Antigen binding proteins targeting common antigens

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By designing antigen-binding proteins that specifically bind to HLA class I molecules, the problem of low targeting efficiency of tumor-associated antigens in existing technologies has been solved, achieving more efficient tumor cell-specific binding and enhancing the efficacy of immunotherapy.

CN121591899APending Publication Date: 2026-03-03GRITSTONE BIO INC

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Patent Information

Application Number: CN202511451743.5
Authority / Receiving Office: CN · China
Patent Type: Applications(China)
Current Assignee / Owner
Priority Date: 2019-07-02
Filing Date: 2019-08-16
Publication Date: 2026-03-03

Application Information

Patent Timeline

02 Jul 2019

Priority

16 Aug 2019

Application

CN202511451743.5

03 Mar 2026

Publication

CN121591899A

IPC: C07K16/28; C07K16/30

CPC: C07K16/2833; C07K16/30; C07K2317/34; C07K2317/32; C07K2317/565; C40B40/08; C40B40/10; C12N15/1037

Inventors: K·朱斯; G·J·A·雷尼

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Peptide libraries Tumor rejection antigen precursors

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Binding peptide Antigen binding

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AI Technical Summary

Technical Problem

Existing technologies have difficulty effectively targeting tumor-associated antigens, resulting in low efficiency of specific binding of immunotherapy agents to tumor cells.

Method used

An antigen-binding protein (ABP) that specifically binds to human leukocyte antigen (HLA) peptide targets is provided. This ABP is capable of binding to specific regions of HLA class I molecules, including specific locations of HLA-restricted peptides EVDPIGHVY or NTDNNLAVY. The binding site includes a peptide-binding groove of the α1/α2 heterodimer portion and contains specific CDR-H3 and CDR-L3 domains.

Benefits of technology

This improved the specific binding ability of immunotherapy reagents to tumor cells, thus enhancing the efficacy of immunotherapy.

✦ Generated by Eureka AI based on patent content.

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Abstract

Provided herein are HLA-peptide targets and antigen binding proteins that bind to the HLA-peptide targets. Also disclosed are methods for identifying HLA-peptide targets and identifying one or more antigen binding proteins that bind to a given HLA-peptide target.

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Description

[0001] This application is a divisional application of Chinese Patent Application No. 201980060989.6, filed on August 16, 2019, entitled "Antigen-binding protein targeting common antigens". Cross-references

[0002] This application claims the benefits of U.S. Provisional Application No. 62 / 719,565, filed August 17, 2018; U.S. Provisional Application No. 62 / 808,775, filed February 21, 2019; and U.S. Provisional Application No. 62 / 869,923, filed July 2, 2019, which are incorporated herein by reference in their entirety. Related applications

[0003] This application relates to PCT / US2018 / 046997, filed August 17, 2018, and PCT / US2018 / 06793, filed December 28, 2018, which are incorporated herein by reference in their entirety.

[0004] sequence list This application includes a sequence list submitted electronically in ASCII format, which is hereby incorporated in its entirety by reference. The ASCII copy was created on September 30, 2019, named GSO-021WO_SL.txt, and has a size of 362,045 bytes. Background Technology

[0005] The immune system employs two types of adaptive immune responses to provide antigen-specific protection against pathogens: humoral immune responses and cellular immune responses, which specifically recognize pathogen antigens through B lymphocytes and T lymphocytes, respectively.

[0006] As antigen-specific effectors of cellular immunity, T lymphocytes play a central role in the body's defense against diseases mediated by intracellular pathogens (such as viruses, intracellular bacteria, mycoplasma, and intracellular parasites) and in combating cancer cells through direct cytolysis of affected cells. The specificity of the T lymphocyte response is conferred and activated by the binding of the T cell receptor (TCR) to MHC molecules (the major histocompatibility complex) on the surface of affected cells. The T cell receptor is an antigen-specific receptor cloned on individual T lymphocytes, whose antigen-specific repertoire is generated via somatic gene rearrangement mechanisms, similar to those involved in the production of antibody gene repertoires. The T cell receptor comprises a heterodimer of transmembrane molecules, primarily consisting of α-β polypeptide dimers and a smaller subset of γ-δ polypeptide dimers. The T lymphocyte receptor subunit contains variable and constant regions similar to immunoglobulins in its extracellular domain, a short hinge region with cysteine residues promoting α and β chain pairing, a transmembrane region, and a short cytoplasmic region. TCR-triggered signal transduction is indirectly mediated by CD3-ζ, which is a related multi-subunit complex containing signal transduction subunits.

[0007] T lymphocyte receptors typically do not recognize natural antigens, but rather complexes displayed on the cell surface, including intracellularly processed antigen fragments that associate with the major histocompatibility complex (MHC) used to present peptide antigens. The MHC gene exhibits high polymorphism across species populations, comprising multiple common alleles for each individual gene. In humans, the MHC is known as human leukocyte antigen (HLA).

[0008] Major histocompatibility complex (MHC) class I molecules are expressed on the surface of almost all nucleated cells in vivo and are dimer molecules containing a transmembrane heavy chain (including a peptide antigen-binding groove) and a smaller extracellular chain called β2-microglobulin. The peptides presented by MHC class I molecules are derived from the degradation of cytoplasmic proteins by the proteasome, a multi-subunit structure in the cytoplasm (Niedermann G., 2002. Curr Top Microbiol Immunol. 268:91-136; for the processing of bacterial antigens, see Wick MJ and Ljunggren H G., 1999. Immunol Rev. 172:153-62). The cleaved peptide is transported to the lumen of the endoplasmic reticulum (ER) via antigen-processing-associated transporters (TAPs), where it binds to the groove of the assembled class I molecule. The resulting MHC / peptide complex is then transported to the cell membrane, enabling antigen presentation to T lymphocytes (Yewdell J W., 2001. Trends Cell Biol. 11:294-7; Yewdell JW and Bennink J R., 2001. Curr Opin Immunol. 13:13-8). Alternatively, the cleaved peptide can be loaded onto MHC class I molecules in a TAP-independent manner and can also present extracellular proteins via cross-presentation. Thus, once the structure (peptide sequence and MHC isotype) of the complex is determined, a given MHC / peptide complex presents a novel protein structure on the cell surface that can be targeted by novel antigen-binding proteins (e.g., antibodies or TCRs).

[0009] Tumor cells can express antigens and display these antigens on their surface. These tumor-associated antigens can be used to develop novel immunotherapeutic agents that specifically target tumor cells. For example, tumor-associated antigens can be used to identify therapeutic antigen-binding proteins, such as TCRs, antibodies, or antigen-binding fragments. These tumor-associated antigens can also be used in pharmaceutical compositions, such as vaccines. Summary of the Invention

[0010] This article provides an isolated antigen-binding protein (ABP) that specifically binds to a human leukocyte antigen (HLA) peptide target, wherein the HLA peptide target comprises an HLA-restricted peptide complexed with an HLA class I molecule, wherein the HLA-restricted peptide is located in the peptide-binding groove of the α1 / α2 heterodimer portion of the HLA class I molecule, wherein the HLA class I molecule is HLA subtype B. 35:01 (Reference sequence: MGSHSMRYFYTAMSRPGRGEPRFIAVGYVDDTQFVRFDSDAASPRTEPRAPWIEQEGPEYWDRNTQIFKTNTQTYRESLRNLRGYYNQSEAGSHIIQRMYGCDLGPDGRLLRGHDQSAYDGKDYIALNEDLSSWTAADTAAQITQRKWEAARVAEQLRAYLEGLCVEWLRRYLENGKETLQRADPPKTHVTHHPVSDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDRTFQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLR (SEQ ID NO: 1)), and the HLA-restricted peptide comprises the sequence EVDPIGHVY (SEQ ID NO: 2), and wherein the ABP is bound to any one or more of the following: (a) the restriction peptide EVDPIGHVY (SEQ ID NO: 2) 2) any one or more of the amino acid positions 2-9; (b) HLA subtype B The amino acid positions of the α1 helix at positions 50, 54, 55, 57, 61, 62, 74, 81, 82, and 85 of the 35:01 helix; and (c) HLA subtype B. Any one or more of amino acid positions 147 and 148 of the α2 helix of 35:01. Note that the enumerated range includes terminal residues. For example, an ABP symptom of at least one of residues 2, 3, 4, 5, 6, 7, 8, and 9 of the restriction peptide EVDPIGHVY (SEQ ID NO: 2) at positions 2-9.

[0011] In some embodiments, the ABP binds to any one or more of amino acid positions 2-8 of the restriction peptide EVDPIGHVY (SEQ ID NO: 2).

[0012] In some embodiments, the ABP binds to any one or more of amino acid positions 5-9 of the restriction peptide EVDPIGHVY (SEQ ID NO: 2).

[0013] In some implementations, HLA class I molecules are HLA subtype B. 35:01, and the HLA-restricted peptide consists of the sequence EVDPIGHVY (SEQ ID NO: 2).

[0014] In some embodiments, the ABP comprises CDR-H3, which comprises a sequence selected from the following: CARDGVRYYGMDVW (SEQ ID NO: 3), CARDGVRGYDRSAGYW (SEQ ID NO: 4), CASHDYGDYGEYFQHW (SEQ ID NO: 5), CARVSWYCSSTSCGVNWFDPW (SEQ ID NO: 6), CAKVNWNDGPYFDYW (SEQ ID NO: 7), CATPTNSGYYGPYYYYGMDVW (SEQ ID NO: 8), CARDVMDVW (SEQ ID NO: 9), CAREGYGMDVW (SEQ ID NO: 10), CARDNGVGVDYW (SEQ ID NO: 11), CARGIADSGSYYGNGRDYYYGMDVW (SEQ ID NO: 12), CARDGDYYFDYW (SEQ ID NO: 13), CARDGTRYYGMDVW (SEQ ID NO: 14), CARDGVRYYGMDVW (SEQ ID NO: 15), CARDGVRYYGMDVW (SEQ ID NO: 16), CARDGVRYYGMDVW (SEQ ID NO: 17), CARDGVRYYGMDVW (SEQ ID NO: 18), CARDGVRYYGMDVW (SEQ ID NO: 19), CARDGVRYYGMDVW (SEQ ID NO: 10), CARDGVRYYGMDVW (SEQ ID NO: 11), CARDGVRYYGMDVW (SEQ ID NO: 12), CARDGVRYYGMDVW (SEQ ID NO: 13), CARDGVRYYGMDVW (SEQ ID NO: 14), CARDGVRYYGMDVW (SEQ ID NO: 15), CARDGVRYYGMDVW (SEQ ID NO: 16), CARDGVRYYGMDVW (SEQ ID NO: 17), CARDGVRYYGMD ID NO: 14), CARDVVANFDYW (SEQ ID NO: 15), CARGHSSGWYYYYGMDVW (SEQ ID NO: 16), CAKDLGSYGGYYW (SEQ ID NO: 17), CARSWFGGFNYHYYGMDVW (SEQ ID NO: 18), CARELPIGYGMDVW (SEQ ID NO: 19) and CARGGSYYYYGMDVW (SEQ ID NO: 20).

[0015] In some embodiments, the ABP includes CDR-L3, which comprises sequences selected from the following: CMQGLQTPITF (SEQ ID NO: 21), CMQALQTPPTF (SEQ ID NO: 22), CQQAISFPLTF (SEQ ID NO: 23), CQQANSFPLTF (SEQ ID NO: 24), CQQANSFPLTF (SEQ ID NO: 24), CQQSYSIPLTF (SEQ ID NO: 25), CQQTYMMPYTF (SEQ ID NO: 26), CQQSYITPWTF (SEQ ID NO: 27), CQQSYITPYTF (SEQ ID NO: 28), CQQYYTTPYTF (SEQ ID NO: 29), CQQSYSTPLTF (SEQ ID NO: 30), CMQALQTPLTF (SEQ ID NO: 31), CQQYGSWPRTF (SEQ ID NO: 32), CQQSYSTPVTF (SEQ ID NO: 33), CQQSYSTPVTF (SEQ ID NO: 34), CQQSYSTPVTF (SEQ ID NO: 35), CQQTYMMPYTF (SEQ ID NO: 26), CQQSYITPWTF (SEQ ID NO: 27), CQQSYITPYTF (SEQ ID NO: 28), CQQYYTTPYTF (SEQ ID NO: 39), CQQSYSTPLTF (SEQ ID NO: 30), CMQALQTPLTF (SEQ ID NO: 31), CQQYGSWPRTF (SEQ ID NO: 32), CQQSYSTPVTF (SEQ ID NO: 33), CQQSYSTPVTF (SEQ ID NO: 34), CQQSYSTPVTF (SEQ ID NO: 35), CQQSYSTPV ... 33), CMQALQTPYTF (SEQ ID NO: 34), CQQANSFPFTF (SEQ ID NO: 35), CMQALQTPLTF (SEQ ID NO: 31) and CQQSYSTPLTF (SEQ ID NO: 30).

