T cell receptor compositions and methods of use thereof

Abstract

The present disclosure provides T cell receptors (TCRs) against peptide-MHC complexes, isolated nucleic acid molecules encoding TCRs against peptide-MHC complexes, T cells expressing TCRs against peptide-MHC complexes, and pharmaceutical compositions for use in the treatment of diseases.

Description

WSGR Docket No.50401-799.601 T CELL RECEPTOR COMPOSITIONS AND METHODS OF USE THEREOF CROSS REFERENCE

[0001] This application claims the benefit of U.S. Provisional Application No.63 / 659,096, filed June 12, 2024, and U.S. Provisional Application No. 63 / 699,276, filed September 26, 2024, each of which is incorporated herein by reference in its entirety. BACKGROUND

[0002] T cell receptors (TCRs) are members of the immunoglobulin superfamily and usually consist of two subunits, namely the α- and β-subunits. These possess one N-terminal immunoglobulin (Ig)-variable (V) domain, one Ig-constant (C) domain, a transmembrane / cell membrane-spanning region, and a short cytoplasmic tail at the C-terminal end. The variable domains of both the TCR α-chain and β-chain have three hypervariable or complementarity determining regions (CDRs), whereas the variable region of the β- chain has an additional area of hypervariability (HV4) that does not normally contact antigen and therefore is not considered a CDR.

[0003] CDR3 is the principal CDR responsible for recognizing processed antigen, although CDR1 of the alpha chain has also been shown to interact with the N-terminal part of the antigenic peptide, whereas CDR1 of the β-chain interacts with the C-terminal part of the peptide. CDR2 is thought to recognize the MHC. The constant domain of the TCR domain consists of short connecting sequences in which a cysteine residue forms disulfide bonds, which forms a link between the two chains. The affinity of TCR’s for a specific antigen makes them valuable for several therapeutic approaches. For example, cancer patients, such as melanoma patients, can be effectively treated by using adoptive immunotherapy as TCRs are exquisitely sensitive for their antigen and can direct immune responses at tumor cells expressing their cognate antigen. Accordingly, there is a need for TCRs against peptide-MHC complexes for development of new and effective therapeutics. SUMMARY

[0004] Provided herein is a recombinant nucleic acid comprising a sequence encoding a T cell receptor (TCR) comprising a TCR beta chain construct and a TCR alpha chain construct, wherein the TCR binds to a mutated epitope from human RAS in complex with a human MHC encoded by an HLA-C03:03 allele and a human MHC encoded by an HLA-C03:04 allele, wherein the mutated epitope from human RAS is characterized by a G12V mutation, wherein the TCR beta chain construct comprises a complementarity determining region 3 (CDR3), wherein the N-terminus of the CDR3 of the TCR beta chain construct comprises at least four amino acids encoded by the 3’ terminal sequence of the TRBV5-6*01 allele, and wherein the CDR3 of the TCR beta chain construct does not comprise a CDR3 sequence of CASSLPRMGSDTEAFF (SEQ ID NO: 83), CASSPTRLGYNEQFF (SEQ ID NO: 135), CASSLRTGEAFF (SEQ ID NO: 179) or CASSIDYRGIGETQYF (SEQ ID NO: 191).WSGR Docket No.50401-799.601

[0005] In some embodiments, the N-terminus of the CDR3 comprises the 5 amino acids encoded by 3’ terminal sequence of the TRBV5-6*01 allele. In some embodiments, the N-terminus of the CDR3 comprises the first 4 amino acids of the last 5 amino acids encoded by 3’ terminal sequence of the TRBV5- 6*01 allele. In some embodiments, the N-terminus of the CDR3 of the TCR beta chain construct comprises the amino acid sequence CASS. In some embodiments, the N-terminus of the CDR3 of the TCR beta chain construct comprises the amino acid sequence CASSL.

[0006] In some embodiments, the TCR beta chain construct comprises a complementarity determining region 1 (CDR1), wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct comprises a complementarity determining region 2 (CDR2), wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20.

[0007] In some embodiments, the N-terminus of the CDR3 of the TCR alpha chain construct comprises at least four amino acids encoded by the 3’ terminal sequence of the TRAV4*01 allele. In some embodiments, the N-terminus of the CDR3 of the TCR alpha chain construct comprises the amino acid sequence CLVG.

[0008] In some embodiments, the TCR alpha chain construct comprises a CDR1 comprising an amino acid sequence of SEQ ID NO: 1. In some embodiments, the TCR alpha chain construct comprises a CDR2 comprising an amino acid sequence of SEQ ID NO: 2.

[0009] Further provided herein is a recombinant nucleic acid comprising a sequence encoding a T cell receptor (TCR) comprising a TCR beta chain construct and a TCR alpha chain construct, wherein the TCR binds to a mutated epitope from human RAS in complex with a human MHC encoded by an HLA-C03:03 allele and a human MHC encoded by an HLA-C03:04 allele, wherein the mutated epitope from human RAS is characterized by a G12V mutation, wherein the TCR alpha chain construct comprises a complementarity determining region 3 (CDR3), wherein the N-terminus of the CDR3 of the TCR alpha chain construct comprises at least four amino acids encoded by the 3’ terminal sequence of the TRAV4*01 allele, and wherein the CDR3 of the TCR alpha chain construct does not comprise a CDR3 sequence CLVGDMDSGNTPLVF (SEQ ID NO: 185), CLVGDLDGQKLLF (SEQ ID NO: 175), CLVGDMDGGYQKVTF (SEQ ID NO: 131), or CLVGDGDNARLMF (SEQ ID NO: 79).

[0010] Further provided herein is a recombinant nucleic acid comprising a sequence encoding a T cell receptor (TCR) comprising a TCR beta chain construct and a TCR alpha chain construct, wherein the TCR binds to a mutated epitope from human RAS in complex with a human MHC encoded by an HLA-C03:03 allele and a human MHC encoded by an HLA-C03:04 allele, wherein the mutated epitope from human RAS is characterized by a G12V mutation, wherein the TCR alpha chain construct comprises a complementarity determining region 3 (CDR3), wherein the N-terminus of the CDR3 of the TCR alpha chain construct comprises at least four amino acids encoded by the 3’ terminal sequence of the TRAV4*01 allele, and wherein a CDR3 of the TCR beta chain construct does not comprise a CDR3 sequence of CASSLPRMGSDTEAFF (SEQ ID NO: 83), CASSPTRLGYNEQFF (SEQ ID NO: 135), CASSLRTGEAFF (SEQ ID NO: 179) or CASSIDYRGIGETQYF (SEQ ID NO: 191).WSGR Docket No.50401-799.601

[0011] In some embodiments, the N-terminus of the CDR3 of the TCR alpha chain construct comprises the 5 amino acids encoded by 3’ terminal sequence of the TRAV4*01 allele. In some embodiments, the N- terminus of the CDR3 of the TCR alpha chain construct comprises the first 4 amino acids of the last 5 amino acids encoded by 3’ terminal sequence of the TRAV4*01 allele. In some embodiments, the N- terminus of the CDR3 of the TCR alpha chain construct comprises the sequence of CLVG. In some embodiments, the N-terminus of the CDR3 of the TCR alpha chain construct comprises the sequence of CLVGD, CLVGDM, or CLVGDMD.

[0012] In some embodiments, the TCR alpha chain construct comprises a CDR1 comprising an amino acid sequence of SEQ ID NO: 1. In some embodiments, the TCR alpha chain construct comprises a CDR2 comprising an amino acid sequence of SEQ ID NO: 2.

[0013] In some embodiments, the N-terminus of a CDR3 of the TCR beta chain construct comprises at least four amino acids encoded by the 3’ terminal sequence of the TRBV5-6*01 allele. In some embodiments, the N-terminus of a CDR3 of the TCR beta chain construct comprises the sequence of CASS.

[0014] In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20. In some embodiments, the TCR beta chain construct comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 363.

[0015] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide.

[0016] In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide.

[0017] In some embodiments, the TCR alpha chain construct comprises a CDR3, wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 359.

[0018] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide.WSGR Docket No.50401-799.601

[0019] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 365, 366, 367, or 368 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 365, 366, 367, or 368 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 361 or 362 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 361 or 362 with or without a signal peptide.

[0020] In some embodiments, the TCR beta chain construct comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 483.

[0021] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide.

[0022] In some embodiments, the TCR alpha chain construct comprises a CDR3, wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 479.

[0023] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide.

[0024] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 485, 486, 487, or 488 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 485, 486, 487, or 488 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 481 or 482 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 481 or 482 with or without a signal peptide.

[0025] In some embodiments, the TCR beta chain construct comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 569. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 287. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 288.WSGR Docket No.50401-799.601

[0026] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 570 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 570 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 570 with or without a signal peptide.

[0027] In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 570 with or without a signal peptide.

[0028] In some embodiments, the TCR alpha chain construct comprises a CDR3, wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 185.

[0029] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 186 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 186 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 186 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 186 with or without a signal peptide.

[0030] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 571, 572, 573, or 574 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 571, 572, 573, or 574 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 187 or 188 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 187 or 188 with or without a signal peptide.

[0031] In some embodiments, the TCR beta chain construct comprises a CDR3, wherein the CDR3 has an amino acid sequence selected from the group consisting of TCR beta chain CDR3 sequences listed in Table 1B. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence selected from the group consisting of TCR beta chain CDR1 sequences listed in Table 1B. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence selected from the group consisting of TCR beta chain CDR2 sequences listed in Table 1B.

[0032] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence selected from the group consisting of TCR beta chain variable region sequences listed in Table 1B. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence selected from the group consisting of TCR beta chain variable region sequences listed in Table 1B. In some embodiments,WSGR Docket No.50401-799.601 the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence selected from the group consisting of TCR beta chain variable region sequences listed in Table 1B. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence selected from the group consisting of TCR beta chain variable region sequences listed in Table 1B.

[0033] In some embodiments, the TCR alpha chain construct comprises a CDR3, wherein the CDR3 has an amino acid sequence selected from the group consisting of TCR beta chain CDR3 sequences listed in Table 1B.

[0034] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence selected from the group consisting of TCR alpha chain variable region sequences listed in Table 1B. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence selected from the group consisting of TCR alpha chain variable region sequences listed in Table 1B. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence selected from the group consisting of TCR alpha chain variable region sequences listed in Table 1B. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence selected from the group consisting of TCR alpha chain variable region sequences listed in Table 1B.

[0035] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence selected from the group consisting of beta chain sequences listed in Table 1B, or an amino acid sequence that is at least 80% identical to an amino acid sequence selected from the group consisting of beta chain sequences listed in Table 1B, (b) an alpha chain having an amino acid sequence selected from the group consisting of alpha chain sequences listed in Table 1B, or an amino acid sequence that is at least 80% identical to an amino acid sequence selected from the group consisting of alpha chain sequences listed in Table 1B.

[0036] In some embodiments, the mutated epitope comprises an amino acid sequence set forth in SEQ ID NOs: 633 or 634.

[0037] In some embodiments, the TCR binds to (i) the mutated epitope from human RAS in complex with the human MHC encoded by the HLA-C03:03 allele with a KD of at most 500 nM, at most 250 nM, at most 50 nM, at most 25 nM, at most 10 nM, or at most 5 nM; and / or (ii) the mutated epitope from human RAS in complex with the human MHC encoded by the HLA-C03:04 allele with a KD of at most 500 nM, at most 250 nM, at most 50 nM, at most 25 nM, at most 10 nM, or at most 5 nM.

[0038] Further provided herein is a recombinant nucleic acid encoding a of T-cell receptors (TCR), wherein the TCR comprises a TCR alpha chain having a TCR alpha variable region, wherein the TCR alpha variable region is derived from a V gene segment of TRAV4*01 and a J gene segment selected from the group consisting of TRAJ10*01, TRAJ13*02, TRAJ16*01, TRAJ16*02, TRAJ21*01, TRAJ23*01, TRAJ26*01, TRAJ29*01, TRAJ3*01, TRAJ30*01, TRAJ31*01, TRAJ32*02, TRAJ33*01, TRAJ34*01,WSGR Docket No.50401-799.601 TRAJ36*01, TRAJ37*01, TRAJ37*02, TRAJ39*01, TRAJ4*01, TRAJ41*01, TRAJ42*01, TRAJ43*01, TRAJ47*01, TRAJ49*01, TRAJ5*01, TRAJ52*01, TRAJ53*01, TRAJ57*01, TRAJ8*01 and TRAJ9*01, wherein the TCR does not bind to a mutated epitope having a G12D mutation from human RAS in complex with a human MHC or the TCR binds to a mutated epitope having a G12D mutation from human RAS in complex with a human MHC with a dissociation constant (KD) of at least 1,000 nM, and wherein the TCR does not comprise a sequence listed in Table 2.

[0039] In some embodiments, the TCR comprises a TCR beta chain having a TCR beta variable region, and wherein the TCR beta variable region is derived from a V gene segment of TRBV5-6*01 and a J gene segment selected from the group consisting of TRBJ2-3*01, TRBJ1-6*02, TRBJ1-1*01, TRBJ1-3*01, TRBJ2-2*01, TRBJ1-5*01, TRBJ2-7*01, TRBJ2-1*01, TRBJ1-2*01, TRBJ1-4*01 and TRBJ2-5*01.

[0040] In some embodiments, the binds to a mutated epitope from human RAS in complex with a human MHC encoded by an HLA-C03:03 allele and a human MHC encoded by an HLA-C03:04 allele, wherein the mutated epitope from human RAS is characterized by a G12V mutation. In some embodiments, the mutated epitope comprises an amino acid sequence set forth in SEQ ID NOs: 633 or 634.

[0041] In some embodiments, a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 21. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20.

[0042] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 22 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 22 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 22 with or without a signal peptide.

[0043] In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 22 with or without a signal peptide.

[0044] In some embodiments, a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 15.

[0045] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at leastWSGR Docket No.50401-799.601 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide.

[0046] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 23, 24, 25, or 26 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 23, 24, 25, or 26 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 17 or 18 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 17 or 18 with or without a signal peptide.

[0047] In some embodiments, a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 63.

[0048] In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20.

[0049] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 64 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 64 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 64 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 64 with or without a signal peptide.

[0050] In some embodiments, a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 59.

[0051] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 60 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 60 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 60 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 60 with or without a signal peptide.

[0052] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 65, 66, 67, or 68 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 65, 66, 67, or 68 with or without a signal peptide, (b) an alpha chainWSGR Docket No.50401-799.601 having an amino acid sequence set forth in SEQ ID NOs: 61 or 62 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 61 or 62 with or without a signal peptide.

[0053] In some embodiments, a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 73. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20.

[0054] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 74 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 74 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 74 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 74 with or without a signal peptide.

[0055] In some embodiments, a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 69.

[0056] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 70 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 70 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 70 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 70 with or without a signal peptide.

[0057] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 75, 76, 77, or 78 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 75, 76, 77, or 78 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 71 or 72 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 71 or 72 with or without a signal peptide.

[0058] In some embodiments, a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 83. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20.WSGR Docket No.50401-799.601

[0059] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 84 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 84 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 84 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 84 with or without a signal peptide.

[0060] In some embodiments, a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 79.

[0061] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 80 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 80 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 80 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 80 with or without a signal peptide.

[0062] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 85, 86, 87, or 88 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 85, 86, 87, or 88 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 81 or 82 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 81 or 82 with or without a signal peptide.

[0063] In some embodiments, a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 93. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20.

[0064] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 94 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 94 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 94WSGR Docket No.50401-799.601 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 94 with or without a signal peptide.

[0065] In some embodiments, a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 99.

[0066] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 90 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 90 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 90 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 90 with or without a signal peptide.

[0067] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 95, 96, 97, or 98 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 95, 96, 97, or 98 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 91 or 92 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 91 or 92 with or without a signal peptide.

[0068] In some embodiments, a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 103. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20.

[0069] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 104 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 104 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 104 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 104 with or without a signal peptide.

[0070] In some embodiments, a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 99.WSGR Docket No.50401-799.601

[0071] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 100 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 100 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 100 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 100 with or without a signal peptide.

[0072] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 105, 106, 107, or 108 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 105, 106, 107, or 108 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 101 or 102 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 101 or 102 with or without a signal peptide.

[0073] In some embodiments, a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 179. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20.

[0074] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 180 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 180 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 180 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 180 with or without a signal peptide.

[0075] In some embodiments, a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 175.

[0076] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 176 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 176 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 176WSGR Docket No.50401-799.601 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 176 with or without a signal peptide.

[0077] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 181, 182, 183, or 184 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 181, 182, 183, or 184 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 177 or 178 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 177 or 178 with or without a signal peptide.

[0078] In some embodiments, a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 231. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20.

[0079] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 232 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 232 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 232 with or without a signal peptide.

[0080] In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 232 with or without a signal peptide.

[0081] In some embodiments, a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 227.

[0082] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 228 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 228 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 228 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 228 with or without a signal peptide.

[0083] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 233, 234, 235, or 236 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 233, 234, 235, or 236 with or without a signal peptide, (b) anWSGR Docket No.50401-799.601 alpha chain having an amino acid sequence set forth in SEQ ID NOs: 229 or 230 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 229 or 230 with or without a signal peptide.

[0084] In some embodiments, a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 247. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20.

[0085] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 248 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 248 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 248 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 248 with or without a signal peptide.

[0086] In some embodiments, a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 69.

[0087] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 70 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 70 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 70 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 70 with or without a signal peptide.

[0088] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 249, 250, 251, or 252 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 249, 250, 251, or 252 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 71 or 72 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 71 or 72 with or without a signal peptide.

[0089] In some embodiments, a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 271. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19. In someWSGR Docket No.50401-799.601 embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20.

[0090] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 272 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 272 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 272 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 272 with or without a signal peptide.

[0091] In some embodiments, a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 267.

[0092] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 268 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 268 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 268 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 268 with or without a signal peptide.

[0093] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 273, 274, 275, or 276 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 273, 274, 275, or 276 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 269 or 270 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 269 or 270 with or without a signal peptide.

[0094] In some embodiments, a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 313. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20.

[0095] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 314 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 314 with or without a signalWSGR Docket No.50401-799.601 peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 314 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 314 with or without a signal peptide.

[0096] In some embodiments, a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 307, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 308, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 309.

[0097] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 310 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 310 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 310 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 310 with or without a signal peptide.

[0098] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 315, 316, 317, or 318 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 315, 316, 317, or 318 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 311 or 312 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 311 or 312 with or without a signal peptide.

[0099] In some embodiments, a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 319. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20.

[0100] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 320 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 320 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 320 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 320 with or without a signal peptide.

[0101] In some embodiments, a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 hasWSGR Docket No.50401-799.601 an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 15.

[0102] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide.

[0103] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 321, 322, 323, or 324 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 321, 322, 323, or 324 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 17 or 18 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 17 or 18 with or without a signal peptide.

[0104] In some embodiments, a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 329. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20.

[0105] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 330 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 330 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 330 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 330 with or without a signal peptide.

[0106] In some embodiments, a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 325.

[0107] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 326 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 326 with or without a signalWSGR Docket No.50401-799.601 peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 326 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 326 with or without a signal peptide.

[0108] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 331, 332, 333, or 334 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 331, 332, 333, or 334 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 327 or 328 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 327 or 328 with or without a signal peptide.

[0109] In some embodiments, a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 363. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20.

[0110] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide.

[0111] In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide.

[0112] In some embodiments, a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 359.

[0113] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide.WSGR Docket No.50401-799.601

[0114] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 365, 366, 367, or 368 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 365, 366, 367, or 368 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 361 or 362 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 361 or 362 with or without a signal peptide.

[0115] In some embodiments, a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 395. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20.

[0116] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 396 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 396 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 396 with or without a signal peptide.

[0117] In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 396 with or without a signal peptide.

[0118] In some embodiments, a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 391.

[0119] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 392 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 392 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 392 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 392 with or without a signal peptide.

[0120] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 397, 398, 399, or 400 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 397, 398, 399, or 400 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 393 or 394 with or without a signalWSGR Docket No.50401-799.601 peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 393 or 394 with or without a signal peptide.

[0121] In some embodiments, a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 417. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20.

[0122] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 418 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 418 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 418 with or without a signal peptide.

[0123] In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 418 with or without a signal peptide.

[0124] In some embodiments, a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 413.

[0125] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 414 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 414 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 414 with or without a signal peptide.

[0126] In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 414 with or without a signal peptide.

[0127] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 419, 420, 421, or 422 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 419, 420, 421, or 422 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 415 or 416 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 415 or 416 with or without a signal peptide.

[0128] In some embodiments, a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 423. In some embodiments, the TCR beta chainWSGR Docket No.50401-799.601 construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20.

[0129] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 424 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 424 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 424 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 424 with or without a signal peptide.

[0130] In some embodiments, a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 151.

[0131] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 152 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 152 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 152 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 152 with or without a signal peptide.

[0132] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 425, 426, 427, or 428 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 425, 426, 427, or 428 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 153 or 154 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 153 or 154 with or without a signal peptide.

[0133] In some embodiments, a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 441. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20.

[0134] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 442 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at leastWSGR Docket No.50401-799.601 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 442 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 442 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 442 with or without a signal peptide.

[0135] In some embodiments, a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 15.

[0136] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide.

[0137] In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide.

[0138] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 443, 444, 445, or 446 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 443, 444, 445, or 446 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 17 or 18 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 17 or 18 with or without a signal peptide.

[0139] In some embodiments, a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 483. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20.

[0140] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide.WSGR Docket No.50401-799.601

[0141] In some embodiments, a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 479.

[0142] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide.

[0143] In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide.

[0144] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 485, 486, 487, or 488 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 485, 486, 487, or 488 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 481 or 482 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 481 or 482 with or without a signal peptide.

[0145] In some embodiments, a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 519. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20.

[0146] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 520 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 520 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 520 with or without a signal peptide.

[0147] In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 520 with or without a signal peptide.

[0148] In some embodiments, a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 295.WSGR Docket No.50401-799.601

[0149] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 296 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 296 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 296 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 296 with or without a signal peptide.

