observed according to the background-subtracted biolayer interferometry analysis, or wherein when the polypeptide is contacted to the first peptide conjugate / MHC complex a maximum binding signal of at least 0.1-fold of a reference binding signal is observed according to a background- subtracted biolayer interferometry analysis and wherein when the polypeptide is contacted to the second peptide conjugate / MHC complex a maximum binding signal of at least 0.1 -fold of a reference binding signal is observed according to the background- subtracted biolayer interferometry analysis, and wherein the reference binding signal is the maximum binding signal of the polypeptide binding to X#X#+ 1 X#+2X#+3X#+4(X#+5)X#+6X#+7X#+8X#+9. In some embodiments, A comprises two residues X?Xs. In some embodiments, B comprises seven residues X9X10X11X12X13X14X15. In some embodiments, C comprises one residue Xi6.

[0293] In some embodiments, the formula A-B-C is the formula X7X8X9X10X11X12X13X14X15X16. In some embodiments, the first peptide conjugate of the first peptide conjugate / MHC complex is formed by the covalent reaction of the first targeted covalent inhibitor or fragment thereof with X12 of the peptide. In some embodiments, the second peptide conjugate of the second peptide conjugate / MHC complex is formed by the covalent reaction of the second targeted covalent inhibitor or fragment thereof with X13 of the peptide, wherein the second targeted covalent inhibitor is the same as the first targeted covalent inhibitor. In some embodiments, the polypeptide binds to the second peptide conjugate / MHC complex with a KD that is at most 100,000 fold higher than the KD of the polypeptide to the first peptide conjugate / MHC complex.

[0294] In some embodiments, the polypeptide binds to the second peptide conjugate / MHC complex with an KD that is at most 100,000 fold higher than the KD of the polypeptide to the first peptide conjugate / MHC complex, and wherein the residue covalently linked to the first targeted covalent inhibitor or fragment thereof of the peptide of the first peptide conjugate / MHC complex is selected from the group of consisting of X9, X10, X11, and X12, and the residue covalently linked to the second targeted covalent inhibitor or fragment thereof of the peptide of the second peptide conjugate / MHC complex is X13, X14, and X15.

[0295] In some embodiments, the peptide is a RAS peptide. In some embodiments, the RAS peptide comprises a mutation. In some embodiments, the mutation is G12C or G13C. In some embodiments, the RAS peptide comprises a sequence selected from the group consisting of VVVGACGVGK, VVGACGVGK, and KLVVVGACGV. In some embodiments, the RAS peptide comprises a sequence selected from the group consisting of VVVGAGCVGK, VVGAGCVGK, or KLVVVGAGCV. In some embodiments, the same MHC is selected from the group consisting of HL A-A* 03:01, HLA-A* 11 :01, HLA-A*02:01, HLA-A*68:01, HLA- A*31:01, HLA-A*30:01, HLA-A*33:03, HLA-A*33:01, HLA-A*74:01, HLA-A*34:02, HLA-A*66:01, HLA-A*68:02, HLA-A*02:05, HLA-A*02:02, and HLA-A* 02: 06. In some embodiments, the targeted covalent inhibitor or fragment thereof comprises sotorasib. In some embodiments, the peptide is a RAS peptide, and wherein X12 is G12C mutation, and X13 is G13C mutation.

[0296] In some embodiments, the polypeptide binds to the first peptide conjugate / MHC complex having a Cys of the G12C mutation covalently linked to the first targeted covalent inhibitor or fragment thereof with a KD that is at most 100 nM and binds to the second peptide conjugate / MHC complex having a Cys of the G13C mutation covalently linked to the second targeted covalent inhibitor or fragment thereof with an KD that is most 100 nM, or wherein when the polypeptide is contacted to the first peptide conjugate / MHC complex a maximum wavelength shift of at least 0.1 nm is observed according to a background- subtracted biolayer interferometry analysis and wherein when the polypeptide is contacted to the second peptide conjugate / MHC complex a maximum wavelength shift of at least 0.1 nm is observed according to the background- subtracted biolayer interferometry analysis, or wherein when the polypeptide is contacted to the first peptide conjugate / MHC complex a maximum binding signal of at least 0.1-fold of a reference binding signal is observed according to a background-subtracted biolayer interferometry analysis and wherein when a polypeptide is contact to the second peptide conjugate / MHC complex a maximum binding signal of at least 0.1 -fold of a reference binding signal is observed according to a background- subtracted biolayer interferometry analysis, and wherein the reference binding signal is the maximum binding signal of the polypeptide binding to X#X#+lX#+2X#+3X#+4X#+5X#+6X#+7X#+8X#+9.

[0297] In some embodiments, the polypeptide binds to the second peptide conjugate / MHC complex having a Cys of the G13C mutation covalently linked to the second targeted covalent inhibitor or fragment thereof with a KD that is at most 100,000 fold higher that the KD of the polypeptide to the first peptide conjugate / MHC complex having a Cys of the G12C mutation covalently linked to the first targeted covalent inhibitor or fragment thereof, or wherein a maximum wavelength shift of the polypeptide binding to the second peptide conjugate / MHC complex is at least 10-fold less than a maximum wavelength shift of the polypeptide binding to the first peptide conjugate / MHC complex, or wherein a maximum binding signal of the polypeptide binding to the second peptide conjugate / MHC complex is at least 10-fold less than a maximum binding signal of the polypeptide binding to the first peptide conjugate / MHC complex.

[0298] In some aspects, the present disclosure provides a composition comprising: a polypeptide that binds to a first peptide conjugate / MHC complex and a second peptide conjugate / MHC complex different from the first peptide conjugate / MHC complex, wherein each of the first and second peptide conjugate / MHC complexes independently comprises: a different peptide selected from the group consisting of peptides comprising the formula X#X#+iX#+2X#+3X#+4(X#+s)X#+6X#+7X#+8X#+9, and X#X#+ 1 X#+2X#+3 (X#+4)X#+sX#+eX#+7X#+8X#+9, and X#X#+iX#+2(X#+3)X#+4X#+sX#+6X#+7X#+8X#+9, and X#X#+i(X#+2)X#+3X#+4X#+sX#+6X#+7X#+8X#+9, and X#-iX#X#+iX#+2X#+3X#+4(X#+s)X#+6X#+7X#+8X#+9, and X#+iX#+2X#+3X#+4(X#+s)X#+6X#+7X#+8X#+9, wherein the peptide conjugate of the first and second peptide conjugate / MHC complex is formed by the covalent reaction of a targeted covalent inhibitor or fragment thereof with the residue in parenthesis; and (b) the same MHC; wherein the polypeptide binds to the first peptide conjugate / MHC complex with an KD that is at most 100 nM and binds to the second peptide conjugate / MHC complex with an KD that is at most 100 nM, or wherein when the polypeptide is contacted to the first peptide conjugate / MHC complex a maximum wavelength shift of at least 0.1 nm is observed according to a background-subtracted biolayer interferometry analysis and wherein when the polypeptide is contacted to the second peptide conjugate / MHC complex a maximum wavelength shift of at least 0.1 nm is observed according to the background- subtracted biolayer interferometry analysis, or wherein when the polypeptide is contacted to the first peptide conjugate / MHC complex a maximum binding signal of at least 0.1 -fold of a reference binding signal is observed according to a background-subtracted biolayer interferometry analysis and wherein when the polypeptide is contacted to the second peptide conjugate / MHC complex a maximum binding signal of at least 0.1-fold of a reference binding signal is observed according to the background-subtracted biolayer interferometry analysis, and wherein the reference binding signal is the maximum binding signal of the polypeptide binding to X#X#+iX#+2X#+3X#+4(X#+s)X#+6X#+7X#+8X#+9.

[0299] In some embodiments, each of the first and second peptide conjugate / MHC complexes independently comprises: a different peptide selected from the group consisting of peptides comprising the formula X#X#+iX#+2X#+3X#+4(X#+s)X#+6X#+7X#+8X#+9, and X#X#+ 1 X#+2X#+3 (X#+4)X#+sX#+eX#+7X#+8X#+9, and X#X#+iX#+2(X#+3)X#+4X#+sX#+6X#+7X#+8X#+9, and X#X#+l(X#+2)X#+3X#+4X#+5X#+6X#+7X#+8X#+9.

[0300] In some embodiments, each of the first and second peptide conjugate / MHC complexes independently comprises: a different peptide with an amino acid sequence selected from the group consisting of: VVVGACGVGK, VVVGCGGVGK, VVVCAGGVGK, and VVCGAGGVGK.

[0301] In some aspects, the present disclosure provides a composition that binds to a first peptide conjugate / MHC complex and a second peptide conjugate / MHC complex, wherein each of the first and the second peptide conjugate / MHC complex comprises: a peptide comprising the formula X7X8X9X10X11X12X13X14X15X16; and the same MHC; wherein a first peptide conjugate of the first peptide conjugate / MHC complex is formed by the covalent reaction of a targeted covalent inhibitor or fragment thereof with X12 of the peptide, and wherein a second peptide conjugate of the second peptide conjugate / MHC complex is formed by the covalent reaction of the same targeted covalent inhibitor or fragment thereof with X13 of the peptide; wherein a polypeptide binds to the second peptide conjugate / MHC complex with a KD that is at most 100,000 fold higher than the KD of the polypeptide to the first peptide conjugate / MHC complex, or wherein a maximum wavelength shift of the polypeptide binding to the second peptide conjugate / MHC complex is at least 10-fold less than a maximum wavelength shift of the polypeptide binding to the first peptide conjugate / MHC complex, or wherein a maximum binding signal of the polypeptide binding to the second peptide conjugate / MHC complex is at least 10-fold less than a maximum binding signal of the polypeptide binding to the first peptide conjugate / MHC complex.

[0302] In some aspects, the present disclosure provides a composition that binds to a first peptide conjugate / MHC complex and a second peptide conjugate / MHC complex, wherein each of the first and the second peptide conjugate / MHC complex comprises: a peptide comprising the formula X7X8X9X10X11X12X13X14X15X16; and the same MHC; wherein a first peptide conjugate of the first peptide conjugate / MHC complex is formed by the covalent reaction of a targeted covalent inhibitor or fragment thereof with a residue selected from the group consisting of X9, X10, X11, and X12, and wherein a second peptide conjugate of the second peptide conjugate / MHC complex is formed by the covalent reaction of the same targeted covalent inhibitor or fragment thereof with a residue selected from the group consisting of X13, X14, and X15; wherein a polypeptide binds to the second peptide conjugate / MHC com-plex with a KD that is at most 100,000 fold higher that the KD of the polypeptide to the first peptide conjugate / MHC complex, or wherein a maximum wavelength shift of the polypeptide binding to the second peptide conjugate / MHC complex is at least 10-fold less than a maximum wavelength shift of the polypeptide binding to the first peptide conjugate / MHC complex, or wherein a maximum binding signal of the polypeptide binding to the second peptide conjugate / MHC complex is at least 10-fold less than a maximum binding signal of the polypeptide binding to the first peptide conjugate / MHC complex.

[0303] In some aspects, the present disclosure provides a composition that binds to a first peptide conjugate / MHC complex and a second peptide conjugate / MHC complex, wherein each of the first and the second peptide conjugate / MHC complex comprises: a peptide comprising the formula A-B-C, where A comprises no more than three residues having an N- terminal anchor residue, B comprises at least four but no more than seven residues having a residue covalently linked to a targeted covalent inhibitor or fragment thereof, and C comprises no more than three residues having a C-terminal anchor residue, wherein the N- terminal anchor residues and the C-terminal anchor residue bind to an MHC; and the same MHC; wherein the residue covalently linked to a targeted covalent inhibitor or fragment thereof of the peptide of the first peptide conjugate / MHC complex is different from the residue covalently linked to a targeted covalent inhibitor or fragment thereof of the peptide of the second peptide conjugate / MHC complex; and wherein a polypeptide binds to the first peptide conjugate / MHC complex with a KD that is at most 100 nM and binds to the second peptide conjugate / MHC complex with a KD that is at most 100 nM, or wherein when the polypeptide is contacted to the first peptide conjugate / MHC complex a maximum wavelength shift of at least 0.1 nm is observed according to a background- subtracted biolayer interferometry analysis and wherein when the polypeptide is contacted to the second peptide conjugate / MHC complex a maximum wavelength shift of at least 0.1 nm is observed according to the background-subtracted biolayer interferometry analysis, or wherein when the polypeptide is contacted to the first peptide conjugate / MHC complex a maximum binding signal of at least 0.1 -fold of a reference binding signal is observed according to a background- subtracted biolayer interferometry analysis and wherein when the polypeptide is contacted to the second peptide conjugate / MHC complex a maximum binding signal of at least 0.1 -fold of a reference binding signal is observed according to the background- subtracted biolayer interferometry analysis, and wherein the reference binding signal is the maximum binding signal of the polypeptide binding to X#X#+ 1 X#+2X#+3X#+4(X#+5)X#+6X#+7X#+8X#+9.

[0304] In some embodiments, A comprises two residues X?Xs. In some embodiments, B comprises seven residues X9X10X11X12X13X14X15. In some embodiments, C comprises one residue Xi6. In some embodiments, the formula A-B-C is the formula X7X8X9X10X11X12X13X14X15X16. In some embodiments, a first peptide conjugate of the first peptide conjugate / MHC complex is formed by the covalent reaction of the targeted covalent inhibitor or fragment thereof with X12 of the peptide. In some embodiments, a second peptide conjugate of the second peptide conjugate / MHC complex is formed by the covalent reaction of the same targeted covalent inhibitor or fragment thereof with X13 of the peptide. In some embodiments, the polypeptide binds to the second peptide conjugate / MHC complex with a KD that is at most 100,000 fold higher than the KD of the polypeptide to the first peptide conjugate / MHC complex.

[0305] In some embodiments, the polypeptide binds to the second peptide conjugate / MHC complex with an KD that is at most 100,000 fold higher than the KD of the polypeptide to the first peptide conjugate / MHC complex, and wherein the residue covalently linked to the targeted covalent inhibitor or fragment thereof of the peptide of the first peptide conjugate / MHC complex is selected from the group of consisting of X9, X10, X11, and X12, and the residue covalently linked to the targeted covalent inhibitor or fragment thereof of the peptide of the second peptide conjugate / MHC complex is X13, X14, and X15.

[0306] In some embodiments, the peptide is a RAS peptide. In some embodiments, the RAS peptide comprises a mutation. In some embodiments, the mutation is G12C or G13C. In some embodiments, the RAS peptide comprises a sequence selected from the group consisting of VVVGACGVGK, VVGACGVGK, and KLVVVGACGV. In some embodiments, the RAS peptide comprises a sequence selected from the group consisting of VVVGAGCVGK, VVGAGCVGK, or KLVVVGAGCV. In some embodiments, the same MHC is selected from the group consisting of HL A- A* 03: 01, HLA-A* 11:01, HLA-A*02:01, HLA-, HLA- A*68:01, HLA-A*31:01, HLA-A*30:01, HLA-A*33:03, HLA-A*33:01, HLA-A*74:01, HLA-A*34:02, HLA-A*66:01, HLA-A*68:02, HLA-A*02:05, HLA-A*02:02, and HLA- A*02:06. In some embodiments, the targeted covalent inhibitor or fragment thereof comprises sotorasib. In some embodiments, the peptide is a RAS peptide, and wherein X12 is G12C mutation, and X13 is G13C mutation.

[0307] In some embodiments, the polypeptide binds to the first peptide conjugate / MHC complex having a Cys of the G12C mutation covalently linked to the targeted covalent inhibitor or fragment thereof with an KD that is at most 100 nM and binds to the second peptide conjugate / MHC complex having a Cys of the G13C mutation covalently linked to the targeted covalent inhibitor or fragment thereof with an KD that is at most 100 nM, or wherein when the polypeptide is contacted to the first peptide conjugate / MHC complex a maximum wavelength shift of at least 0.1 nm is observed according to a background- subtracted biolayer interferometry analysis and wherein when the polypeptide is contacted to the second peptide conjugate / MHC complex a maximum wavelength shift of at least 0.1 nm is observed according to the background-subtracted biolayer interferometry analysis, or wherein when the polypeptide is contacted to the first peptide conjugate / MHC complex a maximum binding signal of at least 0.1-fold of a reference binding signal is observed according to a background- subtracted biolayer interferometry analysis and wherein when the polypeptide is contacted to the second peptide conjugate / MHC complex a maximum binding signal of at least 0.1 -fold of a reference binding signal is observed according to the background- subtracted biolayer interferometry analysis, and wherein the reference binding signal is the maximum binding signal of the polypeptide binding to X#X#+ 1 X#+2X#+3X#+4(X#+5)X#+6X#+7X#+8X#^9.

[0308] In some embodiments, the polypeptide binds to the second peptide conjugate / MHC complex having a Cys of the G13C mutation covalently linked to the targeted covalent inhibitor or fragment thereof with a KD that is at most 100,000 fold higher that the KD of the polypeptide to the first peptide conjugate / MHC complex having a Cys of the G12C mutation covalently linked to the targeted covalent inhibitor or fragment thereof, or wherein a maximum wavelength shift of the polypeptide binding to the second peptide conjugate / MHC complex is at least 10-fold less than a maximum wavelength shift of the polypeptide binding to the first peptide conjugate / MHC complex, or wherein a maximum binding signal of the polypeptide binding to the second peptide conjugate / MHC complex is at least 10-fold less than a maximum binding signal of the polypeptide binding to the first peptide conjugate / MHC complex.

[0309] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein: (a) the VH comprises: (i) a HC CDR3 comprising the amino acid sequence of FX2X3X4AMDY, wherein X2 is Y, L, T, H, E, A, or R; X3 is D, V, L, E, H, T or R; and X4is L or Y (SEQ ID NO: 267); and / or (b) the VL comprises: (i) a LC CDR3 comprising the amino acid sequence of QQX3SWLX7WX9X10T, wherein X3 is A or S, X7 is Y or H, X9is L, K, V, Y or I, and X10 is L, V, or I (SEQ ID NO: 268).

[0310] In some embodiments, the VH comprises: a HC CDR3 comprising the amino acid sequence of FX2X3X4AMDY, wherein X2 is Q, Y, L, T, H, E, A, or R; X3 is W, D, V, L, E, H, T or R; and X4 is L or Y.

[0311] In some embodiments, the VH comprises a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes. In some embodiments, the VH comprises a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VL comprises a LC CDR1 comprising an amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes. In some embodiments, the VL comprises a LC CDR2 comprising an amino acid sequence of SASSLYS, or a variant thereof comprising 1-3 amino acid changes. In some embodiments, the VH comprises: a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or a HC CDR3 comprising an amino acid sequence of FX2X3X4AMDY, wherein X2 is Y, L, T, H, E, A, or R; X3 is D, V, L, E, H, T or R; and X4 is L or Y. In some embodiments, the VL comprises: a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-3 amino acid changes, and / or a LC CDR3 comprising the amino acid sequence of QQX3SWLX7WX9X10T, wherein X3 is A or S, X7 is Y or H, X9is L, K, V, Y or I, and X10 is L, V, or I.

[0312] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FYDLAMDY (SEQ ID NO.: 273).

[0313] In some embodiments, the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 272). In some embodiments, the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 271). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQASWLYWLIT (SEQ ID NO.: 276). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 275). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 274). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 271), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 272), a HC CDR3 sequence of FYDLAMDY (SEQ ID NO: 273), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 274), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 275), and a LC CDR3 sequence of QQASWLYWLIT (SEQ ID NO: 276). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGL VQPGGSLRLSC AASGFTF S S S SMWVRQAPGKGLEWVASIS S SSGST SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFYDLAMDYWGQGTLV TVSS (SEQ ID NO.: 270). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWLITFGQGTKVEIK (SEQ ID NO.: 269).

[0314] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FLDLAMDY (SEQ ID NO.: 281). In some embodiments, the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 280). In some embodiments, the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 279). In some embodiments, the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQASWLYWKIT (SEQ ID NO.: 284). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 283). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 282). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 279), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 280), a HC CDR3 sequence of FLDLAMDY (SEQ ID NO: 281), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 282), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 283), and a LC CDR3 sequence of QQASWLYWKIT (SEQ ID NO: 284). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGL VQPGGSLRLSC AASGFTF S S S SMWVRQAPGKGLEWVASIS S SSGST SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFLDLAMDYWGQGTLV TVSS (SEQ ID NO.: 278). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWKITFGQGTKVEIK (SEQ ID NO.: 277).

[0315] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FTVLAMDY (SEQ ID NO.: 289).

[0316] In some embodiments, the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 288). In some embodiments, the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 287). In some embodiments, the antigen- binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQASWLYWLIT (SEQ ID NO.: 292). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 291). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 290). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 287), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 288), a HC CDR3 sequence of FTVLAMDY (SEQ ID NO.: 289), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 290), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 291), and a LC CDR3 sequence of QQASWLYWLIT (SEQ ID NO.: 292). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence

[0317] EVQLVESGGGL VQPGGSLRLSC AASGFTF S S S SMWVRQAPGKGLEWVASIS S SSGST SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFTVLAMDYWGQGTLV TVSS (SEQ ID NO.: 286). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence

[0318] DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWLITFGQGTKVEIK (SEQ ID NO.: 285).

[0319] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FTVLAMDY (SEQ ID NO.: 297).

[0320] In some embodiments, the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 296). In some embodiments, the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 295). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQASWLYWKVT (SEQ ID NO.: 300). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 299). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 298). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 295), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 296), a HC CDR3 sequence of FTVLAMDY (SEQ ID NO.: 297), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 297), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 298), and a LC CDR3 sequence of QQASWLYWKVT (SEQ ID NO.: 300). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence

[0321] EVQLVESGGGL VQPGGSLRLSCAASGFTFSSSS WVRQAPGKGLEWVASISSSSGST SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFTVLAMDYWGQGTLV TVSS (SEQ ID NO.: 294). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWKVTFGQGTKVEIK (SEQ ID NO.: 293).

[0322] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FTVLAMDY (SEQ ID NO.: 305).

[0323] In some embodiments, the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 304). In some embodiments, the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 303). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQASWLYWVIT (SEQ ID NO.: 308). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 307). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 306). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 303), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 304), a HC CDR3 sequence of FTVLAMDY (SEQ ID NO.: 305), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 306), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 307), and a LC CDR3 sequence of QQASWLYWVIT (SEQ ID NO.: 308). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGL VQPGGSLRLSC AASGFTF S S S SMWVRQAPGKGLEWVASIS S SSGST SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFTVLAMDYWGQGTLV TVSS (SEQ ID NO.: 302). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWVITFGQGTKVEIK (SEQ ID NO.: 301). In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FHDLAMDY (SEQ ID NO.: 313).

[0324] In some embodiments, the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 312). In some embodiments, the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 311). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQASWLYWKIT (SEQ ID NO.: 316). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 315). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 314). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 311), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 312), a HC CDR3 sequence of FHDLAMDY (SEQ ID NO.: 313), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 314), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 315), and a LC CDR3 sequence of QQASWLYWKIT (SEQ ID NO.: 316). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGL VQPGGSLRLSC AASGFTF S S S SMWVRQAPGKGLEWVASIS S SSGST SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFHDLAMDYWGQGTLV TVSS (SEQ ID NO.: 310). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWKITFGQGTKVEIK (SEQ ID NO.: 309).

[0325] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FHELAMDY (SEQ ID NO.: 321).

[0326] In some embodiments, the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 320). In some embodiments, the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 319). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQASWLYWLIT (SEQ ID NO.: 324). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 323). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 322). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 319), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 320), a HC CDR3 sequence of FHELAMDY (SEQ ID NO.: 321), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 322), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 323), and a LC CDR3 sequence of QQASWLYWLIT (SEQ ID NO.: 324). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence

[0327] EVQLVESGGGL VQPGGSLRLSC AASGFTF S S S SMWVRQAPGKGLEWVASIS S SSGST SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFHELAMDYWGQGTLV TVSS (SEQ ID NO.: 318). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence

[0328] DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWLITFGQGTKVEIK (SEQ ID NO.: 317).

[0329] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FTVLAMDY (SEQ ID NO.: 329).

[0330] In some embodiments, the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 328). In some embodiments, the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 327). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSSWLYWKIT (SEQ ID NO.: 332). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 331). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 330). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 327), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 328), a HC CDR3 sequence of FTVLAMDY (SEQ ID NO.: 329), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 330), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 331), and a LC CDR3 sequence of QQSSWLYWKIT (SEQ ID NO.: 332). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGL VQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGST SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFTVLAMDYWGQGTLV TVSS (SEQ ID NO.: 326). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWKITFGQGTKVEIK (SEQ ID NO.: 325).

[0331] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FELLAMDY (SEQ ID NO.: 337).

[0332] In some embodiments, the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 336). In some embodiments, the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 335). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSSWLYWKIT (SEQ ID NO.: 340). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 339). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 338). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 335), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 336), a HC CDR3 sequence of FELLAMDY (SEQ ID NO.: 337), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 338), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 339), and a LC CDR3 sequence of QQSSWLYWKIT (SEQ ID NO.: 340). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGL VQPGGSLRLSC AASGFTF S S S SIHWVRQAPGKGLEWVASIS S SSGST SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFELLAMDYWGQGTLV TVSS (SEQ ID NO.: 334). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWKITFGQGTKVEIK (SEQ ID NO.: 333).

[0333] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FTVLAMDY (SEQ ID NO.: 345).

[0334] In some embodiments, the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 344). In some embodiments, the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 343). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSSWLYWKVT (SEQ ID NO.: 348). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 347). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 346). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 343), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 344), a HC CDR3 sequence of FTVLAMDY (SEQ ID NO.: 345), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 346), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 347), and a LC CDR3 sequence of QQSSWLYWKVT (SEQ ID NO.: 348). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGL VQPGGSLRLSC AASGFTF S S S SMWVRQAPGKGLEWVASIS S SSGST SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFTVLAMDYWGQGTLV TVSS (SEQ ID NO.: 342). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWKVTFGQGTKVEIK (SEQ ID NO.: 341).

[0335] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FYDLAMDY (SEQ ID NO.: 353).

[0336] In some embodiments, the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 352). In some embodiments, the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 351). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSSWLYWKVT (SEQ ID NO.: 356). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 355). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 354). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 351), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 352), a HC CDR3 sequence of FYDLAMDY (SEQ ID NO.: 353), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 354), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 355), and a LC CDR3 sequence of QQSSWLYWKVT (SEQ ID NO.: 356). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence

[0337] EVQLVESGGGL VQPGGSLRLSC AASGFTF S S S SMWVRQAPGKGLEWVASIS S SSGST SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFYDLAMDYWGQGTLV TVSS (SEQ ID NO.: 350). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWKVTFGQGTKVEIK (SEQ ID NO.: 349).

[0338] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FHELAMDY (SEQ ID NO.: 361).

[0339] In some embodiments, the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 360). In some embodiments, the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 359). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQASWLYWLIT (SEQ ID NO.: 364). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 363). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 362). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 359), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 360), a HC CDR3 sequence of FHELAMDY (SEQ ID NO.: 361), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 362), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 363), and a LC CDR3 sequence of QQASWLYWLIT (SEQ ID NO.: 364). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGL VQPGGSLRLSC AASGFTF S S S SMWVRQAPGKGLEWVASIS S SSGST SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFHELAMDYWGQGTLV TVSS (SEQ ID NO.: 358). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWLITFGQGTKVEIK (SEQ ID NO.: 357).

[0340] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FTVLAMDY (SEQ ID NO.: 369).

[0341] In some embodiments, the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 368). In some embodiments, the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 367). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQASWLYWKVT (SEQ ID NO.: 372). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 371). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 370). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 367), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 368), a HC CDR3 sequence of FTVLAMDY (SEQ ID NO.: 369), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 370), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 371), and a LC CDR3 sequence of QQASWLYWKVT (SEQ ID NO.: 372). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGL VQPGGSLRLSC AASGFTF S S S SMWVRQAPGKGLEWVASIS S SSGST SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFTVLAMDYWGQGTLV TVSS (SEQ ID NO.: 366). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWKVTFGQGTKVEIK (SEQ ID NO.: 365).

[0342] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FYDLAMDY (SEQ ID NO.: 377). In some embodiments, the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 376). In some embodiments, the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 375). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSSWLYWVIT (SEQ ID NO.: 380). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 379). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 378). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 375), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 376), a HC CDR3 sequence of FYDLAMDY (SEQ ID NO.: 377), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 378), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 379), and a LC CDR3 sequence of QQSSWLYWVIT (SEQ ID NO.: 380). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGL VQPGGSLRLSC AASGFTF S S S SMWVRQAPGKGLEWVASIS S SSGST SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFYDLAMDYWGQGTLV TVSS (SEQ ID NO.: 374). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWVITFGQGTKVEIK (SEQ ID NO.: 373).

[0343] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FHELAMDY (SEQ ID NO.: 385).

[0344] In some embodiments, the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 384). In some embodiments, the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 383). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQASWLYWLIT (SEQ ID NO.: 388). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 387). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 386). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 383), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 384), a HC CDR3 sequence of FHELAMDY (SEQ ID NO.: 385), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 386), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 387), and a LC CDR3 sequence of QQASWLYWLIT (SEQ ID NO.: 388). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence

[0345] EVQLVESGGGL VQPGGSLRLSC AASGFTF S S S SMWVRQAPGKGLEWVASIS S SSGST SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFHELAMDYWGQGTLV TVSS (SEQ ID NO.: 382). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWLITFGQGTKVEIK (SEQ ID NO.: 381).

[0346] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FAHLAMDY (SEQ ID NO.: 393).

[0347] In some embodiments, the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 392). In some embodiments, the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 391). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSSWLYWLIT (SEQ ID NO.: 396). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 395). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 394). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 391), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 392), a HC CDR3 sequence of FAHLAMDY (SEQ ID NO.: 393), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 394), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 395), and a LC CDR3 sequence of QQSSWLYWLIT (SEQ ID NO.: 396). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGL VQPGGSLRLSC AASGFTF S S S SMWVRQAPGKGLEWVASIS S SSGST SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFAHLAMDYWGQGTLV TVSS (SEQ ID NO.: 390). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWLITFGQGTKVEIK (SEQ ID NO.: 389).

[0348] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FEDLAMDY (SEQ ID NO.: 401).

[0349] In some embodiments, the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 400). In some embodiments, the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 399). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQASWLYWYIT (SEQ ID NO.: 404). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 403). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 402). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 399), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 400), a HC CDR3 sequence of FEDLAMDY (SEQ ID NO.: 401), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 402), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 403), and a LC CDR3 sequence of QQASWLYWYIT (SEQ ID NO.: 404). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGL VQPGGSLRLSC AASGFTF S S S SMWVRQAPGKGLEWVASIS S SSGST SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFEDLAMDYWGQGTLV TVSS (SEQ ID NO.: 398). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWYITFGQGTKVEIK (SEQ ID NO.: 397).