[0016] In some implementations, the ABP includes CDR-H3 and CDR-L3 from scFv, which are named G5_P7_E7, G5_P7_B3, G5_P7_A5, G5_P7_F6, G5-P1B12, G5-P1C12, G5-P1-E05, G5-P3G01, G5-P3G08, G5-P4B02, G5-P4E04, G5R4-P1D06, G5R4-P1H11, G5R4-P2B10, G5R4-P2H8, G5R4-P3G05, G5R4-P4A07, or G5R4-P4B01.

[0017] In some implementations, the ABP comprises all three heavy chain CDRs and all three light chain CDRs from the scFv, which are named G5_P7_E7, G5_P7_B3, G5_P7_A5, G5_P7_F6, G5-P1B12, G5-P1C12, G5-P1-E05, G5-P3G01, G5-P3G08, G5-P4B02, G5-P4E04, G5R4-P1D06, G5R4-P1H11, G5R4-P2B10, G5R4-P2H8, G5R4-P3G05, G5R4-P4A07, or G5R4-P4B01.

[0018] In some embodiments, the ABP comprises a VH sequence selected from: QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGIINPRSGSTKYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGVRYYGMDVWGQGTTVTVSS (SEQ ID NO: 36), QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSHDINWVRQAPGQGLEWMGWMNPNSGDTGYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGVRGYDRSAGYWGQGTLVIVSS (SEQ ID NO: 37), EVQLLESGGGLVKPGGSLRLSCAASGFSFSSYWMSWVRQAPGKGLEWISYISGDSGYTNYADSVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCASHDYGDYGEYFQHWGQGTLVTVSS (SEQ ID NO: 38), EVQLLQSGGGLVQPGGSLRLSCAASGFTFSNSDMNWVRQAPGKGLEWVAYISSGSSTIYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVSWYCSSTSCGVNWFDPWGQGTLVTVSS (SEQ ID NO: 39), EVQLLESGGGLVQPGGSLRLSCAASGFTFSNSDMNWVRQAPGKGLEWVASISSSGGYINYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKVNWNDGPYFDYWGQGTLVTVSS (SEQ ID NO: 40), QVQLVQSGAEVKKPGSSVKVSCKASGGTFSNFGVSWLRQAPGQGLEWMGGIIPILGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCATPTNSGYYGPYYYYGMDVWGQGTTVTVSS (SEQ ID NO: 41), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYNMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDVMDVWGQGTTVTVSS (SEQ ID NO:42)、QVQLVQSGAEVKKPGASVKVSCKASGGTFSGYLVSWVRQAPGQGLEWMGWINPNSGGTNTAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREGYGMDVWGQGTTVTVSS (SEQID NO: 43)、QVQLVQSGAEVKKPGASVKVSCKASGYIFRNYPMHWVRQAPGQGLEWMGWINPDSGGTKYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDNGVGVDYWGQGTLVTVSS (SEQ ID NO: 44)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWMNPNIGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGIADSGSYYGNGRDYYYGMDVWGQGTTVTVSS (SEQ ID NO: 45)、QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYGISWVRQAPGQGLEWMGWINPNSGVTKYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGDYYFDYWGQGTLVTVSS (SEQ ID NO: 46)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGWINPNSGDTKYSQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGTRYYGMDVWGQGTTVTVSS (SEQ ID NO: 47)、EVQLLESGGGLVKPGGSLRLSCAASGFTFSDYYMSWVRQAPGKGLEWVSYISSSSSYTNYADSVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCARDVVANFDYWGQGTLVTVSS (SEQID NO: 48)、QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWMNPDSGSTGYAQRFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGHSSGWYYYYGMDVWGQGTTVTVSS (SEQ ID NO:49) EVQLLESGGGLVQPGGSLRLSCAASGFTFTSYSMHWVRQAPGKGLEWVSSITSFTNTMYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDLGSYGGYYWGQGTLVTVSS (SEQ ID NO: 50), QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYYMHWVRQAPGQGLEWMGIINPSGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSWFGGFNYHYYGMDVWGQGTTVTVSS (SEQ ID NO: 51), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARELPIGYGMDVWGQGTTVTVSS (SEQ ID NO: 52) and QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIVGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGGSYYYYGMDVWGQGTTVTVSS (SEQ ID NO: 53).

[0019] In some embodiments, the ABP comprises a VL selected from: DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSYRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGLQTPITFGQGTRLEIK (SEQ ID NO: 54), DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSSRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPPTFGPGTKVDIK (SEQ ID NO: 55), DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAISFPLTFGQSTKVEIK (SEQ ID NO: 56), DIQMTQSPSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYSASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPLTFGGGTKVEIK (SEQ ID NO: 57), DIQMTQSPSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPLTFGGGTKVEIK (SEQ ID NO: 58), DIQMTQSPSSLSASVGDRVTITCRASQGISNYLNWYQQKPGKAPKLLIYYASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYMMPYTFGQGTKVEIK (SEQID NO:60)、DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYGASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYITPWTFGQGTKVEIK (SEQ ID NO: 61)、DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYITPYTFGQGTKLEIK (SEQ ID NO: 62)、DIVMTQSPDSLAVSLGERATINCKTSQSVLYRPNNENYLAWYQQKPGQPPKLLIYQASIREPGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYTTPYTFGQGTKLEIK (SEQ ID NO: 63)、DIQMTQSPSSLSASVGDRVTITCRASQSISRFLNWYQQKPGKAPKLLIYGASRPQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGQGTKVEIK (SEQ ID NO: 64)、DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSHRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPLTFGGGTKVEIK (SEQ ID NO: 65)、EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQKPGQAPRLLIYAASARASGIPARFSGSGTEFTLTISSLQSEDFAVYCQQYGSWPRTGQGTKVEIK (SEQ ID NO:66)、DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYGASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPVTFGQGTKVEIK (SEQ ID NO: 67)、DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPYTFGQGTKVEIK (SEQID NO: 68), DIQMTQSPSSSLSASVGDRVTITCQASEDISNHLNWYQQKPGKAPKLLIYDALSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPFTFGPGTKVDIK (SEQ ID NO: 69), DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPLTFGQGTKVEIK (SEQ ID NO: 70) and DIQMTQSPSSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ ID NO: 71).

[0020] In some implementations, the ABP comprises VH and VL sequences from scFv, which are named G5_P7_E7, G5_P7_B3, G5_P7_A5, G5_P7_F6, G5-P1B12, G5-P1C12, G5-P1-E05, G5-P3G01, G5-P3G08, G5-P4B02, G5-P4E04, G5R4-P1D06, G5R4-P1H11, G5R4-P2B10, G5R4-P2H8, G5R4-P3G05, G5R4-P4A07, and G5R4-P4B01.

[0021] This article also provides isolated antigen-binding proteins (ABPs) that specifically bind to human leukocyte antigen (HLA) peptide targets, wherein the HLA peptide targets include HLA-restricted peptides complexed with HLA class I molecules, wherein the HLA-restricted peptides are located in the peptide-binding groove of the α1 / α2 heterodimer portion of the HLA class I molecule, and the HLA class I molecule is HLA subtype A. 01:01 (Reference sequence: MGSHSMRYFFTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQKMEPRAPWIEQEGPEYWDQETRNMKAHSQTDRANLGTLRGYYNQSEDGSHTIQIMYGCDVGPDGRFLRGYRQDAYDGKDYIALNEDLRSWTAADMAAQITKRKWEAVHAAEQRRVYLEGRCVDGLRRYLENGKETLQRTDPPKTHMTHHPISDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLR (SEQ ID NO: 72)), and the HLA-restricted peptide comprises the sequence NTDNNLAVY (SEQ ID NO: 73), and wherein the ABP is bound to any one or more of the following: (a) the restriction peptide NTDNNLAVY (SEQ ID NO: 73) (b) any one or more of residues 3-9 of 73), HLA subtype allele A 01:01 contains any one or more residues 70-85 of the α1 helix, and (c) HLA subtype allele A. Any one or more of residues 140-160 of the α2 helix of 01:01.

[0022] In some embodiments, the ABP binds to any one or more residues 6-9 of the restriction peptide NTDNNLAVY (SEQ ID NO: 73).

[0023] In some embodiments, the ABP binds to any one or more residues 7-8 of the restriction peptide NTDNNLAVY (SEQ ID NO: 73).

[0024] In some implementations, the ABP is associated with the HLA subtype allele A. The α2 helix of 01:01 binds to any one or more of residues 157-160.

[0025] In some embodiments, the ABP is associated with any one or more residues 6-9 of the restriction peptide NTDNNLAVY (SEQ ID NO: 73) and the HLA subtype allele A. The α2 helix of 01:01 binds to any one or more of residues 157-160.

[0026] In some embodiments, the HLA class I molecule is HLA subtype A. 01:01, and the HLA-restricted peptide consists of the sequence NTDNNLAVY (SEQ ID NO: 73).

[0027] In some embodiments, the ABP comprises a CDR-H3, and the CDR-H3 comprises a sequence selected from the following: CAATEWLGVW (SEQ ID NO: 74), CARANWLDYW (SEQ ID NO: 75), CARANWLDYW (SEQ ID NO:75), CARDWVLDYW (SEQ ID NO: 76), CARGEWLDYW (SEQ ID NO: 77), CARGWELGYW (SEQ IDNO: 78), CARDFVGYDDW (SEQ ID NO: 79), CARDYGDLDYW (SEQ ID NO: 80), CARGSYGMDVW(SEQ ID NO: 81), CARDGYSGLDVW (SEQ ID NO: 82), CARDSGVGMDVW (SEQ ID NO: 83), CARDGVAVASDYW (SEQ ID NO: 84), CARGVNVDDFDYW (SEQ ID NO: 85), CARGDYTGNWYFDLW(SEQ ID NO: 86), CARANWLDYW (SEQ ID NO: 75), CARDQFYGGNSGGHDYW (SEQ ID NO: 87), CAREEDYW (SEQ ID NO: 88), CARGDWFDPW (SEQ ID NO: 89), CARGDWFDPW (SEQ ID NO:89), CARGEWFDPW (SEQ ID NO: 90), CARSDWFDPW (SEQ ID NO: 91), CARDSGSYFDYW (SEQID NO: 92), CARDYGGYVDYW (SEQ ID NO: 93), CAREGPAALDVW (SEQ ID NO: 94), CARERRSGMDVW (SEQ ID NO: 95), CARVLQEGMDVW (SEQ ID NO: 96), CASERELPFDIW (SEQID NO: 97), CAKGGGGYGMDVW (SEQ ID NO: 98), CAAMGIAVAGGMDVW (SEQ ID NO: 99), CARNWNLDYW (SEQ ID NO: 100), CATYDDGMDVW (SEQ ID NO: 101), CARGGGGALDYW (SEQ IDNO: 102), CALSGNYYGMDVW (SEQ ID NO: 103), CARGNPWELRLDYW (SEQ IDNO: 104) and CARDKNYYGMDVW (SEQ ID NO: 105).

[0028] In some embodiments, the ABP comprises a CDR-L3, and the CDR-L3 comprises a sequence selected from the following: CQQSYNTPYTF (SEQ ID NO: 106), CQQSYSTPYTF (SEQ ID NO: 107), CQQSYSTPYSF (SEQ ID NO: 108), CQQSYSTPFTF (SEQ ID NO: 109), CQQSYGVPYTF (SEQ ID NO: 110), CQQSYSAPYTF (SEQ ID NO: 111), CQQSYSAPYTF (SEQ ID NO: 111), CQQSYSAPYSF (SEQ ID NO: 112), CQQSYSTPYTF (SEQ ID NO: 107), CQQSYSVPYSF (SEQ ID NO: 113), CQQSYSAPYTF (SEQ ID NO: 111), CQQSYSVPYSF (SEQ ID NO: 113), CQQSYSTPQTF (SEQ ID NO: 114), CQQLDSYPFTF (SEQ ID NO: 115), CQQSYSSPYTF (SEQ ID NO: 116), CQQSYSTPLTF (SEQ ID NO: 30), CQQSYSTPYSF (SEQ ID NO: 108), CQQSYSTPYTF (SEQ ID NO: 107), CQQSYSTPYTF (SEQ ID NO: 107), CQQSYSTPFTF (SEQ ID NO: 109), CQQSYSTPTF (SEQ ID NO: 117), CQQTYAIPLTF (SEQ ID NO: 118), CQQSYSTPYTF (SEQ ID NO: 107), CQQSYIAPFTF (SEQ ID NO: 119), CQQSYSIPLTF (SEQ ID NO: 25), CQQSYSNPTF (SEQ ID NO: 120), CQQSYSTPYSF (SEQ ID NO: 108), CQQSYSDQWTF (SEQ ID NO: 121), CQQSYLPPYSF (SEQ ID NO: 122), CQQSYSSPYTF (SEQ ID NO: 116), CQQSYTTPWTF (SEQ ID NO: 123), CQQSYLPPYSF (SEQ ID NO: 122), CQEGITYTF (SEQ ID NO: 124), CQQYYSYPFTF(SEQID NO: 125) and CQHYGYSPVTF (SEQ ID NO: 126).