[0150] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 521, 522, 523, or 524 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 521, 522, 523, or 524 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 297 or 298 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 297 or 298 with or without a signal peptide.

[0151] In some embodiments, a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 543. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20.

[0152] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 544 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 544 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 544 with or without a signal peptide.

[0153] In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 544 with or without a signal peptide.

[0154] In some embodiments, a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 539.

[0155] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 540 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 540 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at leastWSGR Docket No.50401-799.601 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 540 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 540 with or without a signal peptide.

[0156] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 545, 546, 547, or 548 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 545, 546, 547, or 548 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 541 or 542 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 541 or 542 with or without a signal peptide.

[0157] In some embodiments, a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 563. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20.

[0158] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 564 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 564 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 564 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 564 with or without a signal peptide.

[0159] In some embodiments, a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 559.

[0160] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 560 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 560 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 560 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 560 with or without a signal peptide.

[0161] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 565, 566, 567, or 568 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 565, 566, 567, or 568 with or without a signal peptide, (b) anWSGR Docket No.50401-799.601 alpha chain having an amino acid sequence set forth in SEQ ID NOs: 561 or 562 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 561 or 562 with or without a signal peptide.

[0162] In some embodiments, a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 585. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20.

[0163] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 586 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 586 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 586 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 586 with or without a signal peptide.

[0164] In some embodiments, a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 581.

[0165] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 582 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 582 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 582 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 582 with or without a signal peptide.

[0166] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 587, 588, 589, or 590 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 587, 588, 589, or 590 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 583 or 584 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 583 or 584 with or without a signal peptide.

[0167] In some embodiments, a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 591. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19. In someWSGR Docket No.50401-799.601 embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20.

[0168] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 592 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 592 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 592 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 592 with or without a signal peptide.

[0169] In some embodiments, a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 119.

[0170] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 120 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 120 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 120 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 120 with or without a signal peptide.

[0171] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 593, 594, 595, or 596 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 593, 594, 595, or 596 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 121 or 122 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 121 or 122 with or without a signal peptide.

[0172] In some embodiments, a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 597. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20.

[0173] In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 598 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 598 with or without a signalWSGR Docket No.50401-799.601 peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 598 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 598 with or without a signal peptide.

[0174] In some embodiments, a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 15.

[0175] In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide.

[0176] In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 599, 600, 601, or 602 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 599, 600, 601, or 602 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 17 or 18 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 17 or 18 with or without a signal peptide.

[0177] In some embodiments, the TCR binds to (i) the mutated epitope from human RAS in complex with the human MHC encoded by the HLA-C03:03 allele with a KD of at most 500 nM, at most 250 nM, at most 50 nM, at most 25 nM, at most 10 nM, or at most 5 nM; and / or (ii) the mutated epitope from human RAS in complex with the human MHC encoded by the HLA-C03:04 allele with a KD of at most 500 nM, at most 250 nM, at most 50 nM, at most 25 nM, at most 10 nM, or at most 5 nM.

[0178] Further provided herein is a recombinant nucleic acid comprising a sequence encoding a T cell receptor (TCR) comprising a TCR beta chain construct and a TCR alpha chain construct, wherein the TCR binds to a mutated epitope from human RAS in complex with a human MHC encoded by an HLA-C03:03 allele and a human MHC encoded by an HLA-C03:04 allele, wherein the mutated epitope from human RAS is characterized by a G12V mutation, wherein: (i) each of (a) the CDR1 of the TCR alpha chain construct, (b) the CDR2 of the TCR alpha chain construct, and (c) at least the first four amino acids of the first five N-terminal amino acids of the CDR3 of the TCR alpha chain construct are encoded by the 3’ terminal sequence of the human TRAV4*01 allele; and (ii) each of (a) the CDR1 of the TCR beta chain construct, (b) the CDR2 of the TCR beta chain construct, and (c) at least the first four amino acids of the first five N-terminal amino acids of the CDR3 of the TCR beta chain construct are encoded by the 3’WSGR Docket No.50401-799.601 terminal sequence of a TRBV allele selected from the group consisting of TRBV2*01, TRBV3-1*01, TRBV4-3*01, TRBV5-6*01, TRBV5-8*01, TRBV6-1*01, TRBV6-2*01, TRBV6-5*01, TRBV7-9*03, TRBV9*01, TRBV11-1*01, TRBV12-3*01, TRBV12-4*01, TRBV13*01, TRBV14*01, TRBV15*02, TRBV18*01, TRBV19*01, TRBV20-1*02, TRBV24-1*01 and TRBV28*01; with the proviso that: when the TRBV allele is TRBV28*01 the CDR3 of the TCR beta chain construct is not CASSPTRLGYNEQFF, does not comprise a sequence encoded by the TRBJ2-1*01 allele, or does not comprise an N-terminal sequence of CASSP, when the TRBV allele is TRBV5-6*01 the CDR3 of the TCR beta chain construct is not CASSLPRMGSDTEAFF or CASSLRTGEAFF, or does not comprise a sequence encoded by the TRBJ1-1*01 allele, and when the TRBV allele is TRBV19*01 the CDR3 of the TCR beta chain construct is not CASSIDYRGIGETQYF, or does not comprise a sequence encoded by the TRBJ2-5*01 allele, or does not comprise an N-terminal sequence of CASSI.

[0179] In some embodiments, the mutated epitope comprises an amino acid sequence set forth in SEQ ID NOs: 633 or 634.

[0180] In some embodiments, the TCR binds to (i) the mutated epitope from human RAS in complex with the human MHC encoded by the HLA-C03:03 allele with a KD of at most 500 nM, at most 250 nM, at most 50 nM, at most 25 nM, at most 10 nM, or at most 5 nM; and / or (ii) the mutated epitope from human RAS in complex with the human MHC encoded by the HLA-C03:04 allele with a KD of at most 500 nM, at most 250 nM, at most 50 nM, at most 25 nM, at most 10 nM, or at most 5 nM.

[0181] In some embodiments, the N-terminus of the CDR3 of the TCR alpha chain construct comprises the 5 amino acids encoded by 3’ terminal sequence of the TRAV4*01 allele. In some embodiments, the N- terminus of the CDR3 of the TCR alpha chain construct comprises the first 4 amino acids of the last 5 amino acids encoded by 3’ terminal sequence of the TRAV4*01 allele. In some embodiments, the N- terminus of the CDR3 of the TCR alpha chain construct comprises the sequence of CLVG. In some embodiments, the N-terminus of the CDR3 of the TCR alpha chain construct comprises the sequence of CLVGD, CLVGDM, or CLVGDMD. In some embodiments, the at least the first four amino acids of the first five N-terminal amino acids of the CDR3 of the TCR beta chain construct are encoded by the 3’ terminal sequence of TRBV6-5*01. In some embodiments, the N-terminus of the CDR3 of the TCR beta chain construct comprises the 5 amino acids encoded by 3’ terminal sequence of the TRBV5-6*01 allele. In some embodiments, the N-terminus of the CDR3 of the TCR beta chain construct comprises the first 4 amino acids of the last 5 amino acids encoded by 3’ terminal sequence of the TRBV5-6*01 allele. In some embodiments, the N-terminus of the CDR3 of the TCR beta chain construct comprises the amino acid sequence CASS. In some embodiments, the N-terminus of the CDR3 of the TCR beta chain construct comprises the amino acid sequence CASSL.

[0182] Provided herein is a recombinant nucleic acid encoding a T cell receptor (TCR) comprising a TCR beta chain construct comprising a complementarity determining region 3 (CDR3) having an amino acid sequence set forth in SEQ ID NO: 363. In some embodiments, the TCR beta chain construct further comprises a complementarity determining region 1 (CDR1), wherein the CDR1 has an amino acidWSGR Docket No.50401-799.601 sequence set forth in SEQ ID NO: 19. In some embodiments, the TCR beta chain construct further comprises a complementarity determining region 2 (CDR2), wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 20. In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide. In some embodiments, the recombinant nucleic acid further comprises a TCR alpha chain construct having a CDR1, a CDR2, and a CDR3, wherein, the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1; the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2; and, the CDR3 has an amino acid sequence set forth in SEQ ID NO: 359. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide. In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 365, 366, 367, or 368 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 365, 366, 367, or 368 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 361 or 362 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 361 or 362 with or without a signal peptide.

[0183] Further provided herein is a recombinant nucleic acid encoding a T cell receptor (TCR) comprising a TCR beta chain construct comprising a complementarity determining region 3 (CDR3) having an amino acid sequence set forth in SEQ ID NO: 483. In some embodiments, the TCR beta chain construct further comprises a complementarity determining region 1 (CDR1), wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 19. In some embodiments, the TCR beta chain construct further comprises a complementarity determining region 2 (CDR2), wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 20. In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO:WSGR Docket No.50401-799.601 484 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide. In some embodiments, the recombinant nucleic acid further comprises a TCR alpha chain construct having a CDR1, a CDR2, and a CDR3, wherein, the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1; the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2; and, the CDR3 has an amino acid sequence set forth in SEQ ID NO: 479. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide. In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 485, 486, 487, or 488 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 485, 486, 487, or 488 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 481 or 482 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 481 or 482 with or without a signal peptide.

[0184] Further provided herein is a recombinant nucleic acid encoding a T cell receptor (TCR) comprising a TCR beta chain construct comprising a complementarity determining region 3 (CDR3) having an amino acid sequence set forth in SEQ ID NO: 569. In some embodiments, the TCR beta chain construct further comprises a complementarity determining region 1 (CDR1), wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 287. In some embodiments, the TCR beta chain construct further comprises a complementarity determining region 2 (CDR2), wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 288. In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 570 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 570 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 570 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 570 with or without a signal peptide. In some embodiments, the recombinant nucleic acid further comprising a TCR alpha chain construct having a CDR1, a CDR2, and a CDR3, wherein, the CDR1 has an amino acidWSGR Docket No.50401-799.601 sequence set forth in SEQ ID NO: 1; the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2; and, the CDR3 has an amino acid sequence set forth in SEQ ID NO: 185. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 186 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 186 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 186 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 186 with or without a signal peptide. In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 571, 572, 573, or 574 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 571, 572, 573, or 574 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 187 or 188 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 187 or 188 with or without a signal peptide.

[0185] Further provided herein is a recombinant nucleic acid encoding a T cell receptor (TCR) comprising a TCR beta chain construct comprising a complementarity determining region 3 (CDR3) having an amino acid sequence set forth in SEQ ID NO: 638. In some embodiments, the TCR beta chain construct further comprises a complementarity determining region 1 (CDR1), wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 19. In some embodiments, the TCR beta chain construct further comprises a complementarity determining region 2 (CDR2), wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 20. In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 639 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 639 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 639 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 639 with or without a signal peptide. In some embodiments, the recombinant nucleic acid further comprising a TCR alpha chain construct having a CDR1, a CDR2, and a CDR3, wherein, the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1; the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2; and, the CDR3 has an amino acid sequence set forth in SEQ ID NO: 15. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 635 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 635 with or without a signal peptide. In some embodiments, the TCRWSGR Docket No.50401-799.601 alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 635 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 635 with or without a signal peptide. In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 640, 641, 642, or 643 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 640, 641, 642, or 643 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 636 or 637 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 636 or 637 with or without a signal peptide.

[0186] Further provided herein is a recombinant nucleic acid encoding a T cell receptor (TCR) comprising a TCR beta chain construct comprising a complementarity determining region 3 (CDR3) having an amino acid sequence set forth in SEQ ID NO: 648. In some embodiments, the TCR beta chain construct further comprises a complementarity determining region 1 (CDR1), wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 19. In some embodiments, the TCR beta chain construct further comprises a complementarity determining region 2 (CDR2), wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 20. In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 649 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 649 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 649 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 649 with or without a signal peptide. In some embodiments, the recombinant nucleic acid further comprises a TCR alpha chain construct having a CDR1, a CDR2, and a CDR3, wherein, the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1; the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2; and, the CDR3 has an amino acid sequence set forth in SEQ ID NO: 644. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 645 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 645 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 645 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 645 with or without a signal peptide. In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 650, 651, 652, or 653 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 650, 651,WSGR Docket No.50401-799.601 652, or 653 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 646 or 647 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 646 or 647 with or without a signal peptide.

[0187] Further provided herein is a recombinant nucleic acid encoding a T cell receptor (TCR) comprising a TCR beta chain construct comprising a complementarity determining region 3 (CDR3) having an amino acid sequence set forth in SEQ ID NO: 658. In some embodiments, the TCR beta chain construct further comprises a complementarity determining region 1 (CDR1), wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 19. In some embodiments, the TCR beta chain construct further comprises a complementarity determining region 2 (CDR2), wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 20. In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 659 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 659 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 659 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 659 with or without a signal peptide. In some embodiments, the recombinant nucleic acid further comprises a TCR alpha chain construct having a CDR1, a CDR2, and a CDR3, wherein, the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1; the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2; and, the CDR3 has an amino acid sequence set forth in SEQ ID NO: 654. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 655 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 655 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 655 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 655 with or without a signal peptide. In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 660, 661, 662, or 663 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 660, 661, 662, or 663 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 656 or 657 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 656 or 657 with or without a signal peptide.

[0188] In some embodiments, the TCR binds to an epitope from human RAS comprising a mutation G12V. In some embodiments, the epitope from human RAS comprising the mutation G12V is SEQ ID NOs: 633 or 634. In some embodiments, the TCR binds to a complex comprising (i) the epitope fromWSGR Docket No.50401-799.601 human RAS comprising the mutation G12V and (ii) an MHC protein encoded by an HLA-C03:03 allele or HLA-C03:04 allele.

[0189] Further provided herein is a TCR encoded by the recombinant nucleic acid of any one of the embodiments disclosed herein. In some embodiments, the TCR is a soluble TCR.

[0190] Further provided herein is a cell comprising the recombinant nucleic acid of any one of the embodiments disclosed herein.

[0191] Further provided herein is a cell comprising a TCR encoded by the recombinant nucleic acid of any one of the embodiments disclosed herein.

[0192] In some embodiments, the cell is a CD4+ T cell. In some embodiments, the cell is a CD8+ T cell. In some embodiments, the cell is isolated from a subject having a RAS mutation.

[0193] Further provided herein is a pharmaceutical composition comprising: (a) the recombinant nucleic acid of any one of the embodiments disclosed herein; and (b) a pharmaceutically acceptable excipient or diluent.

[0194] In some embodiments, the pharmaceutical composition further comprises an immunomodulatory agent or an adjuvant. In some embodiments, the adjuvant is poly I:C.

[0195] Further provided herein is a pharmaceutical composition comprising: (a) the cell of any one of the embodiments disclosed herein; and (b) a pharmaceutically acceptable excipient or diluent.

[0196] In some embodiments, for use in treating an immune disease or cancer.

[0197] The pharmaceutical composition of the embodiments disclosed herein is for use in treating an immune disease or cancer.

[0198] Further disclosed herein is use of the pharmaceutical composition of any one of the embodiments disclosed herein, for treating an immune disease or cancer.

[0199] Further disclosed herein is use of the pharmaceutical composition of the embodiments disclosed herein, for treating an immune disease or cancer.

[0200] Further disclosed herein is a method of treating a subject having a disease or condition, comprising administering to the subject the pharmaceutical composition of any one of the embodiments disclosed herein.

[0201] Further disclosed herein is a method of treating a subject with cancer comprising administering to the subject the pharmaceutical composition of any one of the embodiments disclosed herein.

[0202] Further disclosed herein is a method of identifying a subject with cancer as a candidate for a therapeutic, wherein the method comprising determining the subject as a subject that expresses a protein encoded by an HLA-C03:03 allele or an HLA-C03:04 allele, wherein the therapeutic is the pharmaceutical composition selected from any one of the embodiments disclosed herein.WSGR Docket No.50401-799.601 INCORPORATION BY REFERENCE

[0203] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. BRIEF DESCRIPTION OF THE DRAWINGS

[0204] The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.

[0205] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:

[0206] FIG. 1 depicts an example flow cytometry analysis of RAS-peptide-HLA-C03:03 complex specific CD8+ T cell expansion from different donors, in response to stimulation with RAS G12V peptide.

[0207] FIG. 2A shows CD69 activation after co-culturing Jurkat cells transduced with RAS TCRs (23- 008, 23-014, 23-016.2, 23-017, 23-018, 23-019.1, 23-020, 23-021, or 23-022) with target cells expressing HLA-C03:03 loaded with RAS G12V peptide or KRAS wildtype peptide (left). FIG.2A also shows CD69 activation after co-culturing Jurkat cells transduced with RAS TCRs (23-292, 23-293, 23-294, 23-296, 23- 297, 23-299, 23-301, 23-302, 23-304, or 23-025) with target cells expressing HLA-C03:04 loaded with RAS G12V peptide or KRAS wildtype peptide (right).

[0208] FIG. 2B shows CD69 activation after co-culturing Jurkat cells transduced with RAS TCR, 24- 041.1, with target cells expressing HLA-C03:04 loaded with RAS G12V 9mer, RAS G12V 10mer, or KRAS wildtype peptide.

[0209] FIG. 3 shows CD69 activation after co-culturing Jurkat cells transduced with RAS TCRs (23- 291, 23-292, 23-293, 23-294, 23-295, 23-296, 23-297, 23-299, 23-301, 23-302, 23-303, 23-304 or 23- 027.2) with target cells expressing HLA-C03:03 loaded or HLA-C03:04 loaded with RAS G12V peptide at various concentrations.

[0210] FIG.4A shows KRAS G12V expression in SW620, NCI-H727, and LCLC97TM1 cell lines.

[0211] FIG. 4B shows percent lysis of HLA-C03:03 expressing LCLC97TM1 (left) and HLA-C03:04 expressing NCI-H727 (right) upon co-culturing with human T cells transduced with TCRs of interest (23- 027.2, 23-014) or irrelevant TCR (Irrv TCR).

[0212] FIG.4C shows percent lysis of HLA-C03:03 expressing SW620 (left), HLA-C03:04 expressing NCI-H727 (middle), and HLA-C03:03 expressing LCLC97TM1 (right) upon co-culturing each tumor cell lines with human T cells transduced with TCRs of interest (23-296, 23-301, 23-027.2) or irrelevant TCR (Irrv).

[0213] FIG.5 shows confirmation of G12V / HLA-C03:04 and -C03:03 specificity for over 50 TCRs.WSGR Docket No.50401-799.601

[0214] FIG. 6 shows CD69 activation after co-culturing Jurkat cells transduced with RAS TCRs (23- 291, 23-292, 23-293, 23-294, 23-295, 23-296, 23-297, 23-301, 23-302, 23-303, 23-304 or 23-027.2) with target cells expressing HLA-C03:04 loaded with RAS G12D peptide at various concentrations.

[0215] FIG. 7 shows percent of CD69 expressing cells after co-culturing Jurkat cells transduced with TCR 24-215 or 24-216 with target cells expressing HLA-C03:04 loaded with RAS G12V or no peptide.

[0216] FIG.8 shows percent lysis of HLA-C03:04 expressing SW620 upon co-culturing with human T cell transduced with TCR 24-215 or 24-216. DETAILED DESCRIPTION Definitions

[0217] 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 disclosure belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present disclosure, the preferred methods and materials are now described. The details of one or more particular embodiments are set forth in the description below.

[0218] The term “about” or “approximately” means within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, e.g., the limitations of the measurement system. For example, “about” can mean within 1 or more than 1 standard deviation, per the practice in the art. Alternatively, “about” can mean a range of up to 20%, up to 10%, up to 5%, or up to 1% of a given value. Alternatively, particularly with respect to biological systems or processes, the term can mean within an order of magnitude, preferably within 5-fold, and more preferably within 2-fold, of a value. Where particular values are described in the application and claims, unless otherwise stated the term “about” meaning within an acceptable error range for the particular value should be assumed.

[0219] Unless otherwise stated, the term “TCR” should be understood to encompass full TCRs as well as antigen-binding portions or antigen-binding fragments (also called MHC-peptide binding fragments) thereof. In some embodiments, the TCR is an intact or full-length TCR. In some embodiments, the TCR is an antigen-binding portion that is less than a full-length TCR but that binds to a specific antigenic peptide bound to (e.g., in the context of) an MHC molecule, e.g., an MHC-peptide complex. In some cases, an antigen-binding portion or fragment of a TCR can contain only a portion of the structural domains of a full-length or intact TCR, but yet is able to bind the epitope (e.g., MHC-peptide complex) to which the full TCR binds. In some cases, an antigen-binding portion or fragment of a TCR contains the variable domains of a TCR, such as variable α chain and variable β chain of a TCR, sufficient to form a binding site for binding to a specific MHC-peptide complex, such as generally where each chain contains three complementarity determining regions. Polypeptides or proteins having a binding domain which is an antigen-binding domain or is homologous to an antigen-binding domain are included. Complementarity determining region (CDR) grafted TCRs and other humanized TCRs (including CDR modifications and framework region modifications) are also contemplated by these terms. It should be noted that whileWSGR Docket No.50401-799.601 reference may be made only to immunoglobulin chains (e.g., heavy chains and lights chains), the disclosed invention can be applied to multiple other different types of paired sequences, e.g., T cell receptor chain pairs (TCRα and TCRβ chains and TCRγ and TCRδ chains), and is not limited to immunoglobulins.

[0220] The terms “complementarity determining region,” and “CDR,” synonymous with “hypervariable region” or “HVR,” are known in the art to refer to non-contiguous sequences of amino acids within TCR variable regions, which confer specificity and / or binding affinity to an MHC-peptide complex. In general, there are three CDRs in each alpha chain variable region (CDR-H1, CDR-H2, CDR-H3) and three CDRs in each beta chain variable region (CDR-L1, CDR-L2, CDR-L3). “Framework regions” and “FR” are known in the art to refer to the non-CDR portions of the variable regions of the alpha and beta chains. In general, there are four FRs in each full-length alpha chain variable region (FR-H1, FR-H2, FR-H3, and FR-H4), and four FRs in each full-length beta chain variable region (FR-L1, FR-L2, FR-L3, and FR-L4).