[0350] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FRTLAMDY (SEQ ID NO.: 409).

[0351] In some embodiments, the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 408). In some embodiments, the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 407). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSSWLYWIIT (SEQ ID NO.: 412). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 411). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 410). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 407), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 408), a HC CDR3 sequence of FRTLAMDY (SEQ ID NO.: 409), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 410), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 411), and a LC CDR3 sequence of QQSSWLYWIIT (SEQ ID NO.: 412). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence

[0352] EVQLVESGGGL VQPGGSLRLSC AASGFTF S S S SMWVRQAPGKGLEWVASIS S SSGST SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFRTLAMDYWGQGTLV TVSS (SEQ ID NO.: 406). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence

[0353] DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWIITFGQGTKVEIK (SEQ ID NO.: 405).

[0354] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FTHYAMDY (SEQ ID NO.: 417).

[0355] In some embodiments, the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 416). In some embodiments, the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 415). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSSWLYWKIT (SEQ ID NO.: 420). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 419). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 418). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 415), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 416), a HC CDR3 sequence of FTHYAMDY (SEQ ID NO.: 417), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 418), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 419), and a LC CDR3 sequence of QQSSWLYWKIT (SEQ ID NO.: 420). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence

[0356] EVQLVESGGGL VQPGGSLRLSCAASGFTFSSSS WVRQAPGKGLEWVASISSSSGST SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFTHYAMDYWGQGTLV TVSS (SEQ ID NO.: 414). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWKITFGQGTKVEIK (SEQ ID NO.: 413).

[0357] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FRLYAMDY (SEQ ID NO.: 425).

[0358] In some embodiments, the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 424). In some embodiments, the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 423). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQASWLHWKLT (SEQ ID NO.: 428). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 427). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 426). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 423), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 424), a HC CDR3 sequence of FRLYAMDY (SEQ ID NO.: 425), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 426), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 427), and a LC CDR3 sequence of QQASWLHWKLT (SEQ ID NO.: 428). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGL VQPGGSLRLSC AASGFTF S S S SMWVRQAPGKGLEWVASIS S SSGST SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFRLYAMDYWGQGTLV TVSS (SEQ ID NO.: 422). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLHWKLTFGQGTKVEIK (SEQ ID NO.: 421).

[0359] In an aspect, the present disclosure provides a composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FHRLAMDY (SEQ ID NO.: 433).

[0360] In some embodiments, the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 432). In some embodiments, the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 431). In some embodiments, the antigenbinding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQASWLHWKLT (SEQ ID NO.: 436). In some embodiments, the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 435). In some embodiments, the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 434). In some embodiments, the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 431), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 432), a HC CDR3 sequence of FHRLAMDY (SEQ ID NO.: 433), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 434), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 435), and a LC CDR3 sequence of QQASWLHWKLT (SEQ ID NO.: 436). In some embodiments, the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGL VQPGGSLRLSC AASGFTF S S S SMWVRQAPGKGLEWVASIS S SSGST SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFHRLAMDYWGQGTLV TVSS (SEQ ID NO.: 430). In some embodiments, the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLHWKLTFGQGTKVEIK (SEQ ID NO.: 429).

[0361] In an example, a method of the disclosure includes a method of treating an individual who has received a drug that forms a peptide-drug conjugate by administering a means for specifically binding the peptide-drug conjugate in a complex with an MCH. The means may bind with greater affinity to the peptide-drug conjugate in a complex with an MCH than the affinity the means has for the free drug, or may not detectably bind the free drug. The method of using the means may be used with an individual in need of the means, including but not necessarily limited to a cancer patient, who may have a type of cancer that is resistant to the drug. In an example, the means may bind to two different peptide-drug conjugates that are each present in a different MHC complex.

[0362] BRIEF DESCRIPTION OF THE FIGURES

[0363] FIG. 1 depicts binding of antibody clones to peptide conjugate / MHC complex. The antibody clones were displayed on the yeast cell surface, and binding of the targets conjugated to fluorescently labeled streptavidin was detected by using flow cytometry.

[0364] FIGs. 2A-2C depict binding properties of the RM 010 Fab to peptide conjugate / MHC complex. FIG. 2A shows biolayer interferometry (BLI) sensorgrams of the interaction between peptide conjugate / MHC complexes, with either sotorasib or adagrasib and either HLA-A*03 or HLA-A*11. KD values were estimated from a global fitting curve. FIG. 2B shows BLI sensorgrams of the interaction between RM 010 Fab and adagrasib- P7 / HLA-A*11 in the presence or absence of free adagrasib drug. FIG. 2C shows plotted MHC binding as a function of free-adagrasib concentration. Binding signal intensity was normalized from the value with no free adagrasib and the 0 nm baseline.

[0365] FIGs. 3A-3C depict results of a sotorasib scan. FIG. 3A shows a schematic illustration of the method and the scheme for residues in the panel. Anchor residues are underlined in the sequence. FIG. 3B shows BLI sensorgrams of the binder to the tested soto- p? / MHC complex immobilized on sensor tips. FIG. 3C shows binding signal of the Fab binder to the tested soto-p7 / MHC complexes at 1200 s of the measurement (e.g., Bmax, indicated as the vertical line in FIG. 3B).

[0366] FIGs. 4A-4C depict results of a HLA scan. FIG. 4A shows schematic illustrations of the modified soto-p7 peptides used in the HLA scan. Anchor residues are underlined and the sotorasib -conjugated Cys is highlighted. FIG. 4B shows BLI sensorgrams of the binder to the tested soto-p7 / MHC complexes. FIG. 4C shows binding signal of the Fab binder to the tested soto-p7 / MHC complexes at 1200 s of the measurement (e.g., Bmax, indicated as the vertical line in FIG. 4B).

[0367] FIGs. 5A-5C depict results of a deep mutational scanning and analysis of the variable light (VL) chain region for binding partner RM 010. FIG. 5A shows the residues (underlined) that were diversified in the mutational scanning. FIG. 5B shows enrichment of variants across tested VL positions for adagrasib-p7 in complex with HLA-A*03. FIG. 5C shows enrichment of variants across tested VL positions for adagrasib-p7 in complex with HLA-A*11. FIGs. 6A-6C depict results of a deep mutational scanning and analysis of the variable heavy (VH) chain region for binding partner RM 010. FIG. 6A shows the residues (underlined) that were diversified in the mutational scanning. FIG. 6B shows enrichment of variants across tested VH positions for adagrasib-p7 in complex with HLA-A*03. FIG. 6C shows enrichment of variants across tested VH positions for adagrasib-p7 in complex with HLA-A*11.

[0368] FIG. 7 depicts results of a drug cross-reactivity scan to assess binding response of binding partner RM 010 for peptide-conjugate / MHC complexes with adagrasib (ada- p7 / Al l), sotorasib (soto-p7 / Al l), or divarasib (GDC6036-p7 / Al l). RM_010 showed binding to all complexes at different affinities.

[0369] FIG. 8 depicts results of a sotorasib scan. The location of the covalently bound targeted covalent inhibitor (e.g., sotorasib) on the peptide was varied by introducing a unique cysteine residue to replace the residue at position 7, 9, 10, 11, 12, 13, 14, or 15 of peptide VVVGAGGVGK. Binding partner RM 010 showed the strongest binding response to the peptide-conjugate / MHC complex with haptenated p7 peptide at position 12 (e.g., cysteine residue at position 12 conjugated to the targeted covalent inhibitor).

[0370] FIG. 9 depicts binding of antibody clones to peptide conjugate / MHC complex with adagrasib (adagrasib-p7 / Al 1). Multiple binders showed higher MFI signals after 60 minutes of dissociation in the presence of a nonbiotinylated competitor, compared to MFI signals of the parent clone RM010.

[0371] FIG. 10 depicts binding of antibody clones to peptide conjugate / MHC complex with adagrasib (ada-p7 / Al 1 or ada-p7 / A03). Multiple binders showed higher MFI signals for ada- p7 / Al 1 compared to parent clone RM010, indicating stronger binding. Binder RM119 showed higher MFI signal for ada-p7 / 03 compared to parent clone RM010, indicating stronger binding for this peptide conjugate / MHC complex.

[0372] DETAILED DESCRIPTION

[0373] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0374] Every numerical range given throughout this specification includes its upper and lower values, as well as every narrower numerical range that falls within it, as if such narrower numerical ranges were all expressly written herein. As used in the specification and the appended claims, the singular forms “a” "and” and “the" include plural referents unless the context clearly dictates otherwise. Ranges may be expressed herein as from “about” one particular value, and / or to “about” another particular value. When such a range is expressed, another embodiment includes from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by the use of the antecedent “about” it will be understood that the particular value forms another embodiment. The term “about” in relation to a numerical value encompasses variations of + / -10%, + / - 5%, or + / - 1%.

[0375] This disclosure includes every amino acid sequence described herein and all nucleotide sequences encoding the amino acid sequences. Every antibody sequence and antigen-binding fragments of them are included. Polynucleotide and amino acid sequences having from 80-99% similarity, inclusive, and including all numbers and ranges of numbers there between, with the sequences provided herein, are included in the invention. All of the amino acid sequences described herein can include amino acid substitutions, such as conservative substitutions, that do not adversely affect the function of the protein that comprises the amino acid sequences. In this regard, the disclosure provides alternative residues for certain positions in described binding partner as described below. In certain examples, the alternative residues were identified by deep mutational scanning, which demonstrates binding functionality for each binding partner that contains the described amino acid change(s). The disclosure includes each binding partner with each alternative residue substituted for the original residue alone and in any combination with the described alternative residues. Thus, any binding partner described herein may have any single described residue change or a combination of described changes. Representative changes for particular antibodies are described the Tables. The changes may be in CDR1, CDR2, CDR3, and combinations thereof. The changes can also include amino acid insertions. The disclosure includes each amino acid sequence that is encompassed by the description of alternative amino acids by reference to a specific sequence identifier and those described in the aforementioned Tables.

[0376] As described above, the present disclosure provides antibodies and antigen-binding domains or fragments thereof (collectively “binding partners” and each individually a “binding partner”). The term “antibody” includes each binding partner format herein. The antibody can comprise a polypeptide with an antigen-binding domain or fragment thereof. The binding partners bind with specificity to a protein or fragment thereof, or a peptide provided in peptide form, that comprises a covalently attached molecule. The covalently attached molecule forms a peptide conjugate. A “peptide conjugate” as used herein means any protein or peptide that has been modified so that it is covalently conjugated to another molecule. The peptide conjugate is considered to be a novel antigen, i.e., a neoantigen. The other molecule that is covalently conjugated to the protein or peptide to form the peptide conjugate is not particularly limited, with the proviso that the other molecule is not an additional amino acid that is added to the described peptide conjugates. In embodiments, the molecule that is covalently conjugated to the protein or peptide has or had biological activity before conjugation, or it may be biologically inert before conjugation. In embodiments, the molecule is a drug, including but not necessarily limited to small molecule drugs. As used herein, the molecule that is covalently attached to a peptide to form peptide conjugate is referred to as a “targeted covalent inhibitor (TCI)” or as a “covalent drug.” Representative and non-limiting examples of drugs that covalently attach to a peptide or protein to form a peptide conjugate are described below. Peptide conjugates include but are not limited to covalently modified full length proteins and fragments thereof. Peptide conjugates include fragments of full length proteins that include a covalent modification and are produced, for example, by intracellular processing. In certain embodiments, a full length protein may be covalently modified within a cell and subsequently processed such that a peptide conjugate that is a fragment of the full length protein is produced. In an embodiment, the peptide conjugate comprises a fragment of a full-length protein. As described further below, the produced peptide conjugate may be displayed on a cell surface. The cell surface display of the peptide conjugate may be any form of cell surface display, including but not limited to by way of any receptor having an extracellular segment, or it may be displayed by way of any type of major histocompatibility complex (MHC) or human leukocyte antigen (HLA). Nonlimiting examples of HLA types that display peptide conjugates, and to which the described binding partners bind with specificity, are described further below.

[0377] As used herein, the term “peptide conjugate / MHC complex” refers to a peptide conjugate comprising: a peptide and a chemical fragment of a targeted covalent inhibitor, presented by a major histocompatibility complex (MHC). For example, the peptide conjugate can be formed by the covalent reaction of a targeted covalent inhibitor with a residue (e.g., a cysteine residue) in a peptide. In some embodiments, the peptide conjugate is formed by the covalent reaction of AMG-510 with a KRASG12Cpeptide. In some embodiments, the peptide is externally introduced as a vaccine. In some embodiments, the peptide comprises a nucleophilic or an electrophilic residue. In some embodiments, the residue comprises cysteine, aspartic acid, or arginine. In an embodiment, the MHC is a human leukocyte antigen (HLA). In an embodiment, the HLA is HLA-A*02:01, HLA-A*03:01, or HLA-A*11 :01.

[0378] As used herein, the term “CDR” or “complementarity determining region” means the noncontiguous antigen combining sites found within the variable regions of heavy and light chain polypeptides. These particular regions have been described by, for example, Kabat et al., J. Biol. Chem. 252, 6609-6616 (1977) and Kabat et al., Sequences of protein of immunological interest (1991), by Chothia et al., J. Mol. Biol. 196:901-917 (1987), and by MacCallum et al., J. Mol. Biol. 262:732-745 (1996), all of which are herein incorporated by reference in their entireties, where the definitions include overlapping or subsets of amino acid residues when compared against each other. In certain embodiments, the term “CDR” is a CDR as defined by MacCallum et al., J. Mol. Biol. 262:732-745 (1996) and Martin A. “Protein Sequence and Structure Analysis of Antibody Variable Domains,” in Antibody Engineering, Kontermann and Diibel, eds., Chapter 31, pp. 422-439, Springer-Verlag, Berlin (2001). In certain embodiments, the term “CDR” is a CDR as defined by Kabat et al., J. Biol. Chem. 252, 6609-6616 (1977) and Kabat et al., Sequences of protein of immunological interest (1991). In certain embodiments, heavy chain CDRs and light chain CDRs of an antibody are defined using different conventions. In certain embodiments, heavy chain CDRs and / or light chain CDRs are defined by performing structural analysis of an antibody and identifying residues in the variable region(s) predicted to make contact with an epitope region of a target molecule (e.g., a peptide conjugate). HC CDR1, HC CDR2, and HC CDR3 denote the heavy chain CDRs, and LC CDR1, LC CDR2 and LC CDR3 denote the light chain CDRs. The CDRs for any binders (e.g., binding partners or antigen binding domains) described herein can be designated by Kabat numbering scheme. In some cases, the light chain (LC) CDRs can be designated by Kabat numbering scheme. In some cases, the LC CDRs can be designated by Kabat numbering scheme with modifications. In some cases, the heavy chain (HC) CDRs can be designated by Kabat numbering scheme. In some cases, the HC CDRs can be designated by Kabat numbering scheme with modifications. For example, the CDRs may contain one or more extra amino acids than the CDRs designated by Kabat numbering scheme.

[0379] The determination of “percent identity” between two sequences (e.g., amino acid sequences or nucleic acid sequences) can be accomplished using a mathematical algorithm. A specific, non-limiting example of a mathematical algorithm utilized for the comparison of two sequences is the algorithm of Karlin S & Altschul SF (1990) PNAS 87: 2264-2268, modified as in Karlin S & Altschul SF (1993) PNAS 90: 5873-5877, each of which is herein incorporated by reference in its entirety. Such an algorithm is incorporated into the NBLAST and XBLAST programs of Altschul SF et al., (1990) J Mol Biol 215: 403, which is herein incorporated by reference in its entirety. BLAST nucleotide searches can be performed with the NBLAST nucleotide program parameters set, e.g., for score=100, wordlength=12 to obtain nucleotide sequences homologous to a nucleic acid molecule described herein. BLAST protein searches can be performed with the XBLAST program parameters set, e.g., to score 50, wordlength=3 to obtain amino acid sequences homologous to a protein molecule described herein. To obtain gapped alignments for comparison purposes, Gapped BLAST can be utilized as described in Altschul SF et al., (1997) Nuc Acids Res 25: 3389-3402, which is herein incorporated by reference in its entirety. Alternatively, PSI BLAST can be used to perform an iterated search which detects distant relationships between molecules (Id.). When utilizing BLAST, Gapped BLAST, and PSI Blast programs, the default parameters of the respective programs (e.g., of XBLAST and NBLAST) can be used (see, e.g., National Center for Biotechnology Information (NCBI) on the worldwide web, ncbi.nlm.nih.gov). Another specific, non-limiting example of a mathematical algorithm utilized for the comparison of sequences is the algorithm of Myers and Miller, 1988, CAB IOS 4: 11-17, which is herein incorporated by reference in its entirety. Such an algorithm is incorporated in the ALIGN program (version 2.0) which is part of the GCG sequence alignment software package. When utilizing the ALIGN program for comparing amino acid sequences, a PAM120 weight residue table, a gap length penalty of 12, and a gap penalty of 4 can be used. The percent identity between two sequences can be determined using techniques similar to those described above, with or without allowing gaps. In calculating percent identity, typically only exact matches are counted.

[0380] As used herein, the terms “free targeted covalent inhibitor” or “free drug” refer to a targeted covalent inhibitor that is not covalently linked to a protein or peptide. Once the targeted covalent inhibitor is covalently linked to a protein or peptide, the targeted covalent inhibitor can be referred as a portion or fragment of the free target covalent inhibitor or drug. For example, the protein or fragment thereof can be the chemical fragment that is bonded to the cysteine residue of the peptide upon covalent reaction of the free drug with the cysteine residue of the peptide. As used herein the term “KRASG12C” refers to the KRAS protein (UniProt Accession No. P01116) with a G12C mutation, i.e., a cysteine at amino acid position 12. As used herein the term “KRASG12D” refers to the KRAS protein (UniProt Accession No. P01116) with a G12D mutation, i.e., an aspartic acid at amino acid position 12. As used herein the term “KRASG12R” refers to the KRAS protein (UniProt Accession No. P01116) with a G12R mutation, i.e., an arginine at amino acid position 12. As used herein the term “KRASG12S” refers to the KRAS protein (UniProt Accession No. P01116) with a G12S mutation, i.e., a serine at amino acid position 12.

[0381] In embodiments, the binding partners preferentially bind to (e.g., specifically bind to) the protein or peptide or a complex comprising the protein or peptide when covalently bound to the peptide conjugate, relative to the same protein or peptide that is not bound to the drug. Accordingly, binding partners described herein either do not detectably bind, or bind with a lower affinity, to the same protein or fragment thereof in the absence of the covalently attached molecule. In embodiments, the binding partners bind to the protein or peptide comprising the covalently attached drug with an affinity that is 10 - 10,000 fold, including all numbers and ranges of numbers from 10-10,000, greater than the affinity for the protein or peptide that does not comprise the covalently bound molecule. In this regard, and without intending to be bound by any particular theory, it is considered that the presence of the covalently bound molecule contributes to the epitope to which the binding partners bind with specificity. The term “specifically binds” refers to a molecule (e.g., an antibody or an antigen-binding portion thereof) that binds to an epitope or target or peptide-MHC complex with greater affinity, greater avidity, and / or greater duration to that epitope or target or peptide-MHC complex in a sample than it binds to another epitope or non-target compound or non-target or peptide-MHC complex (e.g., a structurally different antigen, a peptide-MHC complex with a different MHC and different peptide, a peptide-MHC complex with a different MHC and the same peptide or a peptide-MHC complex with the same MHC and different peptide). For example, a molecule (e.g., an antibody or an antigen-binding portion thereof) that specifically binds to an epitope or target or peptide-MHC complex can be an molecule (e.g., an antibody or an antigen-binding portion thereof) that binds this epitope or target or peptide-MHC complex with greater affinity, avidity, more readily, and / or with greater duration than it binds to other epitopes or targets or peptide-MHC complexes. In some embodiments, a molecule (e.g., an antibody or an antigen-binding portion thereof) that specifically binds to an epitope or target or peptide-MHC complex is a molecule (e.g., an antibody or an antigen-binding portion thereof) that binds to the epitope or target or peptide- MHC complex with at least 5-fold greater affinity than other epitopes or non-target compounds or non-target peptide-MHC complex, e.g., at least 5-fold, 10-fold, 100-fold, 1,000-fold, 10,000-fold, or greater affinity. A molecule (e.g., an antibody or an antigenbinding portion thereof) that specifically binds to a particular epitope or target or peptide- MHC complex can be exhibited, for example, by a molecule having an equilibrium dissociation constant KD for the epitope or target or peptide-MHC complex to which it binds of, e.g., 10-4 M or smaller, or 1012M, such as determined by, e.g., immunoassays, surface plasma resonance (e.g., Biacore™ assay), biolayer interferometry, or other assays known in the art. It will be recognized by one of skill in the art that an antibody that specifically binds to a target from one species may also specifically bind to orthologs of that target. In some embodiments, the extent of binding of a molecule (e.g., an antibody or an antigen-binding portion thereof) to an unrelated epitope or unrelated target or unrelated peptide-MHC complex is less than about 0.0001%, 0.001%, 0.01%, 0.1%, 1%, 10% or 20% of the binding of the antibody to the epitope or target or peptide-MHC complex as measured, e.g., by an immunoassay, surface plasma resonance (e.g., Biacore™ assay), biolayer interferometry, or other assay known in the art. Likewise, binding partners of this disclosure preferentially bind to the peptide conjugate relative to binding to the free drug. In embodiments, the binding partners bind to the peptide comprising the covalently attached drug (e.g., the peptide-conjugate / MHC complex) with an affinity that is 10-10,000 fold, including all numbers and ranges of numbers from 10-10,000, greater than the affinity for the free drug. In some embodiments, the interaction between the binding partner and the peptide-conjugate / MHC complex is not inhibited by the free drug. For example, the interaction between the binding partner and the peptide-conjugate / MHC complex is not inhibited by a lOOx, l,000x, 10,000x, 100,000x or more excess of the free drug.

[0382] In some embodiments, the polypeptide comprising the antigen-binding domain may bind to (i) a first peptide conjugate / MHC complex with a dissociation constant (KD) of at most about 100 nM, (ii) a second peptide conjugate / MHC complex with a KD of at most about 100 nM, and (iii) a third peptide conjugate / MHC complex with a KD of at most about 100 nM. The first peptide conjugate / MHC complex can comprise: a first peptide conjugate, wherein the first peptide conjugate of the first peptide conjugate / MHC complex is a first peptide covalently linked to a first targeted covalent inhibitor or fragment thereof; and a first MHC. The second peptide conjugate / MHC complex can comprise: a second peptide conjugate, wherein the second peptide conjugate of the second peptide conjugate / MHC complex is a second peptide covalently linked to a second targeted covalent inhibitor or fragment thereof; and a second MHC. The third peptide conjugate / MHC complex can comprise: a third peptide conjugate, wherein the third peptide conjugate of the third peptide conjugate / MHC complex is a third peptide covalently linked to a third targeted covalent inhibitor or fragment thereof; and a third MHC. In some embodiments, the first targeted covalent inhibitor, the second targeted covalent inhibitor, and the third targeted covalent inhibitor can be different. The first targeted covalent inhibitor can be adagrasib, and the second and third covalent inhibitors can be selected from the group consisting of sotorasib and divarasib. In some embodiments, the antigen-binding domain can bind to (i) the first peptide conjugate / MHC complex with a dissociation constant (KD) of at most about 50 nM, (ii) the second peptide conjugate / MHC complex with a KD of at most about 50 nM, and (iii) the third peptide conjugate / MHC complex with a KD of at most about 50 nM. In some embodiments, the antigen-binding domain can bind to (i) the first peptide conjugate / MHC complex with a dissociation constant (KD) of at most about 10 nM, (ii) the second peptide conjugate / MHC complex with a KD of at most about 10 nM, and (iii) the third peptide conjugate / MHC complex with a KD of at most about 10 nM.

[0383] In some embodiments, a polypeptide described herein may bind with greater affinity to a peptide conjugate / MHC complex comprising a peptide covalently linked to adagrasib compared to an affinity to a peptide conjugate / MHC complex comprising a peptide covalently linked to divarasib. In some embodiments, a polypeptide described herein may bind with greater affinity to a peptide conjugate / MHC complex comprising a peptide covalently linked to adagrasib compared to an affinity to a peptide conjugate / MHC complex comprising a peptide covalently linked to sotorasib.

[0384] In some embodiments, a binding partner described herein may bind to a first peptide conjugate / MHC complex (e.g., peptide conjugate with adagrasib covalently linked to the peptide) with a dissociation constant (KD) that can be at least about 2-fold higher, at least about 5-fold higher, at least about 10-fold higher, at least about 15-fold higher, at least about 20-fold higher, at least about 50-fold higher, at least about 100-fold higher, at least about 150-fold higher, at least about 250-fold higher, at least about 500-fold higher, at least about 1,000-fold higher, at least about 2,500-fold higher, at least about 5,000-fold higher, at least about 10,000-fold higher, at least about 50,000-fold higher, at least about 100,000-fold higher, or greater than about 100,000-fold higher than a dissociation constant (KD) resulting from the binding partner binding to a second conjugate / MHC complex (e.g., peptide conjugate with sotorasib covalently linked to the peptide) or a third conjugate / MHC complex (e.g., peptide conjugate with divarasib covalently linked to the peptide). In some embodiments, a binding partner described herein may bind to a first peptide conjugate / MHC complex (e.g., peptide conjugate with adagrasib covalently linked to the peptide) with a dissociation constant (KD) that can be at most about 100,000-fold higher, at most about 50,000-fold higher, at most about 10,000-fold higher, at most about 5,000-fold higher, at most about 2,500-fold higher, at most about 1,000-fold higher, at most about 500-fold higher, at most about 250-fold higher, at most about 150-fold higher, at most about 100-fold higher, at most about 50-fold higher, at most about 10-fold higher, at most about 5-fold higher, at most about 2-fold higher, or less than about 2-fold higher than a dissociation constant (KD) resulting from the binding partner binding to a second conjugate / MHC complex (e.g., peptide conjugate with sotorasib covalently linked to the peptide) or a third conjugate / MHC complex (e.g., peptide conjugate with divarasib covalently linked to the peptide).

[0385] In embodiments, the molecule that is covalently bound to form the peptide conjugate is a drug and may be any targeted covalent inhibitor (TCI), but the covalent drug need not necessarily inhibit the target peptide. In embodiments, the molecule reacts with a specific residue within the target protein. In embodiments, the molecule reacts at least in part with a segment of the protein or peptide that comprises a nucleophilic, or an electrophilic, residue. In embodiments, the segment of the protein or peptide to which the molecule reacts comprises any of Cys, Lys, Tyr, His, Ser, Thr, or Arg, the latter being described in Ziyang Zhang, Johannes Morstein, Andrew K. Ecker, Keelan Z. Guiley, and Kevan M. Shokat Journal of the American Chemical Society Article ASAP, DOI: 10.1021 / jacs.2c05377, from which the disclosure is incorporated herein by reference. In embodiments, the protein or peptide comprises a selenocysteine. In embodiments, the targeted covalent inhibitor reacts with selenocysteine. In embodiments, the molecule reacts at least in part with a segment of the protein or peptide that comprises a wild type Cys, or a mutation of a residue to a Cys, and thus may be covalently attached by a so-called sulfur tether. In embodiments, the drug is any drug described in Ghosh AK, Samanta I, Mondal A, Liu WR. Covalent Inhibition in Drug Discovery. ChemMedChem. 2019;14(9):889-906. doi: 10.1002 / cmdc.201900107, or in De Cesco, et al., European Journal of Medicinal Chemistry 138 (2017) 96el 14, or in Bauer, RA, Drug Discovery Today, Volume 20, Number 9, September 2015, from which the disclosures of compounds that covalently modify protein targets is incorporated herein by reference.

[0386] In non-limiting embodiments, any of said Asp, Cys, and Arg amino acids are present in the protein or peptide to which the molecule binds because the gene encoding the wild type protein has been mutated to encode a protein that includes one or a combination of the described residues. In non-limiting embodiments, the molecule binds to a protein or peptide that is correlated with a disease or condition, such as a cancer, an autoimmune disease, or other disease or disorder that is treated with a targeted covalent inhibitor. In embodiments, the target (e.g., the protein or peptide to which the molecule covalently binds) is a receptor, including but not necessarily limited to any receptor having a catalytically active segment. In embodiments, the drug binds to an enzyme that is not necessarily a receptor, including but not limited to any kinase. In embodiments, a protein target comprises a receptor with one or more activating mutations, which promote ligand-independent enzyme activity.

[0387] In embodiments, the molecule targets and thus covalently binds to an amino acid sequence present within any of the following proteins and / or variants thereof, which may or may not comprise a mutation, such as a mutation that is related to a particular condition, including but not limited to any type of cancer. In embodiments, the protein is any protein described in Visscher M, et al., Covalent targeting of acquired cysteines in cancer. Curr Opin Chem Biol. 2016;30:61-67. doi: 10.1016 / j.cbpa.2015.11.004, from which the description is incorporated herein by reference. Visscher et al. also teaches methods for identifying disease- associated mutated genes that introduces a Cys residue suitable for covalent modification. In embodiments, the protein is KRAS, Bruton's tyrosine kinase (BTK), any member of the epidermal growth factor receptor (EGFR) family, also referred to as the ERBB family, including but not limited to EGFR (ERBB1), HER2 / NEU (ERBB2), HER3 (ERBB3), and HER4 (ERBB4); a fibroblast growth factor receptor (FGFR); the receptor kinase known in the art as MET, BRAF, a cyclin-dependent kinase (CDK); Acetyl Choline Esterase (ACHE); TP53, IDH1, GNAS, FBXW7, CTNNB1, DNMT3A, any cathepsin, including cathepsin B, C, F, H, K, L, O, S, V, W and X; any caspase; any protein involved in obesity, such as Pancreatic lipase and METAP2, or any Cancer Testis Antigen. In embodiments, the drug targets and therefore covalently binds to any viral protein, including but not limited to a polymerase, including any viral DNA polymerase, RNA polymerase, reverse transcriptase, or RNA-dependent RNA polymerase, or a viral protein that is required, for example, viral cell entry, or a protein encoded by any a transposable element. In embodiments, the drug targets EGFR and may be selected from PD168393, PF00299804 (dacomitinib), EKB569 (pelitinib), afatinib, WZ4002, osimertinib (formerly known as AZD9291), PF-06459988, nazartinib, naquotinib, olmutinib, avitinib, and rociletinib, neratinib, pyrotinib, poziotinib, and derivatives thereof. In embodiments, the drug targets Bruton’s tyrosine kinase (BTK), and may be selected from ibrutinib, acalabrutinib, zanubrutinib, CHMFL-BTK-11, ONO / GS-405, PRN1008, and CC-292. In embodiments, the drug targets any p90 ribosomal S6 kinase (RSK), and may be selected from fluoromethylketone (FMK) and dimethyl fumarate. In embodiments, the drug targets any FGFR, and may be selected from FIIN-1, FIIN-2, FIIN-3, BGJ398, AZD4547, PRN1371, FGF401. In an embodiment, the targeted covalent inhibitor targets an E3 ligase, such as RNF4, HOIP, RSP5, SMURF1, E6AP, HUWE1, and NEDD4-1. In an embodiment, the targeted covalent inhibitor targets a DDB1- and CUL4- associated factor (DCAF), such as DCAF1 or DCAF15. In an embodiment, the targeted covalent inhibitor targets any cancer testis antigen, any endogenous retroviral protein, a long interspersed element-1 (LINE-1), or a short interspersed element (SINE). In an embodiment, the targeted covalent inhibitor targets a short interspersed element that is optionally Alu. In an embodiment, the targeted covalent inhibitor is iniparib, abiraterone, carfilzomib, afatinib, or neratinib. In some embodiments, the targeted covalent inhibitor can be a targeted covalent agent. The targeted covalent agent may not inhibit the cancer testis antigen, endogenous retroviral protein, long interspersed element- 1 (LINE-1), or short interspersed element (SINE).