[0029] In some implementations, the ABP includes CDR-H3 and CDR-L3 from scFv, which are named G2-P1H11, G2-P2E07, G2-P2E03, G2-P2A11, G2-P2C06, G2-P1G01, G2-P1C02, G2-P1H01, G2-P1B12, G2-P1B06, G2-P2H10, G2-P1H10, G2-P2C11, G2-P1C09, and G2-P1A10. G2-P1B10, G2-P1D07, G2-P1E05, G2-P1D03, G2-P1G12, G2-P2H11, G2-P1C03, G2-P1G07, G2-P1F12, G2-P1G03, G2-P2B08, G2-P2A10, G2-P2D04, G2-P1C06, G2-P2A09, G2-P1B08, G2-P1E03, G2-P2A03, G2-P2F01 or G2-P1D06.

[0030] In some implementations, the ABP includes CDR-H3 and CDR-L3 from scFv named G2-P1H11.

[0031] In some implementations, the ABP comprises all three heavy chain CDRs and all three light chain CDRs from the scFv, which are named G2-P1H11, G2-P2E07, G2-P2E03, G2-P2A11, G2-P2C06, G2-P1G01, G2-P1C02, G2-P1H01, G2-P1B12, G2-P1B06, G2-P2H10, G2-P1H10, G2-P2C11, G2-P1C09, G2-P1 A10, G2-P1B10, G2-P1D07, G2-P1E05, G2-P1D03, G2-P1G12, G2-P2H11, G2-P1C03, G2-P1G07, G2-P1F12, G2-P1G03, G2-P2B08, G2-P2A10, G2-P2D04, G2-P1C06, G2-P2A09, G2-P1B08, G2-P1E03, G2-P2A03, G2-P2F01 or G2-P1D06.

[0032] In some implementations, the ABP comprises all three heavy chain CDRs and all three light chain CDRs from the scFv named G2-P1H11.

[0033] In some embodiments, the ABP comprises a VH sequence selected from: QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYYMHWVRQAPGQGLEWMGMINPSGGGTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGNPWELRLDYWGQGTLVTVSS (SEQ ID NO: 127), QVQLVQSGAEVKKPGASVKVSCKASGGTFSSATISWVRQAPGQGLEWMGWIYPNSGGTVYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAATEWLGVWGQGTTVTVSS (SEQ ID NO: 128), EVQLLQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWINPNSGGTISAPNFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARANWLDYWGQGTLVTVSS (SEQ ID NO:129), EVQLLESGAEVKKPGASVKVSCKASGYTFTTYDLAWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARANWLDYWGQGTLVTVSS (SEQ ID NO: 130), QVQLVQSGAEVKKPGASVKVSCKSSGYSFDSYVVNWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDWVLDYWGQGTLVTVSS (SEQ ID NO: 131), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWMNPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGEWLDYWGQGTLVTVSS (SEQ ID NO: 132), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGWELGYWGQGTLVTVSS (SEQ IDNO:133)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYTINWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDFVGYDDWGQGTLVTVSS (SEQ ID NO: 134)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGITWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYCARDYGDLDYWGQGTLVTVSS (SEQ ID NO: 135). 136), QVQLVQSGAEVKKPGASVKVSCKASGYSFTRYNMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGYSGLDVWGKGGTTVTVSS (SEQ ID NO: 137), QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWINPNNGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGVAVASDYWGQGTTVTVSS (SEQ ID NO: 138), QVQLVQSGAEVKKPGASVKVSCKASGGTFNNYAFSWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGVAVASDYWGQGTLVTVSS (SEQ ID NO: 139).140). 141)、EVQLLESGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWINPYSGGTNYAQKLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYCARANWLDYWGQGTLVTVSS (SEQ ID NO:142)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGYTNYAQNLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDQFYGGNSGGHDYWGQGTLVTVSS (SEQ ID NO: 143)、QVQLVQSGAEVKKPGASVKVSCKASGYTFDTDYNMHWVRQAPGQGLEWMGWMNPNSGGTNYAQKFQGRVTMTRDTSTVYMELSSLRSEDTAVYYCAREEDYWGQGTLVTVSS (SEQ ID NO: 144)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYTINWVRQAPGQGLEWMGWINPNSGGANYAQKFQGRVTMTRDTSTVYMELSSLRSEDTAVYYCARGDWFDPWGQGTLVTVSS (SEQ ID NO: 145)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYLMHWVRQAPGQGLEWMGWISPNSGGTNYAQKFQGRVTMTRDTSTVYMELSSLRSEDTAVYYCARGDWFDPWGQGTLVTVSS (SEQ ID NO: 146).147)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTTYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSDWFDPWGQGTLVTVSS (SEQ ID NO: 148)、QVQLVQSGAEVKKPGASVKVSCKASGGTFSNYAINWVRQAPGQGLEWMGWISPYSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDSGSYFDYWGQGTLVTVSS (SEQ ID NO: 149)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYMHWVRQAPGQGLEWMGWIYPNTGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDYGGYVDYWGQGTLVTVSS (SEQID NO: 150)、EVQLLESGAEVKKPGASVKVSCKASGYTFTSYAMNWVRQAPGQGLEWMGWMNPNSGGTKYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREGPAALDVWGQGTLVTVSS (SEQ ID NO: 151)、QVQLVQSGAEVKKPGASVKVSCKASGYTLTSHLIHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARERRSGMDVWGQGTTVTVSS (SEQ ID NO: 152)、EVQLLESGAEVKKPGASVKVSCKASGYSFTDYIVHWVRQAPGQGLEWMGWINPYSGGTKYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARVLQEGMDVWGQGTLVTVSS (SEQ ID NO: 153)、QVQLVQSGAEVKKPGASVKVSCKASGYTFSNFLINWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCASERELPFDIWGQGTMVTVSS (SEQ ID NO:154), QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYQMFWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKGGGGYGMDVWGQGTTVTVSS (SEQ ID NO:155), QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAAMGIAVAGGMDVWGQGTLVTVSS (SEQ ID NO: 156), QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYHMHWVRQAPGQGLEWMGWIHPDSGGTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARNWNLDYWGQGTLVTVSS (SEQ ID NO: 157), QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCATYDDGMDVWGQGTTVTVSS (SEQ ID NO: 158), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYTVNWVRQAPGQGLEWMGWINPNSGGTKYAQNFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGGGALDYWGQGTLVTVSS (SEQID NO: 159), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGMINPRDDTTDYARDFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCALSGNYYGMDVWGQGTTVTVSS (SEQ ID NO: 160) and QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSQYMHWVRQAPGQGLEWMGRIIPLLGIVNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDKNYYGMDVWGQGTTVTVSS (SEQ ID NO: 161).

[0034] In some embodiments, the ABP comprises a VL sequence selected from: DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYYSYPFTFGPGTKVDIK (SEQ ID NO: 162), DIQMTQSPSSLSASVGDRVTITCRASQSISTWLAWYQQKPGKAPKLLIYAASSLRSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYNTPYTFGQGTKLEIK (SEQ ID NO:163), DIQMTQSPSSLSASVGDRVTITCRASQSISRWLAWYQQKPGKAPKLLIYAASTVQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK (SEQ ID NO: 164), DIQMTQSPSSLSASVGDRVTITCRASQDISRWLAWYQQKPGKAPKLLIYAASRLQAGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYSFGQGTKLEIK (SEQ ID NO: 165), DIQMTQSPSSLSASVGDRVTITCRASQTISSWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPFTFGPGTKVDIK (SEQ ID NO: 166), DIQMTQSPSSLSASVGDRVTITCRASQTISSWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYGVPYTFGQGTKVEIK (SEQ ID NO: 167), DIQMTQSPSSLSASVGDRVTITCRASQSISNWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSAPYTFGPGTKVDIK (SEQ ID NO:168)、DIQMTQSPSSLSASVGDRVTITCRASQSVGNWLAWYQQKPGKAPKLLIYGASSLQTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSAPYTFGQGTKVEIK (SEQ ID NO: 169)、DIQMTQSPSSLSASVGDRVTITCRASQNIGNWLAWYQQKPGKAPKLLIYAASTLQTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSAPYSFGQGTKLEIK (SEQ ID NO: 170)、DIQMTQSPSSLSASVGDRVTITCRASQSISRWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK(SEQ ID NO: 171)、DIQMTQSPSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYGASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSVPYSFGQGTKLEIK (SEQ ID NO: 172)、DIQMTQSPSSLSASVGDRVTITCRASQSISKWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSAPYTFGQGTKVEIK (SEQ ID NO: 173)、DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSVPYSFGQGTKLEIK (SEQID NO: 174)、DIQMTQSPSSLSASVGDRVTITCRASQTISNYLNWYQQKPGKAPKLLIYAASNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPQTFGQGTKVEIK (SEQ ID NO: 175)、DIQMTQSPSSLSASVGDRVTITCRASRDIGRAVGWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQLDSYPFTFGPGTKVDIK (SEQ ID NO:176)、DIQMTQSPSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSSPYTFGPGTKVDIK (SEQ ID NO:177)、DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKLEIK (SEQ ID NO: 178)、DIQMTQSPSSLSASVGDRVTITCRASQSIGRWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYSFGQGTKVEIK (SEQ ID NO: 179)、DIQMTQSPSSLSASVGDRVTITCRASQSISTWLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFAQGTKLEIK (SEQ ID NO: 180)、DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYGASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK (SEQ ID NO: 181)、DIQMTQSPSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPFTFGPGTKVDIK (SEQ ID NO: 182)、DIQMTQSPSSLSASVGDRVTITCRASQSVSNWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPTFGQGTKLEIK (SEQ ID NO: 183)、DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYAIPLTFGGGTKVEIK (SEQ ID NO:184)、DIQMTQSPSSLSASVGDRVTITCQASQDIGSWLAWYQQKPGKAPKLLIYATSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK(SEQ ID NO: 185)、DIQMTQSPSSLSASVGDRVTITCRASQGISRWLAWYQQKPGKAPKLLIYAASTLQPGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYIAPFTFGPGTKVDIK (SEQ ID NO: 186)、DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYAASRLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSIPLTFGGGTKVEIK (SEQ ID NO: 187)、DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYGVSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSNPTFGQGTKVEIK (SEQ ID NO: 188)、DIQMTQSPSSLSASVGDRVTITCRASQSISSWVAWYQQKPGKAPKLLIYGASNLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYSFGQGTKLEIK (SEQ ID NO: 189)、DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYSFGQGTKLEIK (SEQ ID NO: 190)、DIQMTQSPSSLSASVGDRVTITCRASQSISRWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYLPPYSFGQGTKVEIK (SEQ ID NO: 190) NO:191)、DIQMTQSPSSLSASVGDRVTITCRASQSISNWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTYFTLTISSLQPEDFATYYCQQSYSSPYTFGQGTKLEIK (SEQ ID NO:192), DIQMTQSPSSSLSASVGDRVTITCRASQSISHYLNWYQQKPGKAPKLLIYGASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYTTPWTFGQGTRLEIK (SEQ ID NO: 193),DIQMTQSPSSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYLPPYSFGQGTKLEIK (SEQ ID NO: 194), DIQMTQSPSSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYGASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQEGITYTFGQGTKVEIK (SEQ ID NO: 195) and EIVMTQSPATLSVSPGERATLSCRASQSVSRNLAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQHYGYSPVTFGQGTKLEIK (SEQ ID NO: 196).

[0035] In some implementations, the ABP comprises VH and VL sequences from scFv, wherein the scFv is named G2-P1H11, G2-P2E07, G2-P2E03, G2-P2A11, G2-P2C06, G2-P1G01, G2-P1C02, G2-P1H01, G2-P1B12, G2-P1B06, G2-P2H10, G2-P1H10, G2-P2C11, G2-P1C09, G2-P1A10, G... 2-P1B10, G2-P1D07, G2-P1E05, G2-P1D03, G2-P1G12, G2-P2H11, G2-P1C03, G2-P1G07, G2-P1F12, G2-P1G03, G2-P2B08, G2-P2A10, G2-P2D04, G2-P1C06, G2-P2A09, G2-P1B08, G2-P1E03, G2-P2A03, G2-P2F01 or G2-P1D06.

[0036] In some implementations, the ABP comprises a VH sequence and a VL sequence from an scFv named G2-P1H11.

[0037] This article also provides isolated antigen-binding proteins (ABPs) that specifically bind to human leukocyte antigen (HLA) peptide targets, wherein the HLA peptide targets include HLA-restricted peptides complexed with HLA class I molecules, wherein the HLA-restricted peptides are located in the peptide-binding groove of the α1 / α2 heterodimer portion of the HLA class I molecule, and wherein the HLA class I molecule is HLA subtype A. 02:01 (Reference sequence: MGSHSMRYFFTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYWDGETRKVKAHSQTHRVDLGTLRGYYNQSEAGSHTVQRMYGCDVGSDWRFLRGYHQYAYDGKDYIALKEDLRSWTAADMAAQTTKHKWEAAHVAEQLRAYLEGTCVEWLRRYLENGKETLQRTDAPKTHMTHHAVSDHEATLRCWALSFYPAEITLTWQRDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGQEQRYTCHVQHEGLPKPLTLR (SEQ ID NO: 197)), wherein the HLA-restricted peptide comprises the sequence AIFPGAVPAA (SEQ ID NO: 198), and wherein the ABP is bound to any one or more of the following: (a) the restriction peptide AIFPGAVPAA (SEQ ID NO: (b) any one or more of the amino acid positions 1-6 of 198), HLA subtype A The amino acid positions of the α1 helix at positions 46, 49, 55, 61, 74, 76, 77, 78, 81, and 84 in 02:01, (c) HLA subtype A 02:01 The amino acid positions of the α1 helix are any one or more of 45-60, 66, 67, and 73, (d) HLA subtype A The amino acid positions of the α2 helix at 02:01 are any one or more of 138, 145, 147, 152-156, 164, and 167, and (e) HLA subtype A. The amino acid positions of 02:01 are any one or more of the following: 56, 59, 60, 63, 64, 66, 67, 70, 73, 74, 132, 150-153, 155, 156, 158-160, 162-164, 166-168, 170, and 171.