[0221] The term “variable region” or “variable domain” refers to the domain of a TCR alpha, beta, gamma, or delta chain, that is involved in binding the TCR to antigen-MHC complexes. The variable domains of the alpha chain and beta chain (Vα and Vβ, respectively), and the gamma chain and delta chain (Vγ and Vδ, respectively) of a native TCR generally have similar structures, with each domain comprising four conserved framework regions (FRs) and three CDRs. A single Vα or Vβ domain, or Vγ or Vδ domain, may be sufficient to confer binding specificity to a peptide-MHC complex.

[0222] Also provided herein are TCR fragments, including antigen-binding fragments. In some embodiments, the TCR is an antigen-binding portion thereof, such as a variant of a full-length TCR not containing the transmembrane and / or cytoplasmic region(s) thereof, which may be referred to as a full soluble TCR. In some embodiments, the TCR is a dimeric TCR (dTCR). In some embodiments, the TCR is a single-chain TCR (scTCR), such as a scTCR having a structure as described in PCT patent publication numbers WO2003 / 020763, WO2004 / 033685, or WO2011 / 044186. In certain embodiments, the TCR is a single-chain TCR fragment comprising an alpha chain variable region linked to a beta chain variable region, such as a scTv. In some embodiments, a scTv is also referred to as a scFv. A single-chain Tv or scTv refers in some aspects TCR fragments that comprise the variable alpha or gamma chain (Vα or Vγ) and variable beta or delta chain (Vβ or Vδ) domains of a TCR, wherein these domains are present in a single polypeptide chain. Generally, the Tv polypeptide further comprises a polypeptide linker between the Vα and Vβ domains or Vγ and Vδ domains which enables the scTv to form the desired structure for antigen binding. A diabody refers in some aspects to TCR fragments with two antigen-binding sites, which fragments comprise a Vα connected to a Vβ in the same polypeptide chain (Vα-Vβ) or a Vγ connected to a Vδ in the same polypeptide chain (Vγ-Vδ). By using a linker that is too short to allow pairing between the two domains on the same chain, the domains are forced to pair with the complementary domains of another chain and create two antigen-binding sites. Exemplary diabodies are described more fully in, for example, EP404097 and WO93111161. Fv refers in some aspects to a TCR fragment which contains a complete peptide-MHC complex recognition and peptide-MHC complex binding site. This region consists of a dimer of one TCRα chain and one TCRβ chain or one TCRγ chain and one TCRδ chain in tight, non-WSGR Docket No.50401-799.601 covalent association. It is in this configuration that the three CDRs of each variable domain interact to define a peptide-MHC complex binding site on the surface of the Vα-Vβ dimer or Vγ-Vδ dimer. Collectively, a combination of one or more of the CDRs from each of the Vα-Vβ chains or Vγ-Vδ chains confers peptide-MHC complex binding specificity to the TCR. For example, it would be understood that, for example, the CDRα3 and CDRβ3 or CDRγ3 and CDRδ3 could be sufficient to confer antigen-binding specificity to a TCR when transferred to Vα and Vβ chains or Vγ-Vδ chains of a recipient selected TCR or antigen-binding fragment thereof and this combination of CDRs can be tested for binding, affinity, etc. Furthermore, although the two domains of a Tv fragment (Vα and Vβ or Vγ and Vδ ), are coded for by separate genes, they can be joined using recombinant methods by a synthetic linker that enables them to be made as a single protein chain in which the Vα and Vβ or Vγ and Vδ chain regions pair to form monovalent molecules (known as single chain Tv (scTv). Such scTvs are also intended to be encompassed within the peptide-MHC complex binding portion of a TCR.

[0223] Among the provided TCRs are humanized and human TCRs. A “humanized” TCR is a TCR in which all or substantially all CDR amino acid residues are derived from non-human CDRs and all or substantially all FR amino acid residues are derived from human FRs. A humanized TCR optionally may include at least a portion of a TCR constant region derived from a human TCR. A “humanized form” of a non-human TCR, refers to a variant of the non-human TCR that has undergone humanization, typically to reduce immunogenicity to humans, while retaining the specificity and affinity of the parental non-human TCR. In some embodiments, some FR residues in a humanized TCR are substituted with corresponding residues from a non-human TCR (e.g., the TCR from which the CDR residues are derived), e.g., to restore or improve TCR specificity or affinity. A “human TCR” is a TCR with an amino acid sequence corresponding to that of a TCR produced by a human or a human cell, or non-human source that utilizes human TCR repertoires or other human TCR-encoding sequences, including human TCR libraries. The term excludes humanized forms of non-human TCRs comprising non-human peptide-MHC complex binding regions, such as those in which all or substantially all CDRs are non-human. Human TCRs may be prepared by administering an immunogen to a transgenic animal that has been modified to produce intact human TCRs or intact TCRs with human variable regions in response to antigenic challenge. Such animals typically contain all or a portion of the human TCR loci, which replace the endogenous TCR loci, or which are present extrachromosomally or integrated randomly into the animal’s chromosomes. In such transgenic animals, the endogenous TCR loci have generally been inactivated. Human TCRs also may be derived from human TCR libraries, including phage display and cell-free libraries, containing TCR- encoding sequences derived from a human repertoire.

[0224] The term “cancer neoantigen” or “neoantigen” or “neoepitope” can refer to antigens that are not encoded in a normal, non-mutated host genome. A neoantigen can relate to an antigen including one or more amino acid modifications compared to the parental antigen. For example, a neoantigen may be a tumor-associated neoantigen, wherein the term “tumor-associated neoantigen” can include a peptide or protein including amino acid modifications due to tumor-specific mutations. In some instances, aWSGR Docket No.50401-799.601 neoantigen represents either oncogenic viral proteins or abnormal proteins that arise as a consequence of somatic mutations. For example, a neoantigen can arise by the disruption of cellular mechanisms through the activity of viral proteins. Another example can be an exposure of a carcinogenic compound, which in some cases can lead to a somatic mutation. This somatic mutation can ultimately lead to the formation of a tumor / cancer. A neoantigen can be a class of tumor antigens which arise from tumor-specific changes in proteins. Neoantigens encompass, but are not limited to, tumor antigens which arise from, for example, a substitution in a protein sequence, a frame shift mutation, a fusion polypeptide, an in-frame deletion, an insertion, and expression of an endogenous retroviral polypeptide. A neoepitope can be an epitope that is not present in a reference, such as a non-diseased cell, e.g., a non-cancerous cell or a germline cell, but is found in a diseased cell, e.g., a cancer cell. This includes situations where a corresponding epitope is found in a normal non-diseased cell or a germline cell but, due to one or more mutations in a diseased cell, e.g., a cancer cell, the sequence of the epitope is changed so as to result in the neoepitope.

[0225] An “epitope” refers in some aspects to a portion of an antigen or other macromolecule capable of forming a binding interaction with the variable region binding pocket of a TCR. In some aspects, an epitope refers to a portion of a peptide-MHC complex capable of forming a binding interaction with the variable region binding pocket of a TCR. Such binding interactions can be manifested as an intermolecular contact with one or more amino acid residues of one or more CDRs. Peptide-MHC complex binding can involve, for example, a CDR3, a CDR3 pair, or in some instances, interactions of up to all six CDRs of the Vα and Vβ chains or Vγ or Vδ chains. An epitope can be a linear peptide sequence (e.g., “continuous”) or can be composed of noncontiguous amino acid sequences (e.g., “conformational” or “discontinuous”). A TCR can recognize one or more amino acid sequences. Therefore, an epitope can define more than one distinct amino acid sequence. In some aspects, a TCR can recognize one or more amino acid sequences or epitopes in the context of an MHC. Epitopes recognized by TCRs can be determined by peptide mapping and sequence analysis techniques well known to one of skill in the art. Binding interactions are manifested as intermolecular contacts with one or more amino acid residues of a CDR. An epitope can refer to an antigenic determinant in a molecule such as an antigen, e.g., to a part in or fragment of the molecule that is recognized by the immune system, for example, that is recognized by a T cell, in particular when presented in the context of MHC molecules. An epitope of a protein such as a tumor antigen can comprise a continuous or discontinuous portion of the protein and can be between 5 and 100, 5 and 50, 8 and 30, or 10 and 25 amino acids in length, for example, the epitope may be 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 2021, 22, 23, 24 or 25 amino acids in length.

[0226] The term “binding” refers to a direct association between two molecules, due to, for example, covalent, electrostatic, hydrophobic, and ionic and / or hydrogen-bond interactions under physiological conditions, and includes interactions such as salt bridges and water bridges, as well as any other conventional means of binding.

[0227] In some embodiments, reference to a TCR with “specific binding” refers to a situation in which a TCR will not show any significant binding to molecules other than the peptide-MHC complex containingWSGR Docket No.50401-799.601 the epitope recognized by the TCR. The term is also applicable where for example, an antigen binding domain is specific for a particular epitope which is carried by a number of peptide-MHC complexes, in which case the selected TCR or peptide-MHC complex binding fragment thereof carrying the peptide- MHC complex binding domain will be able to bind to the various peptide-MHC complexes carrying the epitope. The terms “preferentially binds” or “specifically binds” mean that the TCRs or fragments thereof bind to an epitope with greater affinity than it binds unrelated amino acid sequences, and, if cross-reactive to other polypeptides containing the epitope, are not toxic at the levels at which they are formulated for administration to human use. In one aspect, such affinity is at least 1-fold greater, at least 2-fold greater, at least 3-fold greater, at least 4-fold greater, at least 5-fold greater, at least 6-fold greater, at least 7-fold greater, at least 8-fold greater, at least 9-fold greater, 10-fold greater, at least 20-fold greater, at least 30- fold greater, at least 40-fold greater, at least 50-fold greater, at least 60-fold greater, at least 70-fold greater, at least 80-fold greater, at least 90-fold greater, at least 100-fold greater, or at least 1000-fold greater than the affinity of the TCR or fragment thereof for unrelated amino acid sequences.

[0228] The term “affinity” refers to a measure of the strength of binding between two members of a binding pair (e.g., a human leukocyte antigen (HLA)-binding peptide and a class I or II HLA, or a peptide- HLA complex and a T cell receptor (TCR)). Affinity can be expressed as an equilibrium constant of the reversible binding of two agents and can be expressed as KD, KA, Koffor Kon. KDrefers to the dissociation constant between two members of a binding pair and has units of molarity. KArefers to the affinity constant between two members of a binding pair is the inverse of the dissociation constant. Affinity may be determined experimentally, for example by surface plasmon resonance (SPR) using commercially available Biacore SPR units. Koffrefers to the off-rate constant of two members of a binding pair, (e.g., the off-rate constant of an HLA-binding peptide and a class I or II HLA, or a peptide-HLA complex and a TCR). Konrefers to the on-rate constant of two members of a binding pair, (e.g., the on-rate constant of an HLA-binding peptide and a class I or II HLA, or a peptide-HLA complex and a TCR). Affinity of a binding protein to a ligand such as affinity of a TCR for an epitope can be, for example, from about 100 nanomolar (nM) to about 0.1 nM, from about 100 nM to about 1 picomolar (pM), or from about 100 nM to about 1 femtomolar (fM).

[0229] The term “avidity” refers to the resistance of a complex of two or more agents to dissociation after dilution.

[0230] Throughout this disclosure, “binding data” results may be expressed in terms of an “IC50.” Affinity may also be expressed as the inhibitory concentration 50 (IC50), or the concentration at which 50% of a first member of a binding pair (e.g., a peptide) is displaced. Likewise, ln(IC50) refers to the natural log of the IC50. For example, an IC50may be the concentration of a tested peptide in a binding assay at which 50% inhibition of binding of a labeled reference peptide is observed. Given the conditions in which the assays are run (e.g., limiting HLA protein concentrations and / or labeled reference peptide concentrations), these values can approximate KDvalues. Assays for determining binding are well known in the art and are described in detail, for example, in PCT publications WO 94 / 20127 and WO 94 / 03205, and otherWSGR Docket No.50401-799.601 publications such as Sidney et al., Current Protocols in Immunology 18.3.1 (1998); Sidney, et al., J. Immunol. 154:247 (1995); and Sette, et al., Mol. Immunol. 31:813 (1994). Alternatively, binding can be expressed relative to binding by a reference standard peptide. Binding can also be determined using other assay systems including those using: live cells (e.g., Ceppellini et al., Nature 339:392 (1989); Christnick et al., Nature 352:67 (1991); Busch et al., Int. Immunol. 2:443 (1990); Hill et al., J. Immunol. 147:189 (1991); del Guercio et al., J. Immunol. 154:685 (1995)), cell free systems using detergent lysates (e.g., Cerundolo et al., J. Immunol. 21:2069 (1991)), immobilized purified MHC (e.g., Hill et al., J. Immunol. 152, 2890 (1994); Marshall et al., J. Immunol.152:4946 (1994)), ELISA systems (e.g., Reay et al., EMBO J.11:2829 (1992)), surface plasmon resonance (e.g., Khilko et al., J. Biol. Chem.268:15425 (1993)); high flux soluble phase assays (Hammer et al., J. Exp. Med.180:2353 (1994)), and measurement of class I MHC stabilization or assembly (e.g., Ljunggren et al., Nature 346:476 (1990); Schumacher et al., Cell 62:563 (1990); Townsend et al., Cell 62:285 (1990); Parker et al., J. Immunol.149:1896 (1992)).

[0231] The terms “major histocompatibility complex” and the abbreviation “MHC” can include MHC class I and MHC class II molecules and relate to a complex of genes which occurs in all vertebrates. MHC proteins or molecules can be important for signaling between lymphocytes and antigen presenting cells or diseased cells in immune reactions, wherein the MHC proteins or molecules bind peptides and present them for recognition by T cell receptors. The proteins encoded by the MHC can be expressed on the surface of cells, and display both self-antigens (peptide fragments from the cell itself) and non-self-antigens (e.g., fragments of invading microorganisms) to a T cell. The MHC region can be divided into three subgroups, class I, class II, and class III. MHC class I proteins can contain an α-chain and β2-microglobulin (not part of the MHC encoded by chromosome 15). They can present antigen fragments to cytotoxic T cells. MHC class II proteins can contain α- and β-chains and they can present antigen fragments to T-helper cells. MHC class III region can encode for other immune components, such as complement components and cytokines. The MHC can be both polygenic (there are several MHC class I and MHC class II genes) and polymorphic (there are multiple alleles of each gene).

[0232] The term “haplotype” can refer to the human leukocyte antigen (HLA) alleles found on one chromosome and the proteins encoded thereby. Haplotype may also refer to the allele present at any one locus within the MHC. Each class of MHC is represented by several loci: e.g., HLA-A (Human Leukocyte Antigen-A). HLA-B, HLA-C, HLA-E, HLA-F, HLA-G, HLA-H, HLA-J, HLA-K, HLA-L, HLA-P and HLA-V for class I and HLA-DRA, HLA-DRB1-9, HLA-DQA1, HLA-DQB1, HLA-DPA1, HLA-DPB1, HLA-DPB2, HLA-DMA, HLA-DMB, HLA-DOA, and HLA-DOB for class II. The terms “HLA allele” and “MHC allele” are used interchangeably herein.

[0233] The terms “polynucleotide,” “nucleotide”, “nucleotide sequence”, “nucleic acid” and “oligonucleotide” are used interchangeably. They can refer to a polymeric form of nucleotides of any length, either deoxyribonucleotides or ribonucleotides, or analogs thereof. Polynucleotides may have any three dimensional structure, and may perform any function, known or unknown. The following are non- limiting examples of polynucleotides: coding or non-coding regions of a gene or gene fragment, loci (locus)WSGR Docket No.50401-799.601 defined from linkage analysis, exons, introns, messenger RNA (mRNA), transfer RNA (tRNA), ribosomal RNA (rRNA), short interfering RNA (siRNA), short-hairpin RNA (shRNA), micro-RNA (miRNA), ribozymes, cDNA, recombinant polynucleotides, branched polynucleotides, plasmids, vectors, isolated DNA of any sequence, isolated RNA of any sequence, nucleic acid probes, and primers. A polynucleotide may comprise one or more modified nucleotides, such as methylated nucleotides and nucleotide analogs. If present, modifications to the nucleotide structure may be imparted before or after assembly of the polymer. Polynucleotides can include nonstandard nucleotides, such as nucleotide analogs or modified nucleotides. In some embodiments, nonstandard nucleotides can stabilize hybrid formation. In some embodiments, nonstandard nucleotides can destabilize hybrid formation. In some embodiments, nonstandard nucleotides can enhance hybridization specificity. In some embodiments, nonstandard nucleotides can reduce hybridization specificity. Examples of nonstandard nucleotide modifications include 2’ O-Me, 2’ O-allyl, 2’ O-propargyl, 2’ O-alkyl, 2’ fluoro, 2’ arabino, 2’ xylo, 2’ fluoro arabino, phosphorothioate, phosphorodithioate, phosphoroamidates, 2’ Amino, 5-alkyl-substituted pyrimidine, 3’ deoxyguanosine, 5-halo-substituted pyrimidine, alkyl-substituted purine, halo-substituted purine, bicyclic nucleotides, 2’MOE, PNA molecules, LNA-molecules, LNA-like molecules, diaminopurine, S2T, 5- fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xantine, 4-acetylcytosine, 5- (carboxyhydroxylmethyl)uracil, 5-carboxymethylaminomethyl-2-thiouridine, 5- carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine, inosine, N6- isopentenyladenine, 1-methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2- methylguanine, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methyl guanine, 5- methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, beta-D-mannosylqueosine, 5’- methoxycarboxymethyluracil, 5-methoxyuracil, 2-methylthio-D46-isopentenyladenine, uracil-5-oxyacetic acid (v), wybutoxosine, pseudouracil, queosine, 2-thiocytosine, 5- methyl-2-thiouracil, 2-thiouracil, 4- thiouracil, 5-methyluracil, uracil-5-oxyacetic acid methylester, uracil-5-oxy acetic acid (v), 5-methyl-2- thiouracil, 3-(3-amino-3-N-2- carboxypropyl) uracil, (acp3)w, 2,6-diaminopurine, and derivatives thereof. The sequence of nucleotides may be interrupted by non-nucleotide components. A polynucleotide may be further modified after polymerization, such as by conjugation with a labeling component.

[0234] “Complementarity” can refer to the ability of a nucleic acid to form hydrogen bond(s) with another nucleic acid sequence by either traditional Watson-Crick or other non-traditional types. A percent complementarity can indicate the percentage of residues in a nucleic acid molecule which can form hydrogen bonds (e.g., Watson-Crick base pairing) with a second nucleic acid sequence (e.g., 5, 6, 7, 8, 9, 10 out of 10 being 50%, 60%, 70%, 80%, 90%, and 100% complementary, respectively). “Perfectly complementary” can mean that all the contiguous residues of a nucleic acid sequence will hydrogen bond with the same number of contiguous residues in a second nucleic acid sequence. “Substantially complementary” refers to a degree of complementarity that is at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 97%, 98%, 99%, or 100% over a region of 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50, or more nucleotides, or can refer to two nucleic acids that hybridize underWSGR Docket No.50401-799.601 stringent conditions. Sequence identity, such as for the purpose of assessing percent complementarity, may be measured by any suitable alignment algorithm, including but not limited to the Needleman-Wunsch algorithm (e.g., the EMBOSS Needle aligner available at www.ebi.ac.uk / Tools / psa / emboss_needle / nucleotide.html, optionally with default settings), the BLAST algorithm (see e.g., the BLAST alignment tool available at blast.ncbi.nlm.nih.gov / Blast.cgi, optionally with default settings), or the Smith-Waterman algorithm. Optimal alignment may be assessed using any suitable parameters of a chosen algorithm, including default parameters.

[0235] The terms “polypeptide” and “protein” are used interchangeably to refer to a polymer of amino acid residues, and are not limited to a minimum length. For example, a polypeptide can comprise at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900, or 1000 peptides or amino acids. Examples of polypeptides include, but are not limited to, amino acid chains, proteins, peptides, hormones, polypeptide saccharides, lipids, glycolipids, phospholipids, antibodies, enzymes, kinases, receptors, transcription factors, and ligands. Polypeptides, including the provided TCRs and TCR chains and other peptides, e.g., linkers and binding peptides, may include amino acid residues including natural and / or non-natural amino acid residues. The terms also include post-expression modifications of the polypeptide, for example, glycosylation, sialylation, acetylation, phosphorylation, and the like. In some aspects, the polypeptides may contain modifications with respect to a native or natural sequence, as long as the protein maintains the desired activity. These modifications may be deliberate, as through site-directed mutagenesis, or may be accidental, such as through mutations of hosts which produce the proteins or errors due to PCR amplification.

[0236] As used herein, the twenty conventional amino acids and their abbreviations known to one skilled in the art follow conventional usage. Stereoisomers (e.g., D-amino acids) of the twenty conventional amino acids, unnatural amino acids such as α-, α-disubstituted amino acids, N-alkyl amino acids, lactic acid, and other unconventional amino acids may also be suitable components for polypeptides of the present invention. Examples of unconventional amino acids include: 4-hydroxyproline, γ-carboxyglutamate, ε- N,N,N-trimethyllysine, ε-N-acetyllysine, O-phosphoserine, N-acetylserine, N-formylmethionine, 3- methylhistidine, 5-hydroxylysine, σ-N-methylarginine, and other similar amino acids and imino acids (e.g., 4-hydroxyproline). In the polypeptide notation used herein, the left hand direction is the amino terminal direction and the right hand direction is the carboxy-terminal direction, in accordance with standard usage and convention. Percent (%) sequence identity with respect to a reference polypeptide sequence (or nucleic acid sequence) is the percentage of amino acid residues (or nucleotides in case of nucleic acid sequence) in a candidate sequence that are identical with the amino acid residues (or nucleotides) in the reference polypeptide sequence (or nucleic acid sequence), after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR)WSGR Docket No.50401-799.601 software. Those skilled in the art can determine appropriate parameters for aligning sequences, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared. For purposes herein, however, % amino acid sequence identity values are generated using the sequence comparison computer program ALIGN-2. The ALIGN-2 sequence comparison computer program was authored by Genentech, Inc., and the source code has been filed with user documentation in the U.S. Copyright Office, Washington D.C., 20559, where it is registered under U.S. Copyright Registration No. TXU510087. The ALIGN-2 program is publicly available from Genentech, Inc., South San Francisco, Calif., or may be compiled from the source code. The ALIGN-2 program should be compiled for use on a UNIX operating system, including digital UNIX V4.0D. All sequence comparison parameters are set by the ALIGN-2 program and do not vary. In situations where ALIGN-2 is employed for amino acid sequence comparisons, the % amino acid sequence identity of a given amino acid sequence A to, with, or against a given amino acid sequence B (which can alternatively be phrased as a given amino acid sequence A that has or comprises a certain % amino acid sequence identity to, with, or against a given amino acid sequence B) is calculated as follows: 100 times the fraction X / Y, where X is the number of amino acid residues scored as identical matches by the sequence alignment program ALIGN-2 in that program's alignment of A and B, and where Y is the total number of amino acid residues in B. It will be appreciated that where the length of amino acid sequence A is not equal to the length of amino acid sequence B, the % amino acid sequence identity of A to B will not equal the % amino acid sequence identity of B to A. Unless specifically stated otherwise, all % amino acid sequence identity values used herein are obtained as described in the immediately preceding paragraph using the ALIGN-2 computer program.