[0388] In embodiments, the molecule that becomes covalently bound to form the peptide conjugate targets any RAS oncogene protein product, including but not necessarily limited to HRAS, NRAS, KRAS4A, and KRAS4B. The amino acid sequences of RAS proteins are known in the art, and residue numbering is identical for the relevant part of all RAS isotypes that are discussed in this disclosure for which the amino acid sequence is available from, for example, UniProt P01116, from which the amino acid sequence is incorporated herein as of the effective filing date of this application or patent. The G12 position is numbered according to the known amino acid sequence, regardless of whether or not the G12 is the twelfth amino acid in an express RAS peptide sequence of this disclosure.

[0389] In one embodiment, the molecule covalently binds to a KRAS protein or peptide that comprises a mutation. In embodiments, the mutation is at least one of KRAS residues 12, 13, or 61. Reference to any drug herein includes its name in capitalized and un-capitalized form.

[0390] In some embodiments, the drug targets a KRAS protein comprising a KRAS G12C mutation. In some embodiments, the drug targets a KRAS protein comprising a KRAS G12D mutation. In some embodiments, the drug targets a KRAS protein comprising a KRAS G12R mutation. In some embodiments, the drug targets a KRAS protein comprising a KRAS G12S mutation. In non-limiting embodiments, the drug that targets a KRAS protein is selected from 2E07, 6H05, SML-8-73-1, MRTX849 (e.g., adagrasib), JNJ74699157, LY3499446, ARS- 853, ARS-1620, ARS-3284, GDC-6036 (e.g., divarasib), D-1553, JDQ443, RMC-6291, RMC-9805, BI 1823911, MRTX1257, AMG-510 (e.g., sotorasib), or derivatives thereof. Examples of additional compounds that can covalently target a KRAS peptide containing a G12C mutation can be found in Internal Application No. PCT / IB2019 / 050993, Internal Application No. PCT / EP2018 / 083853, and U.S. Application No. US16 / 917,128, each of which is incorporated herein by reference in its entirety. In an embodiment the drug comprises a proteolysis targeting chimera (PROTAC) derivative of a covalent drug, a non- limiting description of which is available in doi: 10.1021 / acscentsci.0c00411, from which the description of PROTACs is incorporated herein by reference. In embodiments, the PROTAC is LC-1 or LC-2. In embodiments, the disclosure relates to an autophagy-mediated degrader, referred to as an AUTAC, as described in doi.org / 10.1080 / 15548627.2020.1718362, from which the description of AUTACs is incorporated herein by reference.

[0391] The peptide conjugate described herein can be formed by the covalent reaction of a free targeted covalent inhibitor with a KRAS peptide. The peptide conjugate can be formed by the covalent reaction of a free targeted covalent inhibitor with a KRASG12Cpeptide, a KRASG12Dpeptide, a KRASG12Rpeptide, or a KRASG12Speptide. The free targeted covalent inhibitor can be any free targeted covalent inhibitor described herein. For example, the free targeted covalent inhibitor can be AMG-510 (e.g., sotorasib), MRTX849 (e.g., adagrasib), or GDC6036 (e.g., divarasib). In some cases, the peptide conjugate can be formed by the covalent reaction of AMG-510 with a KRASG12Cpeptide. The peptide can comprise or consist of the amino acid sequence of VVVGACGVGK, VVGACGVGK, or KLVVVGACGV. In some cases, the targeted covalent inhibitor may be beta-lactones G12Si- 1, G12Si-2, G12Si-3, G12Si-4 or G12Si-5.

[0392] The antigen-binding domain of the polypeptide described herein or the binding partner described herein can bind to a peptide conjugate / MHC complex presented by different HLAs. For example, in certain embodiments, the antigen-binding domain can have specificity to: (i) a peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, (ii) a peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, or (iii) both. In certain other embodiments, the antigen-binding domain can have specificity to: (i) a peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, (ii) a peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a targeted covalent inhibitor or fragment thereof presented by HLA-A* 11 :01, or (iii) both. In other embodiments, the antigen-binding domain can have specificity to: (i) a peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, (ii) a peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01, (iii) a peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a targeted covalent inhibitor or fragment thereof presented by HLA-A* 11 :01, (iv) a peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01, or (v) any combination of (i) - (iv) (e.g., (i) and (ii); or (i), (ii), and (iv)), or (vi) all of (i)-(iv). In certain specific embodiments, the polypeptide binds to: (i) a peptide conjugate / HLA-A*03:01 MHC complex containing a peptide consisting of the amino acid sequence VVGACGVGK, (ii) a peptide conjugate / HLA-A*03:01 MHC complex containing a peptide consisting of the amino acid sequence VVVGACGVGK, (iii) a peptide conjugate / HLA-A* 11:01 MHC complex containing a peptide consisting of the amino acid sequence VVVGACGVGK, and / or (iv) a peptide conjugate / HLA-A*02:01 MHC complex containing a peptide consisting of the amino acid sequence KLVVVGACGV. In still other embodiments, the polypeptide binds to: (i) a peptide conjugate / HLA-A*03:01 MHC complex containing a peptide consisting of the amino acid sequence VVGACGVGK and a peptide conjugate / HLA- A*03:01 MHC complex containing a peptide consisting of the amino acid sequence VVVGACGVGK; (ii) a peptide conjugate / HLA-A*03:01 MHC complex containing a peptide consisting of the amino acid sequence VVVGACGVGK and a peptide conjugate / HLA-A* 11:01 MHC complex containing a peptide consisting of the amino acid sequence VVVGACGVGK; (iii) a peptide conjugate / HLA-A* 02:01 MHC complex containing a peptide consisting of the amino acid sequence KLVVVGACGV; or any combination of (i)- (iii) (e.g., (i) and (ii); or (i) and (iii)); or all of (i) - (iii). The covalent inhibitor that targets the peptide conjugate / MHC complex can have a chemical structure comprising C-Rl, where C is a chemical fragment linked to R1 of any compound illustrated below.

[0393]

[0394] R1 of the C-Rl chemical structure of the covalent inhibitor can be any of the structures illustrated below. Compound (1) designates AMG-510 (sotorasib), Compound (2) designates MRTX849 (adagrasib), and Compound (3) designates GDC6036 (divarasib).

[0395] The targeted covalent inhibitor with the structure comprising C-Rl can form a covalent bond to several different amino acid residues on the peptide. For example, the targeted covalent inhibitor can form a covalent bond to the cysteine residue in a peptide comprising the amino acid sequence of VVVGACGVGK, VVGACGVGK, or KLVVVGACGV. In other embodiments, the targeted covalent inhibitor can form a covalent bond to the aspartic acid residue, the serine residue, or the arginine residue in a peptide comprising the amino acid sequence of VVVGADGVGK, VVGADGVGK, or KLVVVGADGV. In some embodiments, the antigen-binding domain of the polypeptide recognizes the C portion of the targeted covalent inhibitor with the structure comprising C-Rl of the peptide conjugate / MHC complex. In certain other embodiments, the antigen-binding domain of the polypeptide recognizes C portion but not R1 portion of the targeted covalent inhibitor of the peptide conjugate / MHC complex.

[0396] Small molecules (e.g., targeted covalent inhibitors) having an electrophilic warhead group can undergo covalent reaction with a cysteine residue of a peptide to form a peptide- small molecule conjugate. This type of reaction is illustrated in the following scheme for AMG-510 (sotorasib).

[0397] The table below lists targeted covalent inhibitors, along with the chemical structure of the fragment (“chemical fragment”) that is bonded to the cysteine residue of the peptide upon covalent reaction of the drug with the cysteine. In an embodiment, the binding partners disclosed herein bind to a peptide conjugate / MHC complex comprising a peptide conjugated to a chemical fragment in Table A below and an MHC. Table A. Structures of targeted covalent inhibitors and the chemical fragments after covalent reaction with a cysteine residue.

[0398]

[0399] In a non-limiting embodiment, the binding partner binds with specificity to a site comprising a neoantigen that includes a covalently linked small molecule drug or other covalently linked molecule as a component of an antigen in a specific MHC context. In an aspect, provided herein is a binding partner that specifically binds to a peptide conjugate / MHC complex, wherein the peptide conjugate is formed by the covalent reaction of a targeted covalent inhibitor with a peptide. In an embodiment, the binding partner binds to the peptide conjugate / MHC complex with a greater affinity than to the peptide or free targeted covalent inhibitor.

[0400] In an aspect, the present disclosure provides a binding partner that specifically binds to a peptide conjugate / MHC complex, wherein the peptide conjugate / MHC complex comprises: (a) a peptide conjugate formed by the covalent reaction of a targeted covalent inhibitor or fragment thereof with a peptide; and(b) an MHC.

[0401] In some embodiments, the binding partner binds to the peptide conjugate / MHC complex with a greater affinity than to the peptide or free targeted covalent inhibitor. In some embodiments, the affinity of the binding partner for the peptide conjugate / MHC complex is 100-10,000 times greater than the affinity of the binding partner for the peptide or free targeted covalent inhibitor.

[0402] In some embodiments, the MHC is a human leukocyte antigen (HLA), optionally wherein the HLA is an HLA-A, HLA-B, or HLA-C. In some embodiments, the HLA is HLA- A* 02 : 01 , HL A- A* 03 : 01 , or HLA-A* 11 :01.

[0403] In some embodiments, the peptide comprises a nucleophilic or an electrophilic residue, said residue optionally being one of cysteine, aspartic acid, or arginine.

[0404] In some embodiments, the peptide comprises a cysteine residue.

[0405] In some embodiments, the peptide conjugate is formed by a covalent reaction between the targeted covalent inhibitor and a cysteine residue in the peptide. In some embodiments, the peptide is a segment of a protein that is associated with a cancer, optionally wherein the protein is encoded by a gene that is mutated in a cancer.

[0406] In some embodiments, the peptide is a segment of an enzyme, and wherein the targeted covalent inhibitor is an inhibitor of the enzyme. In some embodiments, the enzyme is a kinase or a GTPase.

[0407] In some embodiments, the peptide is or is derived from KRAS.

[0408] In some embodiments, the peptide comprises a segment of KRASG12C, KRASG12D, KRASG12S, or KRASG12R.

[0409] In some embodiments, the peptide comprises the amino acid sequence of VVVGACGVGK, VVGACGVGK, or KLVVVGACGV.

[0410] In some embodiments, the targeted covalent inhibitor is (i) a tri-complex KRASG12Cinhibitor or a KRASG12Cdegrader, (ii) a tri-complex KRASG12Dinhibitor or a KRASG12Ddegrader, (iii) a tri-complex KRASG12Rinhibitor or a KRASG12Rdegrader, or (iv) a tri- complex KRASG12Sinhibitor or a KRASG12Sdegrader.

[0411] In some embodiments, the peptide comprises the KRASG12Cmutation, and the targeted covalent inhibitor is a KRASG12Cinhibitor. In some embodiments, the peptide comprises the KRASG12Dmutation, and the targeted covalent inhibitor is a KRASG12Dinhibitor. In some embodiments, the peptide comprises the KRASG12Rmutation, and the targeted covalent inhibitor is a KRASG12Rinhibitor. In some embodiments, the peptide comprises the KRASG12Smutation, and the targeted covalent inhibitor is a KRASG12Sinhibitor.

[0412] In some embodiments, the targeted covalent inhibitor is sotorasib (e.g., AMG-510), adagrasib (e.g., MRTX849), divarasib (e.g., GDC6036), or any combination thereof.

[0413] In some cases, the targeted covalent inhibitor is 2E07, 6H05, SML-8-73-1, MRTX849, JNJ74699157, LY3499446, ARS-853, ARS-1620, ARS-3284, GDC-6036, D- 1553, JDQ443, BI 1823911, or derivatives thereof.

[0414] In some embodiments, the peptide is a full length protein that is processed in the cell after the covalent reaction with the targeted covalent inhibitor, such that smaller peptide fragments are produced.

[0415] In some embodiments, the peptide conjugate comprises a compound selected from the group consisting of compounds (1) and (2):

[0416] covalently bonded to the cysteine residue in a peptide comprising the amino acid sequence of VVVGACGVGK, VVGACGVGK, or KLVVVGACGV.

[0417] In some embodiments, the MHC is HLA-A*02:01, HLA-A*03:01, and / or HLA- A*l l:01.

[0418] In some embodiments, the peptide comprises the amino acid sequence of VVVGACGVGK or VVGACGVGK and the MHC is HLA-A*03 :01 or HLA-A* 11 :01. In some embodiments, the peptide comprises the amino acid sequence of KLVVVGACGV and the MHC is HLA-A*02:0L

[0419] In some embodiments, the MHC is HLA-A*01:01.

[0420] In some embodiments, the binding partner specifically binds to a peptide conjugate / MHC complex, wherein the peptide conjugate is formed by the covalent reaction of AMG-510 or MRTX849 with a KRASG12Cpeptide, wherein the binding partner comprises a heavy chain variable region (VH) and a light chain variable region (VL). In some embodiments, the VH comprises: (i) a HC CDR1 comprising the amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (ii) a HC CDR2 comprising the amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (iii) a HC CDR3 comprising the amino acid sequence of LWASGLDY. In some embodiments, the VL comprises: (i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7is I, F, or V. In some embodiments, the binding partner specifically binds to a peptide conjugate / MHC complex, wherein the peptide conjugate is formed by the covalent reaction of AMG-510 or MRTX849 with a KRASG12Cpeptide, wherein the binding partner comprises a heavy chain variable region (VH) and a light chain variable region (VL). In some embodiments, the VH comprises: (i) a HC CDR1 comprising the amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (ii) a HC CDR2 comprising the amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (iii) a HC CDR3 comprising the amino acid sequence of SYYGFWQALWALDY. In some embodiments, the VL comprises: (i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

[0421] In some embodiments, the binding partner specifically binds to a peptide conjugate / MHC complex, wherein the peptide conjugate is formed by the covalent reaction of AMG-510 or MRTX849 with a KRASG12Cpeptide, wherein the binding partner comprises a heavy chain variable region (VH) and a light chain variable region (VL). In some embodiments, the VH comprises: (i) a HC CDR1 comprising the amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (ii) a HC CDR2 comprising the amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (iii) a HC CDR3 comprising the amino acid sequence of GYYYPYYAMDY. In some embodiments, the VL comprises: (i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4YPX5T, wherein Xi is W or S, X2 is K, W, or S, X3 is W, T, or A, X4is S, W, or Y, and X5is I, L, or V.

[0422] In some embodiments, the binding partner specifically binds to a peptide conjugate / MHC complex, wherein the peptide conjugate is formed by the covalent reaction of AMG-510 or MRTX849 with a KRASG12Cpeptide, wherein the binding partner comprises a heavy chain variable region (VH) and a light chain variable region (VL). In some embodiments, the VH comprises: (i) a HC CDR1 comprising the amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (ii) a HC CDR2 comprising the amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (iii) a HC CDR3 comprising the amino acid sequence of GYYYPYYAMDY. In some embodiments, the VL comprises: (i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7is I, F, or V.

[0423] In some embodiments, the binding partner specifically binds to a peptide conjugate / MHC complex, wherein the peptide conjugate is formed by the covalent reaction of AMG-510 or MRTX849 with a KRASG12Cpeptide, wherein the binding partner comprises a heavy chain variable region (VH) and a light chain variable region (VL). In some embodiments, the VH comprises: (i) a HC CDR1 comprising the amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (ii) a HC CDR2 comprising the amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (iii) a HC CDR3 comprising the amino acid sequence of X1X2X3X4X5MDY, wherein Xi is F or G, X2 is Q or Y, X3 is W or G, X4is Y or W, and X5 is A or G. In some embodiments, the VL comprises: (i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

[0424] In some embodiments, the binding partner specifically binds to a peptide conjugate / MHC complex, wherein the peptide conjugate is formed by the covalent reaction of AMG-510 or MRTX849 with a KRASG12Cpeptide, wherein the binding partner comprises a heavy chain variable region (VH) and a light chain variable region (VL). In some embodiments, the VH comprises: (i) a HC CDR1 comprising the amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (ii) a HC CDR2 comprising the amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (iii) a HC CDR3 comprising the amino acid sequence of SGYYSSHWYLQSWYQAMDY. In some embodiments, the VL comprises: (i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4YPX5T, wherein Xi is W or S, X2 is K, W, or S, X3is W, T, or A, X4is S, W, or Y, and X5is I, L, or V.

[0425] In some embodiments, the binding partner specifically binds to a peptide conjugate / MHC complex, wherein the peptide conjugate is formed by the covalent reaction of AMG-510 or MRTX849 with a KRASG12Cpeptide, wherein the binding partner comprises a heavy chain variable region (VH) and a light chain variable region (VL). In some embodiments, the VH comprises: (i) a HC CDR1 comprising the amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (ii) a HC CDR2 comprising the amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (iii) a HC CDR3 comprising the amino acid sequence of SGYYSSHWYLQSWYQAMDY. In some embodiments, the VL comprises: (i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6T, wherein Xi is G or A, X2 is S or Y, X3 is S or Y, X4is G, D, or S, X5 is P or L, and Xe is I or L.

[0426] In some embodiments, the binding partner specifically binds to a peptide conjugate / MHC complex, wherein the peptide conjugate is formed by the covalent reaction of AMG-510 or MRTX849 with a KRASG12Cpeptide, wherein the binding partner comprises a heavy chain variable region (VH) and a light chain variable region (VL). In some embodiments, the VH comprises: (i) a HC CDR1 comprising the amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (ii) a HC CDR2 comprising the amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (iii) a HC CDR3 comprising the amino acid sequence of HYSEKWWGWYTMYIDAMDY. In some embodiments, the VL comprises: (i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2is N, W, S, or D, X3is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

[0427] In some embodiments, the binding partner specifically binds to a peptide conjugate / MHC complex, wherein the peptide conjugate is formed by the covalent reaction of AMG-510 or MRTX849 with a KRASG12Cpeptide, wherein the binding partner comprises a heavy chain variable region (VH) and a light chain variable region (VL). In some embodiments, the VH comprises: (i) a HC CDR1 comprising the amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (ii) a HC CDR2 comprising the amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (iii) a HC CDR3 comprising the amino acid sequence of Xi WYYX2GMD Y, wherein Xi is G or Y and X2 is M or L. In some embodiments, the VL comprises: (i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4YPX5T, wherein Xi is W or S, X2 is K, W, or S, X3 is W, T, or A, X4is S, W, or Y, and X5 is I, L, or V.

[0428] In some embodiments, the binding partner specifically binds to a peptide conjugate / MHC complex, wherein the peptide conjugate is formed by the covalent reaction of AMG-510 or MRTX849 with a KRASG12Cpeptide, wherein the binding partner comprises a heavy chain variable region (VH) and a light chain variable region (VL). In some embodiments, the VH comprises: (i) a HC CDR1 comprising the amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (ii) a HC CDR2 comprising the amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (iii) a HC CDR3 comprising the amino acid sequence of Xi WYYX2GMD Y, wherein Xi is G or Y and X2 is M or L. In some embodiments, the VL comprises: (i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (iii) a LC CDR3 comprising the amino acid sequence of QQXiX2X3X4X5X6T, wherein Xi is G or A, X2 is S or Y, X3 is S or Y, X4is G, D, or S, X5is P or L, and Xe is I or L.

[0429] In some embodiments, the binding partner specifically binds to a peptide conjugate / MHC complex, wherein the peptide conjugate is formed by the covalent reaction of AMG-510 or MRTX849 with a KRASG12Cpeptide, wherein the binding partner comprises a heavy chain variable region (VH) and a light chain variable region (VL). In some embodiments, the VH comprises: (i) a HC CDR1 comprising the amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (ii) a HC CDR2 comprising the amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (iii) a HC CDR3 comprising the amino acid sequence of Xi WYYX2GMD Y, wherein Xi is G or Y and X2 is M or L. In some embodiments, the VL comprises: (i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

[0430] In some embodiments, the binding partner specifically binds to a peptide conjugate / MHC complex, wherein the peptide conjugate is formed by the covalent reaction of AMG-510 or MRTX849 with a KRASG12Cpeptide, wherein the binding partner comprises a heavy chain variable region (VH) and a light chain variable region (VL). In some embodiments, the VH comprises: (i) a HC CDR1 comprising the amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes; (ii) a HC CDR2 comprising the amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or (iii) a HC CDR3 comprising the amino acid sequence of SSRQYYHSQVEPPMAMDY. In some embodiments, the VL comprises: (i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes; (ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or (iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4YPX5T, wherein Xi is W or S, X2 is K, W, or S, X3is W, T, or A, X4is S, W, or Y, and X5is I, L, or V.

[0431] In some embodiments, the binding partner specifically binds to a peptide conjugate / MHC complex, wherein the peptide conjugate is formed by the covalent reaction of AMG-510 or MRTX849 with a KRASG12Cpeptide, wherein the binding partner comprises the HC CDR1, HC CDR2, and HC CDR3 amino acid sequences of a VH amino acid sequence and / or the LC CDR1, LC CDR2, and LC CDR3 amino acid sequences of a VL amino acid sequence of a binding partner selected from the group consisting of RM 001, RM_002, RM_003, RM_004, RM_005, RM_006, RM_007, RM_008, RM_009, RM_010, RM_011, RM_012, RM_013, RM_014, RM_015, RM_016, RM_017, RM_018, RM_019, RM_020, RM_021, RM_022, , RM_023, RM_024, RM_025, RM_026, RM_027, RM_028 , RM-029, RM-030, RM_031, and RM_032; or a variant thereof comprising 1-5 amino acid changes in one or more of the CDR amino acid sequences.

[0432] In some embodiments, the binding partner comprises the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 amino acid sequences of a binding partner selected from the group consisting of RM_001, RM_002, RM_003, RM_004, RM_005, RM_006, RM_007, RM_008, RM_009, RM_010, RM_011, RM_012, RM_013, RM_014, RM_015, RM_016, RM_017, RM_018, RM_019, RM_020, RM_021, RM_022, , RM_023, RM_024, RM_025, RM_026, RM_027, RM_028 , RM_029, RM_030, RM_031, and RM-032 (Tables A, B, and C), or a variant thereof comprising 1-5 amino acid changes in one or more of the CDR amino acid sequences.

[0433] In some embodiments, the binding partner comprises a VH and / or a VL amino acid sequence that is 90%, 95%, or 100% identical to the following VH and VL sequences:

[0434] RM-001

[0435] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSG VPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTV

[0436] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTISSSSIHWVRQAPGKGLEWVASISSYYG STSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARLWASGLDYWGQGTL VTVSS

[0437] RM_002

[0438] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSG VP

[0439] SRFSGSRSGTDFTL TISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTV

[0440] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSYYG STSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARLWASGLDYWGQGTL VTVSS

[0441] RM_003

[0442] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSG VPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQWWYGSPLFTFGQGTKVEIKRTV

[0443] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGS TSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSYYGFWQALWALDY WGQGTL VTVSS

[0444] RM_004

[0445] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSG VPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQWWYGSPLFTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVASISSSSG

[0446] STSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSYYGFWQALWALDY WGQGTLVTVSS

[0447] RM_005

[0448] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSG

[0449] VPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV

[0450] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYY

[0451] GSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWG QGTLVTVSS

[0452] RM_006

[0453] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSG

[0454] VPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV

[0455] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISPYY

[0456] GSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWG QGTLVTVSS

[0457] RM_007

[0458] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0459] PSRFSGSRSGTDFTL TISSLQPEDFATYYCQQTSWYHSLITFGQGTKVEIKRTV

[0460] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGS

[0461] TYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQG TLVTVSS

[0462] RM_008

[0463] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0464] PSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV

[0465] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVASISSYYG

[0466] STYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQG TLVTVSS

[0467] RM_009

[0468] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0469] PSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV

[0470] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGS

[0471] TYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQG TLVTVSS

[0472] RM_010

[0473] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0474] PSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSSWLYWLVTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGST

[0475] SYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFQWYAMDYWGQGTLVTV SS

[0476] RM_011

[0477] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0478] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTV

[0479] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTISSYSIHWVRQAPGKGLEWVAYISSYSGY

[0480] TSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYGWGMDYWGQGTLV TVSS

[0481] RM_012

[0482] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0483] PSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTV

[0484] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTISYSSIHWVRQAPGKGLEWVAYISSSSGY

[0485] TSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSGYYSSHWYLQSWYQA MDYWGQGTLVTVSS

[0486] RM_013

[0487] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0488] PSRFSGSRSGTDFTL TISSLQPEDFATYYCQQASYGPITFGQGTKVEIKRTV

[0489] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGS

[0490] TYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSGYYSSHWYLQSWYQA MDYWGQGTLVTVSS

[0491] RM_014

[0492] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0493] PSRFSGSRSGTDFTL TISSLQPEDFATYYCQQWWSSSQLITFGQGTKVEIKRTV

[0494] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYSSIHWVRQAPGKGLEWVASISSYYGS

[0495] TYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARHYSEKWWGWYTMYID AMDYWGQGTLVTVSS

[0496] RM_015

[0497] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0498] PSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV

[0499] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSG

[0500] YTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGT LVTVSS

[0501] RM_016

[0502] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0503] PSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSY

[0504] TSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTL VTVSS

[0505] RM_017

[0506] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0507] PSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV

[0508] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSG

[0509] YTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGT L VTVSS

[0510] RM_018

[0511] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0512] PSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV

[0513] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVAYISPYSG

[0514] YTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGT

[0515] L VTVSS

[0516] RM_019

[0517] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0518] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV

[0519] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVASISPYSSY

[0520] TSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTL VTVSS

[0521] RM_020

[0522] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0523] PSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTV

[0524] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSG

[0525] YTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGT L VTVSS

[0526] RM_021

[0527] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0528] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV

[0529] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSY

[0530] TSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTL VTVSS

[0531] RM_022

[0532] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0533] PSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSY TSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTL VTVSS

[0534] RM_023

[0535] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0536] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSYYEELITFGQGTKVEIKRTV

[0537] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSY

[0538] TSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTL VTVSS

[0539] RM_024

[0540] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0541] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQAYSDPLTFGQGTKVEIKRTV

[0542] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSY

[0543] TSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTL VTVSS

[0544] RM 025

[0545] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0546] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGSSSLLTFGQGTKVEIKRTV

[0547] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSY

[0548] TSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTL VTVSS

[0549] RM_026

[0550] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0551] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSGSYLLITFGQGTKVEIKRTV

[0552] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSY

[0553] TSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTL VTVSS

[0554] RM_027

[0555] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0556] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQADYEFGLITFGQGTKVEIKRTV

[0557] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSY

[0558] TSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTL VTVSS

[0559] RM_028

[0560] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0561] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVAYISSSYGY TSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAM DYWGQGTLVTVSS

[0562] RM_029

[0563] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV

[0564] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVAYISSSYG YTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMA MDYWGQGTLVTVSS

[0565] RM_030

[0566] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV

[0567] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSSSIHWVRQAPGKGLEWVAYISSSYGY TSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAM DYWGQGTLVTVSS

[0568] RM_031

[0569] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV

[0570] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYSSIHWVRQAPGKGLEWVAYISSSYG YTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMA MDYWGQGTLVTVSS

[0571] RM_032

[0572] VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGSSSLLTFGQGTKVEIKRTV

[0573] VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVAYISPYSG YTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYLGMDYWGQGT LVTVSS

[0574] In some embodiments, the binding partner has a higher affinity for the peptide conjugate / MHC complex comprising a first HLA than for the peptide conjugate / MHC complex comprising a second HLA.

[0575] In some embodiments, the first and second HLAs are each selected from the group consisting of HL A-A* 02:01, HLA-A*03:01, and / or HLA-A* 11 :01.

[0576] In some embodiments, the binding partner is an intact antibody, a bispecific antibody, a multispecific antibody, an antigen-binding (Fab) fragment, an Fab’ fragment, an (Fab’)2 fragment, an Fd, an Fv, a dAb, a single domain fragment or single monomeric variable antibody domain, a single-chain Diabody (scDb), a diabody (Db), a dual-affinity retargeting (DART) molecule, a single-chain variable fragment (scFv), a camelid antibody, a bi-specific T-cell engager (BiTE), bispecific killer cell engager (BiKE), CrossMab, a tri-specific binding partner, a chimeric antigen receptor (CAR), a monobody (e.g., adnectin), a DARPin, an anticalin, an affibody, or an affimer. In some embodiments, the binding partner is bispecific. In some embodiments, the binding partner specifically binds to the peptide conjugate / MHC complex and a T cell antigen. In some embodiments, the binding partner specifically binds to the peptide conjugate / MHC complex and human CD3.

[0577] In some embodiments, the binding partner comprises the VH and / or VL amino acid sequences of

[0578] UCHT1:

[0579] VH:EVQLQQSGPELVKPGASMKISCKASGYSFTGYTMNWVKQSHGKNLEWMGLINPYKGVS TYNQKFKDKATLTVDKSSSTAYMELLSLTSEDSAVYYCARSGYYGDSDWYFDVWGQGTTL TVSS VL:DIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSGVPSK FSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIK.