[0038] In some embodiments, the ABP binds to any one or more of amino acid positions 1-5 of the restriction peptide AIFPGAVPAA (SEQ ID NO: 198).

[0039] In some embodiments, the ABP is bound to one or both of amino acid positions 4 and 5 of the restriction peptide AIFPGAVPAA (SEQ ID NO: 198).

[0040] In some embodiments, the ABP binds to one or both of amino acid positions 5 and 6 of the restriction peptide AIFPGAVPAA (SEQ ID NO: 198).

[0041] In some embodiments, the ABP binds to amino acid position 6 of the restriction peptide AIFPGAVPAA (SEQ ID NO: 198).

[0042] In some implementations, the ABP is related to HLA subtype A. The α1 helix of 02:01 binds to any one or more of the amino acid positions 46, 49, 55, 66, 67, and 73.

[0043] In some embodiments, the ABP comprises a VH region containing complementary sites, the complementary sites comprising at least one, two, three, or four residues of Tyr32, Gly99, Asp100, and Tyr100A from the VH region as shown in the Kabat numbering sequence QVQLVQSGAEVKKPGASVKVSCKASGGTLSSYPINWVRQAPGQGLEWMGWISTYSGHADYAQKLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSYDYGDYLNFDYWGQGTLVTVSS (SEQ ID NO: 199).

[0044] In some embodiments, the ABP comprises a VH region containing complementary sites, the complementary sites comprising residues Thr28, Leu 29, Ser 30, Ser 31, Tyr 32, Pro 33, Trp 47, Trp50, Ser 52, Tyr 53, Ser 54, His 56, Asp 58, Tyr 59, Gln 61, Gln 64, Asp 97, Tyr At least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty, twelve, or twenty-two residues from 98, Gly99, Asp100, Tyr100A, Leu100B, and Asn100C.

[0045] In some embodiments, the complementary site comprises at least one, two, three, four, five, six, or seven residues selected from the VH region residues Ser30, Ser31, Tyr32, Tyr98, Gly99, Asp100, and Tyr100A, as numbered according to the Kabat numbering system.

[0046] In some embodiments, the ABP comprises a VL region containing complementary sites, the complementary sites comprising at least one, two, or three residues of Tyr32, Ser 91, and Tyr 92 from the VL region as shown in the Kabat numbering sequence DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSIPPTFGGGTKVDIK (SEQ ID NO: 200).

[0047] In some embodiments, the ABP comprises a VL region containing complementary sites, the complementary sites comprising at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, or 13 residues of the VL region as shown in the Kabat numbering sequence DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSIPPTFGGGTKVDIK (SEQ ID NO: 200) as selected from Asp1, Ser30, Asn31, Tyr32, Tyr49, Ala50, Ser53, Ser67, Ser91, Tyr92, Ser93, Ile94, and Pro95.

[0048] In some embodiments, the complementary site comprises at least one, two, three, four, five, or six residues from the VL region selected as Asp1, Asn31, Tyr32, Ser91, Tyr92, and Ile94, as numbered according to the Kabat numbering system.

[0049] In some implementations, HLA class I molecules are HLA subtype A. 02:01, and the HLA-restricted peptide consists of the sequence AIFPGAVPAA (SEQ ID NO: 198).

[0050] In some embodiments, the ABP comprises CDR-H3, which comprises a sequence selected from the following: CARDDYGDYVAYFQHW (SEQ ID NO: 201), CARDLSYYYGMDVW (SEQ ID NO: 202), CARVYDFWSVLSGFDIW (SEQ ID NO: 203), CARVEQGYDIYYYYYMDVW (SEQ ID NO: 204), CARSYDYGDYLNFDYW (SEQ ID NO: 205), CARASGSGYYYYYGMDVW (SEQ ID NO: 206), CAASTWIQPFDYW (SEQ ID NO: 207), CASNGNYYGSGSYYNYW (SEQ ID NO: 208), CARAVYYDFWSGPFDYW (SEQ ID NO: 209), CAKGGIYYGSGSYPSW (SEQ ID NO: 210), CARGLYYMDVW (SEQ ID NO: 201). NO: 211), CARGLYGDYFLYYGMDVW (SEQ ID NO: 212), CARGLLGFGEFLTYGMDVW (SEQ ID NO: 213), CARDRDSSWTYYYYGMDVW (SEQ ID NO: 214), CARGLYGDYFLYYGMDVW (SEQ ID NO: 212), CARGDYYDSSGYYFPVYFDYW (SEQ ID NO: 215) and CAKDPPFWSGHYYYYGMDVW (SEQ ID NO: 216).

[0051] In some embodiments, the ABP includes CDR-L3, which comprises sequences selected from: CQQNYNSVTF (SEQ ID NO: 217), CQQSYNTPWTF (SEQ ID NO: 218), CGQSYSTPPTF (SEQ ID NO: 219), CQQSYSAPYTF (SEQ ID NO: 111), CQQSYSIPPTF (SEQ ID NO: 220), CQQSYSAPYTF (SEQ ID NO: 111), CQQHNSYPPTF (SEQ ID NO: 221), CQQYSTYPITI (SEQ ID NO: 222), CQQANSFPWTF (SEQ ID NO: 223), CQQSHSTPQTF (SEQ ID NO: 224), CQQSYSTPLTF (SEQ ID NO: 30), CQQSYSTPLTF (SEQ ID NO: 30), CQQTYSTPWTF (SEQ ID NO: 225), CQQYGSSPYTF. (SEQ ID NO: 226), CQQSHSTPLTF (SEQ ID NO: 227), CQQANGFPLTF (SEQ ID NO: 228) and CQQSYSTPLTF (SEQ ID NO: 30).

[0052] In some implementations, the ABP includes CDR-H3 and CDR-L3 from scFv, which are named G8-P1A03, G8-P1A04, G8-P1A06, G8-P1B03, G8-P1C11, G8-P1D02, G8-P1H08, G8-P2B05, G8-P2E06, R3G8-P2C10, R3G8-P2E04, R3G8-P4F05, R3G8-P5C03, R3G8-P5F02, R3G8-P5G08, G8-P1C01, or G8-P2C11.

[0053] In some implementations, the ABP comprises all three heavy chain CDRs and all three light chain CDRs from the scFv, which are named G8-P1A03, G8-P1A04, G8-P1A06, G8-P1B03, G8-P1C11, G8-P1D02, G8-P1H08, G8-P2B05, G8-P2E06, R3G8-P2C10, R3G8-P2E04, R3G8-P4F05, R3G8-P5C03, R3G8-P5F02, R3G8-P5G08, G8-P1C01, or G8-P2C11.

[0054] In some embodiments, the ABP comprises a VH sequence selected from: QVQLVQSGAEVKKPGASVKVSCKASGGTFSRSAITWVRQAPGQGLEWMGWINPNSGATNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDDYGDYVAYFQHWGQGTLVTVSS (SEQ ID NO: 229), QVQLVQSGAEVKKPGASVKVSCKASGYPFIGQYLHWVRQAPGQGLEWMGIINPSGDSATYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDLSYYYGMDVWGQGTTVTVSS (SEQ ID NO: 230), QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYYMHWVRQAPGQGLEWMGWMNPIGGGTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARVYDFWSVLSGFDIWGQGTLVTVSS(SEQ ID NO: 231), EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMSWVRQAPGKGLEWVSGINWNGGSTGYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVEQGYDIYYYYYMDVWGKGTTVTVSS (SEQ ID NO:232), QVQLVQSGAEVKKPGASVKVSCKASGGTLSSYPINWVRQAPGQGLEWMGWISTYSGHADYAQKLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSYDYGDYLNFDYWGQGTLVTVSS (SEQ ID NO: 199), EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYWMSWVRQAPGKGLEWVSSISGRGDNTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARASGSGYYYYYGMDVWGQGTTVTVSS (SEQ ID NO: 233), QVQLVQSGAEVKKPGASVKVSCKASGYTFGNYFMHWVRQAPGQGLEWMGMVNPSGGSETFAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAASTWIQPFDYWGQGTLVTVSS (SEQ ID NO:234)、EVQLLESGGGLVQPGGSLRLSCAASGFDFSIYSMNWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASNGNYYGSGSYYNYWGQGTLVTVSS (SEQ ID NO: 235)、QVQLVQSGAEVKKPGASVKVSCKASGYTLTTYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARAVYYDFWSGPFDYWGQGTLVTVSS(SEQ ID NO: 236)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGWINPYSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKGGIYYGSGSYPSWGQGTLVTVSS (SEQ ID NO:237)、QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYGVSWVRQAPGQGLEWMGWISPYSGNTDYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGLYYMDVWGKGTTVTVSS (SEQ ID NO: 238)、QVQLVQSGAEVKKPGASVKVSCKASGYTFSNMYLHWVRQAPGQGLEWMGWINPNTGDTNYAQTFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGLYGDYFLYYGMDVWGQGTKVTVSS (SEQ ID NO: 239)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGLLGFGEFLTYGMDVWGQGTLVTVSS (SEQ ID NO: 240)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYIHWVRQAPGQGLEWMGVINPSGGSTTYAQKLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDRDSSWTYYYYGMDVWGQGTTVTVSS (SEQ ID NO:241), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSNYMHWVRQAPGQGLEWMGWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGLYGDYFLYYGMDVWGQGTTVTVSS (SEQ ID NO: 242), QVQLVQSGAEVKKPGASVKVSCKASGGTFSSHAISWVRQAPGQGLEWMGVIIPSGGTSYTQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGDYYDSSGYYFPVYFDYWGQGTLVTVSS (SEQID NO: 243) and QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYAMNWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDPFWSGHYYYYGMDVWGQGTTVTVSS (SEQ ID NO:244).

[0055] In some embodiments, the ABP comprises a VL sequence selected from: DIQMTQSPSSLSASVGDRVTITCRASQSITSYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQNYNSVTFGQGTKLEIK (SEQ ID NO: 245), DIQMTQSPSSLSASVGDRVTITCWASQGISSYLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYNTPWTFGPGTKVDIK (SEQ ID NO:246), DIQMTQSPSSLSASVGDRVTITCRASQAISNSLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCGQSYSTPPTFGQGTKLEIK (SEQ ID NO: 247), DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSAPYTFGPGTKVDIK (SEQ ID NO: 248), DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSIPPTFGGGTKVDIK (SEQ ID NO: 200), DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSAPYTFGGGTKVEIK (SEQ ID NO: 249), DIQMTQSPSSLSASVGDRVTITCRASQGINSYLAWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHNSYPPTFGQGTKLEIK (SEQ ID NO:250)、DIQMTQSPSSLSASVGDRVTITCRASQSISRWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYSTYPITIGQGTKVEIK (SEQ ID NO: 251)、DIQMTQSPSSLSASVGDRVTITCRASQGISNSLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPWTFGQGTKLEIK (SEQ ID NO: 252)、DIQMTQSPSSLSASVGDRVTITCRASQDVSTWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSHSTPQTFGQGTKVEIK(SEQ ID NO: 253)、DIQMTQSPSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKLEIK (SEQ ID NO: 254)、DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ ID NO: 255)、DIQMTQSPSSLSASVGDRVTITCRASQGISNWLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSTPWTFGQGTKLEIK (SEQID NO: 256)、EIVMTQSPATLSVSPGERATLSCRASQSVGNSLAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYGSSPYTFGQGTKVEIK (SEQ ID NO: 257)、DIQMTQSPSSLSASVGDRVTITCRASQSISGYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSHSTPLTFGQGTKVEIK (SEQ ID NO:258), DIQMTQSPSSSLSASVGDRVTITCRASQNIYTYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANGFPLTFGGGTKVEIK (SEQ ID NO: 259) and DIQMTQSPSSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ ID NO: 71).

[0056] In some implementations, the ABP comprises a VH sequence and a VL sequence from an scFv, which is named G8-P1A03, G8-P1A04, G8-P1A06, G8-P1B03, G8-P1C11, G8-P1D02, G8-P1H08, G8-P2B05, G8-P2E06, R3G8-P2C10, R3G8-P2E04, R3G8-P4F05, R3G8-P5C03, R3G8-P5F02, R3G8-P5G08, G8-P1C01, or G8-P2C11.