[0237] A “subject,” “individual”, “host” or “patient” refers to living organisms such as mammals. Examples of subjects and hosts include, but are not limited to, horses, cows, camels, sheep, pigs, goats, dogs, cats, rabbits, guinea pigs, rats, mice (e.g., humanized mice), gerbils, non-human primates (e.g., macaques), humans and the like, non-mammals, including, e.g., non-mammalian vertebrates, such as birds (e.g., chickens or ducks) fish (e.g., sharks) or frogs (e.g., Xenopus), and non-mammalian invertebrates, as well as transgenic species thereof. In certain aspects, a subject refers to a single organism (e.g., human). In certain aspects, or a group of individuals composing a small cohort having either a common immune factor to study and / or disease, and / or a cohort of individuals without the disease (e.g., negative / normal control) are provided. A subject from whom samples are obtained can either be inflicted with a disease and / or disorder (e.g., one or more allergies, infections, cancers or autoimmune disorders or the like) and can be compared against a negative control subject which is not affected by the disease.

[0238] A “kit” refers to a delivery system for delivering materials or reagents for carrying out a method disclosed herein. In some embodiments, kits include systems that allow for the storage, transport, or delivery of reaction reagents (e.g., probes, enzymes, etc. in the appropriate containers) and / or supporting materials (e.g., buffers, written instructions for performing the assay etc.) from one location to another. For example, kits include one or more enclosures (e.g., boxes) containing the relevant reaction reagents and / or supporting materials. Such contents may be delivered to the intended recipient together or separately. ForWSGR Docket No.50401-799.601 example, a first container may contain an enzyme for use in an assay, while a second container contains a plurality of primers. A packaging material refers to a physical structure housing the components of the kit. The packaging material can maintain the components sterilely and can be made of material commonly used for such purposes (e.g., paper, corrugated fiber, glass, plastic, foil, ampules, etc.). The label or packaging insert can include appropriate written instructions. Kits, therefore, can additionally include labels or instructions for using the kit components in any method of the invention. A kit can include a compound in a pack, or dispenser together with instructions for administering the compound in a method described herein. T Cell Receptors (TCRs)

[0239] Disclosed herein are T cell receptors (TCRs) and recombinant nucleic acids encoding the same. In some aspects, provided herein is a recombinant nucleic acid encoding a TCR comprising a TCR beta construct and a TCR alpha chain construct that recognizes epitopes (e.g., mutated epitope from human RAS) in complex with a human MHC.

[0240] The ability of T cells to recognize antigens associated with infectious organisms or cancers is conferred by its TCR, which is made up of both an alpha (α) chain and a beta (β) chain or a gamma (γ) and a delta (δ) chain. The proteins which make up these chains are encoded by DNA, which employs a unique mechanism for generating the diversity of the TCR. This multi-subunit immune recognition receptor can associate with the CD3 complex and bind peptides presented by the MHC class I and II proteins on the surface of antigen-presenting cells (APCs). The first signal in activation of T cells can be provided by binding of the T-cell receptor to a short peptide presented by the MHC on another cell. This ensures that only a T cell with a TCR specific to that peptide is activated. The partner cell is usually an antigen- presenting cell such as a professional antigen-presenting cell, usually a dendritic cell in the case of naive responses, although B-cells and macrophages can be important APCs. Binding of a TCR to the antigenic peptide on the APC can be a central event in T cell activation, which occurs at an immunological synapse at the point of contact between the T cell and the APC.

[0241] Each TCR can comprise variable complementarity determining regions (CDRs), as well as framework regions (FRs) and a constant region. The TCR described herein may be in soluble form. The TCR described herein may not comprise a constant region. The TCR described herein may comprise a functional fragment of a full-length TCR. The TCR described herein may comprise the variable region of the alpha chain or beta chain only. The amino acid sequence of the third complementarity-determining region (CDR3) loops of the alpha (or α) and beta (or β) chain variable domains largely determines the sequence diversity of αβ T cells arising from recombination between variable (Vβ), diversity (Dβ), and joining (Jβ) gene segments in the β chain locus, and between analogous Vα and Jα gene segments in the α chain locus, respectively. The existence of multiple such gene segments in the TCR α and β chain loci allows for a large number of distinct CDR3 sequences to be encoded. Independent addition and deletion of nucleotides at the Vβ-Dβ, Dβ-Jβ, and Vα-Jα junctions during the process of TCR gene rearrangement further increases CDR3 sequence diversity. In this respect, immunocompetence is reflected in the diversityWSGR Docket No.50401-799.601 of TCRs. The γδ TCR is distinctive from the αβ TCR in that it encodes a receptor that interacts closely with the innate immune system. TCRγδ, is expressed early in development, has specialized anatomical distribution, has unique pathogen and small-molecule specificities, and has a broad spectrum of innate and adaptive cellular interactions. Early in ontogeny, as the restricted subsets of TCRγδ cells populate various tissues prenatally, a biased pattern of TCRγ V and J segment expression is established.

[0242] TCRs can bind to a peptide: MHC complex. In some cases, the TCR can bind to an MHC peptide complex comprising an epitope from an antigen or candidate antigen described herein. In some cases, the TCR can bind to an MHC peptide complex comprising an epitope of protein encoded by the genome of a cancer cell. The binding of the TCR complex and the epitope bound with the MHC molecule (e.g., MHC class I or MHC class II) can trigger signal transduction pathways that lead to regulation of immune responses against the antigenic peptide. In some embodiments, the TCR disclosed herein binds to an MHC- peptide complex with a KDor an IC50of 1 μM to 1 nM. In some embodiments, the TCR disclosed herein binds to an MHC-peptide complex with a KDor an IC50of less than 500 nM, 250 nM, 150 nM, 100 nM, 50 nM, 25 nM or 10 nM. In some embodiments, the TCR disclosed herein binds to an MHC-peptide complex with a KDor an IC50of less than 500 nM. In some embodiments, the TCR disclosed herein binds to an MHC-peptide complex with a KDor an IC50of less than 250 nM. In some embodiments, the TCR disclosed herein binds to an MHC-peptide complex with a KDor an IC50of less than 150 nM. In some embodiments, the TCR disclosed herein binds to an MHC-peptide complex with a KDor an IC50of less than 100 nM. In some embodiments, the TCR disclosed herein binds to an MHC-peptide complex with a KDor an IC50of less than 50 nM. In some embodiments, the TCR disclosed herein binds to an MHC- peptide complex with a KDor an IC50of less than 25 nM. In some embodiments, the TCR disclosed herein binds to an MHC-peptide complex with a KDor an IC50of less than 10 nM. In some embodiments, the TCR disclosed herein binds to a mutated epitope from human RAS in complex with the human encoded by the HLA-C03:03 allele with a KDof at least 500 nM, at least 250 nM, at least 50 nM, at least 25 nM, at least 10 nM, or at least 5 nM. In some embodiments, the TCR disclosed herein binds to a mutated epitope from human RAS in complex with the human encoded by the HLA-C03:03 allele with a KDof at most 500 nM, at most 250 nM, at most 50 nM, at most 25 nM, at most 10 nM, or at most 5 nM. In some embodiments, the TCR disclosed herein binds to a mutated epitope from human RAS in complex with the human encoded by the HLA-C03:04 allele with a KDof at least 500 nM, at least 250 nM, at least 50 nM, at least 25 nM, at least 10 nM, or at least 5 nM. In some embodiments, the TCR disclosed herein binds to a mutated epitope from human RAS in complex with the human encoded by the HLA-C03:04 allele with a KDof at most 500 nM, at most 250 nM, at most 50 nM, at most 25 nM, at most 10 nM, or at most 5 nM.

[0243] In some embodiments, the TCR sequence is comprised of human sequences. In some embodiments, the TCR sequence is comprised of non-human animal sequences that have been humanized using any method of humanization known in the art. The TCRs disclosed herein can be engineered TCRs. In some embodiments, the TCR is a soluble TCR.WSGR Docket No.50401-799.601

[0244] In some aspects, provided herein is a TCR or a recombinant nucleic acid comprising a sequence encoding thereof. In some embodiments, a TCR or a recombinant nucleic acid disclosed herein comprises a sequence encoding thereof comprises a TCR beta chain construct. In some embodiments, a TCR or a recombinant nucleic acid disclosed herein comprises a sequence encoding thereof comprises a TCR alpha chain construct.

[0245] In some embodiments, a TCR disclosed herein binds to a mutated epitope from human RAS. In some embodiments, the mutated epitope from human RAS is characterized by a G12V mutation. In some embodiments, a TCR disclosed herein binds to a mutated epitope from human RAS in complex with a human MHC encoded by an HLA-C03:03 allele. In some embodiments, a TCR disclosed herein binds to a mutated epitope from human RAS in complex with a human MHC encoded by an HLA-C03:04 allele. In some embodiments, a TCR disclosed herein binds to a mutated epitope from human RAS in complex with a human MHC encoded by an HLA-C03:03 allele and a human MHC encoded by an HLA-C03:04 allele. In some embodiments, the TCR binds to (i) the mutated epitope from human RAS in complex with the human MHC encoded by the HLA-C03:03 allele with a KD of at most 500 nM, at most 250 nM, at most 50 nM, at most 25 nM, at most 10 nM, or at most 5 nM; and / or (ii) the mutated epitope from human RAS in complex with the human MHC encoded by the HLA-C03:04 allele with a KD of at most 500 nM, at most 250 nM, at most 50 nM, at most 25 nM, at most 10 nM, or at most 5 nM. In some embodiments, the mutated epitope comprises an amino acid sequence set forth in SEQ ID NOs: 633 or 634.

[0246] In some embodiments, a TCR disclosed herein comprises a TCR beta chain construct. In some embodiments, the TCR beta chain construct comprises a complementarity determining region 3 (CDR3). In some embodiments, a N-terminus of the CDR3 of the TCR beta chain construct comprises at least two, at least three, at least four, at least five, or at least six amino acids encoded by the 3’ terminal sequence of the TRBV5-6*01 allele. In some embodiments, the CDR3 of the TCR beta chain construct does not comprise a CDR3 sequence of CASSLPRMGSDTEAFF (SEQ ID NO: 83), CASSPTRLGYNEQFF (SEQ ID NO: 135), CASSLRTGEAFF (SEQ ID NO: 179) or CASSIDYRGIGETQYF (SEQ ID NO: 191). In some embodiments, the N-terminus of the CDR3 comprises the 5 amino acids encoded by 3’ terminal sequence of the TRBV5-6*01 allele. In some embodiments, the N-terminus of the CDR3 comprises the first 4 amino acids of the last 5 amino acids encoded by 3’ terminal sequence of the TRBV5-6*01 allele. In some embodiments, the N-terminus of the CDR3 of the TCR beta chain construct comprises the amino acid sequence CASS. In some embodiments, the N-terminus of the CDR3 of the TCR beta chain construct comprises the amino acid sequence CASSL. In some embodiments, the N-terminus of the CDR3 of the TCR alpha chain construct comprises at least four amino acids encoded by the 3’ terminal sequence of the TRAV4*01 allele. In some embodiments, the N-terminus of a CDR3 of the TCR beta chain construct comprises the sequence of CASS.

[0247] In some embodiments, the TCR beta chain construct comprises a complementarity determining region 1 (CDR1), wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to an amino acid sequenceWSGR Docket No.50401-799.601 set forth in SEQ ID NO: 19. In some embodiments, the TCR beta chain construct comprises a CDR1 wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct comprises a complementarity determining region 2 (CDR2), wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 20. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20.

[0248] In some embodiments, a TCR disclosed herein comprises a TCR alpha chain construct. In some embodiments, the TCR alpha chain construct comprises a CDR3. In some embodiments, a N-terminus of the CDR3 of the TCR alpha chain construct comprises at least two, at least three, at least four, at least five, or at least six amino acids encoded by the 3’ terminal sequence of the TRAV4*01 allele. In some embodiments, the N-terminus of the CDR3 of the TCR alpha chain construct comprises the 5 amino acids encoded by 3’ terminal sequence of the TRAV4*01 allele. In some embodiments, the N-terminus of the CDR3 of the TCR alpha chain construct comprises the first 4 amino acids of the last 5 amino acids encoded by 3’ terminal sequence of the TRAV4*01 allele. In some embodiments, the N-terminus of the TCR alpha chain construct comprises the amino acid sequence CLVG. In some embodiments, the N-terminus of the CDR3 of the TCR alpha chain construct comprises the sequence of CLVGD, CLVGDM, or CLVGDMD. In some embodiments, the CDR3 of the TCR alpha chain construct does not comprise a CDR3 sequence CLVGDMDSGNTPLVF (SEQ ID NO: 185), CLVGDLDGQKLLF (SEQ ID NO: 175), CLVGDMDGGYQKVTF (SEQ ID NO: 131), or CLVGDGDNARLMF (SEQ ID NO: 79).

[0249] In some embodiments, the TCR alpha chain construct comprises a CDR1 having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to an amino acid sequence forth in SEQ ID NO: 1. In some embodiments, the TCR alpha chain construct comprises a CDR1 comprising an amino acid sequence forth in SEQ ID NO: 1. In some embodiments, the TCR alpha chain construct comprises a CDR2 having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to an amino acid sequence forth in SEQ ID NO: 2. In some embodiments, the TCR alpha chain construct comprises a CDR2 comprising an amino acid sequence of SEQ ID NO: 2.

[0250] In some embodiments, the TCR beta chain construct comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to an amino acid sequence of SEQ ID NO: 363. In some embodiments, the CDR3 has an amino acid sequence of SEQ ID NO: 363. In some embodiments, the TCR beta chain construct comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 364 with or without aWSGR Docket No.50401-799.601 signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a CDR3 having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to an amino acid sequence forth in SEQ ID NO: 359. In some embodiments, the TCR alpha chain construct comprises a CDR3, wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 359. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide. In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 365, 366, 367, or 368 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% identical to SEQ ID NOs: 365, 366, 367, or 368 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 361 or 362 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% identical to SEQ ID NOs: 361 or 362 with or without a signal peptide.

[0251] In some embodiments, the TCR beta chain construct comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to an amino acid sequence of SEQ ID NO: 483. In some embodiments, the TCR beta chain construct comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 483. In some embodiments, the TCR beta chain construct comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 479. In some embodiments, the TCR alpha chain construct comprises a CDR3, wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 479. In some embodiments, the TCR alphaWSGR Docket No.50401-799.601 chain construct comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide. In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 485, 486, 487, or 488 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% identical to SEQ ID NOs: 485, 486, 487, or 488 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 481 or 482 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% identical to SEQ ID NOs: 481 or 482 with or without a signal peptide.

[0252] In some embodiments, the TCR beta chain construct comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to an amino acid sequence of SEQ ID NO: 569. In some embodiments, the TCR beta chain construct comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 569. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to an amino acid sequence of SEQ ID NO: 287. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 287. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to an amino acid sequence of SEQ ID NO: 288. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 288. In some embodiments, the TCR beta chain construct comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 570 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 570 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% identity to an amino acid sequence set forth in SEQ ID NO: 570 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequenceWSGR Docket No.50401-799.601 set forth in SEQ ID NO: 570 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 185. In some embodiments, the TCR alpha chain construct comprises a CDR3, wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 185. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 186 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 186 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% identity to an amino acid sequence set forth in SEQ ID NO: 186 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 186 with or without a signal peptide. In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 571, 572, 573, or 574 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% identical to SEQ ID NOs: 571, 572, 573, or 574 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 187 or 188 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% identical to SEQ ID NOs: 187 or 188 with or without a signal peptide.

[0253] In some embodiments, the TCR beta chain construct comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to an amino acid sequence selected from the group consisting of TCR beta chain CDR3 sequences listed in Table 1B. In some embodiments, the TCR beta chain construct comprises a CDR3, wherein the CDR3 has an amino acid sequence selected from the group consisting of TCR beta chain CDR3 sequences listed in Table 1B. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to an amino acid sequence selected from the group consisting of TCR beta chain CDR1 sequences listed in Table 1B. In some embodiments, the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence selected from the group consisting of TCR beta chain CDR1 sequences listed in Table 1B. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to an amino acid sequence selected from the group consisting of TCR beta chainWSGR Docket No.50401-799.601 CDR2 sequences listed in Table 1B. In some embodiments, the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence selected from the group consisting of TCR beta chain CDR2 sequences listed in Table 1B. In some embodiments, the TCR beta chain construct comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to an amino acid sequence selected from the group consisting of TCR beta chain variable region sequences listed in Table 1B. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence selected from the group consisting of TCR beta chain variable region sequences listed in Table 1B. In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence selected from the group consisting of TCR beta chain variable region sequences listed in Table 1B. In some embodiments, the TCR alpha chain construct comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to an amino acid sequence selected from the group consisting of TCR beta chain CDR3 sequences listed in Table 1B. In some embodiments, the TCR alpha chain construct comprises a CDR3, wherein the CDR3 has an amino acid sequence selected from the group consisting of TCR beta chain CDR3 sequences listed in Table 1B. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to an amino acid sequence selected from the group consisting of TCR alpha chain variable region sequences listed in Table 1B. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence selected from the group consisting of TCR alpha chain variable region sequences listed in Table 1B. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% identity to an amino acid sequence selected from the group consisting of TCR alpha chain variable region sequences listed in Table 1B. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence selected from the group consisting of TCR alpha chain variable region sequences listed in Table 1B. In some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence selected from the group consisting of beta chain sequences listed in Table 1B, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% identical to an amino acid sequence selected from the group consisting of beta chain sequences listed in Table 1B, (b) an alpha chain having an amino acid sequence selected from the group consisting of alpha chain sequences listed in Table 1B, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% or at least 99% identical to an amino acid sequence selected from the group consisting of alpha chain sequences listed in Table 1B. TableWSGR Docket No.50401-799.601 1B provides amino acid sequences of the TCRs disclosed herein. The signal peptide for each variable sequences are bolded.

[0254] In some aspects, provided herein is a recombinant nucleic acid encoding a TCR, wherein the TCR comprises a TCR alpha chain having a TCR alpha variable region, wherein the TCR alpha variable region is derived from a V gene segment of TRAV4*01 and a J gene segment selected from the group consisting of TRAJ10*01, TRAJ13*02, TRAJ16*01, TRAJ16*02, TRAJ21*01, TRAJ23*01, TRAJ26*01, TRAJ29*01, TRAJ3*01, TRAJ30*01, TRAJ31*01, TRAJ32*02, TRAJ33*01, TRAJ34*01, TRAJ36*01, TRAJ37*01, TRAJ37*02, TRAJ39*01, TRAJ4*01, TRAJ41*01, TRAJ42*01, TRAJ43*01, TRAJ47*01, TRAJ49*01, TRAJ5*01, TRAJ52*01, TRAJ53*01, TRAJ57*01, TRAJ8*01 and TRAJ9*01. In some embodiments, the TCR does not bind to a mutated epitope having a G12D mutation from human RAS in complex with a human MHC or the TCR binds to a mutated epitope having a G12D mutation from human RAS in complex with a human MHC with a dissociation constant (KD) of at least 1000 nM, at least 5000 nM, at least 10,000 nM, at least 50,000 nM, at least 100,000 nM, at least 500,000 nM, at least 1,000,000 nM or more. In some embodiments, the TCR disclosed herein comprises a TCR beta variable region, wherein the TCR beta variable region is derived from a V gene segment of TRBV5-6*01 and a J gene segment selected from the group consisting of TRBJ2-3*01, TRBJ1-6*02, TRBJ1-1*01, TRBJ1-3*01, TRBJ2-2*01, TRBJ1-5*01, TRBJ2-7*01, TRBJ2-1*01, TRBJ1-2*01, TRBJ1-4*01 and TRBJ2-5*01. In some embodiments, the TCRs do not comprise a TCR having a sequence listed in Table 2. Table 2 provides amino acid sequences of the TCRs disclosed herein. The signal peptide for each variable sequences are bolded.

[0255] In some embodiments, a TCR beta chain construct of a TCR disclosed herein comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 21. In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 20. In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 22 with or without a signal peptide.

[0256] In some embodiments, a TCR alpha chain construct of a TCR disclosed herein comprises a CDR1, CDR2, CDR3, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, atWSGR Docket No.50401-799.601 least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 15. In some embodiments, the TCR alpha chain construct of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide.

[0257] In some embodiments, a TCR disclosed herein comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 23, 24, 25, or 26 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 23, 24, 25, or 26 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 17 or 18 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 17 or 18 with or without a signal peptide.

[0258] In some embodiments, a TCR beta chain construct of a TCR disclosed herein comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 63. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 20.

[0259] In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 64 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 64 with or without a signal peptide.

[0260] In some embodiments, a TCR alpha chain construct of a TCR disclosed herein comprises a CDR1, CDR2, CDR3, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, atWSGR Docket No.50401-799.601 least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 59. In some embodiments, the TCR alpha chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 60 with or without a signal peptide. In some embodiments, the TCR alpha chain of a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 60 with or without a signal peptide.