[0580] In some embodiments, the binding partner is a single-chain Diabody (scDb) and comprises a sequence that is at least 90% identical to any of the following sequences:

[0581] RM 001 UCHT1 scDb

[0582] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0583] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTVGGGGSEVQL VESGGGLVQPGGSLRLSCAASGFTISSSSIHWVRQAPGKGLEWVASISSYYGSTSYADSVKGR

[0584] FTISADTSKNTAYLQMNSLRAEDTAVYYCARLWASGLDYWGQGTLVTVSSGGGGSGGGGS

[0585] GGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSG VPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESG

[0586] GGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTIS

[0587] ADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0588] RM 002 UCHT1 scDb

[0589] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0590] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTVGGGGSEVQL VESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSYYGSTSYADSVKG

[0591] RFTISADTSKNTAYLQMNSLRAEDTAVYYCARLWASGLDYWGQGTLVTVSSGGGGSGGGG SGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSG

[0592] VPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESG GGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTIS

[0593] ADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0594] RM 003 UCHT1 scDb

[0595] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0596] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWWYGSPLFTFGQGTKVEIKRTVGGGGSEVQL VESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGR

[0597] FTISADTSKNTAYLQMNSLRAEDTAVYYCARSYYGFWQALWALDYWGQGTLVTVSSGGGG SGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYT

[0598] SRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEV QLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVK

[0599] GRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0600] RM 004 UCHT1 scDb

[0601] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0602] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWWYGSPLFTFGQGTKVEIKRTVGGGGSEVQL

[0603] VESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGR

[0604] FTISADTSKNTAYLQMNSLRAEDTAVYYCARSYYGFWQALWALDYWGQGTLVTVSSGGGG

[0605] SGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYT

[0606] SRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEV

[0607] QLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVK

[0608] GRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0609] RM 005 UCHT1 scDb

[0610] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0611] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTVGGGGSEVQLVE

[0612] SGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRF

[0613] TISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSSGGGGSGG

[0614] GGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRL

[0615] HSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLV

[0616] ESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRF

[0617] TISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0618] RM 006 UCHT1 scDb

[0619] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0620] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTVGGGGSEVQLVE

[0621] SGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISPYYGSTYYADSVKGRF

[0622] TISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSSGGGGSGG

[0623] GGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRL

[0624] HSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLV

[0625] ESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRF

[0626] TISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0627] RM 007 UCHT1 scDb

[0628] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0629] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQTSWYHSLITFGQGTKVEIKRTVGGGGSEVQLV

[0630] ESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGR

[0631] FTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSSGGGGSGG

[0632] GGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRL

[0633] HSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLV

[0634] ESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRF

[0635] TISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0636] RM 008 UCHT1 scDb

[0637] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0638] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTVGGGGSEVQLVE

[0639] SGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRF

[0640] TISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSSGGGGSGG

[0641] GGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRL

[0642] HSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLV

[0643] ESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRF

[0644] TISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS RM 009 UCHT1 scDb

[0645] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0646] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTVGGGGSEVQLV

[0647] ESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGR

[0648] FTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDYWGQGTLVTVSSGGGGSGG

[0649] GGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRL

[0650] HSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLV

[0651] ESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRF

[0652] TISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0653] RM 010 UCHT1 scDb

[0654] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0655] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWLVTFGQGTKVEIKRTVGGGGSEVQL

[0656] VESGGGLVQPGGSLRLSCAASGFTFSSSSIHWVRQAPGKGLEWVASISSSSGSTSYADSVKGR

[0657] FTISADTSKNTAYLQMNSLRAEDTAVYYCARFQWYAMDYWGQGTLVTVSSGGGGSGGGGS

[0658] GGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSG

[0659] VPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESG

[0660] GGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTIS

[0661] ADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0662] RM Oil UCHT1 scDb

[0663] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0664] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTVGGGGSEVQL

[0665] VESGGGLVQPGGSLRLSCAASGFTISSYSIHWVRQAPGKGLEWVAYISSYSGYTSYADSVKG

[0666] RFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYGWGMDYWGQGTLVTVSSGGGGSGGG

[0667] GSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHS

[0668] GVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVES

[0669] GGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTI

[0670] SADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0671] RM 012 UCHT1 scDb

[0672] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0673] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTVGGGGSEVQLV

[0674] ESGGGLVQPGGSLRLSCAASGFTISYSSIHWVRQAPGKGLEWVAYISSSSGYTSYADSVKGRF

[0675] TISADTSKNTAYLQMNSLRAEDTAVYYCARSGYYSSHWYLQSWYQAMDYWGQGTLVTVS

[0676] SGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKL

[0677] LIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGG

[0678] GSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYA

[0679] DSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0680] RM 013 UCHT1 scDb

[0681] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0682] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASYGPITFGQGTKVEIKRTVGGGGSEVQLVES

[0683] GGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFT

[0684] ISADTSKNTAYLQMNSLRAEDTAVYYCARSGYYSSHWYLQSWYQAMDYWGQGTLVTVSS

[0685] GGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLL

[0686] IYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGG

[0687] SEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYAD

[0688] SVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0689] RM 014 UCHT1 scDb

[0690] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0691] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWWSSSQLITFGQGTKVEIKRTVGGGGSEVQL

[0692] VESGGGLVQPGGSLRLSCAASGFTVSYSSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKG RFTISADTSKNTAYLQMNSLRAEDTAVYYCARHYSEKWWGWYTMYIDAMDYWGQGTLVT VSSGGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTV KLLIYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKG GGGSEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTS YADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0693] RM 015 UCHT1 scDb

[0694] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTVGGGGSEVQLVE SGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRF TISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSSGGGGSGGGG SGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSG VPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESG GGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTIS ADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0695] RM 016 UCHT1 scDb

[0696] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTVGGGGSEVQLVE SGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRF TISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSSGGGGSGGGG SGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSG VPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESG GGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTIS ADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0697] RM 017 UCHT1 scDb

[0698] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTVGGGGSEVQLV ESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGR FTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSSGGGGSGGG GSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHS GVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVES GGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTI SADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0699] RM 018 UCHT1 scDb

[0700] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTVGGGGSEVQLV ESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGR FTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSSGGGGSGGG GSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHS GVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVES GGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTI SADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0701] RM 019 UCHT1 scDb

[0702] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTVGGGGSEVQLV ESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRF TISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSSGGGGSGGGG SGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSG VPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESG GGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTIS

[0703] ADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0704] RM 020 UCHT1 scDb

[0705] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0706] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTVGGGGSEVQLV

[0707] ESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGR

[0708] FTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSSGGGGSGGG

[0709] GSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHS

[0710] GVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVES

[0711] GGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTI

[0712] SADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0713] RM 021 UCHT1 scDb

[0714] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0715] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTVGGGGSEVQLV

[0716] ESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGR

[0717] FTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSSGGGGSGGG

[0718] GSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHS

[0719] GVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVES

[0720] GGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTI

[0721] SADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0722] RM 022 UCHT1 scDb

[0723] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0724] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTVGGGGSEVQLV

[0725] ESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGR

[0726] FTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSSGGGGSGGG

[0727] GSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHS

[0728] GVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVES

[0729] GGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTI

[0730] SADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0731] RM 023 UCHT1 scDb

[0732] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0733] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSYYEELITFGQGTKVEIKRTVGGGGSEVQLV

[0734] ESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGR

[0735] FTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSSGGGGSGGG

[0736] GSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHS

[0737] GVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVES

[0738] GGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTI

[0739] SADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0740] RM 024 UCHT1 scDb

[0741] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0742] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQAYSDPLTFGQGTKVEIKRTVGGGGSEVQLVES

[0743] GGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTI

[0744] SADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSSGGGGSGGGGS

[0745] GGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSG

[0746] VPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESG

[0747] GGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTIS ADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0748] RM 025 UCHT1 scDb DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGSSSLLTFGQGTKVEIKRTVGGGGSEVQLVES GGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTI SADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSSGGGGSGGGGS GGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSG

[0749] VPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESG GGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTIS ADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0750] RM 026 UCHT1 scDb

[0751] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV

[0752] PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSGSYLLITFGQGTKVEIKRTVGGGGSEVQLVE SGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRF TISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSSGGGGSGGGG SGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHSG VPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVESG

[0753] GGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTIS ADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0754] RM 027 UCHT1 scDb

[0755] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQADYEFGLITFGQGTKVEIKRTVGGGGSEVQLV ESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGR FTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSSGGGGSGGG GSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLLIYYTSRLHS

[0756] GVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGGSEVQLVES GGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYADSVKGRFTI SADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0757] RM 028 UCHT1 scDb

[0758] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTVGGGGSEVQLV ESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVAYISSSYGYTSYADSVKGR FTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAMDYWGQGTLVTVSS GGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLL

[0759] IYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGG SEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYAD SVKGRFT1SADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0760] RM 029 UCHT1 scDb

[0761] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTVGGGGSEVQLV ESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVAYISSSYGYTSYADSVKGR FTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAMDYWGQGTLVTVSS GGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLL

[0762] IYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGG SEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYAD SVKGRFT1SADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTVSS

[0763] RM 030 UCHT1 scDb

[0764] DIVRSDIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGV PSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTVGGGGSEVQLV ESGGGLVQPGGSLRLSCAASGFTVSSSSIHWVRQAPGKGLEWVAYISSSYGYTSYADSVKGR FTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPPMAMDYWGQGTLVTVSS GGGGSGGGGSGGGGSDIQMTQTTSSLSASLGDRVTISCRASQDIRNYLNWYQQKPDGTVKLL

[0765] IYYTSRLHSGVPSKFSGSGSGTDYSLTISNLEQEDIATYFCQQGNTLPWTFAGGTKLEIKGGGG SEVQLVESGGGLVQPGGSLRLSCAASGFTISSSYIHWVRQAPGKGLEWVAYISPSYGSTSYAD SVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCAREYVTMALDYWGQGTLVTV...

Claims

CLAIMSWhat is claimed is:

1. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain binds to (i) a first peptide conjugate / MHC complex with a dissociation constant (KD) of at most about 100 nM and (ii) a second peptide conjugate / MHC complex with a KD of at most about 100 nM, wherein the first peptide conjugate / MHC complex comprises:(a) a first peptide conjugate, wherein the first peptide conjugate of the first peptide conjugate / MHC complex is a first peptide covalently linked to a first targeted covalent inhibitor or fragment thereof; and(b) a first MHC; wherein the second peptide conjugate / MHC complex comprises:(a) a second peptide conjugate, wherein the second peptide conjugate of the second peptide conjugate / MHC complex is a second peptide covalently linked to a second targeted covalent inhibitor or fragment thereof; and(b) a second MHC; and wherein the first targeted covalent inhibitor is different from the second targeted covalent inhibitor.

2. The composition of claim 1, wherein the antigen-binding domain binds to (i) the first peptide conjugate / MHC complex with a dissociation constant (KD) of at most about 50 nM and / or (ii) the second peptide conjugate / MHC complex with a KD of at most about 50 nM.

3. The composition of claim 1, wherein the antigen-binding domain binds to (i) the first peptide conjugate / MHC complex with a dissociation constant (KD) of at most about 10 nM and / or (ii) the second peptide conjugate / MHC complex with a KD of at most about 10 nM.

4. The composition of claim 1, wherein the antigen-binding domain binds to (i) the first peptide conjugate / MHC complex with a dissociation constant (KD) of at most about 5 nM and / or (ii) the second peptide conjugate / MHC complex with a KD of at most about 5 nM.

5. The composition of any one of claims 1-4, wherein the first targeted covalent inhibitor is a covalent inhibitor of a RAS protein and the second targeted covalent inhibitor is a covalent inhibitor of a RAS protein.

6. The composition of any one of claims 1-5, wherein the first targeted covalent inhibitor is a covalent inhibitor of KRASG12Cand the second targeted covalent inhibitor is a covalent inhibitor of KRASG12C.

7. The composition of any one of claims 1-6, wherein (i) the first targeted covalent inhibitor is adagrasib and the second targeted covalent inhibitor is sotorasib; (ii) the first targeted covalent inhibitor is adagrasib and the second targeted covalent inhibitor is divarasib; or (iii) the first targeted covalent inhibitor is divarasib and the second targeted covalent inhibitor is sotorasib.

8. The composition of any one of claims 1-7, wherein the antigen-binding domain(i) does not bind to a free first targeted covalent inhibitor that is not conjugated to a peptide with a dissociation constant (KD) of less than 200 nM,(ii) does not bind to the first peptide with a KD of less than 200 nM,(iii) does not bind to a free first peptide conjugate that is not complexed with an MHC with a KD of less than 200 nM, or(iv) any combination above.

9. The composition of claim 8, wherein the antigen-binding domain binds to the first peptide conjugate / MHC complex with a greater affinity than to the first peptide, the free first targeted covalent inhibitor, and / or the free first peptide conjugate.

10. The composition of claim 8 or 9, wherein the affinity of the antigen-binding domain for the first peptide conjugate / MHC complex is 100-10,000 times greater than the affinity of the antigen-binding domain for the first peptide or the free first targeted covalent inhibitor.

11. The composition of any one of claims 1-10, wherein the antigen-binding domain does not detectably bind to a complex of the first peptide with the first MHC, wherein the first peptide is not covalently bound to the first targeted covalent inhibitor or fragment thereof.

12. The composition of any one of claims 8-11, wherein the antigen-binding domain does not detectably bind to the free first targeted covalent inhibitor.

13. The composition of any one of claims 1-12, wherein the antigen-binding domain binds to a free first peptide conjugate with a dissociation constant KD that is at least 2.5 times more than a KD of the antibody or the antigen-binding fragment to the first peptide conjugate / MHC complex.

14. The composition of any one of claims 1-13, wherein the antigen-binding domain(i) does not bind to a free second targeted covalent inhibitor that is not conjugated to a peptide with a dissociation constant (KD) of less than 200 nM,(ii) does not bind to the second peptide with a KD of less than 200 nM,(iii) does not bind to a free second peptide conjugate that is not complexed with an MHC with a KD of less than 200 nM, or(iv) any combination above.

15. The composition of claim 14, wherein the antigen-binding domain binds to the second peptide conjugate / MHC complex with a greater affinity than to the second peptide, the free second targeted covalent inhibitor, and / or the free second peptide conjugate.

16. The composition of claim 14 or 15, wherein the affinity of the antigen-binding domain for the second peptide conjugate / MHC complex is 100-10,000 times greater than the affinity of the antigen-binding domain for the second peptide or the free second targeted covalent inhibitor.

17. The composition of any one of claims 1-16, wherein the antigen-binding domain does not detectably bind to a complex of the second peptide with the second MHC, wherein the second peptide is not covalently bound to the second targeted covalent inhibitor or fragment thereof.

18. The composition of any one of claims 14-17, wherein the antigen-binding domain does not detectably bind to the free second targeted covalent inhibitor.

19. The composition of any one of claims 1-18, wherein the antigen-binding domain binds to a free second peptide conjugate with a dissociation constant (KD that is at least 2.5 times more than a KD of the antibody or the antigen-binding fragment to the second peptide conjugate / MHC complex.

20. The composition of any one of claims 1-19, wherein the first peptide and the second peptide comprise the same amino acid sequence.

21. The composition of any one of claims 1-20, wherein the first peptide and the second peptide consist of the same amino acid sequence.

22. The composition of claim 20 or 21, wherein the first peptide or the second peptide comprises the amino acid sequence of VVVGACGVGK.

23. The composition of any one of claims 1-22, wherein the first peptide and second peptide comprise a different amino acid sequence.

24. The composition of claim 23, wherein the first peptide and the second peptide comprise a shared contiguous amino acid sequence that is at least 3, 4, 5, 6, 7, 8, or 9 amino acids in length.

25. The composition of any one of claims 22-24, wherein the first peptide and / or the second peptide comprises an amino acid sequence of VVVGACGVGK, VVGACGVGK, or KLVVVGACGV.

26. The composition of any one of claims 1-25, wherein the first MHC or the second MHC is encoded by an HL A, wherein the HL A is HLA-A*02:01, HLA-A*03:01, or HLA-A* 11 :01.

27. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain binds to a peptide conjugate / MHC complex, wherein the peptide conjugate of the peptide conjugate / MHC complex is a peptide covalently linked to a targeted covalent inhibitor or fragment thereof and a MHC; and wherein the antigen-binding domain binds to the peptide conjugate / MHC complex with a dissociation constant (KD) of at most about 50 nM; wherein the targeted covalent inhibitor is adagrasib.

28. The composition of claim 27, wherein the peptide conjugate / MHC complex is a first peptide conjugate / MHC complex comprising a first peptide conjugate comprising a first peptide and a first targeted covalent inhibitor or fragment thereof; and wherein the antigen-binding domain further binds to a second peptide conjugate / MHC complex comprising (a) a second peptide conjugate, wherein the second peptide conjugate of the second peptide conjugate / MHC complex is a second peptide covalently linked to a second targeted covalent inhibitor or fragment thereof; and (b) a second MHC.

29. The composition of claim 28, wherein the antigen-binding domain binds to the second peptide conjugate / MHC complex with a KD of at most about 50 nM.

30. The composition of claim 28, wherein the antigen-binding domain binds to (i) the first peptide conjugate / MHC complex with a dissociation constant (KD) of at most about 10 nM and (ii) the second peptide conjugate / MHC complex with a KD of at most about 10 nM.

31. The composition of claim 28, wherein the antigen-binding domain binds to (i) the first peptide conjugate / MHC complex with a dissociation constant (KD) of at most about 5 nM and (ii) the second peptide conjugate / MHC complex with a KD of at most about 5 nM.

32. The composition of any one of claims 28-31, wherein the second targeted covalent inhibitor is sotorasib or divarasib.

33. The composition of any one of claims 28-32, wherein the antigen-binding domain does not bind to a free first targeted covalent inhibitor with a dissociation constant (KD) of less than 200 nM.

34. The composition of claim 33, wherein the antigen-binding domain binds to the first peptide conjugate / MHC complex with a greater affinity than to the first peptide or the free first targeted covalent inhibitor.

35. The composition of claim 33 or 34, wherein the affinity of the antigen-binding domain for the first peptide conjugate / MHC complex is 100-10,000 times greater than the affinity of the antigen-binding domain for the first peptide or the free first targeted covalent inhibitor.

36. The composition of any one of claims 28-35, wherein the antigen-binding domain does not detectably bind to a complex of the first peptide with a first MHC, wherein the first peptide is not covalently bound to the first targeted covalent inhibitor or fragment thereof.

37. The composition of any one of claims 33-36, wherein the antigen-binding domain does not detectably bind to the free first targeted covalent inhibitor.

38. The composition of any one of claims 28-37, wherein the antigen-binding domain binds to a free first peptide conjugate with a dissociation constant KD that is at least 2.5 times more than a KD of the antibody or the antigen-binding fragment to the first peptide conjugate / MHC complex.

39. The composition of any one of claims 28-38, wherein the antigen-binding domain does not bind to a free second targeted covalent inhibitor with a dissociation constant (KD) of less than 200 nM.

40. The composition of claim 39, wherein the antigen-binding domain binds to the second peptide conjugate / MHC complex with a greater affinity than to the second peptide or the free second targeted covalent inhibitor.

41. The composition of claim 39 or 40, wherein the affinity of the antigen-binding domain for the second peptide conjugate / MHC complex is 100-10,000 times greater than the affinity of the antigen-binding domain for the second peptide or the free second targeted covalent inhibitor.

42. The composition of any one of claims 28-41, wherein the antigen-binding domain does not detectably bind to a complex of the second peptide with the second MHC, wherein the second peptide is not covalently bound to the second targeted covalent inhibitor or fragment thereof.

43. The composition of any one of claims 39-42, wherein the antigen-binding domain does not detectably bind to the free second targeted covalent inhibitor.

44. The composition of any one of claims 28-43, wherein the antigen-binding domain binds to a free second peptide conjugate with a dissociation constant ( o) that is at least 2.5 times more than a Ko of the antibody or the antigen-binding fragment to the second peptide conjugate / MHC complex.

45. The composition of any one of claims 28-44, wherein the first peptide and the second peptide comprise the same amino acid sequence.

46. The composition of any one of claims 28-45, wherein the first peptide and the second peptide consist of the same amino acid sequence.

47. The composition of claim 46, wherein the first peptide or the second peptide comprises the amino acid sequence of VVVGACGVGK.

48. The composition of any one of claims 28-44, wherein the first peptide and second peptide comprise a different amino acid sequence.

49. The composition of claim 48, wherein the first peptide or the second peptide comprises an amino acid sequence of VVVGACGVGK, VVGACGVGK, or KLVVVGACGV.

50. The composition of any one of claims 28-49, wherein the MHC or the second MHC is an HL A, and wherein the HL A i s HL A- A* 02 : 01 , HL A- A* 03 : 01 , or HL A- A* 11 :01.

51. The composition of any one of claims 1-26 and 28-50, wherein the first peptide or the second peptide comprises a nucleophilic or an electrophilic residue, wherein the residue comprises cysteine, aspartic acid, or arginine.

52. The composition of any one of claims 1-26 and 28-51, wherein the first peptide or the second peptide comprises a cysteine residue.

53. The composition of any one of claims 1-26 and 28-52, wherein the first peptide conjugate is formed by a covalent reaction between the first targeted covalent inhibitor and a cysteine residue in the first peptide.

54. The composition of any one of claims 1-26 and 28-53, wherein the second peptide conjugate is formed by a covalent reaction between the second targeted covalent inhibitor and a cysteine residue in the second peptide.

55. The composition of any one of claims 1-26 and 28-54, wherein the first peptide or the second peptide is a segment of a protein that is associated with a cancer, optionally wherein the protein is encoded by a gene that is mutated in a cancer.

56. The composition of any one of claims 1-26 and 28-55, wherein the first peptide or the second peptide is a segment of an enzyme, and wherein the first targeted covalent inhibitor or second targeted covalent inhibitor is an inhibitor of the enzyme.

57. The composition of claim 56, wherein the enzyme is a kinase or GTPase.

58. The composition of any one of claims 1-26 and 28-57, wherein the first peptide or the second peptide is or is derived from KRAS.

59. The composition of any one of claims 1-26 and 28-58, wherein the first peptide or the second peptide comprises a segment of KRASG12C, KRASG12D, KRASG12R, or KRASG12S.

60. The composition of any one of claims 1-26 and 28-59, wherein the first targeted covalent inhibitor or the second targeted covalent inhibitor is (i) a tri-complex KRASGI2Cinhibitor or a KRASG12Cdegrader, (ii) a tri-complex KRASGI2Dinhibitor or a KRASG12Ddegrader, (iii) a tri-complex KRASG12Rinhibitor or a KRASG12Rdegrader, (iv) a tri-complex KRASG12Sinhibitor or a KRASG12Sdegrader.

61. The composition of any one of claims 1-26 and 28-60, wherein the first peptide conjugate or the second peptide conjugate comprises a compound selected from the group consisting of compounds 1, 2, and 3:wherein the compound is covalently bonded to a cysteine residue in a peptide, wherein the peptide comprises an amino acid sequence of VVVGACGVGK, VVGACGVGK, or KLVVVGACGV.

62. The composition of claim 61, wherein the peptide comprises the amino acid sequence of VVVGACGVGK or VVGACGVGK and the MHC is HLA-A*03:01 or HLA-A*l l:01.

63. The composition of claim 61, wherein the peptide comprises the amino acid sequence of KLVVVGACGV and the MHC is HLA-A*02:01.

64. The composition of any one of claims 1-26 and 28-63, wherein the first peptide conjugate is formed by the covalent reaction of adagrasib with a KRASG12Cpeptide.

65. The composition of any one of claims 1-26 and 28-64, wherein the second peptide conjugate is formed by the covalent reaction of sotorasib or divarasib with a KRASG12Cpeptide66. The composition of any one of claims 1-26 and 28-66, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein(a) the VH comprises:(i) a HC CDR1 comprising an amino acid sequence of X1SX3X4SIH, whereinXi is I, F or V,X3 is S or Y, andXHs S or Y;(ii) a HC CDR2 comprising an amino acid sequence of X1ISX4X5X6X7X8TX10YADSVKG, whereinXi is S or Y, X4is S or P, Xs is S or Y, Xe is S or Y, X7is S or G, Xs is S or Y, and Xio is S or Y, and(iii) a HC CDR3 comprising an amino acid sequence of XNX1X2DY, whereinXN IS an amino acid sequence selected from LWAS, FQWY, GYGW, GWYYL, YWYYM, YWYYL, GYYYPYY, SYYGFWQALW, SSRQYYHSQVEPPM, SGYYSSHWYLQSWYQ, and HYSEKWWGWYTMYID,Xi is G or A, andX2 is L or M; and / or(b) the VL comprises:(i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;(ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and(iii) a LC CDR3 comprising the amino acid sequence of QQX3X4X5X6X7X8X9X10T, whereinX3is W, T, S, A or G,X4is N, W, S, G, Y, D or K,X5is W, Y, S, A or T,Xe is G, S, Y, L, W, E or D,X7is W, S, H, Y, E, F or absent,Xs is P, Q, S, W, E, L, G or absent, X9 is L or P, andX10 is I, L, F, or V.

67. The composition of any one of claims 1-26 and 28-66, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein(a) the VH comprises:(i) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes;(ii) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or(iii) a HC CDR3 comprising an amino acid sequence of LWASGLDY; and / or(b) the VL comprises:(i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;(ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or(iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

68. The composition of any one of claims 1-26 and 28-66, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein(a) the VH comprises:(i) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes;(ii) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or(iii) a HC CDR3 comprising an amino acid sequence of SYYGFWQALWALDY; and / or(b) the VL comprises:(i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;(ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or(iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

69. The composition of any one of claims 1-26 and 28-66, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein(a) the VH comprises:(i) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes;(ii) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or(iii) a HC CDR3 comprising an amino acid sequence of GYYYPYYAMDY; and / or(b) the VL comprises:(i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;(ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or(iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4YPX5T, wherein Xi is W or S, X2 is K, W, or S, X3 is W, T, or A, X4is S, W, or Y, and X5 is I, L, or V.

70. The composition of any one of claims 1-26 and 28-66, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein(a) the VH comprises:(i) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes;(ii) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or(iii) a HC CDR3 comprising an amino acid sequence of GYYYPYYAMDY; and / or(b) the VL comprises:(i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;(ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or(iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

71. The composition of any one of claims 1-26 and 28-66, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein(a) the VH comprises:(i) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes;(ii) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or(iii) a HC CDR3 comprising an amino acid sequence of X1X2X3X4X5MDY, wherein Xi is F or G, X2 is Q or Y, X3 is W or G, X4is Y or W, and X5 is A or G; and / or(b) the VL comprises:(i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;(ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or(iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

72. The composition of any one of claims 1-26 and 28-66, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein(a) the VH comprises:(i) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes;(ii) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or(iii) a HC CDR3 comprising an amino acid sequence of SGYYSSHWYLQSWYQAMDY; and / or(b) the VL comprises:(i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;(ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or(iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4YPX5T, wherein Xi is W or S, X2 is K, W, or S, X3 is W, T, or A, X4is S, W, or Y, and X5 is I, L, or V.

73. The composition of any one of claims 1-26 and 28-66, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein(a) the VH comprises:(i) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes;(ii) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or(iii) a HC CDR3 comprising an amino acid sequence of SGYYSSHWYLQSWYQAMDY; and / or(b) the VL comprises:(i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;(ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or(iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6T, wherein Xi is G or A, X2 is S or Y, X3 is S or Y, X4 is G, D, or S, X5 is P or L, and Xe is I or L.

74. The composition of any one of claims 1-26 and 28-66, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein(a) the VH comprises:(i) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes;(ii) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or(iii) a HC CDR3 comprising an amino acid sequence of HYSEKWWGWYTMYIDAMDY; and / or(b) the VL comprises:(i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;(ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or(iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, orD, X3is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

75. The composition of any one of claims 1-26 and 28-66, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein(a) the VH comprises:(i) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes;(ii) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or(iii) a HC CDR3 comprising an amino acid sequence of X1WYYX2GMDY, wherein Xi is G or Y and X2 is M or L; and / or(b) the VL comprises:(i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;(ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or(iii) a LC CDR3 comprising the amino acid comprising the amino acid sequence of QQX1X2X3X4YPX5T, wherein Xi is W or S, X2 is K, W, or S, X3is W, T, or A, X4is S, W, or Y, and X5is I, L, or V.

76. The composition of any one of claims 1-26 and 28-66, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein(a) the VH comprises:(i) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes;(ii) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or(iii) a HC CDR3 comprising an amino acid sequence of X1WYYX2GMDY, wherein Xi is G or Y and X2 is M or L; and / or(b) the VL comprises:(i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;(ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or(iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6T, wherein Xi is G or A, X2 is S or Y, X3 is S or Y, X4 is G, D, or S, X5 is P or L, and Xe is I or L.

77. The composition of any one of claims 1-26 and 28-66, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein(a) the VH comprises:(i) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes;(ii) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or(iii) a HC CDR3 comprising an amino acid sequence of X1WYYX2GMDY, wherein Xi is G or Y and X2 is M or L; and / or(b) the VL comprises:(i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;(ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or(iii) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

78. The composition of any one of claims 1-26 and 28-66, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein(a) the VH comprises:(i) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes;(ii) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or(iii) a HC CDR3 comprising an amino acid sequence of SSRQYYHSQVEPPMAMDY; and / or(b) the VL comprises:(i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;(ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or(iii) a LC CDR3 comprising the amino acid comprising the amino acid sequence of QQX1X2X3X4YPX5T, wherein Xi is W or S, X2 is K, W, or S, X3is W, T, or A, X4is S, W, or Y, and X5is I, L, or V.

79. The composition of any one of claims 1-26 and 28-78, wherein the antigen-binding domain comprises the HC CDR1, HC CDR2, and HC CDR3 amino acid sequences of a VH amino acid sequence and / or the LC CDR1, LC CDR2, and LC CDR3 amino acid sequences of a VL amino acid sequence of a polypeptide selected from the group consisting of RM_001, RM_002, RM_003, RM_004, RM_005, RM_006, RM_007, RM_008, RM_009, RM_010, RM_011, RM_012, RM_013, RM_014, RM_015, RM_016, RM_017, RM_018, RM_019, RM_020, RM_021, RM_022, , RM_023, RM_024, RM 025, RM_026, RM_027, RM_028 , RM_029, RM_030, RM_031, and RM 032; or a variant thereof comprising 1-5 amino acid changes in one or more of the CDR amino acid sequences.

80. The composition of any one of claims 1-26 and 28-79, wherein the antigen-binding domain comprises the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 amino acid sequences of a polypeptide selected from the group consisting of RM_001, RM_002, RM_003, RM_004, RM_005, RM_006, RM_007, RM_008, RM_009, RM_010, RM_011, RM_012, RM_013, RM_014, RM_015, RM_016, RM_017, RM_018, RM_019, RM_020, RM_021, RM_022, , RM_023, RM_024, RM 025, RM_026, RM_027, RM_028 , RM_029, RM_030, RM_031, andRM 032, or a variant thereof comprising 1-5 amino acid changes in one or more of the CDR amino acid sequences.