[0057] This article also provides an isolated antigen-binding protein (ABP) that specifically binds to human leukocyte antigen (HLA) peptide targets, wherein the HLA peptide targets comprise HLA-restricted peptides complexed with HLA class I molecules, wherein the HLA-restricted peptides are located in the peptide-binding groove of the α1 / α2 heterodimer portion of the HLA class I molecule, and wherein the HLA class I molecule is HLA subtype A. 01:01 (Reference sequence: MGSHSMRYFFTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQKMEPRAPWIEQEGPEYWDQETRNMKAHSQTDRANLGTLRGYYNQSEDGSHTIQIMYGCDVGPDGRFLRGYRQDAYDGKDYIALNEDLRSWTAADMAAQITKRKWEAVHAAEQRRVYLEGRCVDGLRRYLENGKETLQRTDPPKTHMTHHPISDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLR (SEQ ID NO: 72)), and the HLA-restricted peptide comprises the sequence ASSLPTTMNY (SEQ ID NO: 260), and wherein the ABP is bound to any one or more of the following: (a) the restricted peptide ASSLPTTMNY (SEQ ID NO: (b) HLA subtype A 01:01, any one or more of the amino acid positions 49-56, (c) HLA subtype A 01:01, any one or more amino acids at positions 59-66, (d) HLA subtype A 01:01 amino acid positions 136-147 of any one or more, and (e) HLA subtype A 01:01 refers to any one or more amino acids at positions 157-160.

[0058] In some embodiments, the ABP binds to any one or more of amino acid positions 6-9 of the restriction peptide ASSLPTTMNY (SEQ ID NO: 260).

[0059] In some embodiments, the ABP binds to any one or more of amino acid positions 6-7 in the restriction peptide ASSLPTTMNY (SEQ ID NO: 260).

[0060] In some embodiments, the ABP binds to amino acid position 6 of the restriction peptide ASSLPTTMNY (SEQ ID NO: 260).

[0061] In some implementations, the ABP is combined with: (a) HLA subtype A (b) HLA subtype A 01:01, any one or more of the amino acid positions 136-139, (c) HLA subtype A 01:01, any one or more of the amino acid positions 141-147, or (d) HLA subtype A 01:01 any one or more of amino acid positions 136-139 and any one or more of amino acid positions 141-147.

[0062] In some embodiments of an ABP containing an antibody or its antigen-binding fragment, the HLA class I molecule is an HLA subtype A. 01:01, and the HLA-restricted peptide consists of the sequence ASSLPTTMNY (SEQ ID NO: 260).

[0063] In some embodiments, the ABP comprises CDR-H3, which comprises a sequence selected from the following: CARDQDTIFGVVITWFDPW (SEQ ID NO: 261), CARDKVYGDGFDPW (SEQ ID NO: 262), CARDEDDSMDVW (SEQ ID NO: 263), CARDSSGLDPW (SEQ ID NO: 264), CARGVGNLDYW (SEQ ID NO: 265), CARDHAHQYYDFWSGYYSGTYYYGMDVW (SEQ ID NO: 266), CAREQWPSYWYFDLW (SEQ ID NO: 267), CADRGYSYGYFDYW (SEQ ID NO: 268), CARGSGDPNYYYYYGLDVW (SEQ ID NO: 269), CARDTGDHFDYW (SEQ ID NO: 270), CARAENGMDVW (SEQ ID NO: 269), CARDTGDHFDYW (SEQ ID NO: 270), CARAENGMDVW (SEQ ID NO: 269), CARDGDHFDYW (SEQ ID NO: 270), CARAENGMDVW (SEQ ID NO: 269), CARDGDHFDYW (SEQ ID NO: 260), CARAENGMDV ...RAENGMDVW (SEQ ID NO: 260), CARAENGMDVW (SEQ ID NO: 260), CARAENGMDVW (SEQ ID NO: 260), CARAENGMDVW (SEQ ID NO: 260), CARAENGMDVW (SEQ ID NO: 260), CARAENGMDVW (SEQ ID NO: 260), CARAENGMDVW (SEQ ID 271), CARDPGGYMDVW (SEQ ID NO: 272), CARDGDAFDIW (SEQ ID NO: 273), CARDMGDAFDIW (SEQ ID NO: 274), CAREEDGMDVW (SEQ ID NO: 275), CARDTGDHFDYW (SEQ ID NO: 270), CARGEYSSGFFFVGWFDLW (SEQ ID NO: 276) and CARETGDDAFDIW (SEQ ID NO: 277).

[0064] In some embodiments, the ABP includes CDR-L3, which comprises sequences selected from: CQQYFTTPYTF (SEQ ID NO: 278), CQQAEAFPYTF (SEQ ID NO: 279), CQQSYSTPITF (SEQ ID NO: 280), CQQSYIIPYTF (SEQ ID NO: 281), CHQTYSTPLTF (SEQ ID NO: 282), CQQAYSFPWTF (SEQ ID NO: 283), CQQGYSTPLTF (SEQ ID NO: 284), CQQANSFPRTF (SEQ ID NO: 285), CQQANSLPYTF (SEQ ID NO: 286), CQQSYSTPFTF (SEQ ID NO: 109), CQQSYSTPFTF (SEQ ID NO: 109), CQQSYGVPTF (SEQ ID NO: 287), CQQSYSTPLTF (SEQ ID NO: 30), CQQSYSTPLTF. (SEQ ID NO: 30), CQQYYSYPWTF (SEQ ID NO: 288), CQQSYSTPFTF (SEQ ID NO: 109), CMQTLKTPLSF (SEQ ID NO: 289) and CQQSYSTPLTF (SEQ ID NO: 30).

[0065] In some implementations, the ABP includes CDR-H3 and CDR-L3 from scFv, which are named R3G10-P1A07, R3G10-P1B07, R3G10-P1E12, R3G10-P1F06, R3G10-P1H01, R3G10-P1H08, R3G10-P2C04, R3G10-P2G11, R3G10-P3E04, R3G10-P4A02, R3G10-P4C05, R3G10-P4D04, R3G10-P4D10, R3G10-P4E07, R3G10-P4E12, R3G10-P4G06, R3G10-P5A08, or R3G10-P5C08.

[0066] In some implementations, the ABP comprises all three heavy chain CDRs and all three light chain CDRs from the scFv, which are named R3G10-P1A07, R3G10-P1B07, R3G10-P1E12, R3G10-P1F06, R3G10-P1H01, R3G10-P1H08, and R3G10-P2C. 04, R3G10-P2G11, R3G10-P3E04, R3G10-P4A02, R3G10-P4C05, R3G10-P4D04, R3G10-P4D10, R3G10-P4E07, R3G10-P4E12, R3G10-P4G06, R3G10-P5A08 or R3G10-P5C08.

[0067] In some embodiments, the ABP comprises a VH sequence selected from: EVQLLESGGGLVKPGGSLRLSCAASGFTFSSYWMSWVRQAPGKGLEWVSGISARSGRTYYADSVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCARDQDTIFGVVITWFDPWGQGTLVTVSS (SEQ ID NO: 290), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGIIHPGGGTTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDKVYGDGFDPWGQGTLVTVSS (SEQ ID NO: 291), QVQLVQSGAEVKKPGASVKVSCKASGYIFTGYYMHWVRQAPGQGLEWMGMIGPSDGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREDDSMDVWGKGTTVTVSS(SEQ ID NO: 292), QVQLVQSGAEVKKPGASVKVSCKASGYTFIGYYMHWVRQAPGQGLEWMGMIGPSDGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDSSGLDPWGQGTLVTVSS (SEQ ID NO: 293), QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGMIGPSDGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGVGNLDYWGQGTLVTVSS (SEQ ID NO: 294), QVQLVQSGAEVKKPGASVKVSCKASGVTFSTSAISWVRQAPGQGLEWMGWISPYNGNTDYAQMLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDAHQYYDFWSGYYSGTYYYGMDVWGQGTTVTVSS (SEQ ID NO: 295), QVQLVQSGAEVKKPGASVKVSCKASGGTFSNSIINWVRQAPGQGLEWMGWMNPNSGNTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREQWPSYWYFDLWGRGTLVTVSS (SEQ ID NO:296)、QVQLVQSGAEVKKPGASVKVSCKASGGTFSTHDINWVRQAPGQGLEWMGVINPSGGSAIYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDRGYSYGYFDYWGQGTLVTVSS (SEQ ID NO: 297)、QVQLVQSGAEVKKPGASVKVSCKASGNTFIGYYVHWVRQAPGQGLEWVGIINPNGGSISYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGSGDPNYYYYYGLDVWGQGTTVTVSS(SEQ ID NO: 298)、QVQLVQSGAEVKKPGASVKVSCKASGYTLSYYYMHWVRQAPGQGLEWMGMIGPSDGSTSYAQRFQGRVTMTRDTSTGTVYMELSSLRSEDTAVYYCARDTGDHFDYWGQGTLVTVSS (SEQ ID NO: 299)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGIIGPSDGSTTYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARAENGMDVWGQGTTVTVSS (SEQ ID NO: 300)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQGLEWMGIIAPSDGSTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDPGGYMDVWGKGTTVTVSS (SEQ ID NO: 301)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYLHWVRQAPGQGLEWMGMIGPSDGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGDAFDIWGQGTMVTVSS (SEQ ID NO: 302)、QVQLVQSGAEVKKPGSSVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGRISPSDGSTTYAPKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDMGDAFDIWGQGTTVTVSS (SEQ IDNO: 303), QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGMIGPSDGSTSYAQRFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREEDGMDVWGQGTTVTVSS (SEQ ID NO: 304), QVQLVQSGAEVKKPGASVKVSCKASGYTLSYYYMHWVRQAPGQGLEWMGMIGPSDGSTSYAQRFQGRVTMTRDTSTGTVYMELSSLRSEDTAVYYCARDTGDHFDYWGQGTLVTVSS (SEQ ID NO: 299), QVQLVQSGAEVKKPGSSVKVSCKASGGTFNNFAISWVRQAPGQGLEWMGGIIPIFDATNYAQKFQGRVTFTADESTSTAYMELSSLRSEDTAVYYCARGEYSSGFFFVGWFDLWGRGTQVTVSS (SEQ ID NO: 305) and QVQLVQSGAEVKKPGASVKVSCKASGYNFTGYYMHWVRQAPGQGLEWMGIIAPSDGSTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARETGDDAFDIWGQGTMVTVSS (SEQ ID NO: 306).

[0068] In some embodiments, the ABP comprises a VL sequence selected from: DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYAASSLQGGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYFTTPYTFGQGTKLEIK (SEQ ID NO: 307), DIQMTQSPSSLSASVGDRVTITCRASQSISRWLAWYQQKPGKAPKLLIFDASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAEAFPYTFGQGTKVEIK (SEQ ID NO:308), DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPITFGQGTRLEIK (SEQ ID NO: 309), DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYIIPYTFGQGTKLEIK (SEQ ID NO: 310), DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCHQTYSTPLTFGQGTKVEIK (SEQ ID NO: 311), DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYSASNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAYSFPWTFGQGTKVEIK (SEQ ID NO: 312), DIQMTQSPSSLSASVGDRVTITCRASQNISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGYSTPLTFGQGTRLEIK (SEQ ID NO:313)、DIQMTQSPSSLSASVGDRVTITCRASQDISRYLAWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPRTFGQGTKVEIK (SEQ ID NO: 314). ID NO: 316)、DIQMTQSPSSLSASVGDRVTITCRASQRISSYLNWYQQKPGKAPCLLIYSASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPTFGPGTKVDIK (SEQ ID NO: 317), DIQMTQSPSSLSASVGDRVTITCRASQSISSYLAWYQQKPGKAPKLLIYDASKLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYGVPTFGQGTKLEIK (SEQ ID NO: 318), DIQMTQSPSSLSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ ID NO: 319), DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ ID NO: 71), DIQMTQSPSSLSASVGDRVTITCRASQGISTYLAWYQQKPGKAPKLLIYDASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYYSYPWTFGQGTRLEIK (SEQ ID NO:320),DIQMTQSPSSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASTLQNGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPFTFGPGTKVDIK (SEQ ID NO:316), DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQTLKTPLSFGGTKVEIK (SEQ ID NO: 321) and DIQMTQSPSSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ ID NO: 71).

[0069] In some implementations, the ABP comprises a VH sequence and a VL sequence from an scFv, which is named R3G10-P1A07, R3G10-P1B07, R3G10-P1E12, R3G10-P1F06, R3G10-P1H01, R3G10-P1H08, R3G10-P2C04, R3G10-P2G11, R3G10-P3E04, R3G10-P4A02, R3G10-P4C05, R3G10-P4D04, R3G10-P4D10, R3G10-P4E07, R3G10-P4E12, R3G10-P4G06, R3G10-P5A08, or R3G10-P5C08.