[0261] In some embodiments, a TCR disclosed herein comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 65, 66, 67, or 68 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 65, 66, 67, or 68 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 61 or 62 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 61 or 62 with or without a signal peptide.

[0262] In some embodiments, a TCR beta chain construct of a TCR disclosed herein comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 73. In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 20. In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 74 with or without a signal peptide. In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 74 with or without a signal peptide.

[0263] In some embodiments, a TCR alpha chain construct of a TCR disclosed herein comprises a CDR1, CDR2, CDR3, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequenceWSGR Docket No.50401-799.601 set forth in SEQ ID NO: 1, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 69. In some embodiments, the TCR alpha chain construct of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 70 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 70 with or without a signal peptide.

[0264] In some embodiments, a TCR disclosed herein of a TCR disclosed herein comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 75, 76, 77, or 78 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 75, 76, 77, or 78 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 71 or 72 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 71 or 72 with or without a signal peptide.

[0265] In some embodiments, a TCR beta chain construct of a TCR disclosed herein comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 83. In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 20. In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 84 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 84 with or without a signal peptide.

[0266] In some embodiments, a TCR alpha chain construct of a TCR disclosed herein comprises a CDR1, CDR2, CDR3, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, atWSGR Docket No.50401-799.601 least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 79. In some embodiments, the TCR alpha chain construct of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 80 with or without a signal peptide. In some embodiments, the TCR alpha chain construct of a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 80 with or without a signal peptide.

[0267] In some embodiments, a TCR disclosed herein comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 85, 86, 87, or 88 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 85, 86, 87, or 88 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 81 or 82 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 81 or 82 with or without a signal peptide.

[0268] In some embodiments, a TCR beta chain construct of a TCR disclosed herein comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 93. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 20. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 94 with or without a signal peptide. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 94 with or without a signal peptide.

[0269] In some embodiments, a TCR alpha chain construct of a TCR disclosed herein comprises a CDR1, CDR2, CDR3, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an aminoWSGR Docket No.50401-799.601 acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 99. In some embodiments, the TCR alpha chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 90 with or without a signal peptide. In some embodiments, the TCR alpha chain of a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 90 with or without a signal peptide.

[0270] In some embodiments, a TCR disclosed herein comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 95, 96, 97, or 98 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 95, 96, 97, or 98 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 91 or 92 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 91 or 92 with or without a signal peptide.

[0271] In some embodiments, a TCR beta chain construct of a TCR disclosed herein comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 103. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 20. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100%sequence identity to an amino acid sequence set forth in SEQ ID NO: 104 with or without a signal peptide. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 104 with or without a signal peptide.

[0272] In some embodiments, a TCR alpha chain construct of a TCR disclosed herein comprises a CDR1, CDR2, CDR3, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an aminoWSGR Docket No.50401-799.601 acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 99. In some embodiments, the TCR alpha chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 100 with or without a signal peptide. In some embodiments, the TCR alpha chain of a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 100 with or without a signal peptide.

[0273] In some embodiments, a TCR disclosed herein comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 105, 106, 107, or 108 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 105, 106, 107, or 108 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 101 or 102 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 101 or 102 with or without a signal peptide.

[0274] In some embodiments, a TCR beta chain construct of a TCR disclosed herein comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 179. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 20. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 180 with or without a signal peptide. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 180 with or without a signal peptide.

[0275] In some embodiments, a TCR alpha chain of a TCR disclosed herein comprises a CDR1, CDR2, CDR3, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an aminoWSGR Docket No.50401-799.601 acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 175. In some embodiments, the TCR alpha chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 176 with or without a signal peptide. In some embodiments, the TCR alpha chain of a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 176 with or without a signal peptide.

[0276] In some embodiments, a TCR disclosed herein comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 181, 182, 183, or 184 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 181, 182, 183, or 184 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 177 or 178 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 177 or 178 with or without a signal peptide.

[0277] In some embodiments, a TCR beta chain construct of a TCR disclosed herein comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 231. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 20. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 232 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 232 with or without a signal peptide.

[0278] In some embodiments, a TCR alpha chain construct of a TCR disclosed herein comprises a CDR1, CDR2, CDR3, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an aminoWSGR Docket No.50401-799.601 acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 227. In some embodiments, the TCR alpha chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 228 with or without a signal peptide. In some embodiments, the TCR alpha chain of a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 228 with or without a signal peptide.

[0279] In some embodiments, a TCR disclosed herein comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 233, 234, 235, or 236 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 233, 234, 235, or 236 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 229 or 230 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 229 or 230 with or without a signal peptide.

[0280] In some embodiments, a TCR beta chain construct of a TCR disclosed herein comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 247. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 20. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 248 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 248 with or without a signal peptide.

[0281] In some embodiments, a TCR alpha chain construct of a TCR disclosed herein comprises a CDR1, CDR2, CDR3, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an aminoWSGR Docket No.50401-799.601 acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 69. In some embodiments, the TCR alpha chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 70 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 70 with or without a signal peptide.

[0282] In some embodiments, a TCR disclosed herein comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 249, 250, 251, or 252 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 249, 250, 251, or 252 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 71 or 72 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 71 or 72 with or without a signal peptide.

[0283] In some embodiments, a TCR beta chain construct of a TCR disclosed herein comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 271. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 20. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 272 with or without a signal peptide. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 272 with or without a signal peptide.

[0284] In some embodiments, a TCR alpha chain construct of a TCR disclosed herein disclose herein comprises a CDR1, CDR2, CDR3, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequenceWSGR Docket No.50401-799.601 identity to an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 267. In some embodiments, the TCR alpha chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 268 with or without a signal peptide. In some embodiments, the TCR alpha chain of a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 268 with or without a signal peptide.

[0285] In some embodiments, a TCR disclosed herein comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 273, 274, 275, or 276 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 273, 274, 275, or 276 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 269 or 270 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 269 or 270 with or without a signal peptide.

[0286] In some embodiments, a TCR beta chain construct of a TCR disclosed herein comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 313. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 20. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 314 with or without a signal peptide. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 314 with or without a signal peptide.

[0287] In some embodiments, a TCR alpha chain construct of a TCR disclosed herein comprises a CDR1, CDR2, CDR3, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 307, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an aminoWSGR Docket No.50401-799.601 acid sequence set forth in SEQ ID NO: 308, and wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 309. In some embodiments, the TCR alpha chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 310 with or without a signal peptide. In some embodiments, the TCR alpha chain of a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 310 with or without a signal peptide.

[0288] In some embodiments, a TCR disclosed herein comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 315, 316, 317, or 318 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 315, 316, 317, or 318 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 311 or 312 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 311 or 312 with or without a signal peptide.

[0289] In some embodiments, a TCR beta chain construct of a TCR disclosed herein comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 319. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 20. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 320 with or without a signal peptide. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 320 with or without a signal peptide.

[0290] In some embodiments, a TCR alpha chain construct of a TCR disclosed herein comprises a CDR1, CDR2, CDR3, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an aminoWSGR Docket No.50401-799.601 acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 15. In some embodiments, the TCR alpha chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide. In some embodiments, the TCR alpha chain construct of a TCR disclosed herein disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide.

[0291] In some embodiments, a TCR disclosed herein comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 321, 322, 323, or 324 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 321, 322, 323, or 324 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 17 or 18 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 17 or 18 with or without a signal peptide.

[0292] In some embodiments, a TCR beta chain construct of a TCR disclosed herein comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 329. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 20. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 330 with or without a signal peptide. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 330 with or without a signal peptide.

[0293] In some embodiments, a TCR alpha chain construct of a TCR disclosed herein comprises a CDR1, CDR2, CDR3, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an aminoWSGR Docket No.50401-799.601 acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 325. In some embodiments, the TCR alpha chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 326 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 326 with or without a signal peptide.

[0294] In some embodiments, a TCR disclosed herein comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 331, 332, 333, or 334 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 331, 332, 333, or 334 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 327 or 328 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 327 or 328 with or without a signal peptide.

[0295] In some embodiments, a TCR beta chain construct of a TCR disclosed herein comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 363. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 20. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide.

[0296] In some embodiments, a TCR alpha chain construct of a TCR disclosed herein comprises a CDR1, CDR2, CDR3, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an aminoWSGR Docket No.50401-799.601 acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 359. In some embodiments, the TCR alpha chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide.

[0297] In some embodiments, a TCR disclosed herein comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 365, 366, 367, or 368 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 365, 366, 367, or 368 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 361 or 362 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 361 or 362 with or without a signal peptide.

[0298] In some embodiments, a TCR beta chain construct of a TCR disclosed herein comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 395. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 20. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 396 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 396 with or without a signal peptide.

[0299] In some embodiments, a TCR alpha chain construct of a TCR disclosed herein comprises a CDR1, CDR2, CDR3, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an aminoWSGR Docket No.50401-799.601 acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 391. In some embodiments, the TCR alpha chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 392 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 392 with or without a signal peptide.

[0300] In some embodiments, a TCR disclosed herein comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 397, 398, 399, or 400 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 397, 398, 399, or 400 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 393 or 394 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 393 or 394 with or without a signal peptide.

[0301] In some embodiments, a TCR beta chain construct of a TCR disclosed herein comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 417. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 20. In some embodiments, the TCR beta chain construct comprises disclosed herein a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 418 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 418 with or without a signal peptide.

[0302] In some embodiments, a TCR alpha chain construct of a TCR disclosed herein comprises a CDR1, CDR2, CDR3, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an aminoWSGR Docket No.50401-799.601 acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 413. In some embodiments, the TCR alpha chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 414 with or without a signal peptide. In some embodiments, the TCR alpha chain of a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 414 with or without a signal peptide.

[0303] In some embodiments, a TCR disclosed herein comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 419, 420, 421, or 422 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 419, 420, 421, or 422 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 415 or 416 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 415 or 416 with or without a signal peptide.

[0304] In some embodiments, a TCR beta chain construct of a TCR disclosed herein comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 423. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 20. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 424 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 424 with or without a signal peptide.

[0305] In some embodiments, a TCR alpha chain construct of a TCR disclosed herein comprises a CDR1, CDR2, CDR3, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an aminoWSGR Docket No.50401-799.601 acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 151. In some embodiments, the TCR alpha chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 152 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 152 with or without a signal peptide.

[0306] In some embodiments, a TCR disclosed herein comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 425, 426, 427, or 428 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 425, 426, 427, or 428 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 153 or 154 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 153 or 154 with or without a signal peptide.

[0307] In some embodiments, a TCR beta chain of a TCR disclosed herein comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 441. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 20. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 442 with or without a signal peptide. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 442 with or without a signal peptide.

[0308] In some embodiments, a TCR alpha chain of a TCR disclosed herein comprises a CDR1, CDR2, CDR3, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an aminoWSGR Docket No.50401-799.601 acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 15. In some embodiments, the TCR alpha chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide. In some embodiments, the TCR alpha chain of a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide.

[0309] In some embodiments, a TCR disclosed herein comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 443, 444, 445, or 446 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 443, 444, 445, or 446 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 17 or 18 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 17 or 18 with or without a signal peptide.

[0310] In some embodiments, a TCR beta chain of a TCR disclosed herein comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 483. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 20. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide. In some embodiments, the TCR beta chain of a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide.

[0311] In some embodiments, a TCR alpha chain construct of a TCR disclosed herein comprises a CDR1, CDR2, CDR3, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an aminoWSGR Docket No.50401-799.601 acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 479. In some embodiments, the TCR alpha chain construct of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide. In some embodiments, the TCR alpha chain construct of a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide.

[0312] In some embodiments, a TCR disclosed herein comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 485, 486, 487, or 488 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 485, 486, 487, or 488 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 481 or 482 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 481 or 482 with or without a signal peptide.

[0313] In some embodiments, a TCR beta chain construct a TCR disclosed herein comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 519. In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 20. In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 520 with or without a signal peptide. In some embodiments, the TCR beta chain construct a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 520 with or without a signal peptide.

[0314] In some embodiments, a TCR alpha chain construct of a TCR disclosed herein comprises a CDR1, CDR2, CDR3, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, atWSGR Docket No.50401-799.601 least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 295. In some embodiments, the TCR alpha chain construct of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 296 with or without a signal peptide. In some embodiments, the TCR alpha chain construct of a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 296 with or without a signal peptide.

[0315] In some embodiments, a TCR disclosed herein comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 521, 522, 523, or 524 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 521, 522, 523, or 524 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 297 or 298 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 297 or 298 with or without a signal peptide.

[0316] In some embodiments, a TCR beta chain construct of a TCR disclosed herein comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 543. In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 20. In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 544 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 544 with or without a signal peptide.

[0317] In some embodiments, a TCR alpha chain construct of a TCR disclosed herein comprises a CDR1, CDR2, CDR3, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, atWSGR Docket No.50401-799.601 least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 539. In some embodiments, the TCR alpha chain construct of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 540 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 540 with or without a signal peptide.

[0318] In some embodiments, a TCR disclosed herein comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 545, 546, 547, or 548 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 545, 546, 547, or 548 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 541 or 542 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 541 or 542 with or without a signal peptide.

[0319] In some embodiments, a TCR beta chain construct of a TCR disclosed herein comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 563. In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 20. In some embodiments, the TCR beta chain construct comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 564 with or without a signal peptide. In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 564 with or without a signal peptide.

[0320] In some embodiments, a TCR alpha chain construct of a TCR disclosed herein comprises a CDR1, CDR2, CDR3, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, atWSGR Docket No.50401-799.601 least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 559. In some embodiments, the TCR alpha chain construct of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 560 with or without a signal peptide. In some embodiments, the TCR alpha chain construct of a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 560 with or without a signal peptide.

[0321] In some embodiments, a TCR disclosed herein comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 565, 566, 567, or 568 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 565, 566, 567, or 568 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 561 or 562 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 561 or 562 with or without a signal peptide.

[0322] In some embodiments, a TCR beta chain construct of a TCR disclosed herein comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 585. In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 20. In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 586 with or without a signal peptide. In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 586 with or without a signal peptide.

[0323] In some embodiments, a TCR alpha chain construct of a TCR disclosed herein comprises a CDR1, CDR2, CDR3, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequenceWSGR Docket No.50401-799.601 set forth in SEQ ID NO: 1, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 581. In some embodiments, the TCR alpha chain construct of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 582 with or without a signal peptide. In some embodiments, the TCR alpha chain construct of a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 582 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 582 with or without a signal peptide.

[0324] In some embodiments, a TCR disclosed herein comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 587, 588, 589, or 590 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 587, 588, 589, or 590 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 583 or 584 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 583 or 584 with or without a signal peptide.

[0325] In some embodiments, a TCR beta chain construct of a TCR disclosed herein comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 591. In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 20. In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 592 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 592 with or without a signal peptide.WSGR Docket No.50401-799.601

[0326] In some embodiments, a TCR alpha chain construct of a TCR disclosed herein comprises a CDR1, CDR2, CDR3, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 119. In some embodiments, the TCR alpha chain construct of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 120 with or without a signal peptide. In some embodiments, the TCR alpha chain construct of a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 120 with or without a signal peptide.

[0327] In some embodiments, a TCR disclosed herein comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 593, 594, 595, or 596 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 593, 594, 595, or 596 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 121 or 122 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 121 or 122 with or without a signal peptide.

[0328] In some embodiments, a TCR beta chain construct of a TCR disclosed herein comprises a CDR3, wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 597. In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 19. In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence of SEQ ID NO: 20.

[0329] In some embodiments, the TCR beta chain construct of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 598 with or without a signal peptide. In some embodiments, the TCR beta chain constructWSGR Docket No.50401-799.601 comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 598 with or without a signal peptide.

[0330] In some embodiments, a TCR alpha chain construct of a TCR disclosed herein comprises a CDR1, CDR2, CDR3, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 15. In some embodiments, the TCR alpha chain construct of a TCR disclosed herein comprises a variable region having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide. In some embodiments, the TCR alpha chain construct of a TCR disclosed herein comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide.

[0331] In some embodiments, a TCR disclosed herein comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 599, 600, 601, or 602 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 599, 600, 601, or 602 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 17 or 18 with or without a signal peptide, or an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% identical to SEQ ID NOs: 17 or 18 with or without a signal peptide.

[0332] In some aspects, provided herein is a recombinant nucleic acid comprising a sequence encoding a T cell receptor (TCR) comprising a TCR beta chain construct and a TCR alpha chain construct, wherein the TCR binds to a mutated epitope from human RAS in complex with a human MHC encoded by an HLA- C03:03 allele and a human MHC encoded by an HLA-C03:04 allele, wherein the mutated epitope from human RAS is characterized by a G12V mutation, wherein: (i) each of (a) the CDR1 of the TCR alpha chain construct, (b) the CDR2 of the TCR alpha chain construct, and (c) at least the first four amino acids of the first five N-terminal amino acids of the CDR3 of the TCR alpha chain construct are encoded by the 3’ terminal sequence of the human TRAV4*01 allele; and (ii) each of (a) the CDR1 of the TCR beta chain construct, (b) the CDR2 of the TCR beta chain construct, and (c) at least the first four amino acids of the first five N-terminal amino acids of the CDR3 of the TCR beta chain construct are encoded by the 3’ terminal sequence of a TRBV allele selected from the group consisting of TRBV2*01, TRBV3-1*01, TRBV4-3*01, TRBV5-6*01, TRBV5-8*01, TRBV6-1*01, TRBV6-2*01, TRBV6-5*01, TRBV7-9*03, TRBV9*01, TRBV11-1*01, TRBV12-3*01, TRBV12-4*01, TRBV13*01, TRBV14*01, TRBV15*02,WSGR Docket No.50401-799.601 TRBV18*01, TRBV19*01, TRBV20-1*02, TRBV24-1*01 and TRBV28*01; with the proviso that: when the TRBV allele is TRBV28*01 the CDR3 of the TCR beta chain construct is not CASSPTRLGYNEQFF, does not comprise a sequence encoded by the TRBJ2-1*01 allele, or does not comprise an N-terminal sequence of CASSP, when the TRBV allele is TRBV5-6*01 the CDR3 of the TCR beta chain construct is not CASSLPRMGSDTEAFF or CASSLRTGEAFF, or does not comprise a sequence encoded by the TRBJ1-1*01 allele, and when the TRBV allele is TRBV19*01 the CDR3 of the TCR beta chain construct is not CASSIDYRGIGETQYF, or does not comprise a sequence encoded by the TRBJ2-5*01 allele, or does not comprise an N-terminal sequence of CASSI. In some embodiments, the mutated epitope comprises an amino acid sequence set forth in SEQ ID NOs: 633 or 634. In some embodiments, the TCR binds to (i) the mutated epitope from human RAS in complex with the human MHC encoded by the HLA-C03:03 allele with a KD of at most 500 nM, at most 250 nM, at most 50 nM, at most 25 nM, at most 10 nM, or at most 5 nM; and / or (ii) the mutated epitope from human RAS in complex with the human MHC encoded by the HLA-C03:04 allele with a KD of at most 500 nM, at most 250 nM, at most 50 nM, at most 25 nM, at most 10 nM, or at most 5 nM. In some embodiments, the N-terminus of the CDR3 of the TCR alpha chain construct comprises the 5 amino acids encoded by 3’ terminal sequence of the TRAV4*01 allele. In some embodiments, the N-terminus of the CDR3 of the TCR alpha chain construct comprises the first 4 amino acids of the last 5 amino acids encoded by 3’ terminal sequence of the TRAV4*01 allele. In some embodiments, the N-terminus of the CDR3 of the TCR alpha chain construct comprises the sequence of CLVG. In some embodiments, the N-terminus of the CDR3 of the TCR alpha chain construct comprises the sequence of CLVGD, CLVGDM, or CLVGDMD. In some embodiments, the at least the first four amino acids of the first five N-terminal amino acids of the CDR3 of the TCR beta chain construct are encoded by the 3’ terminal sequence of TRBV6-5*01. In some embodiments, the N-terminus of the CDR3 of the TCR beta chain construct comprises the 5 amino acids encoded by 3’ terminal sequence of the TRBV5-6*01 allele. In some embodiments, the N-terminus of the CDR3 of the TCR beta chain construct comprises the first 4 amino acids of the last 5 amino acids encoded by 3’ terminal sequence of the TRBV5- 6*01 allele. In some embodiments, the N-terminus of the CDR3 of the TCR beta chain construct comprises the amino acid sequence CASS. In some embodiments, the N-terminus of the CDR3 of the TCR beta chain construct comprises the amino acid sequence CASSL.

[0333] In some aspects, provided herein is a recombinant nucleic acid encoding a TCR comprising a TCR beta chain construct comprising a CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 363. In some embodiments, the TCR beta chain construct further comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 19. In some embodiments, the TCR beta chain construct further comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acidWSGR Docket No.50401-799.601 sequence set forth in SEQ ID NO: 20. In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide. In some embodiments, the recombinant nucleic acid further comprises a TCR alpha chain construct having a CDR1, a CDR2, and a CDR3, wherein, the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 1; the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 2; and, the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 359. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide. In some embodiments, the TCR comprises: (a) a beta chain has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NOs: 365, 366, 367, or 368 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 365, 366, 367, or 368 with or without a signal peptide, (b) an alpha chain has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NOs: 361 or 362 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 361 or 362 with or without a signal peptide.