81. The composition of any one of claims 1-26 and 28-80, wherein the antigen-binding domain comprises a VH and / or a VL amino acid sequence that is 90%, 95%, or 100% identical to the following VH and VL sequences:RM_001VL :DIQMTQ SP S SLS AS VGDRVTITCRASQ S VS S AV AW YQQKPGKAPKLLI YS AS SL YSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTVVH:EVQLVESGGGL VQPGGSLRLSC AASGFTIS S S SIHWVRQAPGKGLEWVASIS S Y YGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARLWASGLDYWGQGTLVTVSSRM_002VL :DIQMTQ SP S SLS AS VGDRVTITCRASQ S VS S AV AW YQQKPGKAPKLLI YS AS SL YSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTV VH:EVQLVESGGGL VQPGGSLRLSC AASGFTF S S S SIHWVRQAPGKGLEWVASIS SY YGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARLWASGLDYWG QGTLVTVSSRM_003VL :DIQMTQ SP S SLS AS VGDRVTITCRASQ S VS S AV AW YQQKPGKAPKLLI YS AS SL YSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWWYGSPLFTFGQGTKVEIKRTVVH:EVQLVESGGGL VQPGGSLRLSC AASGFTF S S S SIHWVRQAPGKGLEWVASIS S S SGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSYYGFWQALW ALD YWGQGTL VT VS SRM_004VL :DIQMTQ SP S SLS AS VGDRVTITCRASQ S VS S AV AW YQQKPGKAPKLLI YS AS SL YSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWWYGSPLFTFGQGTKVEIKRTVVH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVASISSS SGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSYYGFWQALW ALD YWGQGTL VT VS SRM_005VL :DIQMTQ SP S SLS AS VGDRVTITCRASQ S VS S AV AW YQQKPGKAPKLLI YS AS SL YSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISS YYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAM D YWGQGTL VTVSSRM_006VL :DIQMTQ SP S SLS AS VGDRVTITCRASQ S VS S AV AW YQQKPGKAPKLLI YS AS SL YSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISP YYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAM DYWGQGTLVTVSSRM_007VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQTSWYHSLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDY WGQGTLVTVSSRM_008VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTVVH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVASISSY YGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDY WGQGTLVTVSSRM_009VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPYYAMDY WGQGTLVTVSSRM_010VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSSWLYWLVTFGQGTKVEIKRTV VH:EVQLVESGGGL VQPGGSLRLSC AASGFTF S S S SIHWVRQAPGKGLEWVASIS S SS GSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFQWYAMDYWGQGTLVTVSSRM_011VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQWNWGWPLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTISSYSIHWVRQAPGKGLEWVAYISSYS GYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYGWGMDYWGQGTLVTVSSRM_012VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTVVH:EVQLVESGGGLVQPGGSLRLSCAASGFTISYSSIHWVRQAPGKGLEWVAYISSSS GYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSGYYSSHWYLQS W YQ AMD YWGQGTL VT VS SRM_013VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQASYGPITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSGYYSSHWYLQS W YQ AMD YWGQGTL VT VS SRM_014VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQWWSSSQLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYSSIHWVRQAPGKGLEWVASISSYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARHYSEKWWGWY TMYID AMD YWGQGTL VT VS SRM_015VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTVVH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSSRM_016VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGKTYYPITFGQGTKVEIKRTVVH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSSRM_017VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTVVH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSSRM_018VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTVVH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYW GQGTLVTVSSRM_019VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTVVH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWG QGTLVTVSSRM_020VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTVVH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYISPYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLGMDYWGQGTLVTVSSRM_021VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTVVH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSSRM_022VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEIKRTVVH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSSRM_023VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSSYYEELITFGQGTKVEIKRTVVH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSSRM_024VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQAYSDPLTFGQGTKVEIKRTVVH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSSRM 025VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLYSGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGSSSLLTFGQGTKVEIKRTVVH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWGQGTLVTVSSRM_026VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSGSYLLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYS SYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWG QGTLVTVSSRM_027VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQADYEFGLITFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISPYS SYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMGMDYWG QGTLVTVSSRM_028VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVAYISSSY GYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPP MAMD YWGQGTL VT VS SRM_029VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVAYISSS YGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEP PMAMD YWGQGTL VT VS SRM_030VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSSSIHWVRQAPGKGLEWVAYISSSY GYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEPP MAMD YWGQGTL VT VS SRM_031VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSC AASGFT VS YS SIHWVRQAPGKGLEWVAYIS S S YGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYYHSQVEP PMAMD YWGQGTL VT VS SRM_032VL:DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASSLY SGVPSRFSGSRSGTDFTL TISSLQPEDFATYYCQQGSSSLLTFGQGTKVEIKRTV VH:EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVAYISPY SGYTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYLGMDYW GQGTLVTVSS82. The composition of any one of claims 1-26 and 28-81, wherein the polypeptide specifically binds to the first peptide conjugate / MHC complex and a T cell antigen.

83. The composition of claim 82, wherein the polypeptide specifically binds to the first peptide conjugate / MHC complex and human CD3.

84. The composition of any one of claims 1-26 and 28-83, wherein the polypeptide specifically binds to the second peptide conjugate / MHC complex and a T cell antigen.

85. The composition of claim 84, wherein the polypeptide specifically binds to the second peptide conjugate / MHC complex and human CD3.

86. The composition of any one of claims 1-85, wherein the polypeptide comprises a heavy chain constant region selected from the group consisting of human IgM, IgGi, IgG2, IgGs, IgG4, IgAi, and IgA.

87. The composition of claim 86, wherein the heavy chain constant region comprises one or more amino acid substitutions, deletions, or additions in the Fc region.

88. The composition of any one of claims 1-87, wherein the polypeptide is conjugated to a detectable label, a chemotherapeutic agent, a radioisotope, an enzyme, or a toxin.

89. The composition of any one of claims 1-88, wherein the polypeptide is comprised within a chimeric antigen receptor.

90. The composition of claim 89, wherein the polypeptide is expressed by a T cell, a killer macrophage, a neutrophil or a natural killer cell.

91. A polynucleotide encoding the polypeptide of any one of claims 1-90.

92. A polynucleotide encoding a heavy chain variable region and / or a light chain variable region of the polypeptide of any one of claims 1-91.

93. A vector comprising the polynucleotide of claim 91 or 92.

94. The vector of claim 93, wherein the vector is a viral vector.

95. The vector of claim 94, wherein the viral vector is an adenoviral vector, lentiviral vector, retroviral vector, or adeno-associated viral vector.

96. A recombinant host cell comprising:(a) the polynucleotide of claim 91 or 92;(b) the vector of any one of claims 93-95;(c) a first polynucleotide encoding a VH or a heavy chain of the polypeptide of any one of claims 1-90, and a second polynucleotide encoding a VL or a light chain of the polypeptide of any one of claims 1-90; or(d) a first vector comprising a first polynucleotide encoding a VH or a heavy chain of the polypeptide of any one of claims 1-90, and a second vectorcomprising a second polynucleotide encoding a VL or a light chain of the polypeptide of any one of claims 1-90.

97. A pharmaceutical composition comprising the polypeptide of any one of claims 1-90, the polynucleotide of claim 91 or 92, the vector of any one of claims 93-95, or the host cell of claim 96 and a pharmaceutically acceptable carrier or excipient.

98. A method of producing a polypeptide, the method comprising culturing the host cell of claim 96 under suitable conditions so that the polynucleotide is expressed and the binding partner is produced.

99. An eukaryotic cell comprising the polynucleotide of claim 91 or 92 or the vector of any one of claims 93-95, wherein the cell is optionally a totipotent, multipotent, or pluripotent stem cell, wherein optionally the stem cell has an induced stem cell phenotype, or wherein the cell is optionally a leukocyte, optionally a CD4+ T cell, optionally a CD8+ T cell, optionally a y5 T cell, optionally a natural killer cell , a neutrophil or a macrophage.

100. A method comprising administering to an individual in need thereof the polypeptide of any one of claims 1-90, the polynucleotide of claim 91 or 92, the vector of any one of claims 93-95, the pharmaceutical composition of claim 97, or the cell of claim 96.

101. A cell free peptide conjugate / MHC complex comprising:(a) an isolated peptide conjugate formed by the covalent reaction of a targeted covalent inhibitor with a peptide; and(b) an MHC, wherein the targeted covalent inhibitor is sotorasib, adagrasib, or divarasib, wherein the MHC is an HL A, and wherein the HLA is HLA-A*02:01, HLA-A*03:01, or HLA-A*11:01.

102. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein(a) the VH comprises:(i) a HC CDR3 comprising an amino acid sequence of XNX1X2DY, whereinX\ is an amino acid sequence selected from LWAS, FQWY, GYGW, GWYYL, YWYYM, YWYYL, GYYYPYY, SYYGFWQALW,SSRQYYHSQVEPPM, SGYYSSHWYLQSWYQ, andHYSEKWWGWYTMYID,Xi is G or A, andX2 is L or M; and / or(b) the VL comprises:(i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;(ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and(iii) a LC CDR3 comprising the amino acid sequence of QQX3X4X5X6X7X8X9X10T, whereinX3is W, T, S, A or G,X4is N, W, S, G, Y, D or K,X5is W, Y, S, A or T,Xe is G, S, Y, L, W, E or D,X7is W, S, H, Y, E, F or absent,Xs is P, Q, S, W, E, L, G or absent,X9 is L or P, andX10 is I, L, F, or V.

103. The composition of claim 102, wherein the VH comprises a HC CDR1 comprising an amino acid sequence of X1SX3X4SIH, whereinXi is I, F or V,X3 is S or Y, andX4is S or Y.

104. The composition of claim 102 or 103, wherein the VH comprises a HC CDR2 comprising an amino acid sequence of X1ISX4X5X6X7X8TX10YADSVKG, whereinXi is S or Y,X4is S or P,X5 is S or Y,Xe is S or Y,X7is S or G,Xs is S or Y, andXio is S or Y.

105. The composition of any one of claims 102-104, wherein the VL comprises a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes.

106. The composition of any one of claims 102-105, wherein the VL comprises a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes.

107. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein(a) the VH comprises:(i) a HC CDR1 comprising an amino acid sequence of X1SX3X4SIH, whereinXi is I, F or V,X3 is S or Y, andXHs S or Y;(ii) a HC CDR2 comprising an amino acid sequence of X1ISX4X5X6X7X8TX10YADSVKG, whereinXi is S or Y,X4is S or P,X5 is S or Y,Xe is S or Y,X?is S or G,Xs is S or Y, andXio is S or Y, and(iii) a HC CDR3 comprising an amino acid sequence of XNX1X2DY, whereinXN IS an amino acid sequence selected from LWAS, FQWY, GYGW, GWYYL, YWYYM, YWYYL, GYYYPYY, SYYGFWQALW, SSRQYYHSQVEPPM, SGYYSSHWYLQSWYQ, andHYSEKWWGWYTMYID,Xi is G or A, andX2 is L or M; and / or(b) the VL comprises:(i) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;(ii) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and(iii) a LC CDR3 comprising the amino acid sequence of QQX3X4X5X6X7X8X9X10T, whereinX3is W, T, S, A or G, X4is N, W, S, G, Y, D or K, X5is W, Y, S, A or T, Xe is G, S, Y, L, W, E or D, X7is W, S, H, Y, E, F or absent, Xs is P, Q, S, W, E, L, G or absent, X9 is L or P, andX10 is I, L, F, or V.

108. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of LWASGLDY (SEQ ID NO: 5).

109. The composition of any one of claims 102-108, wherein the VH comprises a HC CDR2 sequence of SISSYYGSTSYADSVKG (SEQ ID NO: 4).

110. The composition of any one of claims 102-109, wherein the VH comprises a HC CDR1 sequence of ISSSSIH (SEQ ID NO: 3).

111. The composition of any one of claims 102-110, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQWNWGWPLIT (SEQ ID NO: 8).

112. The composition of any one of claims 102-111, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 7).

113. The composition of any one of claims 102-112, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 6).

114. The composition of any one of claims 102-113, wherein the antigen-binding domain comprises: a HC CDR1 sequence of ISSSSIH (SEQ ID NO: 3),a HC CDR2 sequence of SISSYYGSTSYADSVKG (SEQ ID NO: 4), a HC CDR3 sequence of LWASGLDY (SEQ ID NO: 5), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 6), a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 7), and a LC CDR3 sequence of QQWNWGWPLIT (SEQ ID NO: 8).

115. The composition of any one of claims 102-114, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTIS S S SIHWVRQAPGKGLEWVASIS S YYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARLWASGL DYWGQGTLVTVSS (SEQ ID NO: 2).

116. The composition of any one of claims 102-115, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWNWGWPLITFGQGTKV EIKRTV (SEQ ID NO: 1).

117. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of LWASGLDY (SEQ ID NO: 13).

118. The composition of claim 117, wherein the VH comprises a HC CDR2 sequence of SISSYYGSTSYADSVKG (SEQ ID NO: 12).

119. The composition of claim 117 or 118, wherein the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 11).

120. The composition of any one of claims 117-119, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQWNWGWPLIT (SEQ ID NO: 16).

121. The composition of any one of claims 117-120, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 15).

122. The composition of any one of claims 117-121, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 14).

123. The composition of any one of claims 117-122, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 11),a HC CDR2 sequence of SISSYYGSTSYADSVKG (SEQ ID NO: 12), a HC CDR3 sequence of LWASGLDY (SEQ ID NO: 13), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 14), a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 15), and a LC CDR3 sequence of QQWNWGWPLIT (SEQ ID NO: 16).

124. The composition of any one of claims 117-123, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTFS S S SMWVRQAPGKGLEWVASIS S YYGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARLWASGL DYWGQGTLVTVSS (SEQ ID NO: 10).

125. The composition of any one of claims 117-124, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWNWGWPLITFGQGTKV EIKRTV (SEQ ID NO: 9).

126. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of SYYGFWQALWALDY (SEQ ID NO: 21).

127. The composition of claim 126, wherein the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 20).

128. The composition of claim 126 or 127, wherein the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 19).

129. The composition of any one of claims 126-128, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQWWYGSPLFT (SEQ ID NO: 24).

130. The composition of any one of claims 126-129, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 23).

131. The composition of any one of claims 126-130, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 22).

132. The composition of any one of claims 126-131, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 19),a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 20), a HC CDR3 sequence of SYYGFWQALWALDY (SEQ ID NO: 21), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 22), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 23), and a LC CDR3 sequence of QQWWYGSPLFT (SEQ ID NO: 24).

133. The composition of any one of claims 126-132, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTFS S S SMWVRQAPGKGLEWVASIS S SSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSYYGFWQ ALWALDYWGQGTLVTVSS (SEQ ID NO: 18).

134. The composition of any one of claims 126-133, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWWYGSPLFTFGQGTKV EIKRT (SEQ ID NO: 17).

135. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of SYYGFWQALWALDY (SEQ ID NO: 29).

136. The composition of claim 135, wherein the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 28).

137. The composition of claim 135 or 136, wherein the VH comprises a HC CDR1 sequence of FSSYSIH (SEQ ID NO: 27).

138. The composition of any one of claims 135-137, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQWWYGSPLFT (SEQ ID NO: 32).

139. The composition of any one of claims 135-138, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 31).

140. The composition of any one of claims 135-139, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 30).

141. The composition of any one of claims 135-140, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSSYSIH (SEQ ID NO: 27),a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 28), a HC CDR3 sequence of SYYGFWQALWALDY (SEQ ID NO: 29), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 30), a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 31), and a LC CDR3 sequence of QQWWYGSPLFT (SEQ ID NO: 32).

142. The composition of any one of claims 135-141, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTF S S YSIHWVRQAPGKGLEW VASIS S SSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSYYGFWQ ALWALDYWGQGTLVTVSS (SEQ ID NO: 26).

143. The composition of any one of claims 135-142, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWWYGSPLFTFGQGTKV EIKRT (SEQ ID NO: 25).

144. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of GYYYP YYAMD Y (SEQ ID NO: 37).

145. The composition of claim 144, wherein the VH comprises a HC CDR2 sequence of SISSYYGSTYYADSVKG (SEQ ID NO: 36).

146. The composition of claim 144 or 145, wherein the VH comprises a HC CDR1 sequence of FSYYSIH (SEQ ID NO: 35).

147. The composition of any one of claims 144-146, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQGKTYYPIT (SEQ ID NO: 40).

148. The composition of any one of claims 144-147, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 39).

149. The composition of any one of claims 144-148, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 38).

150. The composition of any one of claims 144-149, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSYYSIH (SEQ ID NO: 35),a HC CDR2 sequence of SISSYYGSTYYADSVKG (SEQ ID NO: 36), a HC CDR3 sequence of GYYYP YYAMD Y (SEQ ID NO: 37), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 38), a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 39), and a LC CDR3 sequence of QQGKTYYPIT (SEQ ID NO: 40).

151. The composition of any one of claims 144-150, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTF S YYSIHWVRQAPGKGLEWVASIS S YYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPY YAMDYWGQGTLVTVSS (SEQ ID NO: 34).

152. The composition of any one of claims 144-151, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEI KRTV (SEQ ID NO: 33).

153. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of GYYYP YYAMD Y (SEQ ID NO: 45).

154. The composition of claim 153, wherein the VH comprises a HC CDR2 sequence of SISPYYGSTYYADSVKG (SEQ ID NO: 44).

155. The composition of claim 153 or 154, wherein the VH comprises a HC CDR1 sequence of FSYYSIH (SEQ ID NO: 43).

156. The composition of any one of claims 153-155, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQGKTYYPIT (SEQ ID NO: 48).

157. The composition of any one of claims 153-156, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 47).

158. The composition of any one of claims 153-157, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 46).

159. The composition of any one of claims 153-158, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSYYSIH (SEQ ID NO: 43),a HC CDR2 sequence of SISPYYGSTYYADSVKG (SEQ ID NO: 44), a HC CDR3 sequence of GYYYP YYAMD Y (SEQ ID NO: 45), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 46), a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 47), and a LC CDR3 sequence of QQGKTYYPIT (SEQ ID NO: 48).

160. The composition of any one of claims 153-159, wherein the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVASISP YYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPY YAMDYWGQGTLVTVSS (SEQ ID NO: 42).

161. The composition of any one of claims 153-160, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEI KRTV (SEQ ID NO: 41).

162. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of GYYYP YYAMD Y (SEQ ID NO: 53).

163. The composition of claim 162, wherein the VH comprises a HC CDR2 sequence of SISSYYGSTYYADSVKG (SEQ ID NO: 52).

164. The composition of claim 162 or 163, wherein the VH comprises a HC CDR1 sequence of FSYYSIH (SEQ ID NO: 51).

165. The composition of any one of claims 162-164, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQTSWYHSLIT (SEQ ID NO: 56).

166. The composition of any one of claims 162-165, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 55).

167. The composition of any one of claims 162-166, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 54).

168. The composition of any one of claims 162-167, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSYYSIH (SEQ ID NO: 51),a HC CDR2 sequence of SISSYYGSTYYADSVKG (SEQ ID NO: 52), a HC CDR3 sequence of GYYYP YYAMD Y (SEQ ID NO: 53), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 54), a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 55), and a LC CDR3 sequence of QQTSWYHSLIT (SEQ ID NO: 56).

169. The composition of any one of claims 162-168, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTF S YYSIHWVRQAPGKGLEWVASIS S YYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPY YAMDYWGQGTLVTVSS (SEQ ID NO: 50).

170. The composition of any one of claims 162-169, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQTSWYHSLITFGQGTKVE IKRTV (SEQ ID NO: 49).

171. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of GYYYP YYAMD Y (SEQ ID NO: 61).

172. The composition of claim 171, wherein the VH comprises a HC CDR2 sequence of SISSYYGSTYYADSVKG (SEQ ID NO: 60).

173. The composition of claim 171 or 172, wherein the VH comprises a HC CDR1 sequence of VSYYSIH (SEQ ID NO: 59).

174. The composition of any one of claims 171-173, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQGKTYYPIT (SEQ ID NO: 64).

175. The composition of any one of claims 171-174, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 63).

176. The composition of any one of claims 171-175, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 62).

177. The composition of any one of claims 171-176, wherein the antigen-binding domain comprises: a HC CDR1 sequence of VSYYSIH (SEQ ID NO: 59),a HC CDR2 sequence of SISSYYGSTYYADSVKG (SEQ ID NO: 60), a HC CDR3 sequence of GYYYP YYAMD Y (SEQ ID NO: 61), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 62), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 63), and a LC CDR3 sequence of QQGKTYYPIT (SEQ ID NO: 64).

178. The composition of any one of claims 171-177, wherein the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVASIS SYYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYP YYAMD YWGQGTLVTVSS (SEQ ID NO: 58).

179. The composition of any one of claims 171-178, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEI KRTV (SEQ ID NO: 57).

180. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of GYYYP YYAMD Y (SEQ ID NO: 69).

181. The composition of claim 180, wherein the VH comprises a HC CDR2 sequence of SISSYYGSTYYADSVKG (SEQ ID NO: 68).

182. The composition of claim 180 or 181, wherein the VH comprises a HC CDR1 sequence of FSYYSIH (SEQ ID NO: 67).

183. The composition of any one of claims 180-182, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSWWSYPLT (SEQ ID NO: 72).

184. The composition of any one of claims 180-183, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 71).

185. The composition of any one of claims 180-184, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 70).

186. The composition of any one of claims 180-185, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSYYSIH (SEQ ID NO: 67),a HC CDR2 sequence of SISSYYGSTYYADSVKG (SEQ ID NO: 68), a HC CDR3 sequence of GYYYP YYAMD Y (SEQ ID NO: 69), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 70), a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 71), and a LC CDR3 sequence of QQSWWSYPLT (SEQ ID NO: 72).

187. The composition of any one of claims 180-186, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTF S YYSIHWVRQAPGKGLEWVASIS S YYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYYYPY YAMDYWGQGTLVTVSS (SEQ ID NO: 66).

188. The composition of any one of claims 180-187, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEI KRTV (SEQ ID NO: 65).

189. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of FQWYAMDY (SEQ ID NO: 77).

190. The composition of claim 189, wherein the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 76).

191. The composition of claim 189 or 190, wherein the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 75).

192. The composition of any one of claims 189-191, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSSWLYWLVT (SEQ ID NO: 80).

193. The composition of any one of claims 189-192, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 79).

194. The composition of any one of claims 189-193, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 78).

195. The composition of any one of claims 189-194, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 75),a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 76), a HC CDR3 sequence of FQWYAMDY (SEQ ID NO: 77), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 78), a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 79), and a LC CDR3 sequence of QQSSWLYWLVT (SEQ ID NO: 80).

196. The composition of any one of claims 189-195, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTFS S S SMWVRQAPGKGLEWVASIS S SSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFQWYAM DYWGQGTLVTVSS (SEQ ID NO: 74).

197. The composition of any one of claims 189-196, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWLVTFGQGTKV EIKRTV (SEQ ID NO: 73).

198. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of GYGWGMDY (SEQ ID NO: 85).

199. The composition of claim 198, wherein the VH comprises a HC CDR2 sequence of YISSYSGYTSYADSVKG (SEQ ID NO: 84).

200. The composition of claim 198 or 199, wherein the VH comprises a HC CDR1 sequence of ISSYSIH (SEQ ID NO: 83).

201. The composition of any one of claims 198-200, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQWNWGWPLIT (SEQ ID NO: 88).

202. The composition of any one of claims 198-201, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 87).

203. The composition of any one of claims 198-202, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 86).

204. The composition of any one of claims 198-203, wherein the antigen-binding domain comprises: a HC CDR1 sequence of ISSYSIH (SEQ ID NO: 83),a HC CDR2 sequence of YISSYSGYTSYADSVKG (SEQ ID NO: 84), a HC CDR3 sequence of GYGWGMDY (SEQ ID NO: 85), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 86), a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 87), and a LC CDR3 sequence of QQWNWGWPLIT (SEQ ID NO: 88).

205. The composition of any one of claims 198-204, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTIS S YSMWVRQAPGKGLEWVAYIS S YSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGYGWG MDYWGQGTLVTVSS (SEQ ID NO: 82).

206. The composition of any one of claims 198-205, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWNWGWPLITFGQGTKV EIKRTV (SEQ ID NO: 81).

207. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of SGYYSSHWYLQSWYQAMDY (SEQ ID NO: 93).

208. The composition of claim 207, wherein the VH comprises a HC CDR2 sequence of YISSSSGYTSYADSVKG (SEQ ID NO: 92).

209. The composition of claim 207 or 208, wherein the VH comprises a HC CDR1 sequence of ISYS SIH (SEQ ID NO: 91).

210. The composition of any one of claims 207-209, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSSAWYPVT (SEQ ID NO: 96).

211. The composition of any one of claims 207-210, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 95).

212. The composition of any one of claims 207-211, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 94).

213. The composition of any one of claims 207-212, wherein the antigen-binding domain comprises: a HC CDR1 sequence of ISYS SIH (SEQ ID NO: 91),a HC CDR2 sequence of YISSSSGYTSYADSVKG (SEQ ID NO: 92), a HC CDR3 sequence of SGYYSSHWYLQSWYQAMDY (SEQ ID NO: 93), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 94), a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 95), and a LC CDR3 sequence of QQSSAWYPVT (SEQ ID NO: 96).

214. The composition of any one of claims 207-213, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTIS YS SMWVRQAPGKGLEWVAYIS S SSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSGYYSSH WYLQSWYQAMDYWGQGTLVTVSS (SEQ ID NO: 90).

215. The composition of any one of claims 207-214, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEI KRTV (SEQ ID NO: 89).

216. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of SGYYSSHWYLQSWYQAMDY (SEQ ID NO: 101).

217. The composition of claim 216, wherein the VH comprises a HC CDR2 sequence of SISSYYGSTYYADSVKG (SEQ ID NO: 100).

218. The composition of claim 216 or 217, wherein the VH comprises a HC CDR1 sequence of FSYYSIH (SEQ ID NO: 99).

219. The composition of any one of claims 216-218, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQASYGPIT (SEQ ID NO: 104).

220. The composition of any one of claims 216-219, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 103).

221. The composition of any one of claims 216-220, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 102).

222. The composition of any one of claims 216-221, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSYYSIH (SEQ ID NO: 99),a HC CDR2 sequence of SISSYYGSTYYADSVKG (SEQ ID NO: 100), a HC CDR3 sequence of SGYYSSHWYLQSWYQAMDY (SEQ ID NO: 101), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 102), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 103), and a LC CDR3 sequence of QQASYGPIT (SEQ ID NO: 104).

223. The composition of any one of claims 216-222, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTF S YYSIHWVRQAPGKGLEWVASIS S YYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSGYYSS HWYLQSWYQAMDYWGQGTLVTVSS (SEQ ID NO: 98).

224. The composition of any one of claims 216-223, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASYGPITFGQGTKVEIKR TV (SEQ ID NO: 97).

225. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of HYSEKWWGWYTMYIDAMDY (SEQ ID NO: 109).

226. The composition of claim 225, wherein the VH comprises a HC CDR2 sequence of SISSYYGSTYYADSVKG (SEQ ID NO: 108).

227. The composition of claim 225 or 226, wherein the VH comprises a HC CDR1 sequence of VSYSSIH (SEQ ID NO: 107).

228. The composition of any one of claims 225-227, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQWWSSSQLIT (SEQ ID NO: 112).

229. The composition of any one of claims 225-228, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 111).

230. The composition of any one of claims 225-229, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 110).

231. The composition of any one of claims 225-230, wherein the antigen-binding domain comprises: a HC CDR1 sequence of VSYSSIH (SEQ ID NO: 107),a HC CDR2 sequence of SISSYYGSTYYADSVKG (SEQ ID NO: 108), a HC CDR3 sequence of HYSEKWWGWYTMYIDAMDY (SEQ ID NO: 109), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 110), a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 111), and a LC CDR3 sequence of QQWWSSSQLIT (SEQ ID NO: 112).

232. The composition of any one of claims 225-231, wherein the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSYSSIHWVRQAPGKGLEWVASISS YYGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARHYSEKW WGWYTMYIDAMDYWGQGTLVTVSS (SEQ ID NO: 106).

233. The composition of any one of claims 225-232, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQWWSSSQLITFGQGTKVE IKRTV (SEQ ID NO: 105).

234. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of GWYYLGMDY (SEQ ID NO: 117).

235. The composition of claim 234, wherein the VH comprises a HC CDR2 sequence of YISPYSGYTSYADSVKG (SEQ ID NO: 116).

236. The composition of claim 234 or 235, wherein the VH comprises a HC CDR1 sequence of VSYYSIH (SEQ ID NO: 115).

237. The composition of any one of claims 234-236, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQGKTYYPIT (SEQ ID NO: 120).

238. The composition of any one of claims 234-237, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 119).

239. The composition of any one of claims 234-238, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 118).

240. The composition of any one of claims 234-239, wherein the antigen-binding domain comprises: a HC CDR1 sequence of VSYYSIH (SEQ ID NO: 115),a HC CDR2 sequence of YISPYSGYTSYADSVKG (SEQ ID NO: 116), a HC CDR3 sequence of GWYYLGMDY (SEQ ID NO: 117), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 118), a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 119), and a LC CDR3 sequence of QQGKTYYPIT (SEQ ID NO: 120).

241. The composition of any one of claims 234-240, wherein the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYIS PYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYL GMDYWGQGTLVTVSS (SEQ ID NO: 114).

242. The composition of any one of claims 234-241, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEI KRTV (SEQ ID NO: 113).

243. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of GWYYLGMDY (SEQ ID NO: 125).

244. The composition of claim 243, wherein the VH comprises a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 124).

245. The composition of claim 243 or 244, wherein the VH comprises a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 123).

246. The composition of any one of claims 243-245, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQGKTYYPIT (SEQ ID NO: 128).

247. The composition of any one of claims 243-246, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 127).

248. The composition of any one of claims 243-247, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 126).

249. The composition of any one of claims 243-248, wherein the antigen-binding domain comprises: a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 123),a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 124), a HC CDR3 sequence of GWYYLGMDY (SEQ ID NO: 125), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 126), a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 127), and a LC CDR3 sequence of QQGKTYYPIT (SEQ ID NO: 128).

250. The composition of any one of claims 243-249, wherein the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISP YSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLG MDYWGQGTLVTVSS (SEQ ID NO: 122).

251. The composition of any one of claims 243-250, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGKTYYPITFGQGTKVEI KRTV (SEQ ID NO: 121).

252. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of GWYYLGMDY (SEQ ID NO: 133).

253. The composition of claim 252, wherein the VH comprises a HC CDR2 sequence of YISPYSGYTSYADSVKG (SEQ ID NO: 132).

254. The composition of claim 252 or 253, wherein the VH comprises a HC CDR1 sequence of VSYYSIH (SEQ ID NO: 131).

255. The composition of any one of claims 252-254, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSWWSYPLT (SEQ ID NO: 136).