[0070] This article also provides an isolated antigen-binding protein (ABP) that specifically binds to human leukocyte antigen (HLA) peptide targets, wherein the HLA peptide targets include HLA-restricted peptides complexed with HLA class I molecules, wherein the HLA-restricted peptides are located in the peptide-binding groove of the α1 / α2 heterodimer portion of the HLA class I molecule, and wherein the HLA class I molecule is HLA subtype A. 02:01 (Reference sequence: MGSHSMRYFFTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYWDGETRKVKAHSQTHRVDLGTLRGYYNQSEAGSHTVQRMYGCDVGSDWRFLRGYHQYAYDGKDYIALKEDLRSWTAADMAAQTTKHKWEAAHVAEQLRAYLEGTCVEWLRRYLENGKETLQRTDAPKTHMTHHAVSDHEATLRCWALSFYPAEITLTWQRDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGQEQRYTCHVQHEGLPKPLTLR (SEQ ID NO: 197)), and the HLA-restricted peptide comprises the sequence LLASSILCA (SEQ ID NO: 322), and wherein the ABP is bound to any one or more of the following: (a) the restricted peptide LLASSILCA (SEQ ID NO: (b) any one or more of residues 1-5 of HLA-A 02:01 Any one or more of residues 49-85 of the α1 helix, and (c) the HLA-A 02:01 Any one or more of residues 57-67 of the α1 helix.

[0071] In some embodiments of an ABP containing an antibody or its antigen-binding fragment, the HLA class I molecule is an HLA subtype A. 02:01, and the HLA-restricted peptide consists of the sequence LLASSILCA (SEQ ID NO: 322).

[0072] In some embodiments, the ABP comprises CDR-H3, which comprises a sequence selected from the following: CARDGYDFWSGYTSDDYW (SEQ ID NO: 323), CASDYGDYR (SEQ ID NO: 324), CARDLMTTVVTPGDYGMDVW (SEQ ID NO: 325), CARQDGGAFAFDIW (SEQ ID NO: 326), CARELGYYYGMDVW (SEQ ID NO: 327), CALAIFGVPLLPYGMDVW (SEQ ID NO: 328), CAKDLATVGEPYYYYGMDVW (SEQ ID NO: 329), and CARLWFGELHYYYYYGMDVW (SEQ ID NO: 330).

[0073] In some embodiments, the ABP includes CDR-L3, which comprises a sequence selected from the following: CHHYGRSHTF (SEQ ID NO: 331), CQQANAFPPTF (SEQ ID NO: 332), CQQYYSIPLTF (SEQ ID NO: 333), CQQSYSTPPTF (SEQ ID NO: 334), CQQSYSFPYTF (SEQ ID NO: 335), CMQALQTPLTF (SEQ ID NO: 31), CQQGNTFPLTF (SEQ ID NO: 336), and CMQGSHWPPSF (SEQ ID NO: 337).

[0074] In some implementations, the ABP includes CDR-H3 and CDR-L3 from scFv, which are named G7R3-P1C6, G7R3-P1G10, 1-G7R3-P1B4, 2-G7R4-P2C2, 3-G7R4-P1A3, 4-G7R4-B5-P2E9, 5-G7R4-B10-P1F8 or B7 (G7R3-P3A9).

[0075] In some implementations, the ABP comprises all three heavy chain CDRs and all three light chain CDRs from the scFv, which is named G7R3-P1C6, G7R3-P1G10, 1-G7R3-P1B4, 2-G7R4-P2C2, 3-G7R4-P1A3, 4-G7R4-B5-P2E9, 5-G7R4-B10-P1F8 or B7 (G7R3-P3A9).

[0076] In some embodiments, the ABP comprises a VH sequence selected from the following: QVQLVQSGAEVKKPGASVKVSCKASGGTFSNYGISWVRQAPGQGLEWMGIINPGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGYDFWSGYTSDDYWGQGTLVTVSS (SEQ ID NO: 338), EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVSGISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASDYGDYRGQGTLVTVSS (SEQ ID NO: 339), QVQLVQSGAEVKKPGASVKVSCKASGYTFSNYYIHWVRQAPGQGLEWMGWLNPNSGNTGYAQRFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDLMTTVVTPGDYGMDVWGQGTTVTVSS (SEQID NO: 340), QVQLVQSGAEVKKPGASMKVSCKASGYTFTTDGISWVRQAPGQGLEWMGRIYPHSGYTEYAKKFKGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARQDGGAFAFDIWGQGTMVTVSS (SEQ ID NO: 341), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSQYMHWVRQAPGQGLEWMGWISPNNGDTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARELGYYYGMDVWGQGTTVTVSS (SEQ ID NO: 342), QVQLVQSGAEVKKPGSSVKVSCKASRYTFTSYDINWVRQAPGQGLEWMGRIIPMLNIANYAPKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARALIFGVPLLPYGMDVWGQGTTVTVSS (SEQ ID NO: 343), EVQLLQSGGGLVQPGGSLRLSCAASGFTFSSSWMHWVRQAPGKGLEWVSFISTSSGYIYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDLATVGEPYYYYGMDVWGQGTTVTVSS (SEQ ID NO:344) and QVQLVQSGAEVKKPGSSVKVSCKASGDTFNTYALSWVRQAPGQGLEWMGWMNPNSGNAGYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARLWFGELHYYYYYGMDVWGQGTMVTVSS (SEQ ID NO: 345).

[0077] In some embodiments, the ABP comprises a VL sequence selected from: EIVMTQSPATLSVSPGERATLSCRASQSVSSSNLAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCHHYGRSHTFGQGTKVEIK (SEQ ID NO: 346), DIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANAFPPTFGQGTKVEIK (SEQ ID NO: 347), DIVMTQSPDSLAVSLGERATINCKSSQSVFYSSNNKNQLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSIPLTFGQGTKLEIK (SEQ ID NO: 348), DIQMTQSPSSLSASVGDRVTITCQASQDIFKYLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPTFGQGTRLEIK (SEQ ID NO: 349), DIQMTQSPSSLSASVGDRVTITCRASQSISTWLAWYQQKPGKAPKLLIYYASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPYTFGQGTKVEIK (SEQ ID NO: 350), DIVMTQSPLSLPVTPGEPASISCSSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPLTFGGGTKVEIK (SEQ ID NO: 351), DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYSASNLRSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGNTFPLTFGQGTKVEIK (SEQ ID NO:352) and DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGTDFTLKISRVEAEDVGVYYCMQGSHWPPSFGQGTRLEIK (SEQ ID NO: 353).

[0078] In some implementations, the ABP comprises a VH sequence and a VL sequence from an scFv, which is named G7R3-P1C6, G7R3-P1G10, 1-G7R3-P1B4, 2-G7R4-P2C2, 3-G7R4-P1A3, 4-G7R4-B5-P2E9, 5-G7R4-B10-P1F8, or B7 (G7R3-P3A9).

[0079] In some embodiments, the ABP comprises an antibody or an antigen-binding fragment thereof. In some embodiments, the antigen-binding protein is linked to a scaffold, optionally the scaffold comprises serum albumin or Fc, optionally wherein the Fc is a human Fc and is an isotype of IgG (IgG1, IgG2, IgG3, IgG4), IgA (IgA1, IgA2), IgD, IgE, or IgM. In some embodiments, the antigen-binding protein is linked to the scaffold via a linker, optionally the linker is a peptide linker, optionally the peptide linker is a hinge region of a human antibody. In some embodiments, the antigen-binding protein comprises an Fv fragment, a Fab fragment, an F(ab')2 fragment, a Fab' fragment, a scFv fragment, a scFv-Fc fragment, and / or a single-domain antibody or an antigen-binding fragment thereof. In some embodiments, the antigen-binding protein comprises an scFv fragment. In some embodiments, the antigen-binding protein comprises one or more antibody complementarity-determining regions (CDRs), optionally six antibody CDRs. In some embodiments, the antigen-binding protein comprises an antibody. In some embodiments, the antigen-binding protein is a monoclonal antibody. In some embodiments, the antigen-binding protein is a humanized, human, or chimeric antibody. In some embodiments, the antigen-binding protein is multispecific, optionally bispecific. In some embodiments, the antigen-binding protein binds to more than one antigen or more than one epitope on a single antigen. In some embodiments, the antigen-binding protein comprises a heavy chain constant region selected from classes of IgG, IgA, IgD, IgE, and IgM. In some embodiments, the antigen-binding protein comprises a heavy chain constant region of class human IgG and subclasses selected from IgG1, IgG4, IgG2, and IgG3. In some embodiments, the antigen-binding protein comprises one or more modifications that extend its half-life. In some embodiments, the antigen-binding protein comprises a modified Fc, optionally containing one or more mutations that extend its half-life, optionally YTE.

[0080] In some embodiments of the isolated ABP, the ABP comprises a T cell receptor (TCR) or its antigen-binding portion. In some embodiments, the TCR or its antigen-binding portion comprises a TCR variable region. In some embodiments, the TCR or its antigen-binding portion comprises one or more TCR complementarity-determining regions (CDRs).

[0081] In some embodiments, the TCR comprises α-chains and β-chains. In some embodiments, the TCR comprises γ-chains and δ-chains.

[0082] In some embodiments, the antigen-binding protein is part of a chimeric antigen receptor (CAR) comprising: an extracellular portion containing the antigen-binding protein; and an intracellular signaling domain. In some embodiments, the antigen-binding protein comprises scFv, and the intracellular signaling domain comprises an immune receptor tyrosine activation motif (ITAM). In some embodiments, the intracellular signaling domain comprises a signaling domain of the ζ chain of the CD3-ζ (CD3) chain.

[0083] In some embodiments, the ABP further includes a transmembrane domain connecting the extracellular domain and the intracellular signal transduction domain. In some embodiments, the transmembrane domain includes the transmembrane portion of CD28.

[0084] In some embodiments, the ABP further comprises an intracellular signaling domain of a T-cell co-stimulatory molecule. In some embodiments, the T-cell co-stimulatory molecule is CD28, 4-1BB, OX-40, ICOS, or any combination thereof.

[0085] This article also provides isolated polynucleotides encoding the isolated ABP as described herein.

[0086] In some embodiments of the ABP, the antigen-binding protein binds to the HLA-peptide target via contact sites with HLA class I molecules and with HLA-restricted peptides of the HLA-peptide target. In some embodiments of the ABP, the binding of the ABP to amino acid positions on the restriction peptide or HLA subtype, or the contact sites or residues that directly or indirectly affect the binding of the HLA-peptide target to the ABP, are determined by position scanning, hydrogen-deuterium exchange, or protein crystallography.

[0087] In some embodiments, the ABP can be used as a drug. In some embodiments, the ABP can be used to treat cancer, optionally wherein the cancer expresses or is expected to express an HLA-peptide target. In some embodiments, the ABP can be used to treat cancer, wherein the cancer is selected from solid tumors and hematologic malignancies.

[0088] This article also provides ABP, a conserved modified variant of the ABP described herein. This article also provides antigen-binding proteins (ABPs) that compete with the antigen-binding proteins described herein for binding. This article also provides antigen-binding proteins (ABPs) that bind to the same HLA-peptide epitopes as the antigen-binding proteins described herein.

[0089] This document also provides engineered cells expressing receptors comprising the antigen-binding protein described herein. In some embodiments, the engineered cells are T cells, optionally cytotoxic T cells (CTLs). In some embodiments of the engineered cells, the antigen-binding protein is expressed from a heterologous promoter.

[0090] This article also provides isolated polynucleotides or polynucleotide sequences encoding the antigen-binding proteins or their antigen-binding moieties described herein.

[0091] This article also provides isolated polynucleotides or polynucleotide sequences encoding the HLA / peptide targets described herein.

[0092] This article also provides vectors or vector sets containing the polynucleotides or polynucleotide groups described herein.

[0093] This document also provides a host cell comprising the polynucleotides or polynucleotide groups described herein or the vectors or vector groups described herein, optionally wherein the host cell is CHO or HEK293, or optionally wherein the host cell is a T cell.

[0094] This article also provides methods for generating antigen-binding proteins, including: expressing the antigen-binding protein in host cells as described herein and isolating the expressed antigen-binding protein.

[0095] This article also provides pharmaceutical compositions comprising the antigen-binding protein described herein and pharmaceutically acceptable excipients.

[0096] This document also provides a method for treating a subject's cancer, comprising: administering to the subject an effective amount of the antigen-binding protein described herein or a pharmaceutical composition described herein, optionally wherein the cancer is selected from solid tumors and hematologic malignancies. In some embodiments, the cancer expresses or is expected to express an HLA-peptide target.

[0097] This article also provides kits that include the antigen-binding protein or pharmaceutical composition described herein, along with instructions for use.

[0098] This article also provides compositions comprising at least one HLA-peptide target and adjuvant described herein.

[0099] This article also provides compositions comprising at least one HLA-peptide target described herein and a pharmaceutically acceptable excipient.

[0100] This document also provides compositions comprising amino acid sequences including at least one HLA-peptide target polypeptide disclosed in Table A, Table A1 or Table A2, optionally, the amino acid sequence consisting substantially of or composed of the polypeptide.

[0101] This document also provides viruses comprising the isolated polynucleotides or polynucleotide sequences described herein. In some embodiments, the virus is a filamentous bacteriophage.

[0102] This article also provides yeast cells containing the isolated polynucleotides or polynucleotide groups described herein.