[0334] In some aspects, provided herein is a recombinant nucleic acid encoding a T cell receptor (TCR) comprising a TCR beta chain construct comprising a CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 483. In some embodiments, the TCR beta chain construct further comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, atWSGR Docket No.50401-799.601 least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 19. In some embodiments, the TCR beta chain construct further comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 20. In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide. In some embodiments, the recombinant nucleic acid further comprises a TCR alpha chain construct having a CDR1, a CDR2, and a CDR3, wherein, the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 1; the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 2; and, the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 479. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide. In some embodiments, the TCR comprises: (a) a beta chain has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NOs: 485, 486, 487, or 488 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 485, 486, 487, or 488 with or without a signal peptide, (b) an alpha chain has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NOs: 481 or 482 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 481 or 482 with or without a signal peptide.WSGR Docket No.50401-799.601

[0335] In some aspects, provided herein is a recombinant nucleic acid encoding a T cell receptor (TCR) comprising a TCR beta chain construct comprising a CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 569. In some embodiments, the TCR beta chain construct further comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 287. In some embodiments, the TCR beta chain construct further comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 288. In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 570 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 570 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 570 with or without a signal peptide. In some embodiments, the recombinant nucleic acid further comprising a TCR alpha chain construct having a CDR1, a CDR2, and a CDR3, wherein, the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 1; the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 2; and, the CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 185. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 186 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 186 with or without a signal peptide. In some embodiments, the TCR alpha chain construct comprises a variable region has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 186 with or without a signal peptide. In some embodiments, the TCR comprises: (a) a beta chain has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NOs: 571, 572, 573, or 574 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 571, 572, 573, or 574 with or without a signal peptide, (b) an alpha chain has at least 60%,WSGR Docket No.50401-799.601 at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NOs: 187 or 188 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 187 or 188 with or without a signal peptide.

[0336] In some aspects, provided herein is a recombinant nucleic acid encoding a T cell receptor (TCR) comprising a TCR beta chain construct comprising a CDR3 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 638. In some embodiments, the TCR beta chain construct further comprises a CDR1, wherein the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 19. In some embodiments, the TCR beta chain construct further comprises a CDR2, wherein the CDR2 has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 20. In some embodiments, the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 639 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region having at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 639 with or without a signal peptide. In some embodiments, the TCR beta chain construct comprises a variable region has at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 99%, or 100% sequence identity to an amino acid sequence set forth in SEQ ID NO: 639 with or without a signal peptide. In some embodiments, the recombinant nucleic acid further comprising a TCR alpha chain construct having a CDR1, a CDR2, and a CDR3, wherein, the CDR1 has at least 60%, at least 65%, at least 70%, at least 75%, at le...

Claims

WSGR Docket No.50401-799.601 CLAIMS What is claimed is:

1. A recombinant nucleic acid comprising a sequence encoding a T cell receptor (TCR) comprising a TCR beta chain construct and a TCR alpha chain construct, wherein the TCR binds to a mutated epitope from human RAS in complex with a human MHC encoded by an HLA-C03:03 allele and a human MHC encoded by an HLA-C03:04 allele, wherein the mutated epitope from human RAS is characterized by a G12V mutation, wherein the TCR beta chain construct comprises a complementarity determining region 3 (CDR3), wherein the N-terminus of the CDR3 of the TCR beta chain construct comprises at least four amino acids encoded by the 3’ terminal sequence of the TRBV5-6*01 allele, and wherein the CDR3 of the TCR beta chain construct does not comprise a CDR3 sequence of CASSLPRMGSDTEAFF (SEQ ID NO: 83), CASSPTRLGYNEQFF (SEQ ID NO: 135), CASSLRTGEAFF (SEQ ID NO: 179) or CASSIDYRGIGETQYF (SEQ ID NO: 191).

2. The recombinant nucleic acid of claim 1, wherein the N-terminus of the CDR3 comprises the 5 amino acids encoded by 3’ terminal sequence of the TRBV5-6*01 allele.

3. The recombinant nucleic acid of claim 1 or 2, wherein the N-terminus of the CDR3 comprises the first 4 amino acids of the last 5 amino acids encoded by 3’ terminal sequence of the TRBV5- 6*01 allele.

4. The recombinant nucleic acid of any one of claims 1-3, wherein the N-terminus of the CDR3 of the TCR beta chain construct comprises the amino acid sequence CASS.

5. The recombinant nucleic acid of any one of claims 1-4, wherein the N-terminus of the CDR3 of the TCR beta chain construct comprises the amino acid sequence CASSL.

6. The recombinant nucleic acid of any one of claims 1-5, wherein the TCR beta chain construct comprises a complementarity determining region 1 (CDR1), wherein the CDR1 has an amino acid sequence of SEQ ID NO:

19.

7. The recombinant nucleic acid of any one of claims 1-6, wherein the TCR beta chain construct comprises a complementarity determining region 2 (CDR2), wherein the CDR2 has an amino acid sequence of SEQ ID NO:

20.

8. The recombinant nucleic acid of any one of claims 1-7, wherein the N-terminus of the CDR3 of the TCR alpha chain construct comprises at least four amino acids encoded by the 3’ terminal sequence of the TRAV4*01 allele.

9. The recombinant nucleic acid of any one of claims 1-8, wherein the N-terminus of the CDR3 of the TCR alpha chain construct comprises the amino acid sequence CLVG.

10. The recombinant nucleic acid of any one of claims 1-9, wherein the TCR alpha chain construct comprises a CDR1 comprising an amino acid sequence of SEQ ID NO:

1.

11. The recombinant nucleic acid of any one of claims 1-10, wherein the TCR alpha chain construct comprises a CDR2 comprising an amino acid sequence of SEQ ID NO: 2.WSGR Docket No.50401-799.601 12. A recombinant nucleic acid comprising a sequence encoding a T cell receptor (TCR) comprising a TCR beta chain construct and a TCR alpha chain construct, wherein the TCR binds to a mutated epitope from human RAS in complex with a human MHC encoded by an HLA-C03:03 allele and a human MHC encoded by an HLA-C03:04 allele, wherein the mutated epitope from human RAS is characterized by a G12V mutation, wherein the TCR alpha chain construct comprises a complementarity determining region 3 (CDR3), wherein the N-terminus of the CDR3 of the TCR alpha chain construct comprises at least four amino acids encoded by the 3’ terminal sequence of the TRAV4*01 allele, and wherein the CDR3 of the TCR alpha chain construct does not comprise a CDR3 sequence CLVGDMDSGNTPLVF (SEQ ID NO: 185), CLVGDLDGQKLLF (SEQ ID NO: 175), CLVGDMDGGYQKVTF (SEQ ID NO: 131), or CLVGDGDNARLMF (SEQ ID NO: 79).

13. A recombinant nucleic acid comprising a sequence encoding a T cell receptor (TCR) comprising a TCR beta chain construct and a TCR alpha chain construct, wherein the TCR binds to a mutated epitope from human RAS in complex with a human MHC encoded by an HLA-C03:03 allele and a human MHC encoded by an HLA-C03:04 allele, wherein the mutated epitope from human RAS is characterized by a G12V mutation, wherein the TCR alpha chain construct comprises a complementarity determining region 3 (CDR3), wherein the N-terminus of the CDR3 of the TCR alpha chain construct comprises at least four amino acids encoded by the 3’ terminal sequence of the TRAV4*01 allele, and wherein a CDR3 of the TCR beta chain construct does not comprise a CDR3 sequence of CASSLPRMGSDTEAFF (SEQ ID NO: 83), CASSPTRLGYNEQFF (SEQ ID NO: 135), CASSLRTGEAFF (SEQ ID NO: 179) or CASSIDYRGIGETQYF (SEQ ID NO: 191).

14. The recombinant nucleic acid of claim 12 or 13, wherein the N-terminus of the CDR3 of the TCR alpha chain construct comprises the 5 amino acids encoded by 3’ terminal sequence of the TRAV4*01 allele.

15. The recombinant nucleic acid of any one of claims 12-14, wherein the N-terminus of the CDR3 of the TCR alpha chain construct comprises the first 4 amino acids of the last 5 amino acids encoded by 3’ terminal sequence of the TRAV4*01 allele.

16. The recombinant nucleic acid of any one of claims 12-15, wherein the N-terminus of the CDR3 of the TCR alpha chain construct comprises the sequence of CLVG.

17. The recombinant nucleic acid of any one of claims 12-16, wherein the N-terminus of the CDR3 of the TCR alpha chain construct comprises the sequence of CLVGD, CLVGDM, or CLVGDMD.

18. The recombinant nucleic acid of any one of claims 12-17, wherein the TCR alpha chain construct comprises a CDR1 comprising an amino acid sequence of SEQ ID NO:

1.

19. The recombinant nucleic acid of any one of claims 12-18, wherein the TCR alpha chain construct comprises a CDR2 comprising an amino acid sequence of SEQ ID NO: 2.WSGR Docket No.50401-799.601 20. The recombinant nucleic acid of any one of claims 12-19, wherein the N-terminus of a CDR3 of the TCR beta chain construct comprises at least four amino acids encoded by the 3’ terminal sequence of the TRBV5-6*01 allele.

21. The recombinant nucleic acid of any one of claims 12-20, wherein the N-terminus of a CDR3 of the TCR beta chain construct comprises the sequence of CASS.

22. The recombinant nucleic acid of any one of claims 12-21, wherein the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO:

19.

23. The recombinant nucleic acid of any one of claims 12-22, wherein the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO:

20.

24. The recombinant nucleic acid of any one of claims 12-23, wherein the TCR beta chain construct comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO:

363.

25. The recombinant nucleic acid of any one of claims 12-24, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide.

26. The recombinant nucleic acid of any one of claims 12-25, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide.

27. The recombinant nucleic acid of any one of claims 12-26, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide.

28. The recombinant nucleic acid of any one of claims 12-27, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide.

29. The recombinant nucleic acid of any one of claims 12-28, wherein the TCR alpha chain construct comprises a CDR3, wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO:

359.

30. The recombinant nucleic acid of any one of claims 12-29, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide.

31. The recombinant nucleic acid of any one of claims 12-30, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide.

32. The recombinant nucleic acid of any one of claims 12-31, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide.

33. The recombinant nucleic acid of any one of claims 12-32, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide.WSGR Docket No.50401-799.601 34. The recombinant nucleic acid of any one of claims 12-33, wherein the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 365, 366, 367, or 368 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 365, 366, 367, or 368 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 361 or 362 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 361 or 362 with or without a signal peptide.

35. The recombinant nucleic acid of any one of claims 12-23, wherein the TCR beta chain construct comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO:

483.

36. The recombinant nucleic acid of claim 35, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide.

37. The recombinant nucleic acid of claim 35 or 36, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide.

38. The recombinant nucleic acid of any one of claims 35-37, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide.

39. The recombinant nucleic acid of any one of claims 35-38, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide.

40. The recombinant nucleic acid of any one of claims 35-39, wherein the TCR alpha chain construct comprises a CDR3, wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO:

479.

41. The recombinant nucleic acid of any one of claims 35-40, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide.

42. The recombinant nucleic acid of any one of claims 35-41, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide.

43. The recombinant nucleic acid of any one of claims 35-42, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide.

44. The recombinant nucleic acid of any one of claims 35-43, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide.

45. The recombinant nucleic acid of any one of claims 35-44, wherein the TCR comprises:WSGR Docket No.50401-799.601 (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 485, 486, 487, or 488 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 485, 486, 487, or 488 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 481 or 482 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 481 or 482 with or without a signal peptide.

46. The recombinant nucleic acid of any one of claims 12-19, wherein the TCR beta chain construct comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO:

569.

47. The recombinant nucleic acid of claim 46, wherein the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO:

287.

48. The recombinant nucleic acid of claim 46 or 47, wherein the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO:

288.

49. The recombinant nucleic acid of any one of claims 46-48, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 570 with or without a signal peptide.

50. The recombinant nucleic acid of any one of claims 46-49, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 570 with or without a signal peptide.

51. The recombinant nucleic acid of any one of claims 46-50, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 570 with or without a signal peptide.

52. The recombinant nucleic acid of any one of claims 46-51, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 570 with or without a signal peptide.

53. The recombinant nucleic acid of any one of claims 46-52, wherein the TCR alpha chain construct comprises a CDR3, wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO:

185.

54. The recombinant nucleic acid of any one of claims 46-53, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 186 with or without a signal peptide.

55. The recombinant nucleic acid of any one of claims 46-54, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 186 with or without a signal peptide.

56. The recombinant nucleic acid of any one of claims 46-55, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 186 with or without a signal peptide.WSGR Docket No.50401-799.601 57. The recombinant nucleic acid of any one of claims 46-56, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 186 with or without a signal peptide.

58. The recombinant nucleic acid of any one of claims 46-57, wherein the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 571, 572, 573, or 574 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 571, 572, 573, or 574 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 187 or 188 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 187 or 188 with or without a signal peptide.

59. The recombinant nucleic acid of claim 12 or 13, wherein the TCR beta chain construct comprises a CDR3, wherein the CDR3 has an amino acid sequence selected from the group consisting of TCR beta chain CDR3 sequences listed in Table 1B.

60. The recombinant nucleic acid of claim 59, wherein the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence selected from the group consisting of TCR beta chain CDR1 sequences listed in Table 1B.

61. The recombinant nucleic acid of claim 59 or 60, wherein the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence selected from the group consisting of TCR beta chain CDR2 sequences listed in Table 1B.

62. The recombinant nucleic acid of any one of claims 59-61, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence selected from the group consisting of TCR beta chain variable region sequences listed in Table 1B.

63. The recombinant nucleic acid of any one of claims 59-62, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence selected from the group consisting of TCR beta chain variable region sequences listed in Table 1B.

64. The recombinant nucleic acid of any one of claims 59-63, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence selected from the group consisting of TCR beta chain variable region sequences listed in Table 1B.

65. The recombinant nucleic acid of any one of claims 59-64, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence selected from the group consisting of TCR beta chain variable region sequences listed in Table 1B.

66. The recombinant nucleic acid of any one of claims 59-65, wherein the TCR alpha chain construct comprises a CDR3, wherein the CDR3 has an amino acid sequence selected from the group consisting of TCR beta chain CDR3 sequences listed in Table 1B.WSGR Docket No.50401-799.601 67. The recombinant nucleic acid of any one of claims 59-66, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence selected from the group consisting of TCR alpha chain variable region sequences listed in Table 1B.

68. The recombinant nucleic acid of any one of claims 59-67, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence selected from the group consisting of TCR alpha chain variable region sequences listed in Table 1B.

69. The recombinant nucleic acid of any one of claims 59-68, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence selected from the group consisting of TCR alpha chain variable region sequences listed in Table 1B.

70. The recombinant nucleic acid of any one of claims 59-69, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence selected from the group consisting of TCR alpha chain variable region sequences listed in Table 1B.

71. The recombinant nucleic acid of any one of claims 59-70, wherein the TCR comprises: (a) a beta chain having an amino acid sequence selected from the group consisting of beta chain sequences listed in Table 1B, or an amino acid sequence that is at least 80% identical to an amino acid sequence selected from the group consisting of beta chain sequences listed in Table 1B, (b) an alpha chain having an amino acid sequence selected from the group consisting of alpha chain sequences listed in Table 1B, or an amino acid sequence that is at least 80% identical to an amino acid sequence selected from the group consisting of alpha chain sequences listed in Table 1B.

72. The recombinant nucleic acid of any one of claims 1-71, wherein the mutated epitope comprises an amino acid sequence set forth in SEQ ID NOs: 633 or 634.

73. The recombinant nucleic acid of any one of claims 1-72, wherein the TCR binds to (i) the mutated epitope from human RAS in complex with the human MHC encoded by the HLA- C03:03 allele with a KDof at most 500 nM, at most 250 nM, at most 50 nM, at most 25 nM, at most 10 nM, or at most 5 nM; and / or (ii) the mutated epitope from human RAS in complex with the human MHC encoded by the HLA-C03:04 allele with a KDof at most 500 nM, at most 250 nM, at most 50 nM, at most 25 nM, at most 10 nM, or at most 5 nM.

74. A recombinant nucleic acid encoding a T-cell receptor (TCR), wherein the TCR comprises a TCR alpha chain having a TCR alpha variable region, wherein the TCR alpha variable region is derived from a V gene segment of TRAV4*01 and a J gene segment selected from the group consisting of TRAJ10*01, TRAJ13*02, TRAJ16*01, TRAJ16*02, TRAJ21*01, TRAJ23*01, TRAJ26*01, TRAJ29*01, TRAJ3*01, TRAJ30*01, TRAJ31*01, TRAJ32*02, TRAJ33*01,WSGR Docket No.50401-799.601 TRAJ34*01, TRAJ36*01, TRAJ37*01, TRAJ37*02, TRAJ39*01, TRAJ4*01, TRAJ41*01, TRAJ42*01, TRAJ43*01, TRAJ47*01, TRAJ49*01, TRAJ5*01, TRAJ52*01, TRAJ53*01, TRAJ57*01, TRAJ8*01 and TRAJ9*01, wherein the TCR does not bind to a mutated epitope having a G12D mutation from human RAS in complex with a human MHC or the TCR binds to a mutated epitope having a G12D mutation from human RAS in complex with a human MHC with a dissociation constant (KD) of at least 1,000 nM, and wherein the TCR does not comprise a sequence listed in Table 2.

75. The recombinant nucleic acid of claim 74, wherein the TCR comprises a TCR beta chain having a TCR beta variable region, and wherein the TCR beta variable region is derived from a V gene segment of TRBV5-6*01 and a J gene segment selected from the group consisting of TRBJ2- 3*01, TRBJ1-6*02, TRBJ1-1*01, TRBJ1-3*01, TRBJ2-2*01, TRBJ1-5*01, TRBJ2-7*01, TRBJ2-1*01, TRBJ1-2*01, TRBJ1-4*01 and TRBJ2-5*01.

76. The recombinant nucleic acid of claim 74 or 75, wherein the TCR binds to a mutated epitope from human RAS in complex with a human MHC encoded by an HLA-C03:03 allele and a human MHC encoded by an HLA-C03:04 allele.

77. The recombinant nucleic acid of claim 76 , wherein the mutated epitope from human RAS is characterized by a G12V mutation.

78. The recombinant nucleic acid of claim 75, wherein the mutated epitope comprises an amino acid sequence set forth in SEQ ID NOs: 633 or 634.

79. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO:

21.

80. The recombinant nucleic acid of claim 79, wherein the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO:

19.

81. The recombinant nucleic acid of claim 79 or 80, wherein the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO:

20.

82. The recombinant nucleic acid of any one of claims 79-81, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 22 with or without a signal peptide.

83. The recombinant nucleic acid of any one of claims 79-82, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 22 with or without a signal peptide.

84. The recombinant nucleic acid of any one of claims 79-83, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 22 with or without a signal peptide.

85. The recombinant nucleic acid of any one of claims 79-84, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 22 with or without a signal peptide.WSGR Docket No.50401-799.601 86. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO:

15.

87. The recombinant nucleic acid of claim 86, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide.

88. The recombinant nucleic acid of claim 86 or 87, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide.

89. The recombinant nucleic acid of any one of claims 86-88, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide.

90. The recombinant nucleic acid of any one of claims 86-89, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide.

91. The recombinant nucleic acid of any one of claims 74-78, wherein the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 23, 24, 25, or 26 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 23, 24, 25, or 26 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 17 or 18 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 17 or 18 with or without a signal peptide.

92. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO:

63.

93. The recombinant nucleic acid of claim 92, wherein the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO:

19.

94. The recombinant nucleic acid of claim 92 or 93, wherein the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO:

20.

95. The recombinant nucleic acid of any one of claims 92-94, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 64 with or without a signal peptide.

96. The recombinant nucleic acid of any one of claims 92-95, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 64 with or without a signal peptide.WSGR Docket No.50401-799.601 97. The recombinant nucleic acid of any one of claims 92-96, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 64 with or without a signal peptide.

98. The recombinant nucleic acid of any one of claims 92-97, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 64 with or without a signal peptide.

99. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO:

59.

100. The recombinant nucleic acid of claim 99, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 60 with or without a signal peptide.

101. The recombinant nucleic acid of claim 99 or 100, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 60 with or without a signal peptide.

102. The recombinant nucleic acid of any one of claims 99-101, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 60 with or without a signal peptide.

103. The recombinant nucleic acid of any one of claims 99-102, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 60 with or without a signal peptide.

104. The recombinant nucleic acid of any one of claims 74-78, wherein the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 65, 66, 67, or 68 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 65, 66, 67, or 68 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 61 or 62 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 61 or 62 with or without a signal peptide.

105. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO:

73.

106. The recombinant nucleic acid of claim 105, wherein the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO:

19.

107. The recombinant nucleic acid of claim 105 or 106, wherein the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO: 20.WSGR Docket No.50401-799.601 108. The recombinant nucleic acid of any one of claims 105-107, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 74 with or without a signal peptide.

109. The recombinant nucleic acid of any one of claims 105-108, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 74 with or without a signal peptide.

110. The recombinant nucleic acid of any one of claims 105-109, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 74 with or without a signal peptide.

111. The recombinant nucleic acid of any one of claims 105-110, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 74 with or without a signal peptide.

112. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO:

69.

113. The recombinant nucleic acid of claim 112, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 70 with or without a signal peptide.

114. The recombinant nucleic acid of claim 112 or 113, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 70 with or without a signal peptide.

115. The recombinant nucleic acid of any one of claims 112-114, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 70 with or without a signal peptide.

116. The recombinant nucleic acid of any one of claims 112-115, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 70 with or without a signal peptide.

117. The recombinant nucleic acid of any one of claims 74-78, wherein the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 75, 76, 77, or 78 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 75, 76, 77, or 78 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 71 or 72 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 71 or 72 with or without a signal peptide.

118. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO: 83.WSGR Docket No.50401-799.601 119. The recombinant nucleic acid of claim 118, wherein the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO:

19.

120. The recombinant nucleic acid of claim 118 or 119, wherein the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO:

20.

121. The recombinant nucleic acid of any one of claims 118-120, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 84 with or without a signal peptide.

122. The recombinant nucleic acid of any one of claims 118-121, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 84 with or without a signal peptide.

123. The recombinant nucleic acid of any one of claims 118-122, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 84 with or without a signal peptide.

124. The recombinant nucleic acid of any one of claims 118-123, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 84 with or without a signal peptide.

125. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR alpha chain construct of a TCR the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO:

79.

126. The recombinant nucleic acid of claim 125, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 80 with or without a signal peptide.

127. The recombinant nucleic acid of claim 125 or 126, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 80 with or without a signal peptide.

128. The recombinant nucleic acid of any one of claims 125-127, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 80 with or without a signal peptide.

129. The recombinant nucleic acid of any one of claims 125-128, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 80 with or without a signal peptide.