256. The composition of any one of claims 252-255, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 135).

257. The composition of any one of claims 252-256, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 134).

258. The composition of any one of claims 252-257, wherein the antigen-binding domain comprises: a HC CDR1 sequence of VSYYSIH (SEQ ID NO: 131),a HC CDR2 sequence of YISPYSGYTSYADSVKG (SEQ ID NO: 132), a HC CDR3 sequence of GWYYLGMDY (SEQ ID NO: 133), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 134), a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 135), and a LC CDR3 sequence of QQSWWSYPLT (SEQ ID NO: 136).

259. The composition of any one of claims 252-258, wherein the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYIS PYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYL GMDYWGQGTLVTVSS (SEQ ID NO: 130).

260. The composition of any one of claims 252-259, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEI KRTV (SEQ ID NO: 129).

261. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of GWYYLGMDY (SEQ ID NO: 141).

262. The composition of claim 261, wherein the VH comprises a HC CDR2 sequence of YISPYSGYTSYADSVKG (SEQ ID NO: 140).

263. The composition of claim 261 or 262, wherein the VH comprises a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 139).

264. The composition of any one of claims 261-263, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSWWSYPLT (SEQ ID NO: 144).

265. The composition of any one of claims 261-264, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 143).

266. The composition of any one of claims 261-265, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 142).

267. The composition of any one of claims 261-266, wherein the antigen-binding domain comprises: a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 139),a HC CDR2 sequence of YISPYSGYTSYADSVKG (SEQ ID NO: 140), a HC CDR3 sequence of GWYYLGMDY (SEQ ID NO: 141), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 142), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 143), and a LC CDR3 sequence of QQSWWSYPLT (SEQ ID NO: 144).

268. The composition of any one of claims 261-267, wherein the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVAYIS PYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYL GMDYWGQGTLVTVSS (SEQ ID NO: 138).

269. The composition of any one of claims 261-268, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEI KRTV (SEQ ID NO: 137).

270. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of GWYYLGMDY (SEQ ID NO: 149).

271. The composition of claim 270, wherein the VH comprises a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 148).

272. The composition of claim 270 or 271, wherein the VH comprises a HC CDR1 sequence of FSSYSIH (SEQ ID NO: 147).

273. The composition of any one of claims 270-272, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSWWSYPLT (SEQ ID NO: 152).

274. The composition of any one of claims 270-273, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 151).

275. The composition of any one of claims 270-274, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 150).

276. The composition of any one of claims 270-275, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSSYSIH (SEQ ID NO: 147),a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 148), a HC CDR3 sequence of GWYYLGMDY (SEQ ID NO: 149), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 150), a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 151), and a LC CDR3 sequence of QQSWWSYPLT (SEQ ID NO: 152).

277. The composition of any one of claims 270-276, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTF S S YSIHWVRQAPGKGLEW VASISP YSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYLG MDYWGQGTLVTVSS (SEQ ID NO: 146).

278. The composition of any one of claims 270-277, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEI KRTV (SEQ ID NO: 145).

279. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of GWYYLGMDY (SEQ ID NO: 157).

280. The composition of claim 279, wherein the VH comprises a HC CDR2 sequence of YISPYSGYTSYADSVKG (SEQ ID NO: 156).

281. The composition of claim 279 or 280, wherein the VH comprises a HC CDR1 sequence of VSYYSIH (SEQ ID NO: 155).

282. The composition of any one of claims 279-281, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSSAWYPVT (SEQ ID NO: 160).

283. The composition of any one of claims 279-282, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 159).

284. The composition of any one of claims 279-283, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 158).

285. The composition of any one of claims 279-284, wherein the antigen-binding domain comprises: a HC CDR1 sequence of VSYYSIH (SEQ ID NO: 155),a HC CDR2 sequence of YISPYSGYTSYADSVKG (SEQ ID NO: 156), a HC CDR3 sequence of GWYYLGMDY (SEQ ID NO: 157), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 158), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 159), and a LC CDR3 sequence of QQSSAWYPVT (SEQ ID NO: 160).

286. The composition of any one of claims 279-285, wherein the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSYYSIHWVRQAPGKGLEWVAYIS PYSGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARGWYYL GMDYWGQGTLVTVSS (SEQ ID NO: 154).

287. The composition of any one of claims 279-286, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEI KRTV (SEQ ID NO: 153).

288. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of YWYYMGMDY (SEQ ID NO: 165).

289. The composition of claim 288, wherein the VH comprises a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 164).

290. The composition of claim 288 or 289, wherein the VH comprises a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 163).

291. The composition of any one of claims 288-290, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSWWSYPLT (SEQ ID NO: 168).

292. The composition of any one of claims 288-291, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 167).

293. The composition of any one of claims 288-292, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 166).

294. The composition of any one of claims 288-293, wherein the antigen-binding domain comprises: a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 163),a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 164), a HC CDR3 sequence of YWYYMGMDY (SEQ ID NO: 165), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 166), a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 167), and a LC CDR3 sequence of QQSWWSYPLT (SEQ ID NO: 168).

295. The composition of any one of claims 288-294, wherein the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISP YSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMG MDYWGQGTLVTVSS (SEQ ID NO: 162).

296. The composition of any one of claims 288-295, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEI KRTV (SEQ ID NO: 161).

297. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of YWYYMGMDY (SEQ ID NO: 173).

298. The composition of claim 297, wherein the VH comprises a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 172).

299. The composition of claim 297 or 298, wherein the VH comprises a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 171).

300. The composition of any one of claims 297-299, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSSAWYPVT (SEQ ID NO: 176).

301. The composition of any one of claims 297-300, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 175).

302. The composition of any one of claims 297-301, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 174).

303. The composition of any one of claims 297-302, wherein the antigen-binding domain comprises: a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 171),a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 172), a HC CDR3 sequence of YWYYMGMDY (SEQ ID NO: 173), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 174), a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 175), and a LC CDR3 sequence of QQSSAWYPVT (SEQ ID NO: 176).

304. The composition of any one of claims 297-303, wherein the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISP YSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMG MDYWGQGTLVTVSS (SEQ ID NO: 170).

305. The composition of any one of claims 297-304, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSAWYPVTFGQGTKVEI KRTV (SEQ ID NO: 169).

306. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of YWYYMGMDY (SEQ ID NO: 181).

307. The composition of claim 306, wherein the VH comprises a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 180).

308. The composition of claim 306 or 307, wherein the VH comprises a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 179).

309. The composition of any one of claims 306-308, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSSYYEELIT (SEQ ID NO: 184).

310. The composition of any one of claims 306-309, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 183).

311. The composition of any one of claims 306-310, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 182).

312. The composition of any one of claims 306-311, wherein the antigen-binding domain comprises: a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 179),a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 180), a HC CDR3 sequence of YWYYMGMDY (SEQ ID NO: 181), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 182), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 183), and a LC CDR3 sequence of QQSSYYEELIT (SEQ ID NO: 184).

313. The composition of any one of claims 306-312, wherein the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISP YSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMG MDYWGQGTLVTVSS (SEQ ID NO: 178).

314. The composition of any one of claims 306-313, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSYYEELITFGQGTKVEI KRTV (SEQ ID NO: 177).

315. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of YWYYMGMDY (SEQ ID NO: 189).

316. The composition of claim 315, wherein the VH comprises a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 188).

317. The composition of claim 315 or 316, wherein the VH comprises a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 187).

318. The composition of any one of claims 315-317, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQAYSDPLT (SEQ ID NO: 192).

319. The composition of any one of claims 315-318, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 191).

320. The composition of any one of claims 315-319, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 190).

321. The composition of any one of claims 315-320, wherein the antigen-binding domain comprises: a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 187),a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 188), a HC CDR3 sequence of YWYYMGMDY (SEQ ID NO: 189), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 190), a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 191), and a LC CDR3 sequence of QQAYSDPLT (SEQ ID NO: 192).

322. The composition of any one of claims 315-321, wherein the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISP YSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMG MDYWGQGTLVTVSS (SEQ ID NO: 186).

323. The composition of any one of claims 315-322, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQAYSDPLTFGQGTKVEIK RTV (SEQ ID NO: 185).

324. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of YWYYMGMDY (SEQ ID NO: 197).

325. The composition of claim 324, wherein the VH comprises a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 196).

326. The composition of claim 324 or 325, wherein the VH comprises a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 195).

327. The composition of any one of claims 324-326, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQGSSSLLT (SEQ ID NO: 200).

328. The composition of any one of claims 324-327, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 199).

329. The composition of any one of claims 324-328, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 198).

330. The composition of any one of claims 324-329, wherein the antigen-binding domain comprises: a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 195),a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 196), a HC CDR3 sequence of YWYYMGMDY (SEQ ID NO: 197), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 198), a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 199), and a LC CDR3 sequence of QQGSSSLLT (SEQ ID NO: 200).

331. The composition of any one of claims 324-330, wherein the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISP YSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMG MDYWGQGTLVTVSS (SEQ ID NO: 194).

332. The composition of any one of claims 324-331, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGSSSLLTFGQGTKVEIKR TV (SEQ ID NO: 193).

333. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of YWYYMGMDY (SEQ ID NO: 205).

334. The composition of claim 333, wherein the VH comprises a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 204).

335. The composition of claim 333 or 334, wherein the VH comprises a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 203).

336. The composition of any one of claims 333-335, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSGSYLLIT (SEQ ID NO: 208).

337. The composition of any one of claims 333-336, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 207).

338. The composition of any one of claims 333-337, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 206).

339. The composition of any one of claims 333-338, wherein the antigen-binding domain comprises: a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 203),a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 204), a HC CDR3 sequence of YWYYMGMDY (SEQ ID NO: 205), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 206), a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 207), and a LC CDR3 sequence of QQSGSYLLIT (SEQ ID NO: 208).

340. The composition of any one of claims 333-339, wherein the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISP YSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMG MDYWGQGTLVTVSS (SEQ ID NO: 202).

341. The composition of any one of claims 333-340, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSGSYLLITFGQGTKVEIK RTV (SEQ ID NO: 201).

342. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of YWYYMGMDY (SEQ ID NO: 213).

343. The composition of claim 342, wherein the VH comprises a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 212).

344. The composition of claim 342 or 343, wherein the VH comprises a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 211).

345. The composition of any one of claims 342-344, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQADYEFGLIT (SEQ ID NO: 216).

346. The composition of any one of claims 342-345, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 215).

347. The composition of any one of claims 342-346, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 214).

348. The composition of any one of claims 342-347, wherein the antigen-binding domain comprises: a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 211),a HC CDR2 sequence of SISPYSSYTSYADSVKG (SEQ ID NO: 212), a HC CDR3 sequence of YWYYMGMDY (SEQ ID NO: 213), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 214), a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 215), and a LC CDR3 sequence of QQADYEFGLIT (SEQ ID NO: 216).

349. The composition of any one of claims 342-348, wherein the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVASISP YSSYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYMG MDYWGQGTLVTVSS (SEQ ID NO: 210).

350. The composition of any one of claims 342-349, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQADYEFGLITFGQGTKVEI KRTV (SEQ ID NO: 209).

351. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of SSRQYYHSQVEPPMAMDY (SEQ ID NO: 221).

352. The composition of claim 351, wherein the VH comprises a HC CDR2 sequence of YISSSYGYTSYADSVKG (SEQ ID NO: 220).

353. The composition of claim 351 or 352, wherein the VH comprises a HC CDR1 sequence of FSSYSIH (SEQ ID NO: 219).

354. The composition of any one of claims 351-353, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSWWSYPLT (SEQ ID NO: 224).

355. The composition of any one of claims 351-354, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 223).

356. The composition of any one of claims 351-355, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 222).

357. The composition of any one of claims 351-356, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSSYSIH (SEQ ID NO: 219),a HC CDR2 sequence of YISSSYGYTSYADSVKG (SEQ ID NO: 220), a HC CDR3 sequence of SSRQYYHSQVEPPMAMDY (SEQ ID NO: 221), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 222), a LC CDR2 sequence of SASSLYS (SEQ ID NO: 223), and a LC CDR3 sequence of QQSWWSYPLT (SEQ ID NO: 224).

358. The composition of any one of claims 351-357, wherein the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYSIHWVRQAPGKGLEWVAYISS SYGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYY HSQVEPPMAMDYWGQGTLVTVSS (SEQ ID NO: 218).

359. The composition of any one of claims 351-358, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEI KRTV (SEQ ID NO: 217).

360. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of SSRQYYHSQVEPPMAMDY (SEQ ID NO: 229).

361. The composition of claim 360, wherein the VH comprises a HC CDR2 sequence of YISSSYGYTSYADSVKG (SEQ ID NO: 228).

362. The composition of claim 360 or 361, wherein the VH comprises a HC CDR1 sequence of FSYYSIH (SEQ ID NO: 227).

363. The composition of any one of claims 360-362, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSWWSYPLT (SEQ ID NO: 232).

364. The composition of any one of claims 360-363, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 231).

365. The composition of any one of claims 360-364, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 230).

366. The composition of any one of claims 360-365, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSYYSIH (SEQ ID NO: 227),a HC CDR2 sequence of YISSSYGYTSYADSVKG (SEQ ID NO: 228), a HC CDR3 sequence of SSRQYYHSQVEPPMAMDY (SEQ ID NO: 229), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 230), a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 231), and a LC CDR3 sequence of QQSWWSYPLT (SEQ ID NO: 232).

367. The composition of any one of claims 360-366, wherein the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTFSYYSIHWVRQAPGKGLEWVAYIS SSYGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYY HSQVEPPMAMDYWGQGTLVTVSS (SEQ ID NO: 226).

368. The composition of any one of claims 360-367, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEI KRTV (SEQ ID NO: 225).

369. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of SSRQYYHSQVEPPMAMDY (SEQ ID NO: 237).

370. The composition of claim 369, wherein the VH comprises a HC CDR2 sequence of YISSSYGYTSYADSVKG (SEQ ID NO: 236).

371. The composition of claim 369 or 370, wherein the VH comprises a HC CDR1 sequence of VSSSSIH (SEQ ID NO: 235).

372. The composition of any one of claims 369-371, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSWWSYPLT (SEQ ID NO: 240).

373. The composition of any one of claims 369-372, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 239).

374. The composition of any one of claims 369-373, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 238).

375. The composition of any one of claims 369-374, wherein the antigen-binding domain comprises: a HC CDR1 sequence of VSSSSIH (SEQ ID NO: 235),a HC CDR2 sequence of YISSSYGYTSYADSVKG (SEQ ID NO: 236), a HC CDR3 sequence of SSRQYYHSQVEPPMAMDY (SEQ ID NO: 237), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 238), a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 239), and a LC CDR3 sequence of QQSWWSYPLT (SEQ ID NO: 240).

376. The composition of any one of claims 369-375, wherein the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSSSIHWVRQAPGKGLEWVAYISS SYGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYY HSQVEPPMAMDYWGQGTLVTVSS (SEQ ID NO: 234).

377. The composition of any one of claims 369-376, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEI KRTV (SEQ ID NO: 233).

378. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of SSRQYYHSQVEPPMAMDY (SEQ ID NO: 245).

379. The composition of claim 378, wherein the VH comprises a HC CDR2 sequence of YISSSYGYTSYADSVKG (SEQ ID NO: 244).

380. The composition of claim 378 or 379, wherein the VH comprises a HC CDR1 sequence of VSYSSIH (SEQ ID NO: 243).

381. The composition of any one of claims 378-380, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSWWSYPLT (SEQ ID NO: 248).

382. The composition of any one of claims 378-381, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 247).

383. The composition of any one of claims 378-382, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 246).

384. The composition of any one of claims 378-383, wherein the antigen-binding domain comprises: a HC CDR1 sequence of VSYSSIH (SEQ ID NO: 243),a HC CDR2 sequence of YISSSYGYTSYADSVKG (SEQ ID NO: 244), a HC CDR3 sequence of SSRQYYHSQVEPPMAMDY (SEQ ID NO: 245), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 246), a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 247), and a LC CDR3 sequence of QQSWWSYPLT (SEQ ID NO: 248).

385. The composition of any one of claims 378-384, wherein the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSYSSIHWVRQAPGKGLEWVAYIS SSYGYTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARSSRQYY HSQVEPPMAMDYWGQGTLVTVSS (SEQ ID NO: 242).

386. The composition of any one of claims 378-385, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSWWSYPLTFGQGTKVEI KRTV (SEQ ID NO: 241).

387. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 (HC CDR3) sequence of YWYYLGMDY (SEQ ID NO: 253).

388. The composition of claim 387, wherein the VH comprises a HC CDR2 sequence of YISPYSGYTYYADSVKG (SEQ ID NO: 252).

389. The composition of claim 387 or 388, wherein the VH comprises a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 251).

390. The composition of any one of claims 387-389, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQGSSSLLT (SEQ ID NO: 256).

391. The composition of any one of claims 387-390, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 255).

392. The composition of any one of claims 387-391, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 254).

393. The composition of any one of claims 387-392, wherein the antigen-binding domain comprises: a HC CDR1 sequence of VSSYSIH (SEQ ID NO: 251),a HC CDR2 sequence of YISPYSGYTYYADSVKG (SEQ ID NO: 252), a HC CDR3 sequence of YWYYLGMDY (SEQ ID NO: 253), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 254), a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 255), and a LC CDR3 sequence of QQGSSSLLT (SEQ ID NO: 256).

394. The composition of any one of claims 387-393, wherein the VH comprises a sequence with at least 80% sequence identity to the sequence EVQLVESGGGLVQPGGSLRLSCAASGFTVSSYSIHWVRQAPGKGLEWVAYIS PYSGYTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARYWYYL GMDYWGQGTLVTVSS (SEQ ID NO: 250).

395. The composition of any one of claims 387-394, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQGSSSLLTFGQGTKVEIKR TV (SEQ ID NO: 249).

396. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein(a) the VH comprises:(i) a HC CDR3 comprising the amino acid sequence of LWASGLDY; and / or(b) the VL comprises:(i) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

397. The composition of claim 396, wherein the VH comprises a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes.

398. The composition of claim 396 or 397, wherein the VH comprises a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes.

399. The composition of any one of claims 396-398, wherein the VL comprises a LC CDR1 comprising an amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes.

400. The composition of any one of claims 396-399, wherein the VL comprises a LC CDR2 comprising an amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes.

401. The composition of any one of claims 396-400, wherein the VH comprises:(a) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes;(b) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or(c) a HC CDR3 comprising an amino acid sequence of LWASGLDY.

402. The composition of any one of claims 396-401, wherein the VL comprises:(a) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;(b) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or(c) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

403. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein(a) the VH comprises:(i) a HC CDR3 comprising the amino acid sequence of SYYGFWQALWALDY; and / or(b) the VL comprises:(i) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

404. The composition of claim 403, wherein the VH comprises a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes.

405. The composition of claim 403 or 404, wherein the VH comprises a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes.

406. The composition of any one of claims 403-405, wherein the VL comprises a LC CDR1 comprising an amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes.

407. The composition of any one of claims 403-406, wherein the VL comprises a LC CDR2 comprising an amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes.

408. The composition of any one of claims 403-407, wherein the VH comprises:(a) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes;(b) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or(c) a HC CDR3 comprising an amino acid sequence of SYYGFWQALWALDY.

409. The composition of any one of claims 403-408, wherein the VL comprises:(a) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;(b) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or(c) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

410. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein(a) the VH comprises:(i) a HC CDR3 comprising the amino acid sequence of GYYYPYYAMDY; and / or(b) the VL comprises:(i) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4YPX5T, wherein Xi is W or S, X2 is K, W, or S, X3 is W, T, or A, X4 is S, W, or Y, and X5 is I, L, or V.

411. The composition of claim 410, wherein the VH comprises a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes.

412. The composition of claim 410 or 411, wherein the VH comprises a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes.

413. The composition of any one of claims 410-412, wherein the VL comprises a LC CDR1 comprising an amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes.

414. The composition of any one of claims 410-413, wherein the VL comprises a LC CDR2 comprising an amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes.

415. The composition of any one of claims 410-414, wherein the VH comprises:(a) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes;(b) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or(c) a HC CDR3 comprising an amino acid sequence of GYYYPYYAMDY.

416. The composition of any one of claims 410-415, wherein the VL comprises:(a) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;(b) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or(c) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4YPX5T, wherein Xi is W or S, X2 is K, W, or S, X3 is W, T, or A, X4 is S, W, or Y, and X5is I, L, or V.

417. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein(a) the VH comprises:(i) a HC CDR3 comprising the amino acid sequence of GYYYPYYAMDY; and / or(b) the VL comprises:(i) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

418. The composition of claim 417, wherein the VH comprises a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes.

419. The composition of claim 417 or 418, wherein the VH comprises a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes.

420. The composition of any one of claims 417-419, wherein the VL comprises a LC CDR1 comprising an amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes.

421. The composition of any one of claims 417-420, wherein the VL comprises a LC CDR2 comprising an amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes.

422. The composition of any one of claims 417-421, wherein the VH comprises:(a) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes;(b) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or(c) a HC CDR3 comprising an amino acid sequence of GYYYPYYAMDY.

423. The composition of any one of claims 417-422, wherein the VL comprises:(a) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;(b) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or(c) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

424. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein(a) the VH comprises:(i) a HC CDR3 comprising the amino acid sequence of X1X2X3X4X5MDY, wherein Xi is F or G, X2 is Q or Y, X3 is W or G, X4 is Y or W, and X5 is A or G; and / or(b) the VL comprises:(i) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

425. The composition of claim 424, wherein the VH comprises a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes.

426. The composition of claim 424 or 425, wherein the VH comprises a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes.

427. The composition of any one of claims 424-426, wherein the VL comprises a LC CDR1 comprising an amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes.

428. The composition of any one of claims 424-427, wherein the VL comprises a LC CDR2 comprising an amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes.

429. The composition of any one of claims 424-428, wherein the VH comprises:(a) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes;(b) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or(c) a HC CDR3 comprising an amino acid sequence of X1X2X3X4X5MDY, wherein Xi is F or G, X2 is Q or Y, X3 is W or G, X4 is Y or W, and X5 is A or G.

430. The composition of any one of claims 424-429, wherein the VL comprises:(a) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;(b) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or(c) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

431. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein(a) the VH comprises:(i) a HC CDR3 comprising the amino acid sequence of SGYYSSHWYLQSWYQAMDY; and / or(b) the VL comprises:(i) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4YPX5T, wherein Xi is W or S, X2 is K, W, or S, X3 is W, T, or A, X4is S, W, or Y, and X5 is I, L, or V.

432. The composition of claim 431, wherein the VH comprises a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes.

433. The composition of claim 431 or 432, wherein the VH comprises a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes.

434. The composition of any one of claims 431-433, wherein the VL comprises a LC CDR1 comprising an amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes.

435. The composition of any one of claims 431-434, wherein the VL comprises a LC CDR2 comprising an amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes.

436. The composition of any one of claims 431-435, wherein the VH comprises:(a) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes;(b) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or(c) a HC CDR3 comprising an amino acid sequence of SGYYSSHWYLQSWYQAMDY.

437. The composition of any one of claims 431-436, wherein the VL comprises:(a) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;(b) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or(c) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4YPX5T, wherein Xi is W or S, X2 is K, W, or S, X3 is W, T, or A, X4 is S, W, or Y, and X5is I, L, or V.

438. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein(a) the VH comprises:(i) a HC CDR3 comprising the amino acid sequence of SGYYSSHWYLQSWYQAMDY; and / or(b) the VL comprises:(i) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6T, wherein Xi is G or A, X2 is S or Y, X3 is S or Y, X4 is G, D, or S, X5 is P or L, and Xe is I or L.

439. The composition of claim 438, wherein the VH comprises a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes.

440. The composition of claim 438 or 439, wherein the VH comprises a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes.

441. The composition of any one of claims 438-440, wherein the VL comprises a LC CDR1 comprising an amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes.

442. The composition of any one of claims 438-441, wherein the VL comprises a LC CDR2 comprising an amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes.

443. The composition of any one of claims 438-442, wherein the VH comprises:(a) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes;(b) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or(c) a HC CDR3 comprising an amino acid sequence of SGYYSSHWYLQSWYQAMDY.

444. The composition of any one of claims 438-443, wherein the VL comprises:(a) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;(b) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or(c) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6T, wherein Xi is G or A, X2 is S or Y, X3 is S or Y, X4 is G, D, or S, X5 is P or L, and Xe is I or L.

445. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein(a) the VH comprises:(i) a HC CDR3 comprising the amino acid sequence of HYSEKWWGWYTMYIDAMDY; and / or(b) the VL comprises:(i) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

446. The composition of claim 445, wherein the VH comprises a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes.

447. The composition of claim 445 or 446, wherein the VH comprises a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes.

448. The composition of any one of claims 445-447, wherein the VL comprises a LC CDR1 comprising an amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes.

449. The composition of any one of claims 445-448, wherein the VL comprises a LC CDR2 comprising an amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes.

450. The composition of any one of claims 445-449, wherein the VH comprises:(a) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes;(b) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or(c) a HC CDR3 comprising an amino acid sequence of HYSEKWWGWYTMYIDAMDY.

451. The composition of any one of claims 445-450, wherein the VL comprises:(a) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;(b) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or(c) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

452. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein(a) the VH comprises:(i) a HC CDR3 comprising the amino acid sequence of X1WYYX2GMDY, wherein Xi is G or Y and X2 is M or L; and / or(b) the VL comprises:(i) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4YPX5T, wherein Xi is W or S, X2 is K, W, or S, X3 is W, T, or A, X4 is S, W, or Y, and X5 is I, L, or V.

453. The composition of claim 452, wherein the VH comprises a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes.

454. The composition of claim 452 or 453, wherein the VH comprises a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes.

455. The composition of any one of claims 452-454, wherein the VL comprises a LC CDR1 comprising an amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes.

456. The composition of any one of claims 452-455, wherein the VL comprises a LC CDR2 comprising an amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes.

457. The composition of any one of claims 452-456, wherein the VH comprises:(a) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes;(b) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or(c) a HC CDR3 comprising an amino acid sequence of X1WYYX2GMDY, wherein Xi is G or Y and X2 is M or L.

458. The composition of any one of claims 452-457, wherein the VL comprises:(a) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;(b) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or(c) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4YPX5T, wherein Xi is W or S, X2 is K, W, or S, X3 is W, T, or A, X4 is S, W, or Y, and X5is I, L, or V.

459. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein(a) the VH comprises:(i) a HC CDR3 comprising the amino acid sequence of X1WYYX2GMDY, wherein Xi is G or Y and X2 is M or L; and / or(b) the VL comprises:(i) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6T, wherein Xi is G or A, X2 is S or Y, X3 is S or Y, X4 is G, D, or S, X5 is P or L, and Xe is I or L.

460. The composition of claim 459, wherein the VH comprises a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes.

461. The composition of claim 459 or 460, wherein the VH comprises a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes.

462. The composition of any one of claims 459-461, wherein the VL comprises a LC CDR1 comprising an amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes.

463. The composition of any one of claims 459-462, wherein the VL comprises a LC CDR2 comprising an amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes.

464. The composition of any one of claims 459-463, wherein the VH comprises:(a) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes;(b) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or(c) a HC CDR3 comprising an amino acid sequence of X1WYYX2GMDY, wherein Xi is G or Y and X2 is M or L.

465. The composition of any one of claims 459-464, wherein the VL comprises:(a) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;(b) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or(c) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6T, wherein Xi is G or A, X2 is S or Y, X3 is S or Y, X4 is G, D, or S, X5 is P or L, and Xe is I or L.

466. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein(a) the VH comprises:(i) a HC CDR3 comprising the amino acid sequence of X1WYYX2GMDY, wherein Xi is G or Y and X2 is M or L; and / or(b) the VL comprises:(i) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

467. The composition of claim 466, wherein the VH comprises a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes.

468. The composition of claim 466 or 467, wherein the VH comprises a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes.

469. The composition of any one of claims 466-468, wherein the VL comprises a LC CDR1 comprising an amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes.

470. The composition of any one of claims 466-469, wherein the VL comprises a LC CDR2 comprising an amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes.

471. The composition of any one of claims 466-470, wherein the VH comprises:(a) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes;(b) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or(c) a HC CDR3 comprising an amino acid sequence of X1WYYX2GMDY, wherein Xi is G or Y and X2 is M or L.

472. The composition of any one of claims 466-471, wherein the VL comprises:(a) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;(b) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or(c) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4X5X6LX7T, wherein Xi is W, S, or A, X2 is N, W, S, or D, X3 is W, S, or Y, X4is G, L, S, E or Y, X5is W S, Y, E, or F, X6is P, W, G, E, or Q, and X7 is I, F, or V.

473. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein(a) the VH comprises:(i) a HC CDR3 comprising the amino acid sequence of SSRQYYHSQVEPPMAMDY; and / or(b) the VL comprises:(i) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4YPX5T, wherein XI is W or S, X2 is K, W, or S, X3 is W, T, or A, X4 is S, W, or Y, and X5 is I, L, or V.

474. The composition of claim 473, wherein the VH comprises a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes.

475. The composition of claim 473 or 474, wherein the VH comprises a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes.

476. The composition of any one of claims 473-475, wherein the VL comprises a LC CDR1 comprising an amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes.

477. The composition of any one of claims 473-476, wherein the VL comprises a LC CDR2 comprising an amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes.

478. The composition of any one of claims 473-477, wherein the VH comprises:(a) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes;(b) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or(c) a HC CDR3 comprising an amino acid sequence ofS SRQ YYHSQVEPPMAMD Y.

479. The composition of any one of claims 473-478, wherein the VL comprises:(a) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;(b) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-5 amino acid changes, and / or(c) a LC CDR3 comprising the amino acid sequence of QQX1X2X3X4YPX5T, wherein XI is W or S, X2 is K, W, or S, X3 is W, T, or A, X4 is S, W, or Y, and X5 is I, L, or V.

480. The composition of any one of claims 102-479, wherein the antigen-binding domain binds to a peptide conjugate / MHC complex, wherein the peptide conjugate of the peptide conjugate / MHC complex is a peptide covalently linked to a targeted covalent inhibitor or fragment thereof and a MHC.

481. The composition of claim 480, wherein the targeted covalent inhibitor is adagrasib, sotorasib, or divarasib.

482. The composition of claim 480, wherein the peptide conjugate / MHC complex is a first peptide conjugate / MHC complex comprising a first peptide conjugate comprising a first peptide and a first targeted covalent inhibitor or fragment thereof; and wherein the antigen-binding domain further binds to a second peptide conjugate / MHC complex comprising (a) a second peptide conjugate, wherein the second peptide conjugate of the second peptide conjugate / MHC complex is a second peptide covalently linked to a second targeted covalent inhibitor or fragment thereof; and (b) a second MHC.