[0103] In particular, this application relates to the following: 1. An isolated antigen-binding protein (ABP) that specifically binds to a human leukocyte antigen (HLA)-peptide target, wherein the HLA-peptide target comprises an HLA-restricted peptide complexed with an HLA class I molecule, wherein the HLA-restricted peptide is located in the peptide-binding groove of the α1 / α2 heterodimeric portion of the HLA class I molecule, wherein the HLA class I molecule is an HLA subtype B. 35:01 (Reference sequence: MGSHSMRYFYTAMSRPGRGEPRFIAVGYVDDTQFVRFDSDAASPRTEPRAPWIEQEGPEYWDRNTQIFKTNTQTYRESLRNLRGYYNQSEAGSHIIQRMYGCDLGPDGRLLRGHDQSAYDGKDYIALNEDLSSWTAADTAAQITQRKWEAARVAEQLRAYLEGLCVEWLRRYLENGKETLQRADPPKTHVTHHPVSDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDRTFQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLR (SEQ ID NO: 1)), and the HLA-restricted peptide comprises the sequence EVDPIGHVY (SEQ ID NO: 2), and wherein the ABP binds to any one or more of the following: a. Any one or more of amino acid positions 2-9 of the restricted peptide EVDPIGHVY (SEQ ID NO: 2); b. HLA subtype B The amino acid positions of the α1 helix of 35:01 are any one or more of 50, 54, 55, 57, 61, 62, 74, 81, 82, and 85; and c. HLA subtype B The amino acid positions 147 and 148 of the α2 helix of 35:01.

[0104] 2. The isolated ABP as described in item 1, wherein the ABP is bound to any one or more of amino acid positions 2-8 of the restriction peptide EVDPIGHVY (SEQ ID NO: 2).

[0105] 3. The isolated ABP as described in item 1, wherein the ABP is bound to any one or more of amino acid positions 5-9 of the restriction peptide EVDPIGHVY (SEQ ID NO: 2).

[0106] 4. The isolated ABP as described in any one of items 1 to 3, wherein the HLA class I molecule is an HLA subtype B. 35:01, and the HLA-restricted peptide consists of the sequence EVDPIGHVY (SEQ ID NO: 2).

[0107] 5. The isolated ABP as described in any one of claims 1-4, wherein the ABP comprises CDR-H3, the CDR-H3 comprising a sequence selected from the following: CARDGVRYYGMDVW (SEQ ID NO: 3), CARDGVRGYDRSAGYW (SEQ ID NO: 4), CASHDYGDYGEYFQHW (SEQ ID NO: 5), CARVSWYCSSTSCGVNWFDPW (SEQ ID NO: 6), CAKVNWNDGPYFDYW (SEQ ID NO: 7), CATPTNSGYYGPYYYYGMDVW (SEQ ID NO: 8), CARDVMDVW (SEQ ID NO: 9), CAREGYGMDVW (SEQ ID NO: 10), CARDNGVGVDYW (SEQ ID NO: 11), CARGIADSGSYYGNGRDYYYGMDVW (SEQ ID NO: 12), CARDGDYYFDYW (SEQ ID NO: 13). 13), CARDGTRYYGMDVW (SEQ ID NO: 14), CARDVVANFDYW (SEQ ID NO: 15), CARGHSSGWYYYYGMDVW (SEQ ID NO: 16), CAKDLGSYGGYYW (SEQ ID NO: 17), CARSWFGGFNYHYYGMDVW (SEQ ID NO: 18), CARELPIGYGMDVW (SEQ ID NO: 19) and CARGGSYYYYGMDVW (SEQ ID NO: 20).

[0108] 6. The isolated ABP as described in any one of claims 1-5, wherein the ABP comprises CDR-L3, the CDR-L3 comprising a sequence selected from the following: CMQGLQTPITF (SEQ ID NO: 21), CMQALQTPPTF (SEQ ID NO: 22), CQQAISFPLTF (SEQ ID NO: 23), CQQANSFPLTF (SEQ ID NO: 24), CQQANSFPLTF (SEQ ID NO: 24), CQQSYSIPLTF (SEQ ID NO: 25), CQQTYMMPYTF (SEQ ID NO: 26), CQQSYITPWTF (SEQ ID NO: 27), CQQSYITPYTF (SEQ ID NO: 28), CQQYYTTPYTF (SEQ ID NO: 29), CQQSYSTPLTF (SEQ ID NO: 30), CMQALQTPLTF (SEQ ID NO: 31), CQQYGSWPRTF (SEQ ID NO: 32), CMQGLQTPITF (SEQ ID NO: 23), CMQALQTPPTF (SEQ ID NO: 24), CQQSYSIPLTF (SEQ ID NO: 25), CQQTYMMPYTF (SEQ ID NO: 26), CQQSYITPWTF (SEQ ID NO: 27), CQQSYITPYTF (SEQ ID NO: 28), CQQYYTTPYTF (SEQ ID NO: 29), CQQSYSTPLTF (SEQ ID NO: 30), CMQALQTPLTF (SEQ ID NO: 31), CQQYGSWPRTF (SEQ ID NO: 32), CQQYGSWPRTF (SEQ ID NO: 33), CQQYGSWPRTF (SEQ ID NO: 34), CQQYGSWPRTF (SEQ ID NO: 35), CQQYGSWPRTF (SEQ ID NO: 36), CQQYGSWPRTF (SEQ ID NO: 37), CQQYGSWPRTF (SEQ ID NO: 38), CQQYGSWPRTF ( 32), CQQSYSTPVTF (SEQ ID NO: 33), CMQALQTPYTF (SEQ ID NO: 34), CQQANSFPFTF (SEQ ID NO: 35), CMQALQTPLTF (SEQ ID NO: 31) and CQQSYSTPLTF (SEQ ID NO: 30).

[0109] 7. The isolated ABP as described in any one of items 1-6, wherein the ABP comprises CDR-H3 and CDR-L3 from scFv, the scFv being named G5_P7_E7, G5_P7_B3, G5_P7_A5, G5_P7_F6, G5-P1B12, G5-P1C12, G5-P1-E05, G5-P3G01, G5-P3G08, G5-P4B02, G5-P4E04, G5R4-P1D06, G5R4-P1H11, G5R4-P2B10, G5R4-P2H8, G5R4-P3G05, G5R4-P4A07 or G5R4-P4B01.

[0110] 8. The isolated ABP as described in any one of items 1-7, wherein the ABP comprises all three heavy chain CDRs and all three light chain CDRs from the scFv, the scFv being named G5_P7_E7, G5_P7_B3, G5_P7_A5, G5_P7_F6, G5-P1B12, G5-P1C12, G5-P1-E05, G5-P3G01, G5-P3G08, G5-P4B02, G5-P4E04, G5R4-P1D06, G5R4-P1H11, G5R4-P2B10, G5R4-P2H8, G5R4-P3G05, G5R4-P4A07 or G5R4-P4B01.

[0111] 9. The isolated ABP according to any one of items 1-8, wherein the ABP comprises a VH sequence selected from QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGIINPRSGSTKYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGVRYYGMDVWGQGTTVTVSS (SEQ ID NO: 36), QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSHDINWVRQAPGQGLEWMGWMNPNSGDTGYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGVRGYDRSAGYWGQGTLVIVSS (SEQ ID NO: 37), EVQLLESGGGLVKPGGSLRLSCAASGFSFSSYWMSWVRQAPGKGLEWISYISGDSGYTNYADSVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCASHDYGDYGEYFQHWGQGTLVTVSS (SEQ ID NO: 38), EVQLLQSGGGLVQPGGSLRLSCAASGFTFSNSDMNWVRQAPGKGLEWVAYISSGSSTIYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVSWYCSSTSCGVNWFDPWGQGTLVTVSS (SEQ ID NO: 39), EVQLLESGGGLVQPGGSLRLSCAASGFTFSNSDMNWVRQAPGKGLEWVASISSSGGYINYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKVNWNDGPYFDYWGQGTLVTVSS (SEQID NO: 40), QVQLVQSGAEVKKPGSSVKVSCKASGGTFSNFGVSWLRQAPGQGLEWMGGIIPILGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCATPTNSGYYGPYYYYGMDVWGQGTTVTVSS (SEQ ID NO:41), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYNMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDVMDVWGQGTTVTVSS (SEQ IDNO: 42)、QVQLVQSGAEVKKPGASVKVSCKASGGTFSGYLVSWVRQAPGQGLEWMGWINPNSGGTNTAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREGYGMDVWGQGTTVTVSS (SEQ ID NO: 43)、QVQLVQSGAEVKKPGASVKVSCKASGYIFRNYPMHWVRQAPGQGLEWMGWINPDSGGTKYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDNGVGVDYWGQGTLVTVSS (SEQ ID NO: 44)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWMNPNIGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGIADSGSYYGNGRDYYYGMDVWGQGTTVTVSS(SEQ ID NO: 45)、QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYGISWVRQAPGQGLEWMGWINPNSGVTKYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGDYYFDYWGQGTLVTVSS (SEQ ID NO: 46)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGWINPNSGDTKYSQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGTRYYGMDVWGQGTTVTVSS (SEQ ID NO: 47)、EVQLLESGGGLVKPGGSLRLSCAASGFTFSDYYMSWVRQAPGKGLEWVSYISSSSSYTNYADSVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCARDVVANFDYWGQGTLVTVSS (SEQ ID NO: 48)、QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWMNPDSGSTGYAQRFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGHSSGWYYYYGMDVWGQGTTVTVSS (SEQ ID NO:49) EVQLLESGGGLVQPGGSLRLSCAASGFTFTSYSMHWVRQAPGKGLEWVSSITSFTNTMYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDLGSYGGYYWGQGTLVTVSS (SEQ ID NO: 50), QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYYMHWVRQAPGQGLEWMGIINPSGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSWFGGFNYHYYGMDVWGQGTTVTVSS (SEQ ID NO: 51), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARELPIGYGMDVWGQGTTVTVSS (SEQ ID NO: 52) and QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIVGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGGSYYYYGMDVWGQGTTVTVSS (SEQ ID NO: 53).

[0112] 10. The isolated ABP according to any one of items 1-9, wherein the ABP comprises a VL sequence selected from DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSYRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGLQTPITFGQGTRLEIK (SEQ ID NO: 54), DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSSRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPPTFGPGTKVDIK (SEQ ID NO: 55), DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAISFPLTFGQSTKVEIK (SEQ ID NO:56), DIQMTQSPSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYSASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPLTFGGGTKVEIK (SEQ ID NO: 57), DIQMTQSPSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPLTFGGGTKVEIK (SEQ ID NO: 58), DIQMTQSPSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSIPLTFGGGTKVEIK (SEQ ID NO: 59), DIQMTQSPSSLSASVGDRVTITCRASQGISNYLNWYQQKPGKAPKLLIYYASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYMMPYTFGQGTKVEIK (SEQ ID NO:60)、DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYGASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYITPWTFGQGTKVEIK(SEQ ID NO: 61)、DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYITPYTFGQGTKLEIK (SEQ ID NO: 62)、DIVMTQSPDSLAVSLGERATINCKTSQSVLYRPNNENYLAWYQQKPGQPPKLLIYQASIREPGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYTTPYTFGQGTKLEIK (SEQ ID NO: 63)、DIQMTQSPSSLSASVGDRVTITCRASQSISRFLNWYQQKPGKAPKLLIYGASRPQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGQGTKVEIK(SEQ ID NO: 64)、DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSHRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPLTFGGGTKVEIK (SEQ ID NO: 65)、EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQKPGQAPRLLIYAASARASGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYGSWPRTFGQGTKVEIK (SEQ ID NO: 66)、DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYGASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPVTFGQGTKVEIK (SEQID NO: 67)、DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPYTFGQGTKVEIK (SEQ IDNO: 68), DIQMTQSPSSLSSASVGDRVTITCQASEDISNHLNWYQQKPGKAPKLLIYDALSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPFTFGPGTKVDIK (SEQ ID NO: 69), DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPLTFGQGTKVEIK (SEQID NO: 70) and DIQMTQSPSSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ ID NO: 71).

[0113] 11. The isolated ABP as described in any one of claims 1-10, wherein the ABP comprises a VH sequence and a VL sequence from an scFv named G5_P7_E7, G5_P7_B3, G5_P7_A5, G5_P7_F6, G5-P1B12, G5-P1C12, G5-P1-E05, G5-P3G01, G5-P3G08, G5-P4B02, G5-P4E04, G5R4-P1D06, G5R4-P1H11, G5R4-P2B10, G5R4-P2H8, G5R4-P3G05, G5R4-P4A07, and G5R4-P4B01.

[0114] 12. An isolated antigen-binding protein (ABP) that specifically binds to a human leukocyte antigen (HLA)-peptide target, wherein the HLA-peptide target comprises an HLA-restricted peptide complexed with an HLA class I molecule, wherein the HLA-restricted peptide is located in the peptide-binding groove of the α1 / α2 heterodimeric portion of the HLA class I molecule, and the HLA class I molecule is an HLA subtype A. 01:01 (Reference sequence: MGSHSMRYFFTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQKMEPRAPWIEQEGPEYWDQETRNMKAHSQTDRANLGTLRGYYNQSEDGSHTIQIMYGCDVGPDGRFLRGYRQDAYDGKDYIALNEDLRSWTAADMAAQITKRKWEAVHAAEQRRVYLEGRCVDGLRRYLENGKETLQRTDPPKTHMTHHPISDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLR (SEQ ID NO:72)), and the HLA-restricted peptide comprises the sequence NTDNNLAVY (SEQ ID NO: 73), and wherein the ABP binds to any one or more of the following: a. Any one or more residues 3-9 of the restricted peptide NTDNNLAVY (SEQ ID NO: 73), b. HLA subtype allele A 01:01 α1 helix residues 70-85 of any one or more, and c. HLA subtype allele A Any one or more of residues 140-160 of the α2 helix of 01:01.