130. The recombinant nucleic acid of any one of claims 74-78, wherein the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 85, 86, 87, or 88 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 85, 86, 87, or 88 with or without a signal peptide,WSGR Docket No.50401-799.601 (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 81 or 82 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 81 or 82 with or without a signal peptide.

131. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO:

93.

132. The recombinant nucleic acid of claim 131, wherein the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO:

19.

133. The recombinant nucleic acid of claim 131 or 132, wherein the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO:

20.

134. The recombinant nucleic acid of any one of claims 131-133, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 94 with or without a signal peptide.

135. The recombinant nucleic acid of any one of claims 131-134, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 94 with or without a signal peptide.

136. The recombinant nucleic acid of any one of claims 131-135, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 94 with or without a signal peptide.

137. The recombinant nucleic acid of any one of claims 131-136, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 94 with or without a signal peptide.

138. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO:

99.

139. The recombinant nucleic acid of claim 138, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 90 with or without a signal peptide.

140. The recombinant nucleic acid of claim 138 or 139, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 90 with or without a signal peptide.

141. The recombinant nucleic acid of any one of claims 138-140, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 90 with or without a signal peptide.

142. The recombinant nucleic acid of any one of claims 138-141, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 90 with or without a signal peptide.WSGR Docket No.50401-799.601 143. The recombinant nucleic acid of any one of claims 74-78, wherein the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 95, 96, 97, or 98 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 95, 96, 97, or 98 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 91 or 92 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 91 or 92 with or without a signal peptide.

144. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO:

103.

145. The recombinant nucleic acid of claim 144, wherein the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO:

19.

146. The recombinant nucleic acid of claim 144 or 145, wherein the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO:

20.

147. The recombinant nucleic acid of any one of claims 144-146, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 104 with or without a signal peptide.

148. The recombinant nucleic acid of any one of claims 144-147, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 104 with or without a signal peptide.

149. The recombinant nucleic acid of any one of claims 144-148, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 104 with or without a signal peptide.

150. The recombinant nucleic acid of any one of claims 144-149, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 104 with or without a signal peptide.

151. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO:

99.

152. The recombinant nucleic acid of claim 151, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 100 with or without a signal peptide.

153. The recombinant nucleic acid of claim 151 or 152, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 100 with or without a signal peptide.WSGR Docket No.50401-799.601 154. The recombinant nucleic acid of any one of claims 151-153, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 100 with or without a signal peptide.

155. The recombinant nucleic acid of any one of claims 151-154, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 100 with or without a signal peptide.

156. The recombinant nucleic acid of any one of claims 74-78, wherein the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 105, 106, 107, or 108 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 105, 106, 107, or 108 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 101 or 102 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 101 or 102 with or without a signal peptide.

157. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO:

179.

158. The recombinant nucleic acid of claim 157, wherein the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO:

19.

159. The recombinant nucleic acid of claim 157 or 158, wherein the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO:

20.

160. The recombinant nucleic acid of any one of claims 157-159, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 180 with or without a signal peptide.

161. The recombinant nucleic acid of any one of claims 157-160, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 180 with or without a signal peptide.

162. The recombinant nucleic acid of any one of claims 157-161, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 180 with or without a signal peptide.

163. The recombinant nucleic acid of any one of claims 157-162, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 180 with or without a signal peptide.

164. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 175.WSGR Docket No.50401-799.601 165. The recombinant nucleic acid of claim 164, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 176 with or without a signal peptide.

166. The recombinant nucleic acid of claim 164 or 165, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 176 with or without a signal peptide.

167. The recombinant nucleic acid of any one of claims 164-166, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 176 with or without a signal peptide.

168. The recombinant nucleic acid of any one of claims 164-167, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 176 with or without a signal peptide.

169. The recombinant nucleic acid of any one of claims 74-78, wherein the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 181, 182, 183, or 184 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 181, 182, 183, or 184 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 177 or 178 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 177 or 178 with or without a signal peptide.

170. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO:

231.

171. The recombinant nucleic acid of claim 170, wherein the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO:

19.

172. The recombinant nucleic acid of claim 170 or 171, wherein the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO:

20.

173. The recombinant nucleic acid of any one of claims 170-172, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 232 with or without a signal peptide.

174. The recombinant nucleic acid of any one of claims 170-173, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 232 with or without a signal peptide.

175. The recombinant nucleic acid of any one of claims 170-174, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 232 with or without a signal peptide.WSGR Docket No.50401-799.601 176. The recombinant nucleic acid of any one of claims 170-175, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 232 with or without a signal peptide.

177. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO:

227.

178. The recombinant nucleic acid of claim 177, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 228 with or without a signal peptide.

179. The recombinant nucleic acid of claim 177 or 178, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 228 with or without a signal peptide.

180. The recombinant nucleic acid of any one of claims 177-179, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 228 with or without a signal peptide.

181. The recombinant nucleic acid of any one of claims 177-180, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 228 with or without a signal peptide.

182. The recombinant nucleic acid of any one of claims 74-78, wherein the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 233, 234, 235, or 236 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 233, 234, 235, or 236 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 229 or 230 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 229 or 230 with or without a signal peptide.

183. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO:

247.

184. The recombinant nucleic acid of claim 183, wherein the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO:

19.

185. The recombinant nucleic acid of claim 183 or 184, wherein the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO:

20.

186. The recombinant nucleic acid of any one of claims 183-185, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 248 with or without a signal peptide.WSGR Docket No.50401-799.601 187. The recombinant nucleic acid of any one of claims 183-186, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 248 with or without a signal peptide.

188. The recombinant nucleic acid of any one of claims 183-187, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 248 with or without a signal peptide.

189. The recombinant nucleic acid of any one of claims 183-188, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 248 with or without a signal peptide.

190. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO:

69.

191. The recombinant nucleic acid of claim 190, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 70 with or without a signal peptide.

192. The recombinant nucleic acid of claim 190 or 191, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 70 with or without a signal peptide.

193. The recombinant nucleic acid of any one of claims 190-192, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 70 with or without a signal peptide.

194. The recombinant nucleic acid of any one of claims 190-193, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 70 with or without a signal peptide.

195. The recombinant nucleic acid of any one of claims 74-78, wherein the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 249, 250, 251, or 252 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 249, 250, 251, or 252 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 71 or 72 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 71 or 72 with or without a signal peptide.

196. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO:

271.

197. The recombinant nucleic acid of claim 196, wherein the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19.WSGR Docket No.50401-799.601 198. The recombinant nucleic acid of claim 196 or 197, wherein the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO:

20.

199. The recombinant nucleic acid of any one of claims 196-198, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 272 with or without a signal peptide.

200. The recombinant nucleic acid of any one of claims 196-199, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 272 with or without a signal peptide.

201. The recombinant nucleic acid of any one of claims 196-200, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 272 with or without a signal peptide.

202. The recombinant nucleic acid of any one of claims 196-201, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 272 with or without a signal peptide.

203. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO:

267.

204. The recombinant nucleic acid of claim 203, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 268 with or without a signal peptide.

205. The recombinant nucleic acid of claim 203 or 204, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 268 with or without a signal peptide.

206. The recombinant nucleic acid of any one of claims 203-205, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 268 with or without a signal peptide.

207. The recombinant nucleic acid of any one of claims 203-206, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 268 with or without a signal peptide.

208. The recombinant nucleic acid of any one of claims 74-78, wherein the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 273, 274, 275, or 276 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 273, 274, 275, or 276 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 269 or 270 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 269 or 270 with or without a signal peptide.WSGR Docket No.50401-799.601 209. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO:

313.

210. The recombinant nucleic acid of claim 209, wherein the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO:

19.

211. The recombinant nucleic acid of claim 209 or 210, wherein the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO:

20.

212. The recombinant nucleic acid of any one of claims 209-211, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 314 with or without a signal peptide.

213. The recombinant nucleic acid of any one of claims 209-212, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 314 with or without a signal peptide.

214. The recombinant nucleic acid of any one of claims 209-213, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 314 with or without a signal peptide.

215. The recombinant nucleic acid of any one of claims 209-214, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 314 with or without a signal peptide.

216. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 307, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 308, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO:

309.

217. The recombinant nucleic acid of claim 216, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 310 with or without a signal peptide.

218. The recombinant nucleic acid of claim 216 or 217, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 310 with or without a signal peptide.

219. The recombinant nucleic acid of any one of claims 216-218, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 310 with or without a signal peptide.

220. The recombinant nucleic acid of any one of claims 216-219, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 310 with or without a signal peptide.

221. The recombinant nucleic acid of any one of claims 74-78, wherein the TCR comprises:WSGR Docket No.50401-799.601 (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 315, 316, 317, or 318 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 315, 316, 317, or 318 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 311 or 312 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 311 or 312 with or without a signal peptide.

222. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO:

319.

223. The recombinant nucleic acid of claim 222, wherein the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO:

19.

224. The recombinant nucleic acid of claim 222 or 223, wherein the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO:

20.

225. The recombinant nucleic acid of any one of claims 222-224, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 320 with or without a signal peptide.

226. The recombinant nucleic acid of any one of claims 222-225, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 320 with or without a signal peptide.

227. The recombinant nucleic acid of any one of claims 222-226, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 320 with or without a signal peptide.

228. The recombinant nucleic acid of any one of claims 222-227, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 320 with or without a signal peptide.

229. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO:

15.

230. The recombinant nucleic acid of claim 229, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide.

231. The recombinant nucleic acid of claim 229 or 230, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide.WSGR Docket No.50401-799.601 232. The recombinant nucleic acid of any one of claims 229-231, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide.

233. The recombinant nucleic acid of any one of claims 229-232, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide.

234. The recombinant nucleic acid of any one of claims 74-78, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 321, 322, 323, or 324 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 321, 322, 323, or 324 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 17 or 18 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 17 or 18 with or without a signal peptide.

235. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO:

329.

236. The recombinant nucleic acid of claim 235, wherein the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO:

19.

237. The recombinant nucleic acid of claim 235 or 236, wherein the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO:

20.

238. The recombinant nucleic acid of any one of claims 235-237, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 330 with or without a signal peptide.

239. The recombinant nucleic acid of any one of claims 235-238, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 330 with or without a signal peptide.

240. The recombinant nucleic acid of any one of claims 235-239, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 330 with or without a signal peptide.

241. The recombinant nucleic acid of any one of claims 235-240, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 330 with or without a signal peptide.

242. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 325.WSGR Docket No.50401-799.601 243. The recombinant nucleic acid of claim 242, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 326 with or without a signal peptide.

244. The recombinant nucleic acid of claim 242 or 243, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 326 with or without a signal peptide.

245. The recombinant nucleic acid of any one of claims 242-244, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 326 with or without a signal peptide.

246. The recombinant nucleic acid of any one of claims 242-245, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 326 with or without a signal peptide.

247. The recombinant nucleic acid of any one of claims 74-78, wherein the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 331, 332, 333, or 334 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 331, 332, 333, or 334 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 327 or 328 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 327 or 328 with or without a signal peptide.

248. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR beta chain construct of a TCR the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO:

363.

249. The recombinant nucleic acid of claim 248, wherein the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO:

19.

250. The recombinant nucleic acid of claim 248 or 249, wherein the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO:

20.

251. The recombinant nucleic acid of any one of claims 248-250, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide.

252. The recombinant nucleic acid of any one of claims 248-251, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide.

253. The recombinant nucleic acid of any one of claims 248-252, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide.WSGR Docket No.50401-799.601 254. The recombinant nucleic acid of any one of claims 248-253, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide.

255. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO:

359.

256. The recombinant nucleic acid of claim 255, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide.

257. The recombinant nucleic acid of claim 255 or 256, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide.

258. The recombinant nucleic acid of any one of claims 255-257, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide.

259. The recombinant nucleic acid of any one of claims 255-258, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide.

260. The recombinant nucleic acid of any one of claims 74-78, wherein the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 365, 366, 367, or 368 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 365, 366, 367, or 368 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 361 or 362 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 361 or 362 with or without a signal peptide.

261. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO:

395.

262. The recombinant nucleic acid of claim 261, wherein the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO:

19.

263. The recombinant nucleic acid of claim 261 or 262, wherein the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO:

20.

264. The recombinant nucleic acid of any one of claims 261-263, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 396 with or without a signal peptide.WSGR Docket No.50401-799.601 265. The recombinant nucleic acid of any one of claims 261-264, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 396 with or without a signal peptide.

266. The recombinant nucleic acid of any one of claims 261-265, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 396 with or without a signal peptide.

267. The recombinant nucleic acid of any one of claims 261-266, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 396 with or without a signal peptide.

268. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO:

391.

269. The recombinant nucleic acid of claim 268, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 392 with or without a signal peptide.

270. The recombinant nucleic acid of claim 268 or 269, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 392 with or without a signal peptide.

271. The recombinant nucleic acid of any one of claims 268-270, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 392 with or without a signal peptide.

272. The recombinant nucleic acid of any one of claims 268-271, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 392 with or without a signal peptide.

273. The recombinant nucleic acid of any one of claims 74-78, wherein the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 397, 398, 399, or 400 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 397, 398, 399, or 400 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 393 or 394 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 393 or 394 with or without a signal peptide.

274. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO:

417.

275. The recombinant nucleic acid of claim 274, wherein the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19.WSGR Docket No.50401-799.601 276. The recombinant nucleic acid of claim 274 or 275, wherein the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO:

20.

277. The recombinant nucleic acid of any one of claims 274-276, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 418 with or without a signal peptide.

278. The recombinant nucleic acid of any one of claims 274-277, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 418 with or without a signal peptide.

279. The recombinant nucleic acid of any one of claims 274-278, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 418 with or without a signal peptide.

280. The recombinant nucleic acid of any one of claims 274-279, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 418 with or without a signal peptide.

281. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO:

413.

282. The recombinant nucleic acid of claim 281, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 414 with or without a signal peptide.

283. The recombinant nucleic acid of claim 281 or 282, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 414 with or without a signal peptide.

284. The recombinant nucleic acid of any one of claims 281-283, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 414 with or without a signal peptide.

285. The recombinant nucleic acid of any one of claims 281-284, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 414 with or without a signal peptide.

286. The recombinant nucleic acid of any one of claims 74-78, wherein the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 419, 420, 421, or 422 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 419, 420, 421, or 422 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 415 or 416 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 415 or 416 with or without a signal peptide.WSGR Docket No.50401-799.601 287. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO:

423.

288. The recombinant nucleic acid of claim 287, wherein the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO:

19.

289. The recombinant nucleic acid of claim 287 or 288, wherein the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO:

20.

290. The recombinant nucleic acid of any one of claims 287-289, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 424 with or without a signal peptide.

291. The recombinant nucleic acid of any one of claims 287-290, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 424 with or without a signal peptide.

292. The recombinant nucleic acid of any one of claims 287-291, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 424 with or without a signal peptide.

293. The recombinant nucleic acid of any one of claims 287-292, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 424 with or without a signal peptide.

294. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO:

151.

295. The recombinant nucleic acid of claim 294, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 152 with or without a signal peptide.

296. The recombinant nucleic acid of claim 294 or 295, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 152 with or without a signal peptide.

297. The recombinant nucleic acid of any one of claims 294-296, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 152 with or without a signal peptide.

298. The recombinant nucleic acid of any one of claims 294-297, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 152 with or without a signal peptide.

299. The recombinant nucleic acid of any one of claims 74-78, wherein the TCR comprises:WSGR Docket No.50401-799.601 (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 425, 426, 427, or 428 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 425, 426, 427, or 428 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 153 or 154 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 153 or 154 with or without a signal peptide.

300. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO:

441.

301. The recombinant nucleic acid of claim 300, wherein the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO:

19.

302. The recombinant nucleic acid of claim 300 or 301, wherein the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO:

20.

303. The recombinant nucleic acid of any one of claims 300-302, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 442 with or without a signal peptide.

304. The recombinant nucleic acid of any one of claims 300-303, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 442 with or without a signal peptide.

305. The recombinant nucleic acid of any one of claims 300-304, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 442 with or without a signal peptide.

306. The recombinant nucleic acid of any one of claims 300-305, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 442 with or without a signal peptide.

307. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR alpha chain construct of a TCR the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO:

15.

308. The recombinant nucleic acid of claim 307, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide.

309. The recombinant nucleic acid of claim 307 or 308, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide.WSGR Docket No.50401-799.601 310. The recombinant nucleic acid of any one of claims 307-309, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide.

311. The recombinant nucleic acid of any one of claims 307-310, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide.

312. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 443, 444, 445, or 446 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 443, 444, 445, or 446 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 17 or 18 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 17 or 18 with or without a signal peptide.

313. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR beta chain construct of a TCR the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO:

483.

314. The recombinant nucleic acid of claim 313, wherein the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO:

19.

315. The recombinant nucleic acid of claim 313 or 314, wherein the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO:

20.

316. The recombinant nucleic acid of any one of claims 313-315, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide.

317. The recombinant nucleic acid of any one of claims 313-316, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide.

318. The recombinant nucleic acid of any one of claims 313-317, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide.

319. The recombinant nucleic acid of any one of claims 313-318, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide.

320. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 479.WSGR Docket No.50401-799.601 321. The recombinant nucleic acid of claim 320, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide.

322. The recombinant nucleic acid of claim 320 or 321, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide.

323. The recombinant nucleic acid of any one of claims 320-322, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide.

324. The recombinant nucleic acid of any one of claims 320-323, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide.

325. The recombinant nucleic acid of any one of claims 74-78, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 485, 486, 487, or 488 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 485, 486, 487, or 488 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 481 or 482 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 481 or 482 with or without a signal peptide.

326. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO:

519.

327. The recombinant nucleic acid of claim 326, wherein the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO:

19.

328. The recombinant nucleic acid of claim 326 or 327, wherein the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO:

20.

329. The recombinant nucleic acid of any one of claims 326-328, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 520 with or without a signal peptide.

330. The recombinant nucleic acid of any one of claims 326-329, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 520 with or without a signal peptide.

331. The recombinant nucleic acid of any one of claims 326-330, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 520 with or without a signal peptide.WSGR Docket No.50401-799.601 332. The recombinant nucleic acid of any one of claims 326-331, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 520 with or without a signal peptide.

333. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO:

295.

334. The recombinant nucleic acid of claim 333, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 296 with or without a signal peptide.

335. The recombinant nucleic acid of claim 333 or 334, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 296 with or without a signal peptide.

336. The recombinant nucleic acid of any one of claims 333-335, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 296 with or without a signal peptide.

337. The recombinant nucleic acid of any one of claims 333-336, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 296 with or without a signal peptide.

338. The recombinant nucleic acid of any one of claims 74-78, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 521, 522, 523, or 524 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 521, 522, 523, or 524 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 297 or 298 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 297 or 298 with or without a signal peptide.

339. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO:

543.

340. The recombinant nucleic acid of claim 339, wherein the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO:

19.

341. The recombinant nucleic acid of claim 339 or 340, wherein the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO:

20.

342. The recombinant nucleic acid of any one of claims 339-341, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 544 with or without a signal peptide.WSGR Docket No.50401-799.601 343. The recombinant nucleic acid of any one of claims 339-342, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 544 with or without a signal peptide.

344. The recombinant nucleic acid of any one of claims 339-343, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 544 with or without a signal peptide.

345. The recombinant nucleic acid of any one of claims 339-344, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 544 with or without a signal peptide.

346. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO:

539.

347. The recombinant nucleic acid of claim 346, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 540 with or without a signal peptide.

348. The recombinant nucleic acid of claim 346 or 347, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 540 with or without a signal peptide.

349. The recombinant nucleic acid of any one of claims 346-348, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 540 with or without a signal peptide.

350. The recombinant nucleic acid of any one of claims 346-349, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 540 with or without a signal peptide.

351. The recombinant nucleic acid of any one of claims 74-78, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 545, 546, 547, or 548 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 545, 546, 547, or 548 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 541 or 542 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 541 or 542 with or without a signal peptide.

352. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO:

563.

353. The recombinant nucleic acid of claim 352, wherein the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO: 19.WSGR Docket No.50401-799.601 354. The recombinant nucleic acid of claim 352 or 353, wherein the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO:

20.

355. The recombinant nucleic acid of any one of claims 352-354, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 564 with or without a signal peptide.

356. The recombinant nucleic acid of any one of claims 352-355, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 564 with or without a signal peptide.

357. The recombinant nucleic acid of any one of claims 352-356, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 564 with or without a signal peptide.

358. The recombinant nucleic acid of any one of claims 352-357, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 564 with or without a signal peptide.

359. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO:

559.

360. The recombinant nucleic acid of claim 359, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 560 with or without a signal peptide.

361. The recombinant nucleic acid of claim 359 or 360, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 560 with or without a signal peptide.

362. The recombinant nucleic acid of any one of claims 359-361, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 560 with or without a signal peptide.

363. The recombinant nucleic acid of any one of claims 359-362, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 560 with or without a signal peptide.

364. The recombinant nucleic acid of any one of claims 74-78, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 565, 566, 567, or 568 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 565, 566, 567, or 568 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 561 or 562 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 561 or 562 with or without a signal peptide.WSGR Docket No.50401-799.601 365. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO:

585.

366. The recombinant nucleic acid of claim 365, wherein the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO:

19.

367. The recombinant nucleic acid of claim 365 or 366, wherein the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO:

20.

368. The recombinant nucleic acid of any one of claims 365-367, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 586 with or without a signal peptide.

369. The recombinant nucleic acid of any one of claims 365-368, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 586 with or without a signal peptide.

370. The recombinant nucleic acid of any one of claims 365-369, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 586 with or without a signal peptide.

371. The recombinant nucleic acid of any one of claims 365-370, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 586 with or without a signal peptide.

372. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO:

581.

373. The recombinant nucleic acid of claim 372, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 582 with or without a signal peptide.

374. The recombinant nucleic acid of claim 372 or 373, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 582 with or without a signal peptide.

375. The recombinant nucleic acid of any one of claims 372-374, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 582 with or without a signal peptide.

376. The recombinant nucleic acid of any one of claims 372-375, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 582 with or without a signal peptide.

377. The recombinant nucleic acid of any one of claims 74-78, the TCR comprises:WSGR Docket No.50401-799.601 (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 587, 588, 589, or 590 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 587, 588, 589, or 590 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 583 or 584 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 583 or 584 with or without a signal peptide.

378. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO:

591.

379. The recombinant nucleic acid of claim 378, wherein the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO:

19.

380. The recombinant nucleic acid of claim 378 or 379, wherein the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO:

20.

381. The recombinant nucleic acid of any one of claims 378-380, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 592 with or without a signal peptide.

382. The recombinant nucleic acid of any one of claims 378-381, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 592 with or without a signal peptide.

383. The recombinant nucleic acid of any one of claims 378-382, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 592 with or without a signal peptide.

384. The recombinant nucleic acid of any one of claims 378-383, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 592 with or without a signal peptide.

385. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO:

119.

386. The recombinant nucleic acid of claim 385, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 120 with or without a signal peptide.

387. The recombinant nucleic acid of claim 385 or 386, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 120 with or without a signal peptide.WSGR Docket No.50401-799.601 388. The recombinant nucleic acid of any one of claims 385-387, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 120 with or without a signal peptide.

389. The recombinant nucleic acid of any one of claims 385-388, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 120 with or without a signal peptide.

390. The recombinant nucleic acid of any one of claims 74-78, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 593, 594, 595, or 596 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 593, 594, 595, or 596 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 121 or 122 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 121 or 122 with or without a signal peptide.

391. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR beta chain construct of the TCR comprises a CDR3, wherein the CDR3 has an amino acid sequence of SEQ ID NO:

597.

392. The recombinant nucleic acid of claim 391, wherein the TCR beta chain construct comprises a CDR1, wherein the CDR1 has an amino acid sequence of SEQ ID NO:

19.

393. The recombinant nucleic acid of claim 391 or 392, wherein the TCR beta chain construct comprises a CDR2, wherein the CDR2 has an amino acid sequence of SEQ ID NO:

20.

394. The recombinant nucleic acid of any one of claims 391-393, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 598 with or without a signal peptide.

395. The recombinant nucleic acid of any one of claims 391-394, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 598 with or without a signal peptide.

396. The recombinant nucleic acid of any one of claims 391-395, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 598 with or without a signal peptide.

397. The recombinant nucleic acid of any one of claims 391-396, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 598 with or without a signal peptide.

398. The recombinant nucleic acid of any one of claims 74-78, wherein a TCR alpha chain construct of the TCR comprises a CDR1, CDR2, CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1, wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2, and wherein the CDR3 has an amino acid sequence set forth in SEQ ID NO: 15.WSGR Docket No.50401-799.601 399. The recombinant nucleic acid of claim 398, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide.

400. The recombinant nucleic acid of claim 398 or 399, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide.

401. The recombinant nucleic acid of any one of claims 398-400, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide.

402. The recombinant nucleic acid of any one of claims 398-401, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 16 with or without a signal peptide.

403. The recombinant nucleic acid of any one of claims 74-78, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 599, 600, 601, or 602 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 599, 600, 601, or 602 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 17 or 18 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 17 or 18 with or without a signal peptide.

404. The recombinant nucleic acid of any one of claims 74-403, wherein the TCR binds to (i) the mutated epitope from human RAS in complex with the human MHC encoded by the HLA- C03:03 allele with a KDof at most 500 nM, at most 250 nM, at most 50 nM, at most 25 nM, at most 10 nM, or at most 5 nM; and / or (ii) the mutated epitope from human RAS in complex with the human MHC encoded by the HLA-C03:04 allele with a KDof at most 500 nM, at most 250 nM, at most 50 nM, at most 25 nM, at most 10 nM, or at most 5 nM.

405. A recombinant nucleic acid comprising a sequence encoding a T cell receptor (TCR) comprising a TCR beta chain construct and a TCR alpha chain construct, wherein the TCR binds to a mutated epitope from human RAS in complex with a human MHC encoded by an HLA-C03:03 allele and a human MHC encoded by an HLA-C03:04 allele, wherein the mutated epitope from human RAS is characterized by a G12V mutation, wherein: (i) each of (a) the CDR1 of the TCR alpha chain construct, (b) the CDR2 of the TCR alpha chain construct, and (c) at least the first four amino acids of the first five N-terminal amino acids of the CDR3 of the TCR alpha chain construct are encoded by the 3’ terminal sequence of the human TRAV4*01 allele; and (ii) each of (a) the CDR1 of the TCR beta chain construct, (b) the CDR2 of the TCR beta chain construct, and (c) at least the first four amino acids of the first five N-terminal amino acids of the CDR3 of the TCR beta chain construct are encoded by the 3’ terminal sequence of aWSGR Docket No.50401-799.601 TRBV allele selected from the group consisting of TRBV2*01, TRBV3-1*01, TRBV4-3*01, TRBV5-6*01, TRBV5-8*01, TRBV6-1*01, TRBV6-2*01, TRBV6-5*01, TRBV7-9*03, TRBV9*01, TRBV11-1*01, TRBV12-3*01, TRBV12-4*01, TRBV13*01, TRBV14*01, TRBV15*02, TRBV18*01, TRBV19*01, TRBV20-1*02, TRBV24-1*01 and TRBV28*01; with the proviso that: when the TRBV allele is TRBV28*01 the CDR3 of the TCR beta chain construct is not CASSPTRLGYNEQFF, does not comprise a sequence encoded by the TRBJ2-1*01 allele, or does not comprise an N-terminal sequence of CASSP, when the TRBV allele is TRBV5-6*01 the CDR3 of the TCR beta chain construct is not CASSLPRMGSDTEAFF or CASSLRTGEAFF, or does not comprise a sequence encoded by the TRBJ1-1*01 allele, and when the TRBV allele is TRBV19*01 the CDR3 of the TCR beta chain construct is not CASSIDYRGIGETQYF, or does not comprise a sequence encoded by the TRBJ2-5*01 allele, or does not comprise an N-terminal sequence of CASSI.

406. The recombinant nucleic acid of claim 405, wherein the mutated epitope comprises an amino acid sequence set forth in SEQ ID NOs: 633 or 634.

407. The recombinant nucleic acid of claim 405 or 406, wherein the TCR binds to (i) the mutated epitope from human RAS in complex with the human MHC encoded by the HLA-C03:03 allele with a KDof at most 500 nM, at most 250 nM, at most 50 nM, at most 25 nM, at most 10 nM, or at most 5 nM; and / or (ii) the mutated epitope from human RAS in complex with the human MHC encoded by the HLA-C03:04 allele with a KDof at most 500 nM, at most 250 nM, at most 50 nM, at most 25 nM, at most 10 nM, or at most 5 nM.

408. The recombinant nucleic acid of any one of claims 405-407, wherein the N-terminus of the CDR3 of the TCR alpha chain construct comprises the 5 amino acids encoded by 3’ terminal sequence of the TRAV4*01 allele.

409. The recombinant nucleic acid of any one of claims 405-408, wherein the N-terminus of the CDR3 of the TCR alpha chain construct comprises the first 4 amino acids of the last 5 amino acids encoded by 3’ terminal sequence of the TRAV4*01 allele.

410. The recombinant nucleic acid of any one of claims 405-409, wherein the N-terminus of the CDR3 of the TCR alpha chain construct comprises the sequence of CLVG.

411. The recombinant nucleic acid of any one of claims 405-410, wherein the N-terminus of the CDR3 of the TCR alpha chain construct comprises the sequence of CLVGD, CLVGDM, or CLVGDMD.

412. The recombinant nucleic acid of any one of claims 405-411, wherein the at least the first four amino acids of the first five N-terminal amino acids of the CDR3 of the TCR beta chain construct are encoded by the 3’ terminal sequence of TRBV6-5*01.WSGR Docket No.50401-799.601 413. The recombinant nucleic acid of any one of claims 405-412, wherein the N-terminus of the CDR3 of the TCR beta chain construct comprises the 5 amino acids encoded by 3’ terminal sequence of the TRBV5-6*01 allele.

414. The recombinant nucleic acid of any one of claims 405-413, wherein the N-terminus of the CDR3 of the TCR beta chain construct comprises the first 4 amino acids of the last 5 amino acids encoded by 3’ terminal sequence of the TRBV5-6*01 allele.

415. The recombinant nucleic acid of any one of claims 405-414, wherein the N-terminus of the CDR3 of the TCR beta chain construct comprises the amino acid sequence CASS.

416. The recombinant nucleic acid of any one of claims 405-415, wherein the N-terminus of the CDR3 of the TCR beta chain construct comprises the amino acid sequence CASSL.

417. A recombinant nucleic acid encoding a T cell receptor (TCR) comprising a TCR beta chain construct comprising a complementarity determining region 3 (CDR3) having an amino acid sequence set forth in SEQ ID NO:

363.

418. The recombinant nucleic acid of claim 417, wherein the TCR beta chain construct further comprises a complementarity determining region 1 (CDR1), wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO:

19.

419. The recombinant nucleic acid of claim 417 or 418, wherein the TCR beta chain construct further comprises a complementarity determining region 2 (CDR2), wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO:

20.

420. The recombinant nucleic acid of any one of claims 417-419, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide.

421. The recombinant nucleic acid of any one of claims 417-420, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide.

422. The recombinant nucleic acid of any one of claims 417-421, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide.

423. The recombinant nucleic acid of any one of claims 417-422, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 364 with or without a signal peptide.

424. The recombinant nucleic acid of any one of claims 417-423, further comprising a TCR alpha chain construct having a CDR1, a CDR2, and a CDR3, wherein, the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1; the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2; and, the CDR3 has an amino acid sequence set forth in SEQ ID NO: 359.WSGR Docket No.50401-799.601 425. The recombinant nucleic acid of any one of claims 417-424, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide.

426. The recombinant nucleic acid of any one of claims 417-425, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide.

427. The recombinant nucleic acid of any one of claims 417-426, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide.

428. The recombinant nucleic acid of any one of claims 417-427, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 360 with or without a signal peptide.

429. The recombinant nucleic acid of any one of claims 417-428, wherein the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 365, 366, 367, or 368 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 365, 366, 367, or 368 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 361 or 362 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 361 or 362 with or without a signal peptide.

430. A recombinant nucleic acid encoding a T cell receptor (TCR) comprising a TCR beta chain construct comprising a complementarity determining region 3 (CDR3) having an amino acid sequence set forth in SEQ ID NO:

483.

431. The recombinant nucleic acid of claim 430, wherein the TCR beta chain construct further comprises a complementarity determining region 1 (CDR1), wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO:

19.

432. The recombinant nucleic acid of claim 430 or 431, wherein the TCR beta chain construct further comprises a complementarity determining region 2 (CDR2), wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO:

20.

433. The recombinant nucleic acid of any one of claims 430-432, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide.

434. The recombinant nucleic acid of any one of claims 430-433, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide.

435. The recombinant nucleic acid of any one of claims 430-434, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide.WSGR Docket No.50401-799.601 436. The recombinant nucleic acid of any one of claims 430-435, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 484 with or without a signal peptide.

437. The recombinant nucleic acid of any one of claims 430-436, further comprising a TCR alpha chain construct having a CDR1, a CDR2, and a CDR3, wherein, the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1; the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2; and, the CDR3 has an amino acid sequence set forth in SEQ ID NO:

479.

438. The recombinant nucleic acid of any one of claims 430-437, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide.

439. The recombinant nucleic acid of any one of claims 430-438, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide.

440. The recombinant nucleic acid of any one of claims 430-439, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide.

441. The recombinant nucleic acid of any one of claims 430-440, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 480 with or without a signal peptide.

442. The recombinant nucleic acid of any one of claims 430-441, wherein the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 485, 486, 487, or 488 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 485, 486, 487, or 488 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 481 or 482 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 481 or 482 with or without a signal peptide.

443. A recombinant nucleic acid encoding a T cell receptor (TCR) comprising a TCR beta chain construct comprising a complementarity determining region 3 (CDR3) having an amino acid sequence set forth in SEQ ID NO:

569.

444. The recombinant nucleic acid of claim 443, wherein the TCR beta chain construct further comprises a complementarity determining region 1 (CDR1), wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO:

287.

445. The recombinant nucleic acid of claim 443 or 444, wherein the TCR beta chain construct further comprises a complementarity determining region 2 (CDR2), wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO: 288.WSGR Docket No.50401-799.601 446. The recombinant nucleic acid of any one of claims 443-445, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 570 with or without a signal peptide.

447. The recombinant nucleic acid of any one of claims 443-446, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 570 with or without a signal peptide.

448. The recombinant nucleic acid of any one of claims 443-447, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 570 with or without a signal peptide.

449. The recombinant nucleic acid of any one of claims 443-448, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 570 with or without a signal peptide.

450. The recombinant nucleic acid of any one of claims 443-449, further comprising a TCR alpha chain construct having a CDR1, a CDR2, and a CDR3, wherein, the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1; the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2; and, the CDR3 has an amino acid sequence set forth in SEQ ID NO:

185.

451. The recombinant nucleic acid of any one of claims 443-450, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 186 with or without a signal peptide.

452. The recombinant nucleic acid of any one of claims 443-451, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 186 with or without a signal peptide.

453. The recombinant nucleic acid of any one of claims 443-452, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 186 with or without a signal peptide.

454. The recombinant nucleic acid of any one of claims 443-453, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 186 with or without a signal peptide.

455. The recombinant nucleic acid of any one of claims 443-454, wherein the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 571, 572, 573, or 574 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 571, 572, 573, or 574 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 187 or 188 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 187 or 188 with or without a signal peptide.WSGR Docket No.50401-799.601 456. A recombinant nucleic acid encoding a T cell receptor (TCR) comprising a TCR beta chain construct comprising a complementarity determining region 3 (CDR3) having an amino acid sequence set forth in SEQ ID NO:

638.

457. The recombinant nucleic acid of claim 456, wherein the TCR beta chain construct further comprises a complementarity determining region 1 (CDR1), wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO:

19.

458. The recombinant nucleic acid of claim 456 or 457, wherein the TCR beta chain construct further comprises a complementarity determining region 2 (CDR2), wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO:

20.

459. The recombinant nucleic acid of any one of claims 456-458, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 639 with or without a signal peptide.

460. The recombinant nucleic acid of any one of claims 456-459, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 639 with or without a signal peptide.

461. The recombinant nucleic acid of any one of claims 456-460, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 639 with or without a signal peptide.

462. The recombinant nucleic acid of any one of claims 456-461, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 639 with or without a signal peptide.

463. The recombinant nucleic acid of any one of claims 456-462, further comprising a TCR alpha chain construct having a CDR1, a CDR2, and a CDR3, wherein, the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1; the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2; and, the CDR3 has an amino acid sequence set forth in SEQ ID NO:

15.

464. The recombinant nucleic acid of any one of claims 456-463, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 635 with or without a signal peptide.

465. The recombinant nucleic acid of any one of claims 456-464, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 635 with or without a signal peptide.

466. The recombinant nucleic acid of any one of claims 456-465, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 635 with or without a signal peptide.WSGR Docket No.50401-799.601 467. The recombinant nucleic acid of any one of claims 456-466, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 635 with or without a signal peptide.

468. The recombinant nucleic acid of any one of claims 456-467, wherein the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 640, 641, 642, or 643 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 640, 641, 642, or 643 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 636 or 637 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 636 or 637 with or without a signal peptide.

469. A recombinant nucleic acid encoding a T cell receptor (TCR) comprising a TCR beta chain construct comprising a complementarity determining region 3 (CDR3) having an amino acid sequence set forth in SEQ ID NO:

648.

470. The recombinant nucleic acid of claim 469, wherein the TCR beta chain construct further comprises a complementarity determining region 1 (CDR1), wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO:

19.

471. The recombinant nucleic acid of claim 469 or 470, wherein the TCR beta chain construct further comprises a complementarity determining region 2 (CDR2), wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO:

20.

472. The recombinant nucleic acid of any one of claims 469-471, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 649 with or without a signal peptide.

473. The recombinant nucleic acid of any one of claims 469-472, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 649 with or without a signal peptide.

474. The recombinant nucleic acid of any one of claims 469-473, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 649 with or without a signal peptide.

475. The recombinant nucleic acid of any one of claims 469-474, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 649 with or without a signal peptide.

476. The recombinant nucleic acid of any one of claims 469-475, further comprising a TCR alpha chain construct having a CDR1, a CDR2, and a CDR3, wherein, the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1; the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2; and, the CDR3 has an amino acid sequence set forth in SEQ ID NO: 644.WSGR Docket No.50401-799.601 477. The recombinant nucleic acid of claim 476, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 645 with or without a signal peptide.

478. The recombinant nucleic acid of claim 476 or 477, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 645 with or without a signal peptide.

479. The recombinant nucleic acid of any one of claims 476-478, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 645 with or without a signal peptide.

480. The recombinant nucleic acid of any one of claims 476-479, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 645 with or without a signal peptide.

481. The recombinant nucleic acid of any one of claims 469-480, wherein the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 650, 651, 652, or 653 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 650, 651, 652, or 653 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 646 or 647 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 646 or 647 with or without a signal peptide.

482. A recombinant nucleic acid encoding a T cell receptor (TCR) comprising a TCR beta chain construct comprising a complementarity determining region 3 (CDR3) having an amino acid sequence set forth in SEQ ID NO:

658.

483. The recombinant nucleic acid of claim 482, wherein the TCR beta chain construct further comprises a complementarity determining region 1 (CDR1), wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO:

19.

484. The recombinant nucleic acid of claim 482 or 483, wherein the TCR beta chain construct further comprises a complementarity determining region 2 (CDR2), wherein the CDR2 has an amino acid sequence set forth in SEQ ID NO:

20.

485. The recombinant nucleic acid of any one of claims 482-484, wherein the TCR beta chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 659 with or without a signal peptide.

486. The recombinant nucleic acid of any one of claims 482-485, wherein the TCR beta chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 659 with or without a signal peptide.

487. The recombinant nucleic acid of any one of claims 482-486, wherein the TCR beta chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 659 with or without a signal peptide.WSGR Docket No.50401-799.601 488. The recombinant nucleic acid of any one of claims 482-487, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 659 with or without a signal peptide.

489. The recombinant nucleic acid of claim 488, further comprising a TCR alpha chain construct having a CDR1, a CDR2, and a CDR3, wherein, the CDR1 has an amino acid sequence set forth in SEQ ID NO: 1; the CDR2 has an amino acid sequence set forth in SEQ ID NO: 2; and, the CDR3 has an amino acid sequence set forth in SEQ ID NO:

654.

490. The recombinant nucleic acid of claim 488 or 489, wherein the TCR alpha chain construct comprises a variable region having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 655 with or without a signal peptide.

491. The recombinant nucleic acid of any one of claims 488-490, wherein the TCR alpha chain construct comprises a variable region having at least 90% sequence identity to an amino acid sequence set forth in SEQ ID NO: 655 with or without a signal peptide.

492. The recombinant nucleic acid of any one of claims 488-491, wherein the TCR alpha chain construct comprises a variable region having at least 95%, 96%, 97%, 98% or 99% sequence identity to an amino acid sequence set forth in SEQ ID NO: 655 with or without a signal peptide.

493. The recombinant nucleic acid of any one of claims 488-492, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence set forth in SEQ ID NO: 655 with or without a signal peptide.

494. The recombinant nucleic acid of any one of claims 482-493, wherein the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NOs: 660, 661, 662, or 663 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 660, 661, 662, or 663 with or without a signal peptide, (b) an alpha chain having an amino acid sequence set forth in SEQ ID NOs: 656 or 657 with or without a signal peptide, or an amino acid sequence that is at least 80% identical to SEQ ID NOs: 656 or 657 with or without a signal peptide.

495. The recombinant nucleic acid of any one of claims 417-494, wherein the TCR binds to an epitope from human RAS comprising a mutation G12V.

496. The recombinant nucleic acid of claim 495, wherein the epitope from human RAS comprising the mutation G12V is SEQ ID NOs: 633 or 634.

497. The recombinant nucleic acid of claim 495 or 496, wherein the TCR binds to a complex comprising (i) the epitope from human RAS comprising the mutation G12V and (ii) an MHC protein encoded by an HLA-C03:03 allele or HLA-C03:04 allele.

498. A TCR encoded by the recombinant nucleic acid of any one of the claims 1-497.

499. The TCR of claim 498, wherein the TCR is a soluble TCR.

500. A cell comprising the recombinant nucleic acid of any one of the claims 1-497.WSGR Docket No.50401-799.601 501. A cell comprising a TCR encoded by the recombinant nucleic acid of any one of the claims 1- 497.

502. The cell of claim 500 or 501, wherein the cell is a CD4+ T cell.

503. The cell of claim 500 or 501, wherein the cell is a CD8+ T cell.

504. The cell of claim 500 or 501, wherein the cell is isolated from a subject having a RAS mutation.

505. A pharmaceutical composition comprising: (a) the recombinant nucleic acid of any one of claims 1-73, and 405-497; and (b) a pharmaceutically acceptable excipient or diluent.

506. The pharmaceutical composition of claim 505, further comprising an immunomodulatory agent or an adjuvant.

507. The pharmaceutical composition of claim 506, wherein the adjuvant is poly I:C.

508. A pharmaceutical composition comprising: (a) the TCR of claim 498 or 499, or the cell of any one of claims 500-504; and (b) a pharmaceutically acceptable excipient or diluent.

509. The pharmaceutical composition of any one of claims 505-508, for use in treating an immune disease or cancer.

510. The pharmaceutical composition of claim 509, for use in treating an immune disease or cancer.

511. Use of the pharmaceutical composition of any one of claims 505-510, for treating an immune disease or cancer.

512. Use of the pharmaceutical composition of claim 511, for treating an immune disease or cancer.

513. A method of treating a subject having a disease or condition, comprising administering to the subject the pharmaceutical composition of any one of claims 505-510.

514. A method of treating a subject with cancer comprising administering to the subject the pharmaceutical composition of any one of claims 505-510.

515. A method of identifying a subject with cancer as a candidate for a therapeutic, wherein the method comprising determining the subject as a subject that expresses a protein encoded by an HLA-C03:03 allele or an HLA-C03:04 allele, wherein the therapeutic is the pharmaceutical composition selected from any one of claims 505-510.

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