483. The composition of claim 482, wherein the antigen-binding domain binds to (i) the first peptide conjugate / MHC complex with a dissociation constant (KD) of at most about 50 nM and (ii) the second peptide conjugate / MHC complex with a KD of at most about 50 nM.

484. The composition of claim 482, wherein the antigen-binding domain binds to (i) the first peptide conjugate / MHC complex with a dissociation constant (KD) of at mostabout 10 nM and (ii) the second peptide conjugate / MHC complex with a KD of at most about 10 nM.

485. The composition of claim 482, wherein the antigen-binding domain binds to (i) the first peptide conjugate / MHC complex with a dissociation constant (KD) of at most about 5 nM and (ii) the second peptide conjugate / MHC complex with a KD of at most about 5 nM.

486. The composition of any one of claims 482-485, wherein (i) the first targeted covalent inhibitor is adagrasib and the second targeted covalent inhibitor is sotorasib; (ii) the first targeted covalent inhibitor is adagrasib and the second targeted covalent inhibitor is divarasib; or (iii) the first targeted covalent inhibitor is divarasib and the second targeted covalent inhibitor is sotorasib.

487. The composition of any one of claims 480-486, wherein the antigen-binding domain does not bind to a free first targeted covalent inhibitor with a dissociation constant (KD) of less than 200 nM.

488. The composition of claim 487, wherein the antigen-binding domain binds to the first peptide conjugate / MHC complex with a greater affinity than to the first peptide or the free first targeted covalent inhibitor.

489. The composition of claim 487 or 488, wherein the affinity of the antigen-binding domain for the first peptide conjugate / MHC complex is 100-10,000 times greater than the affinity of the antigen-binding domain for the first peptide or the free first targeted covalent inhibitor.

490. The composition of any one of claims 482-489, wherein the antigen-binding domain does not detectably bind to a complex of the first peptide with a MHC, wherein the first peptide is not covalently bound to the first targeted covalent inhibitor or fragment thereof.

491. The composition of any one of claims 487-490, wherein the antigen-binding domain does not detectably bind to the free first targeted covalent inhibitor.

492. The composition of any one of claims 482-491, wherein the antigen-binding domain binds to a free first peptide conjugate with a dissociation constant KD that is at least 2.5 times more than a KD of the antibody or the antigen-binding fragment to the first peptide conjugate / MHC complex.

493. The composition of any one of claims 482-492, wherein the antigen-binding domain does not bind to a free second targeted covalent inhibitor with a dissociation constant (KD) of less than 200 nM.

494. The composition of claim 493, wherein the antigen-binding domain binds to the second peptide conjugate / MHC complex with a greater affinity than to the second peptide or the free second targeted covalent inhibitor.

495. The composition of claim 493 or 494, wherein the affinity of the antigen-binding domain for the second peptide conjugate / MHC complex is 100-10,000 times greater than the affinity of the antigen-binding domain for the second peptide or the free second targeted covalent inhibitor.

496. The composition of any one of claims 482-495, wherein the antigen-binding domain does not detectably bind to a complex of the second peptide with the second MHC, wherein the second peptide is not covalently bound to the second targeted covalent inhibitor or fragment thereof.

497. The composition of any one of claims 493-496, wherein the antigen-binding domain does not detectably bind to the free second targeted covalent inhibitor.

498. The composition of any one of claims 482-497, wherein the antigen-binding domain binds to a free second peptide conjugate with a dissociation constant ( o) that is at least 2.5 times more than a Ko of the antibody or the antigen-binding fragment to the second peptide conjugate / MHC complex.

499. The composition of any one of claims 482-498, wherein the first peptide and the second peptide comprise the same amino acid sequence.

500. The composition of any one of claims 482-499, wherein the first peptide and the second peptide consist of the same amino acid sequence.

501. The composition of claim 499 or 500, wherein the first peptide or the second peptide comprises the amino acid sequence of VVVGACGVGK.

502. The composition of any one of claims 482-498, wherein the first peptide and second peptide comprise a different amino acid sequence.

503. The composition of claim 502, wherein the first peptide or the second peptide comprises an amino acid sequence of VVVGACGVGK, VVGACGVGK, or KLVVVGACGV.

504. The composition of any one of claims 482-503, wherein the MHC is an HLA, and wherein the HLA is HLA-A*02:01, HLA-A*03:01, or HLA-A*11 :01.

505. The composition of any one of claims 482-504, wherein the first peptide or the second peptide is or is derived from KRAS.

506. The composition of any one of claims 482-505, wherein the first peptide or the second peptide comprises a segment of KRASG12C, KRASG12D, KRASG12R, or KRASG12S.

507. The composition of any one of claims 482-506, wherein the first peptide conjugate is formed by the covalent reaction of a free first targeted covalent inhibitor with a KRASG12Cpeptide, a KRASG12Dpeptide, a KRASG12Speptide, or a KRASG12Rpeptide.

508. The composition of any one of claims 482-507, wherein the second peptide conjugate is formed by the covalent reaction of a second free targeted covalent inhibitor with a KRASG12Cpeptide, a KRASG12Dpeptide, a KRASG12Speptide, or a KRASG12Rpeptide.

509. The composition of claim 507 or 508, wherein the free first targeted covalent inhibitor or the second free targeted covalent inhibitor is sotorasib, adagrasib, or divarasib.

510. The composition of any one of claims 482-509, wherein the first peptide or the second peptide comprises the amino acid sequence of VVVGACGVGK, VVGACGVGK, or KLVVVGACGV.

511. The composition of any one of claims 102-479, wherein the antigen-binding domain binds to(a) a first peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 and a second peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01;(b) a first peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 and a second peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01; or(c) a first peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01 and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01.

512. The composition of any one of claims 102-479, wherein the antigen-binding domain binds to(a) a first peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presentedby HLA-A*03:01 and a second peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01;(b) a first peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01; or(c) a first peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01.

513. The composition of any one of claims 102-479, wherein the antigen-binding domain binds to(a) a first peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 and a second peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HL A- A* 11 :01;(b) a first peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 and a second peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HL A- A* 11 :01; or(c) a first peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01 and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01.

514. The composition of any one of claims 102-479, wherein the antigen-binding domain binds to(a) a first peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presentedby HLA-A*03:01 and a second peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HL A- A* 11 :01;(b) a first peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01; or(c) a first peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01.

515. The composition of any one of claims 102-479, wherein the antigen-binding domain binds to(a) a first peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 and a second peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HL A- A* 11 :01;(b) a first peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 and a second peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HL A- A* 11 :01; or(c) a first peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01 and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01.

516. The composition of any one of claims 102-479, wherein the antigen-binding domain binds to(a) a first peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presentedby HLA-A*03:01 and a second peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HL A- A* 11 :01;(b) a first peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01; or(c) a first peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01 and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01.

517. The composition of any one of claims 102-479, wherein the antigen-binding domain binds to(a) a first peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A* 11 :01 and a second peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01;(b) a first peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A* 11 :01 and a second peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01; or(c) a first peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01 and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01.

518. The composition of any one of claims 102-479, wherein the antigen-binding domain binds to(a) a first peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presentedby HLA-A* 11 :01 and a second peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*03:01;(b) a first peptide conjugate / MHC complex comprising VVVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A* 11 :01 and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01; or(c) a first peptide conjugate / MHC complex comprising VVGACGVGK conjugated to a first targeted covalent inhibitor or fragment thereof presented by HLA-A* 11 :01 and a second peptide conjugate / MHC complex comprising KLVVVGACGV conjugated to a second targeted covalent inhibitor or fragment thereof presented by HLA-A*02:01.

519. The composition of any one of claims 511-518, wherein the first targeted covalent inhibitor or the second targeted covalent inhibitor is sotorasib, adagrasib, or divarasib.

520. The composition of any one of claims 102-519, wherein the VH is linked to the VL via a linker sequence.

521. The composition of claim 520, wherein the linker sequence comprises (G4S)n or (S4G)n, wherein n is any integer from 1 to 10.

522. The composition of claim 520 or 521, wherein the linker comprises the glycine- serine-alanine linker G4SA3 or a glycine-serine linker (G4S)4.

523. The composition of any one of claims 102-522, wherein the polypeptide is an intact antibody, a bispecific antibody, a multispecific antibody, an antigen-binding (Fab) fragment, an Fab’ fragment, an (Fab’)2 fragment, an Fd, an Fv, a dAb, a single domain fragment or single monomeric variable antibody domain, a single-chain Diabody (scDb), a diabody (Db), a dual-affinity retargeting (DART) molecule, a single-chain variable fragment (scFv), a Bi-specific T-cell engager (BiTE), bispecific killer cell engager (BiKE), CrossMab, a tri-specific binding partner, a chimeric antigen receptor (CAR), a camelid antibody, a monobody, a DARPin, an anticalin, an affibody, or an affimer.

524. The composition of any one of claims 102-522, wherein the polypeptide comprises a monobody, a DARPin, an anticalin, an affibody, or an affimer.

525. The composition of any one of claims 102-524, wherein the polypeptide comprises a polypeptide chain comprising the antigen-binding domain.

526. The composition of claim 525, wherein the polypeptide chain further comprises a cytokine or fragment thereof.

527. The composition of claim 526, wherein cytokine comprises IL-2, IL-7, IL-15, IL-12, IL- 18, IL-21, or an interferon (IFN).

528. A pharmaceutical composition comprising a polypeptide of any one of claims 170- 527, and a pharmaceutically acceptable carrier, excipient, adjuvant or diluent.

529. A method of treating cancer in a subject in need thereof wherein the subject has been treated with a free targeted covalent inhibitor, the method comprising administering to the subject the polypeptide of any one of claims 170-527 or the pharmaceutical composition of claim 528.

530. The method of claim 529, wherein the free targeted covalent inhibitor is sotorasib, adagrasib, or divarasib.

531. The method of claim 529 or 530, wherein the subject is refractory to a treatment with the free targeted covalent inhibitor.

532. A method of treating a cancer in a subject in need thereof, the method comprising administering to the subject the polypeptide of any one of claims 170-527 or the pharmaceutical composition of claim 528.

533. The method of claim 532, wherein the method further comprises administering simultaneously a small molecule drug.

534. A method of administering to the subject in need thereof the polypeptide of any one of claims 170-527 or the pharmaceutical composition of claim 528, and a free targeted covalent inhibitor, wherein the free targeted covalent inhibitor is optionally sotorasib, adagrasib, or divarasib.

535. The method of claim 534, wherein the polypeptide of any one of claims 170-527 or the pharmaceutical composition of claim 528 is administered after administration of the free targeted covalent inhibitor or simultaneously with the free targeted covalent inhibitor.

536. A method of manufacturing a T-cell receptor (TCR) that recognizes the first peptide conjugate / MHC complex or the second peptide conjugate / MHC complex of any one of claims 482-510, the method comprising:(a) a plurality of candidate TCRs with the first peptide conjugate / MHC complex or the second peptide conjugate / MHC complex, and(b) identifying at least one TCR that binds to the first peptide conjugate / MHC complex or the second peptide conjugate / MHC complex.

537. The method of claim 536, wherein identifying in (b) further comprises selecting or isolating the at least one TCR.

538. The method of claim 536 or 537, wherein the plurality of candidate TCRs is a plurality of soluble TCRs or a plurality of TCRs expressed on cell surface of a plurality of cells.

539. The method of claim 538, wherein the plurality of candidate TCRs is the plurality of TCRs expressed on cell surface of the plurality of cells, and identifying in (b) comprises isolating or selecting a cell comprising the at least one TCR based on an activation marker of the cell.

540. The method of claim 539, wherein the activation marker is a T cell activation marker.

541. The method of claim 540, wherein the T cell activation marker is CD26, CD27, CD28, CD30, CD154, CD40L, CD134. CD25, CD44, CD69, CD137, PD-1, or KLRG1542. A T-cell receptor (TCR) comprising the at least one TCR of (b) of any one of claims 536-541.

543. The TCR of claim 542, wherein the TCR is a soluble TCR.

544. The TCR of claim 542 or 543, wherein the TCR is a bispecific TCR.

545. The composition of any one of claims 1-90 and 482-510, wherein the first peptide conjugate / MHC complex is different from the second peptide conjugate / MHC complex, wherein each of the first and second peptide conjugate / MHC complexes independently comprises:(a) a different peptide selected from the group consisting of peptides comprising the formulaX#X#+iX#+2X#+3X#+4(X#+5)X#+6X#+7X#+sX#+9, andX#X#+ 1 X#+2X#+3 (X#+4)X#+sX#+eX#+7X#+8X#+9, and X#X#+iX#+2(X#+3)X#+4X#+sX#+6X#+7X#+8X#+9, and X#X#+i(X#+2)X#+3X#+4X#+sX#+6X#+7X#+8X#+9, and X#-iX#X#+iX#+2X#+3X#+4(X#+s)X#+6X#+7X#+8X#+9, and X#+lX#+2X#+3X#+4(X#+5)X#+6X#+7X#+8X#+9, wherein the peptide conjugate of the first and second peptide conjugate / MHC complex is formed by the covalent reaction of the first targeted covalent inhibitor, second targeted covalent inhibitor or fragment thereof with the residue in parenthesis; and(b) the same MHC;wherein the polypeptide binds to the first peptide conjugate / MHC complex with a KD that is at most 100 nM and binds to the second peptide conjugate / MHC complex with an KD that is at most 100 nM, or wherein when the polypeptide is contacted to the first peptide conjugate / MHC complex a maximum wavelength shift of at least 0.1 nm is observed according to a background- subtracted biolayer interferometry analysis and wherein when the polypeptide is contacted to the second peptide conjugate / MHC complex a maximum wavelength shift of at least 0.1 nm is observed according to the biolayer interferometry analysis, or wherein when the polypeptide is contacted to the first peptide conjugate / MHC complex a maximum binding signal of at least 0.1-fold of a reference binding signal is observed according to a background-subtracted biolayer interferometry analysis and wherein when the polypeptide is contacted to the second peptide conjugate / MHC complex a maximum binding signal of at least 0.1-fold of a reference binding signal is observed according to the background-subtracted biolayer interferometry analysis, and wherein the reference binding signal is the maximum binding signal of the polypeptide binding to X#X#+iX#+2X#+3X#+4(X#+s)X#+6X#+7X#+8X#+9.

546. The composition of claim 545, wherein the formula X#X#+iX#+2X#+3X#+4(X#+s)X#+6X#+7X#+8X#+9 is the formula X7X8X9X10X11X12X13X14X15X16, and wherein X12 is covalently linked to the first targeted covalent inhibitor, second targeted covalent inhibitor or fragment thereof.

547. The composition of any one of claims 1-90 and 482-510, wherein the polypeptide binds to the first peptide conjugate / MHC complex and the second peptide conjugate / MHC complex, wherein each of the first and the second peptide conjugate / MHC complex comprises:(a) a peptide comprising the formula X7X8X9X10X11X12X13X14X15X16; and(b) the same MHC; wherein the first peptide conjugate of the first peptide conjugate / MHC complex is formed by the covalent reaction of the first targeted covalent inhibitor or fragment thereof with X12 of the peptide, and wherein the second peptide conjugate of the second peptide conjugate / MHC complex is formed by the covalent reaction of the second targeted covalent inhibitor or fragment thereof with X13 of the peptide, wherein the second targeted covalent inhibitor is the same as the first targeted covalent inhibitor; andwherein the polypeptide binds to the second peptide conjugate / MHC complex with a KD that is at most 100,000-fold higher than the KD of the polypeptide to the first peptide conjugate / MHC complex, or wherein a maximum wavelength shift of the polypeptide binding to the second peptide conjugate / MHC complex is at least 10-fold less than a maximum wavelength shift of the polypeptide binding to the first peptide conjugate / MHC complex, or wherein a maximum binding signal of the polypeptide binding to the second peptide conjugate / MHC complex is at least 10-fold less than a maximum binding signal of the polypeptide binding to the first peptide conjugate / MHC complex.

548. The composition of any one of claims 1-90 and 482-510, wherein the polypeptide binds to the first peptide conjugate / MHC complex and the second peptide conjugate / MHC complex, wherein each of the first and the second peptide conjugate / MHC complex comprises:(a) a peptide comprising the formula X7X8X9X10X11X12X13X14X15X16; and(b) the same MHC; wherein the first peptide conjugate of the first peptide conjugate / MHC complex is formed by the covalent reaction of the first targeted covalent inhibitor or fragment thereof with a residue selected from the group consisting of X9, X10, X11, and X12, and wherein the second peptide conjugate of the second peptide conjugate / MHC complex is formed by the covalent reaction of the second targeted covalent inhibitor or fragment thereof with a residue selected from the group consisting of X13, X14, and X15, wherein the second targeted covalent inhibitor is the same as the first targeted covalent inhibitor; wherein the polypeptide binds to the second peptide conjugate / MHC complex with a KD that is at most 100,000 fold higher that the KD of the polypeptide to the first peptide conjugate / MHC complex, or wherein a maximum wavelength shift of the polypeptide binding to the second peptide conjugate / MHC complex is at least 10-fold less than a maximum wavelength shift of the polypeptide binding to the first peptide conjugate / MHC complex, or wherein a maximum binding signal of the polypeptide binding to the second peptide conjugate / MHC complex is at least 10-fold less than a maximum binding signal of the polypeptide binding to the first peptide conjugate / MHC complex.

549. The composition of any one of claims 1-90 and 482-510, wherein the polypeptide binds to the first peptide conjugate / MHC complex and the second peptideconjugate / MHC complex, wherein each of the first and the second peptide conjugate / MHC complex comprises: a peptide comprising the formula A-B-C, where A comprises no more than three residues having an N-terminal anchor residue, B comprises at least four but no more than seven residues having a residue covalently linked to the first targeted covalent inhibitor or fragment thereof or the second targeted covalent inhibitor or fragment thereof, and C comprises no more than three residues having a C-terminal anchor residue, wherein the N-terminal anchor residues and the C-terminal anchor residue bind to an MHC; and the same MHC; wherein the residue covalently linked to the first targeted covalent inhibitor or fragment thereof of the peptide of the first peptide conjugate / MHC complex is different from the residue covalently linked to the second targeted covalent inhibitor or fragment thereof of the peptide of the second peptide conjugate / MHC complex; and wherein the polypeptide binds to the first peptide conjugate / MHC complex with a KD that is at most 100 nM and binds to the second peptide conjugate / MHC complex with a KD that is at most 100 nM, or wherein when the polypeptide is contacted to the first peptide conjugate / MHC complex a maximum wavelength shift of at least 0.1 nm is observed according to a background- subtracted biolayer interferometry analysis and wherein when the polypeptide is contacted to the second peptide conjugate / MHC complex a maximum wavelength shift of at least 0.1 nm is observed according to the background- subtracted biolayer interferometry analysis, or wherein when the polypeptide is contacted to the first peptide conjugate / MHC complex a maximum binding signal of at least 0.1-fold of a reference binding signal is observed according to a background-subtracted biolayer interferometry analysis and wherein when the polypeptide is contacted to the second peptide conjugate / MHC complex a maximum binding signal of at least 0.1-fold of a reference binding signal is observed according to the background-subtracted biolayer interferometry analysis, and wherein the reference binding signal is the maximum binding signal of the polypeptide binding to X#X#+iX#+2X#+3X#+4(X#+5)X#+6X#+7X#+sX#+9.

550. The composition of claim 549, wherein A comprises two residues X?Xs.

551. The composition of claim 549 or 550, wherein B comprises seven residues X9X10X11X12X13X14X15.

552. The composition of any one of claims 549-551, wherein C comprises one residue Xi6.

553. The composition of any one of claims 549-552, wherein the formula A-B-C is the formula X7X8X9X10X11X12X13X14X15X16.

554. The composition of claim 553, wherein the first peptide conjugate of the first peptide conjugate / MHC complex is formed by the covalent reaction of the first targeted covalent inhibitor or fragment thereof with X12 of the peptide.

555. The composition of claim 553 or 554, wherein the second peptide conjugate of the second peptide conjugate / MHC complex is formed by the covalent reaction of the second targeted covalent inhibitor or fragment thereof with X13 of the peptide, wherein the second targeted covalent inhibitor is the same as the first targeted covalent inhibitor.

556. The composition of claim 555, wherein the polypeptide binds to the second peptide conjugate / MHC complex with a KD that is at most 100,000 fold higher than the KD of the polypeptide to the first peptide conjugate / MHC complex.

557. The composition of any one of claims 551-556, wherein the polypeptide binds to the second peptide conjugate / MHC complex with an KD that is at most 100,000 fold higher than the KD of the polypeptide to the first peptide conjugate / MHC complex, and wherein the residue covalently linked to the first targeted covalent inhibitor or fragment thereof of the peptide of the first peptide conjugate / MHC complex is selected from the group of consisting of X9, X10, X11, and X12, and the residue covalently linked to the second targeted covalent inhibitor or fragment thereof of the peptide of the second peptide conjugate / MHC complex is X13, X14, and X15.

558. The composition of any one of claims 544-557, wherein the peptide is a RAS peptide.

559. The composition of claim 558, wherein the RAS peptide comprises a mutation.

560. The composition of claim 559, wherein the mutation is G12C or G13C.

561. The composition of any one of claims 558-560, wherein the RAS peptide comprises a sequence selected from the group consisting of VVVGACGVGK, VVGACGVGK, and KLVVVGACGV.

562. The composition of any one of claims 558-560, wherein the RAS peptide comprises a sequence selected from the group consisting of VVVGAGCVGK, VVGAGCVGK, or KLVVVGAGCV.

563. The composition of any one of claims 544-562, wherein the same MHC is selected from the group consisting of HLA-A*03:01, HLA-A* 11:01, HLA-A*02:01, HLA- A*68:01, HLA-A*31:01, HLA-A*30:01, HLA-A*33:03, HLA-A*33:01, HLA- A*74:01, HLA-A*34:02, HLA-A*66:01, HLA-A*68:02, HLA-A*02:05, HLA- A*02:02, and HLA-A*02:06.

564. The composition of any one of claims 544-563, wherein the targeted covalent inhibitor or fragment thereof comprises sotorasib.

565. The composition of any one of claims 546-548 and 553-564, wherein the peptide is a RAS peptide, and wherein X12 is G12C mutation, and X13 is G13C mutation.

566. The composition of claim 565, wherein the polypeptide binds to the first peptide conjugate / MHC complex having a Cys of the G12C mutation covalently linked to the first targeted covalent inhibitor or fragment thereof with a KD that is at most 100 nM and binds to the second peptide conjugate / MHC complex having a Cys of the G13C mutation covalently linked to the second targeted covalent inhibitor or fragment thereof with an KD that is most 100 nM, or wherein when the polypeptide is contacted to the first peptide conjugate / MHC complex a maximum wavelength shift of at least 0.1 nm is observed according to a background- subtracted biolayer interferometry analysis and wherein when the polypeptide is contacted to the second peptide conjugate / MHC complex a maximum wavelength shift of at least 0.1 nm is observed according to the background- subtracted biolayer interferometry analysis, or wherein when the polypeptide is contacted to the first peptide conjugate / MHC complex a maximum binding signal of at least 0.1-fold of a reference binding signal is observed according to a background-subtracted biolayer interferometry analysis and wherein when a polypeptide is contact to the second peptide conjugate / MHC complex a maximum binding signal of at least 0.1 -fold of a reference binding signal is observed according to a background-subtracted biolayer interferometry analysis, and wherein the reference binding signal is the maximum binding signal of the polypeptide binding to X#X#+iX#+2X#+3X#+4X#+sX#+6X#+7X#+8X#+9.

567. The composition of claim 565, wherein the polypeptide binds to the second peptide conjugate / MHC complex having a Cys of the G13C mutation covalently linked to the second targeted covalent inhibitor or fragment thereof with a KD that is at most 100,000 fold higher that the KD of the polypeptide to the first peptide conjugate / MHCcomplex having a Cys of the G12C mutation covalently linked to the first targeted covalent inhibitor or fragment thereof, or wherein a maximum wavelength shift of the polypeptide binding to the second peptide conjugate / MHC complex is at least 10-fold less than a maximum wavelength shift of the polypeptide binding to the first peptide conjugate / MHC complex, or wherein a maximum binding signal of the polypeptide binding to the second peptide conjugate / MHC complex is at least 10-fold less than a maximum binding signal of the polypeptide binding to the first peptide conjugate / MHC complex.

568. A composition comprising: a polypeptide that binds to a first peptide conjugate / MHC complex and a second peptide conjugate / MHC complex different from the first peptide conjugate / MHC complex, wherein each of the first and second peptide conjugate / MHC complexes independently comprises:(a) a different peptide selected from the group consisting of peptides comprising the formulaX#X#+iX#+2X#+3X#+4(X#+5)X#+6X#+7X#+sX#+9, andX#X#+ 1 X#+2X#+3 (X#+4)X#+sX#+eX#+7X#+8X#+9, and X#X#+iX#+2(X#+3)X#+4X#+sX#+6X#+7X#+8X#+9, and X#X#+i(X#+2)X#+3X#+4X#+sX#+6X#+7X#+8X#+9, and X#-iX#X#+iX#+2X#+3X#+4(X#+s)X#+6X#+7X#+8X#+9, and X#+lX#+2X#+3X#+4(X#+5)X#+6X#+7X#+8X#+9, wherein the peptide conjugate of the first and second peptide conjugate / MHC complex is formed by the covalent reaction of a targeted covalent inhibitor or fragment thereof with the residue in parenthesis; and(b) the same MHC; wherein the polypeptide binds to the first peptide conjugate / MHC complex with an KD that is at most 100 nM and binds to the second peptide conjugate / MHC complex with an KD that is at most 100 nM, or wherein when the polypeptide is contacted to the first peptide conjugate / MHC complex a maximum wavelength shift of at least 0.1 nm is observed according to a background- subtracted biolayer interferometry analysis and wherein when the polypeptide is contacted to the second peptide conjugate / MHC complex a maximum wavelength shift of at least 0.1 nm is observed according to the background- subtracted biolayer interferometry analysis, orwherein when the polypeptide is contacted to the first peptide conjugate / MHC complex a maximum binding signal of at least O.l-fold of a reference binding signal is observed according to a background-subtracted biolayer interferometry analysis and wherein when the polypeptide is contacted to the second peptide conjugate / MHC complex a maximum binding signal of at least O.l-fold of a reference binding signal is observed according to the background-subtracted biolayer interferometry analysis, and wherein the reference binding signal is the maximum binding signal of the polypeptide binding to X#X#+iX#+2X#+3X#+4(X#+s)X#+6X#+7X#+8X#+9.

569. The composition of claim 568, wherein each of the first and second peptide conjugate / MHC complexes independently comprises: a different peptide selected from the group consisting of peptides comprising the formula X#X#+iX#+2X#+3X#+4(X#+s)X#+6X#+7X#+8X#+9, andX#X#+ 1 X#+2X#+3 (X#+4)X#+sX#+eX#+7X#+8X#+9, and X#X#+iX#+2(X#+3)X#+4X#+sX#+6X#+7X#+8X#+9, and X#X#+l(X#+2)X#+3X#+4X#+5X#+6X#+7X#+8X#+9.

570. The composition of claim 568, wherein each of the first and second peptide conjugate / MHC complexes independently comprises: a different peptide with an amino acid sequence selected from the group consisting of: VVVGACGVGK, VVVGCGGVGK, VVVCAGGVGK, and VVCGAGGVGK.

571. A composition comprising a polypeptide that binds to a first peptide conjugate / MHC complex and a second peptide conjugate / MHC complex, wherein each of the first and the second peptide conjugate / MHC complex comprises:(a) a peptide comprising the formula X7X8X9X10X11X12X13X14X15X16; and(b) the same MHC; wherein a first peptide conjugate of the first peptide conjugate / MHC complex is formed by the covalent reaction of a targeted covalent inhibitor or fragment thereof with X12 of the peptide, and wherein a second peptide conjugate of the second peptide conjugate / MHC complex is formed by the covalent reaction of the same targeted covalent inhibitor or fragment thereof with X13 of the peptide; wherein a polypeptide binds to the second peptide conjugate / MHC complex with a KD that is at most 100,000 fold higher than the KD of the polypeptide to the first peptide conjugate / MHC complex, orwherein a maximum wavelength shift of the polypeptide binding to the second peptide conjugate / MHC complex is at least 10-fold less than a maximum wavelength shift of the polypeptide binding to the first peptide conjugate / MHC complex, or wherein a maximum binding signal of the polypeptide binding to the second peptide conjugate / MHC complex is at least 10-fold less than a maximum binding signal of the polypeptide binding to the first peptide conjugate / MHC complex.

572. A composition comprising a polypeptide that binds to a first peptide conjugate / MHC complex and a second peptide conjugate / MHC complex, wherein each of the first and the second peptide conjugate / MHC complex comprises:(a) a peptide comprising the formula X7X8X9X10X11X12X13X14X15X16; and(b) the same MHC; wherein a first peptide conjugate of the first peptide conjugate / MHC complex is formed by the covalent reaction of a targeted covalent inhibitor or fragment thereof with a residue selected from the group consisting of X9, X10, X11, and X12, and wherein a second peptide conjugate of the second peptide conjugate / MHC complex is formed by the covalent reaction of the same targeted covalent inhibitor or fragment thereof with a residue selected from the group consisting of X13, X14, and X15; wherein a polypeptide binds to the second peptide conjugate / MHC com-plex with a KD that is at most 100,000 fold higher that the KD of the polypeptide to the first peptide conjugate / MHC complex, or wherein a maximum wavelength shift of the polypeptide binding to the second peptide conjugate / MHC complex is at least 10-fold less than a maximum wavelength shift of the polypeptide binding to the first peptide conjugate / MHC complex, or wherein a maximum binding signal of the polypeptide binding to the second peptide conjugate / MHC complex is at least 10-fold less than a maximum binding signal of the polypeptide binding to the first peptide conjugate / MHC complex.

573. A composition comprising a polypeptide that binds to a first peptide conjugate / MHC complex and a second peptide conjugate / MHC complex, wherein each of the first and the second peptide conjugate / MHC complex comprises: a peptide comprising the formula A-B-C, where A comprises no more than three residues having an N-terminal anchor residue, B comprises at least four but no more than seven residues having a residue covalently linked to a targeted covalent inhibitor or fragment thereof, and C comprises no more than three residues having a C-terminalanchor residue, wherein the N-terminal anchor residues and the C-terminal anchor residue bind to an MHC; and the same MHC; wherein the residue covalently linked to a targeted covalent inhibitor or fragment thereof of the peptide of the first peptide conjugate / MHC complex is different from the residue covalently linked to a targeted covalent inhibitor or fragment thereof of the peptide of the second peptide conjugate / MHC complex; and wherein a polypeptide binds to the first peptide conjugate / MHC complex with a KD that is at most 100 nM and binds to the second peptide conjugate / MHC complex with a KD that is at most 100 nM, or wherein when the polypeptide is contacted to the first peptide conjugate / MHC complex a maximum wavelength shift of at least 0.1 nm is observed according to a background- subtracted biolayer interferometry analysis and wherein when the polypeptide is contacted to the second peptide conjugate / MHC complex a maximum wavelength shift of at least 0.1 nm is observed according to the background- subtracted biolayer interferometry analysis, or wherein when the polypeptide is contacted to the first peptide conjugate / MHC complex a maximum binding signal of at least 0.1-fold of a reference binding signal is observed according to a background-subtracted biolayer interferometry analysis and wherein when the polypeptide is contacted to the second peptide conjugate / MHC complex a maximum binding signal of at least 0.1-fold of a reference binding signal is observed according to the background-subtracted biolayer interferometry analysis, and wherein the reference binding signal is the maximum binding signal of the polypeptide binding to X#X#+iX#+2X#+3X#+4(X#+5)X#+6X#+7X#+sX#+9.

574. The composition of claim 573, wherein A comprises two residues X?Xs.

575. The composition of claim 573 or 574, wherein B comprises seven residues X9X10X11X12X13X14X15.

576. The composition of any one of claims 573-575, wherein C comprises one residue X16.

577. The composition of any one of claims 573-576, wherein the formula A-B-C is the formula X7X8X9X10X11X12X13X14X15X16.

578. The composition of claim 577, wherein a first peptide conjugate of the first peptide conjugate / MHC complex is formed by the covalent reaction of the targeted covalent inhibitor or fragment thereof with X12 of the peptide.

579. The composition of claim 577 or 578, wherein a second peptide conjugate of the second peptide conjugate / MHC complex is formed by the covalent reaction of the same targeted covalent inhibitor or fragment thereof with X13 of the peptide.

580. The composition of claim 579, wherein the polypeptide binds to the second peptide conjugate / MHC complex with a KD that is at most 100,000 fold higher than the KD of the polypeptide to the first peptide conjugate / MHC complex.

581. The composition of any one of claims 575-580, wherein the polypeptide binds to the second peptide conjugate / MHC complex with an KD that is at most 100,000 fold higher than the KD of the polypeptide to the first peptide conjugate / MHC complex, and wherein the residue covalently linked to the targeted covalent inhibitor or fragment thereof of the peptide of the first peptide conjugate / MHC complex is selected from the group of consisting of X9, X10, X11, and X12, and the residue covalently linked to the targeted covalent inhibitor or fragment thereof of the peptide of the second peptide conjugate / MHC complex is X13, X14, and X15.

582. The composition of any one of claims 568-581, wherein the peptide is a RAS peptide.

583. The composition of claim 582, wherein the RAS peptide comprises a mutation.

584. The composition of claim 583, wherein the mutation is G12C or G13C.

585. The composition of any one of claims 582-584, wherein the RAS peptide comprises a sequence selected from the group consisting of VVVGACGVGK, VVGACGVGK, and KLVVVGACGV.

586. The composition of any one of claims 582-584, wherein the RAS peptide comprises a sequence selected from the group consisting of VVVGAGCVGK, VVGAGCVGK, or KLVVVGAGCV.

587. The composition of any one of claims 568-586, wherein the same MHC is selected from the group consisting of HL A-A* 03:01, HLA-A* 11:01, HLA-A*02:01, HLA-, HLA-A*68:01, HLA-A*31:01, HLA-A*30:01, HLA-A*33:03, HLA-A*33:01, HLA- A*74:01, HLA-A*34:02, HLA-A*66:01, HLA-A*68:02, HLA-A*02:05, HLA- A*02:02, and HLA-A*02:06.

588. The composition of any one of claims 568-587, wherein the targeted covalent inhibitor or fragment thereof comprises sotorasib.

589. The composition of any one of claims 570-573 and 577-588, wherein the peptide is a RAS peptide, and wherein X12 is G12C mutation, and X13 is G13C mutation.

590. The composition of claim 589, wherein the polypeptide binds to the first peptide conjugate / MHC complex having a Cys of the G12C mutation covalently linked to thetargeted covalent inhibitor or fragment thereof with an KD that is at most 100 nM and binds to the second peptide conjugate / MHC complex having a Cys of the G13C mutation covalently linked to the targeted covalent inhibitor or fragment thereof with an KD that is at most 100 nM, or wherein when the polypeptide is contacted to the first peptide conjugate / MHC complex a maximum wavelength shift of at least 0.1 nm is observed according to a background- subtracted biolayer interferometry analysis and wherein when the polypeptide is contacted to the second peptide conjugate / MHC complex a maximum wavelength shift of at least 0.1 nm is observed according to the background- subtracted biolayer interferometry analysis, or wherein when the polypeptide is contacted to the first peptide conjugate / MHC complex a maximum binding signal of at least 0.1-fold of a reference binding signal is observed according to a background-subtracted biolayer interferometry analysis and wherein when the polypeptide is contacted to the second peptide conjugate / MHC complex a maximum binding signal of at least 0.1-fold of a reference binding signal is observed according to the background-subtracted biolayer interferometry analysis, and wherein the reference binding signal is the maximum binding signal of the polypeptide binding to X X iX :X >X 'X iX X sX591. The composition of claim 589, wherein the polypeptide binds to the second peptide conjugate / MHC complex having a Cys of the G13C mutation covalently linked to the targeted covalent inhibitor or fragment thereof with a KD that is at most 100,000 fold higher that the KD of the polypeptide to the first peptide conjugate / MHC complex having a Cys of the G12C mutation covalently linked to the targeted covalent inhibitor or fragment thereof, or wherein a maximum wavelength shift of the polypeptide binding to the second peptide conjugate / MHC complex is at least 10-fold less than a maximum wavelength shift of the polypeptide binding to the first peptide conjugate / MHC complex, or wherein a maximum binding signal of the polypeptide binding to the second peptide conjugate / MHC complex is at least 10-fold less than a maximum binding signal of the polypeptide binding to the first peptide conjugate / MHC complex.

592. The polynucleotide of claim 91 or 92, wherein the polynucleotide is a modified polynucleotide.

593. The composition of claim 525, wherein the polypeptide chain further comprises an agonist molecule.

594. The composition of claim 593, wherein the agonist molecule is a CD28 agonist or a 4- 1BB agonist.

595. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) and / or a light chain variable region (VL), wherein:(a) the VH comprises:(i) a HC CDR3 comprising the amino acid sequence of FX2X3X4AMDY, wherein X2 is Y, L, T, H, E, A, or R; X3 is D, V, L, E, H, T or R; and X4is L or Y (SEQ ID NO: 267); and / or(b) the VL comprises:(i) a LC CDR3 comprising the amino acid sequence of QQX3SWLX7WX9X10T, wherein X3 is A or S, X7 is Y or H, X9 is L, K, V, Y or I, and X10 is L, V, or I (SEQ ID NO: 268).

596. The composition of claim 595, wherein the VH comprises: a HC CDR3 comprising the amino acid sequence of FX2X3X4AMDY, wherein X2 is Q, Y, L, T, H, E, A, or R; X3is W, D, V, L, E, H, T or R; and X4is L or Y.

597. The composition of claim 595 or 596, wherein the VH comprises a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes.

598. The composition of any one of claims 595-597, wherein the VH comprises a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes.

599. The composition of any one of claims 595-598, wherein the VL comprises a LC CDR1 comprising an amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes.

600. The composition of any one of claims 595-599, wherein the VL comprises a LC CDR2 comprising an amino acid sequence of SASSLYS, or a variant thereof comprising 1-3 amino acid changes.

601. The composition of any one of claims 595-600, wherein the VH comprises:(a) a HC CDR1 comprising an amino acid sequence of FSSSSIH, or a variant thereof comprising 1-3 amino acid changes;(b) a HC CDR2 comprising an amino acid sequence of SISSYYGSTYYADSVKG, or a variant thereof comprising 1-5 amino acid changes; and / or(c) a HC CDR3 comprising an amino acid sequence of FX2X3X4AMDY, wherein X2 is Y, L, T, H, E, A; X3 is D, V, L, E, H, T or R; and X4is L or Y.

602. The composition of any one of claims 595-601, wherein the VL comprises:(a) a LC CDR1 comprising the amino acid sequence of RASQSVSSAVA, or a variant thereof comprising 1-5 amino acid changes;(b) a LC CDR2 comprising the amino acid sequence of SASSLYS, or a variant thereof comprising 1-3 amino acid changes, and / or(c) a LC CDR3 comprising the amino acid sequence of QQX3SWLX7WX9X10T, wherein X3 is A or S, X7 is Y or H, Xs is L, K, V, Y or I, and X9 is L, V, or I.

603. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FYDLAMDY (SEQ ID NO.: 273).

604. The composition of claim 603, wherein the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 272).

605. The composition of claim 603 or 604, wherein the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 271).

606. The composition of any one of claims 603-605, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQASWLYWLIT (SEQ ID NO.: 276).

607. The composition of claim 606, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 275).

608. The composition of claim 606 or 607, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 274).

609. The composition of any one of claims 603-608, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 271), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 272), a HC CDR3 sequence of FYDLAMDY (SEQ ID NO: 273), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 274),a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 275), and a LC CDR3 sequence of QQASWLYWLIT (SEQ ID NO: 276).

610. The composition of any one of claims 603-609, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTFS S S SMWVRQAPGKGLEWVASIS S SSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFYDLAMD YWGQGTLVTVSS (SEQ ID NO.: 270).

611. The composition of any one of claims 606-610, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWLITFGQGTKV EIK (SEQ ID NO.: 269).

612. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FLDLAMDY (SEQ ID NO.: 281).

613. The composition of claim 612, wherein the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 280).

614. The composition of claim 612 or 613, wherein the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 279).

615. The composition of any one of claims 612-614, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQASWLYWKIT (SEQ ID NO.: 284).

616. The composition of claim 615, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 283).

617. The composition of claim 615 or 616, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 282).

618. The composition of any one of claims 612-617, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 279), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 280), a HC CDR3 sequence of FLDLAMDY (SEQ ID NO: 281), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 282),a LC CDR2 sequence of SASSLYS (SEQ ID NO: 283), and a LC CDR3 sequence of QQASWLYWKIT (SEQ ID NO: 284).

619. The composition of any one of claims 612-618, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTFS S S SMWVRQAPGKGLEWVASIS S SSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFLDLAMD YWGQGTLVTVSS (SEQ ID NO.: 278).

620. The composition of any one of claims 615-619, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWKITFGQGTKV EIK (SEQ ID NO.: 277).

621. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FTVLAMDY (SEQ ID NO.: 289).

622. The composition of claim 621, wherein the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 288).

623. The composition of claim 621 or 622, wherein the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 287).

624. The composition of any one of claims 621-623, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQASWLYWLIT (SEQ ID NO.: 292).

625. The composition of claim 624, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 291).

626. The composition of claim 624 or 625, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 290).

627. The composition of any one of claims 621-626, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 287), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 288), a HC CDR3 sequence of FTVLAMDY (SEQ ID NO.: 289), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 290),a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 291), and a LC CDR3 sequence of QQASWLYWLIT (SEQ ID NO.: 292).

628. The composition of any one of claims 621-627, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTFS S S SMWVRQAPGKGLEWVASIS S SSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFTVLAMD YWGQGTLVTVSS (SEQ ID NO.: 286).

629. The composition of any one of claims 624-628, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWLITFGQGTKV EIK (SEQ ID NO.: 285).

630. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FTVLAMDY (SEQ ID NO.: 297).

631. The composition of claim 630, wherein the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 296).

632. The composition of claim 630 or 631, wherein the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 295).

633. The composition of any one of claims 630-632, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQASWLYWKVT (SEQ ID NO.: 300).

634. The composition of claim 633, wherein the VL comprises a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 299).

635. The composition of claim 633 or 634, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 298).

636. The composition of any one of claims 630-635, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 295), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 296), a HC CDR3 sequence of FTVLAMDY (SEQ ID NO.: 297), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 297),a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 298), and a LC CDR3 sequence of QQASWLYWKVT (SEQ ID NO.: 300).

637. The composition of any one of claims 630-636, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTFS S S SMWVRQAPGKGLEWVASIS S SSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFTVLAMD YWGQGTLVTVSS (SEQ ID NO.: 294).

638. The composition of any one of claims 633-637, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWKVTFGQGTKV EIK (SEQ ID NO.: 293).

639. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FTVLAMDY (SEQ ID NO.: 305).

640. The composition of claim 639, wherein the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 304).

641. The composition of claim 639 or 640, wherein the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 303).

642. The composition of any one of claims 639-641, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQASWLYWVIT (SEQ ID NO.: 308).

643. The composition of claim 642, wherein the VL comprises a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 307).

644. The composition of claim 642 or 643, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 306).

645. The composition of any one of claims 639-644, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 303), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 304), a HC CDR3 sequence of FTVLAMDY (SEQ ID NO.: 305), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 306),a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 307), and a LC CDR3 sequence of QQASWLYWVIT (SEQ ID NO.: 308).

646. The composition of any one of claims 639-645, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTFS S S SMWVRQAPGKGLEWVASIS S SSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFTVLAMD YWGQGTLVTVSS (SEQ ID NO.: 302).

647. The composition of any one of claims 642-646, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWVITFGQGTKV EIK (SEQ ID NO.: 301).

648. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FHDLAMDY (SEQ ID NO.: 313).

649. The composition of claim 648, wherein the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 312).

650. The composition of claim 648 or 649, wherein the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 311).

651. The composition of any one of claims 648-650, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQASWLYWKIT (SEQ ID NO.: 316).

652. The composition of claim 651, wherein the VL comprises a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 315).

653. The composition of claim 651 or 652, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 314).

654. The composition of any one of claims 648-653, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 311), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 312), a HC CDR3 sequence of FHDLAMDY (SEQ ID NO.: 313), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 314),a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 315), and a LC CDR3 sequence of QQASWLYWKIT (SEQ ID NO.: 316).

655. The composition of any one of claims 648-654, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTFS S S SMWVRQAPGKGLEWVASIS S SSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFHDLAMD YWGQGTLVTVSS (SEQ ID NO.: 310).

656. The composition of any one of claims 651-655, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWKITFGQGTKV EIK (SEQ ID NO.: 309).

657. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FHELAMDY (SEQ ID NO.: 321).

658. The composition of claim 657, wherein the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 320).

659. The composition of claim 657 or 658, wherein the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 319).

660. The composition of any one of claims 657-659, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQASWLYWLIT (SEQ ID NO.: 324).

661. The composition of claim 660, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 323).

662. The composition of claim 660 or 661, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 322).

663. The composition of any one of claims 657-662, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 319), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 320), a HC CDR3 sequence of FHELAMDY (SEQ ID NO.: 321), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 322),a LC CDR2 sequence of SASSLYS (SEQ ID NO: 323), and a LC CDR3 sequence of QQASWLYWLIT (SEQ ID NO.: 324).

664. The composition of any one of claims 657-663, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTFS S S SMWVRQAPGKGLEWVASIS S SSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFHELAMD YWGQGTLVTVSS (SEQ ID NO.: 318).

665. The composition of any one of claims 660-664, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWLITFGQGTKV EIK (SEQ ID NO.: 317).

666. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FTVLAMDY (SEQ ID NO.: 329).

667. The composition of claim 666, wherein the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 328).

668. The composition of claim 666 or 667, wherein the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 327).

669. The composition of any one of claims 666-668, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSSWLYWKIT (SEQ ID NO.: 332).

670. The composition of claim 669, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 331).

671. The composition of claim 669 or 670, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 330).

672. The composition of any one of claims 666-671, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 327), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 328), a HC CDR3 sequence of FTVLAMDY (SEQ ID NO.: 329), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 330),a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 331), and a LC CDR3 sequence of QQSSWLYWKIT (SEQ ID NO.: 332).

673. The composition of any one of claims 666-672, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTFS S S SMWVRQAPGKGLEWVASIS S SSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFTVLAMD YWGQGTLVTVSS (SEQ ID NO.: 326).

674. The composition of any one of claims 669-673, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWKITFGQGTKV EIK (SEQ ID NO.: 325).

675. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FELLAMDY (SEQ ID NO.: 337).

676. The composition of claim 675, wherein the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 336).

677. The composition of claim 675 or 676, wherein the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 335).

678. The composition of any one of claims 675-677, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSSWLYWKIT (SEQ ID NO.: 340).

679. The composition of claim 678, wherein the VL comprises a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 339).

680. The composition of claim 678 or 679, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 338).

681. The composition of any one of claims 675-680, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 335), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 336), a HC CDR3 sequence of FELLAMDY (SEQ ID NO.: 337), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 338),a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 339), and a LC CDR3 sequence of QQSSWLYWKIT (SEQ ID NO.: 340).

682. The composition of any one of claims 675-681, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTFS S S SMWVRQAPGKGLEWVASIS S SSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFELLAMD YWGQGTLVTVSS (SEQ ID NO.: 334).

683. The composition of any one of claims 678-682, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWKITFGQGTKV EIK (SEQ ID NO.: 333).

684. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FTVLAMDY (SEQ ID NO.: 345).

685. The composition of claim 684, wherein the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 344).

686. The composition of claim 684 or 685, wherein the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 343).

687. The composition of any one of claims 684-686, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSSWLYWKVT (SEQ ID NO.: 348).

688. The composition of claim 687, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 347).

689. The composition of claim 687 or 688, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 346).

690. The composition of any one of claims 684-689, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 343), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 344), a HC CDR3 sequence of FTVLAMDY (SEQ ID NO.: 345), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 346),a LC CDR2 sequence of SASSLYS (SEQ ID NO: 347), and a LC CDR3 sequence of QQSSWLYWKVT (SEQ ID NO.: 348).

691. The composition of any one of claims 684-690, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTFS S S SMWVRQAPGKGLEWVASIS S SSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFTVLAMD YWGQGTLVTVSS (SEQ ID NO.: 342).

692. The composition of any one of claims 687-691, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWKVTFGQGTKV EIK (SEQ ID NO.: 341).

693. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FYDLAMDY (SEQ ID NO.: 353).

694. The composition of claim 693, wherein the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 352).

695. The composition of claim 693 or 694, wherein the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 351).

696. The composition of any one of claims 693-695, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSSWLYWKVT (SEQ ID NO.: 356).

697. The composition of claim 696, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 355).

698. The composition of claim 696 or 697, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 354).

699. The composition of any one of claims 693-698, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 351), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 352), a HC CDR3 sequence of FYDLAMDY (SEQ ID NO.: 353), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 354),a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 355), and a LC CDR3 sequence of QQSSWLYWKVT (SEQ ID NO.: 356).

700. The composition of any one of claims 693-699, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTFS S S SMWVRQAPGKGLEWVASIS S SSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFYDLAMD YWGQGTLVTVSS (SEQ ID NO.: 350).

701. The composition of any one of claims 696-700, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWKVTFGQGTKV EIK (SEQ ID NO.: 349).

702. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FHELAMDY (SEQ ID NO.: 361).

703. The composition of claim 702, wherein the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 360).

704. The composition of claim 702 or 703, wherein the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 359).

705. The composition of any one of claims 702-704, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQASWLYWLIT (SEQ ID NO.: 364).

706. The composition of claim 705, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 363).

707. The composition of claim 705 or 706, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 362).

708. The composition of any one of claims 702-707, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 359), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 360), a HC CDR3 sequence of FHELAMDY (SEQ ID NO : 361), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 362),a LC CDR2 sequence of SASSLYS (SEQ ID NO: 363), and a LC CDR3 sequence of QQASWLYWLIT (SEQ ID NO.: 364).

709. The composition of any one of claims 702-708, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTFS S S SMWVRQAPGKGLEWVASIS S SSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFHELAMD YWGQGTLVTVSS (SEQ ID NO.: 358).

710. The composition of any one of claims 705-709, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWLITFGQGTKV EIK (SEQ ID NO.: 357).

711. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FTVLAMDY (SEQ ID NO.: 369).

712. The composition of claim 711, wherein the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 368).

713. The composition of claim 711 or 712, wherein the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 367).

714. The composition of any one of claims 711-713, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQASWLYWKVT (SEQ ID NO.: 372).

715. The composition of claim 714, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 371).

716. The composition of claim 714 or 715, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 370).

717. The composition of any one of claims 711-716, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 367), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 368), a HC CDR3 sequence of FTVLAMDY (SEQ ID NO.: 369), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 370),a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 371), and a LC CDR3 sequence of QQASWLYWKVT (SEQ ID NO.: 372).

718. The composition of any one of claims 711-717, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTFS S S SMWVRQAPGKGLEWVASIS S SSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFTVLAMD YWGQGTLVTVSS (SEQ ID NO.: 366).

719. The composition of any one of claims 714-718, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWKVTFGQGTKV EIK (SEQ ID NO.: 365).

720. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FYDLAMDY (SEQ ID NO.: 377).

721. The composition of claim 720, wherein the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 376).

722. The composition of claim 720 or 721, wherein the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 375).

723. The composition of any one of claims 720-722, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSSWLYWVIT (SEQ ID NO.: 380).

724. The composition of claim 723, wherein the VL comprises a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 379).

725. The composition of claim 723 or 724, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 378).

726. The composition of any one of claims 720-725, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 375), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 376), a HC CDR3 sequence of FYDLAMDY (SEQ ID NO.: 377), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 378),a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 379), and a LC CDR3 sequence of QQSSWLYWVIT (SEQ ID NO.: 380).

727. The composition of any one of claims 720-726, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTFS S S SMWVRQAPGKGLEWVASIS S SSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFYDLAMD YWGQGTLVTVSS (SEQ ID NO.: 374).

728. The composition of any one of claims 723-727, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWVITFGQGTKV EIK (SEQ ID NO.: 373).

729. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FHELAMDY (SEQ ID NO.: 385).

730. The composition of claim 729, wherein the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 384).

731. The composition of claim 729 or 730, wherein the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 383).

732. The composition of any one of claims 729-731, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQASWLYWLIT (SEQ ID NO.: 388).

733. The composition of claim 732, wherein the VL comprises a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 387).

734. The composition of claim 732 or 733, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 386).

735. The composition of any one of claims 729-734, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 383), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 384), a HC CDR3 sequence of FHELAMDY (SEQ ID NO.: 385), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 386),a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 387), and a LC CDR3 sequence of QQASWLYWLIT (SEQ ID NO.: 388).

736. The composition of any one of claims 729-735, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTFS S S SMWVRQAPGKGLEWVASIS S SSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFHELAMD YWGQGTLVTVSS (SEQ ID NO.: 382).

737. The composition of any one of claims 732-736, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWLITFGQGTKV EIK (SEQ ID NO.: 381).

738. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FAHLAMDY (SEQ ID NO.: 393).

739. The composition of claim 738, wherein the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 392).

740. The composition of claim 738 or 739, wherein the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 391).

741. The composition of any one of claims 738-740, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSSWLYWLIT (SEQ ID NO.: 396).

742. The composition of claim 741, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 395).

743. The composition of claim 741 or 742, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 394).

744. The composition of any one of claims 738-743, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 391), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 392), a HC CDR3 sequence of FAHLAMDY (SEQ ID NO.: 393), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 394),a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 395), and a LC CDR3 sequence of QQSSWLYWLIT (SEQ ID NO.: 396).

745. The composition of any one of claims 738-744, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTFS S S SMWVRQAPGKGLEWVASIS S SSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFAHLAMD YWGQGTLVTVSS (SEQ ID NO.: 390).

746. The composition of any one of claims 741-745, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWLITFGQGTKVE IK (SEQ ID NO.: 389).

747. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FEDLAMDY (SEQ ID NO.: 401).

748. The composition of claim 747, wherein the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 400).

749. The composition of claim 747 or 748, wherein the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 399).

750. The composition of any one of claims 747-749, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQASWLYWYIT (SEQ ID NO.: 404).

751. The composition of claim 750, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 403).

752. The composition of claim 750 or 751, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 402).

753. The composition of any one of claims 747-752, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 399), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 400), a HC CDR3 sequence of FEDLAMDY (SEQ ID NO.: 401), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 402),a LC CDR2 sequence of SASSLYS (SEQ ID NO: 403), and a LC CDR3 sequence of QQASWLYWYIT (SEQ ID NO.: 404).

754. The composition of any one of claims 747-753, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTFS S S SMWVRQAPGKGLEWVASIS S SSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFEDLAMD YWGQGTLVTVSS (SEQ ID NO.: 398).

755. The composition of any one of claims 750-754, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLYWYITFGQGTKV EIK (SEQ ID NO.: 397).

756. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FRTLAMDY (SEQ ID NO.: 409).

757. The composition of claim 756, wherein the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 408).

758. The composition of claim 756 or 757, wherein the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 407).

759. The composition of any one of claims 756-758, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSSWLYWIIT (SEQ ID NO.: 412).

760. The composition of claim 759, wherein the VL comprises a LC CDR2 sequence of SASSLYS (SEQ ID NO: 411).

761. The composition of claim 759 or 760, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 410).

762. The composition of any one of claims 756-761, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 407), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 408), a HC CDR3 sequence of FRTLAMDY (SEQ ID NO.: 409), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 410),a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 411), and a LC CDR3 sequence of QQSSWLYWIIT (SEQ ID NO.: 412).

763. The composition of any one of claims 756-762, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTFS S S SMWVRQAPGKGLEWVASIS S SSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFRTLAMD YWGQGTLVTVSS (SEQ ID NO.: 406).

764. The composition of any one of claims 759-763, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWIITFGQGTKVEI K (SEQ ID NO.: 405).

765. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FTHYAMDY (SEQ ID NO.: 417).

766. The composition of claim 765, wherein the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 416).

767. The composition of claim 765 or 766, wherein the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 415).

768. The composition of any one of claims 765-767, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQSSWLYWKIT (SEQ ID NO.: 420).

769. The composition of claim 768, wherein the VL comprises a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 419).

770. The composition of claim 768 or 769, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 418).

771. The composition of any one of claims 765-770, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 415), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 416), a HC CDR3 sequence of FTHYAMDY (SEQ ID NO.: 417), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 418),a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 419), and a LC CDR3 sequence of QQSSWLYWKIT (SEQ ID NO.: 420).

772. The composition of any one of claims 765-771, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTFS S S SMWVRQAPGKGLEWVASIS S SSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFTHYAMD YWGQGTLVTVSS (SEQ ID NO.: 414).

773. The composition of any one of claims 768-772, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQSSWLYWKITFGQGTKV EIK (SEQ ID NO.: 413).

774. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FRLYAMDY (SEQ ID NO.: 425).

775. The composition of claim 774, wherein the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 424).

776. The composition of claim 774 or 775, wherein the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 423).

777. The composition of any one of claims 774-776, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQASWLHWKLT (SEQ ID NO.: 428).

778. The composition of claim 777, wherein the VL comprises a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 427).

779. The composition of claim 777 or 778, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 426).

780. The composition of any one of claims 774-779, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 423), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 424), a HC CDR3 sequence of FRLYAMDY (SEQ ID NO.: 425), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 426),a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 427), and a LC CDR3 sequence of QQASWLHWKLT (SEQ ID NO.: 428).

781. The composition of any one of claims 774-780, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTFS S S SMWVRQAPGKGLEWVASIS S SSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFRLYAMD YWGQGTLVTVSS (SEQ ID NO.: 422).

782. The composition of any one of claims 777-781, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLHWKLTFGQGTKV EIK (SEQ ID NO.: 421).

783. A composition comprising a polypeptide comprising an antigen-binding domain, wherein the antigen-binding domain comprises a heavy chain variable region (VH) that comprises a heavy chain complementarity determining region 3 FHRLAMDY (SEQ ID NO.: 433).

784. The composition of claim 774, wherein the VH comprises a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO.: 432).

785. The composition of claim 774 or 775, wherein the VH comprises a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 431).

786. The composition of any one of claims 774-776, wherein the antigen-binding domain comprises a light chain variable region (VL) that comprises a light chain complementarity determining region 3 (LC CDR3) sequence of QQASWLHWKLT (SEQ ID NO.: 436).

787. The composition of claim 777, wherein the VL comprises a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 435).

788. The composition of claim 777 or 778, wherein the VL comprises a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 434).

789. The composition of any one of claims 774-779, wherein the antigen-binding domain comprises: a HC CDR1 sequence of FSSSSIH (SEQ ID NO: 431), a HC CDR2 sequence of SISSSSGSTSYADSVKG (SEQ ID NO: 432), a HC CDR3 sequence of FHRLAMDY (SEQ ID NO.: 433), a LC CDR1 sequence of RASQSVSSAVA (SEQ ID NO: 434),a LC CDR2 sequence of SAS SLYS (SEQ ID NO: 435), and a LC CDR3 sequence of QQASWLHWKLT (SEQ ID NO.: 436).

790. The composition of any one of claims 774-780, wherein the VH comprises a sequence with at least 80% sequence identity to the sequenceEVQLVESGGGL VQPGGSLRLSC AASGFTFS S S SMWVRQAPGKGLEWVASIS S SSGSTSYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFHRLAMD YWGQGTLVTVSS (SEQ ID NO.: 430).

791. The composition of any one of claims 777-781, wherein the VL comprises a sequence with at least 80% sequence identity to the sequence DIQMTQSPSSLSASVGDRVTITCRASQSVSSAVAWYQQKPGKAPKLLIYSASS LYSGVPSRFSGSRSGTDFTLTISSLQPEDFATYYCQQASWLHWKLTFGQGTKV EIK (SEQ ID NO.: 429).

792. A pharmaceutical composition comprising a polypeptide of any one of claims 595- 791, and a pharmaceutically acceptable carrier, excipient, adjuvant or diluent.

793. A method of treating cancer in a subject in need thereof wherein the subject has been treated with a free targeted covalent inhibitor, the method comprising administering to the subject the polypeptide of any one of claims 595-791 or the pharmaceutical composition of claim 792.

794. The method of claim 793, wherein the free targeted covalent inhibitor is sotorasib, adagrasib, or divarasib.

795. The method of claim 793 or 794, wherein the subject is refractory to a treatment with the free targeted covalent inhibitor.

796. A method of treating a cancer in a subject in need thereof, the method comprising administering to the subject the polypeptide of any one of claims 595-791 or the pharmaceutical composition of claim 792.

797. The method of claim 796, wherein the method further comprises administering simultaneously a small molecule drug.

798. A method of administering to the subject in need thereof the polypeptide of any one of claims 595-791 or the pharmaceutical composition of claim 792, and a free targeted covalent inhibitor, wherein the free targeted covalent inhibitor is optionally sotorasib, adagrasib, or divarasib.

799. The method of claim 798, wherein the polypeptide of any one of claims 595-791 or the pharmaceutical composition of claim 792 is administered after administration ofthe free targeted covalent inhibitor or simultaneously with the free targeted covalent inhibitor.

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