[0115] 13. The isolated ABP as described in item 12, wherein the ABP is bound to any one or more residues 6-9 of the restriction peptide NTDNNLAVY (SEQ ID NO: 73).

[0116] 14. The isolated ABP as described in item 13, wherein the ABP is bound to any one or more residues 7-8 of the restriction peptide NTDNNLAVY (SEQ ID NO: 73).

[0117] 15. The isolated ABP as described in any one of items 12-14, wherein the ABP is associated with the HLA subtype allele A. The α2 helix of 01:01 may bind to any one or more of residues 157-160.

[0118] 16. The isolated ABP as described in item 15, wherein the ABP is associated with any one or more residues 6-9 of the restriction peptide NTDNNLAVY (SEQ ID NO: 73) and the HLA subtype allele A. The α2 helix of 01:01 may bind to any one or more of residues 157-160.

[0119] 17. The isolated ABP as described in any one of items 12-16, wherein the HLA class I molecule is an HLA subtype A. 01:01, and the HLA-restricted peptide consists of the sequence NTDNNLAVY (SEQ ID NO: 73).

[0120] 18. The isolated ABP as described in any one of claims 12-17, wherein the ABP comprises CDR-H3, the CDR-H3 comprising a sequence selected from: CAATEWLGVW (SEQ ID NO: 74), CARANWLDYW (SEQ ID NO: 75), CARANWLDYW (SEQ ID NO: 75), CARDWVLDYW (SEQ ID NO: 76), CARGEWLDYW (SEQ ID NO: 77), CARGWELGYW (SEQ ID NO: 78), CARDFVGYDDW (SEQ ID NO: 79), CARDYGDLDYW (SEQ ID NO: 80), CARGSYGMDVW (SEQ ID NO: 81), CARDGYSGLDVW (SEQ ID NO: 82), CARDSGVGMDVW (SEQ ID NO: 83), CARDGVAVASDYW (SEQ ID NO: 84), CARGVNVDDFDYW (SEQ ID NO: 85), CAATEWLGVW (SEQ ID NO: 76), CARANWLDYW (SEQ ID NO: 77), CARGYSGLDVW (SEQ ID NO: 88), CARGVVGMDVW (SEQ ID NO: 89), CARGYGDLDYW (SEQ ID NO: 80), CARGSYGMDVW (SEQ ID NO: 81), CARGYSGLDVW (SEQ ID NO: 82), CARGSGVGMDVW (SEQ ID NO: 83), CARGVVAVASDYW (SEQ ID NO: 84), CARGVNVDDFDYW (SEQ ID NO: 85), CARGVNVDDFDYW (SEQ ID NO: 86), CARGVNVDDFDYW (SEQ ID NO: 87), CARGVNVDDFDYW (SEQ ID NO: 88), CARGVNVDDFDYW (SEQ ID NO: 89), CARGVVAVASDYW (SEQ ID NO: 80), CARGYGMDVW 85), CARGDYTGNWYFDLW (SEQ ID NO: 86), CARANWLDYW (SEQ ID NO: 75), CARDQFYGGNSGGHDYW (SEQ ID NO: 87), CAREEDYW (SEQ ID NO: 88), CARGDWFDPW (SEQ ID NO: 89), CARGDWFDPW (SEQ ID NO: 89), CARGEWFDPW (SEQ ID NO: 90), CARSDWFDPW (SEQ ID NO: 91), CARDGSYFDYW (SEQ ID NO: 92), CARDYGGYVDYW (SEQ ID NO: 93), CAREGPAALDVW (SEQ ID NO: 94), CARERRSGMDVW (SEQ ID NO: 95), CARVLQEGMDVW (SEQ ID NO: 96), CASERELPFDIW (SEQ ID NO: 97), CAKGGGGYGMDVW (SEQ ID NO: 98), CAAMGIAVAGGMDVW (SEQ ID NO: 99), CARNWNLDYW (SEQ ID NO: 100), CATYDDGMDVW (SEQ ID NO: 101), CARGGGGALDYW (SEQ ID NO: 102), CALSGNYYGMDVW (SEQ ID NO:103), CARGNPWELRLDYW (SEQ ID NO: 104) and CARDKNYYGMDVW (SEQ ID NO: 105).

[0121] 19. The isolated ABP according to any one of items 12-18, wherein the ABP comprises CDR-L3, and the CDR-L3 comprises a sequence selected from the following: CQQSYNTPYTF (SEQ ID NO: 106), CQQSYSTPYTF (SEQ ID NO:107), CQQSYSTPYSF (SEQ ID NO: 108), CQQSYSTPFTF (SEQ ID NO: 109), CQQSYGVPYTF(SEQ ID NO: 110), CQQSYSAPYTF (SEQ ID NO: 111), CQQSYSAPYTF (SEQ ID NO: 111), CQQSYSAPYSF (SEQ ID NO: 112), CQQSYSTPYTF (SEQ ID NO: 107), CQQSYSVPYSF (SEQ IDNO: 113), CQQSYSAPYTF (SEQ ID NO: 111), CQQSYSVPYSF (SEQ ID NO: 113), CQQSYSTPQTF (SEQ ID NO: 114), CQQLDSYPFTF (SEQ ID NO: 115), CQQSYSSPYTF (SEQ IDNO: 116), CQQSYSTPLTF (SEQ ID NO: 30), CQQSYSTPYSF (SEQ ID NO: 108), CQQSYSTPYTF(SEQ ID NO: 107), CQQSYSTPYTF (SEQ ID NO: 107), CQQSYSTPFTF (SEQ ID NO: 109), CQQSYSTPTF (SEQ ID NO: 117), CQQTYAIPLTF (SEQ ID NO: 118), CQQSYSTPYTF (SEQ IDNO: 107), CQQSYIAPFTF (SEQ ID NO: 119), CQQSYSIPLTF (SEQ ID NO: 25), CQQSYSNPTF(SEQ ID NO: 120), CQQSYSTPYSF (SEQ ID NO: 108), CQQSYSDQWTF (SEQ ID NO: 121), CQQSYLPPYSF (SEQ ID NO: 122), CQQSYSSPYTF (SEQ ID NO: 116), CQQSYTTPWTF (SEQ IDNO: 123), CQQSYLPPYSF (SEQ ID NO: 122), CQEGITYTF (SEQ ID NO:124), CQQYYSYPFTF (SEQ ID NO: 125) and CQHYGYSPVTF (SEQ ID NO: 126).

[0122] 20. The isolated ABP as described in any one of claims 12-19, wherein the ABP comprises CDR-H3 and CDR-L3 from scFv, the scFv being named G2-P1H11, G2-P2E07, G2-P2E03, G2-P2A11, G2-P2C06, G2-P1G01, G2-P1C02, G2-P1H01, G2-P1B12, G2-P1B06, G2-P2H10, G2-P1H10, G2-P2C11, G2-P1C09, G2-P1A10, G2-P1B10, G2-P1D07, G2-P1E05, G2-P1D03, G2-P1G12, G2-P2H11, G2-P1C03, G2-P1G07, G2-P1F12, G2-P1G03, G2-P2B08, G2-P2A10, G2-P2D04, G2-P1C06, G2-P2A09, G2-P1B08, G2-P1E03, G2-P2A03, G2-P2F01 or G2-P1D06.

[0123] 21. The isolated ABP as described in item 20, wherein the ABP comprises CDR-H3 and CDR-L3 from scFv named G2-P1H11.

[0124] 22. The isolated ABP as described in any one of items 12-21, wherein the ABP comprises all three heavy chain CDRs and all three light chain CDRs from scFv, wherein the scFv is named G2-P1H11, G2-P2E07, G2-P2E03, G2-P2A11, G2-P2C06, G2-P1G01, G2-P1C02, G2-P1H01, G2-P1B12, G2-P1B06, G2-P2H10, G2-P1H10, G2-P2C11, G2-P1C 09, G2-P1A10, G2-P1B10, G2-P1D07, G2-P1E05, G2-P1D03, G2-P1G12, G2-P2H11, G2-P1C03, G2-P1G07, G2-P1F12, G2-P1G03, G2-P2B08, G2-P2A10, G2-P2D04, G2-P1C06, G2-P2A09, G2-P1B08, G2-P1E03, G2-P2A03, G2-P2F01 or G2-P1D06.

[0125] 23. The isolated ABP as described in item 22, wherein the ABP comprises all three heavy chain CDRs and all three light chain CDRs from scFv named G2-P1H11.

[0126] 24. The isolated ABP according to any one of items 12-23, wherein the ABP comprises a VH sequence selected from: QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYYMHWVRQAPGQGLEWMGMINPSGGGTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGNPWELRLDYWGQGTLVTVSS (SEQ ID NO: 127), QVQLVQSGAEVKKPGASVKVSCKASGGTFSSATISWVRQAPGQGLEWMGWIYPNSGGTVYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAATEWLGVWGQGTTVTVSS (SEQ ID NO: 128), EVQLLQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWINPNSGGTISAPNFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARANWLDYWGQGTLVTVSS (SEQ ID NO: 129), EVQLLESGAEVKKPGASVKVSCKASGYTFTTYDLAWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARANWLDYWGQGTLVTVSS (SEQ IDNO: 130), QVQLVQSGAEVKKPGASVKVSCKSSGYSFDSYVVNWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDWVLDYWGQGTLVTVSS (SEQ ID NO: 131), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWMNPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGEWLDYWGQGTLVTVSS (SEQ ID NO: 132), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGWELGYWGQGTLVTVSS (SEQ ID NO:133), QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYTINWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDFVGYDDWGQGTLVTVSS (SEQ ID NO: 134), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGITWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDYGQGTLVTVSS (SEQ ID NO: 135), QVQLVQSGAEVKKPGASVKVSCKASGGTFSNYILSWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGSYGMDVWGQGTLVTVSS (SEQ ID NO: 136). 137). 138). 139).140)、QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAFSWVRQAPGQGLEWMGWINPDTGYTRYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGDYTGNWYFDLWGRGTLVTVSS (SEQ ID NO: 141)、EVQLLESGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWINPYSGGTNYAQKLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARANWLDYWGQGTLVTVSS (SEQ ID NO: 142)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGYTNYAQNLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDQFYGGNSGGHDYWGQGTLVTVSS(SEQ ID NO: 143)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYNMHWVRQAPGQGLEWMGWMNPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREEDYWGQGTLVTVSS(SEQ ID NO: 144)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYTINWVRQAPGQGLEWMGWINPNSGGANYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGDWFDPWGQGTLVTVSS (SEQ ID NO: 145)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYLMHWVRQAPGQGLEWMGWISPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGDWFDPWGQGTLVTVSS (SEQ ID NO: 146)、QVQLVQSGAEVKKPGASVKVSCKASGYTFSDYYVHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGEWFDPWGQGTLVTVSS (SEQID NO:147)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTTYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSDWFDPWGQGTLVTVSS (SEQ ID NO: 148)、QVQLVQSGAEVKKPGASVKVSCKASGGTFSNYAINWVRQAPGQGLEWMGWISPYSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDSGSYFDYWGQGTLVTVSS (SEQ ID NO: 149)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYMHWVRQAPGQGLEWMGWIYPNTGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDYGGYVDYWGQGTLVTVSS (SEQ ID NO: 150)、EVQLLESGAEVKKPGASVKVSCKASGYTFTSYAMNWVRQAPGQGLEWMGWMNPNSGGTKYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREGPAALDVWGQGTLVTVSS(SEQ ID NO: 151)、QVQLVQSGAEVKKPGASVKVSCKASGYTLTSHLIHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARERRSGMDVWGQGTTVTVSS (SEQ ID NO: 152)、EVQLLESGAEVKKPGASVKVSCKASGYSFTDYIVHWVRQAPGQGLEWMGWINPYSGGTKYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARVLQEGMDVWGQGTLVTVSS (SEQ ID NO: 153)、QVQLVQSGAEVKKPGASVKVSCKASGYTFSNFLINWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCASERELPFDIWGQGTMVTVSS (SEQ ID NO:154) QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYQMFWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKGGGGYGMDVWGQGTTVTVSS (SEQ ID NO: 155), QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAAMGIAVAGGMDVWGQGTLVTVSS (SEQ ID NO: 156), QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYHMHWVRQAPGQGLEWMGWIHPDSGGTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARNWNLDYWGQGTLVTVSS (SEQ ID NO: 157), QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCATYDDGMDVWGQGTTVTVSS (SEQ ID NO: 158), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYTVNWVRQAPGQGLEWMGWINPNSGGTKYAQNFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGGGALDYWGQGTLVTVSS (SEQ ID NO: 159), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGMINPRDDTTDYARDFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCALSGNYYGMDVWGQGTTVTVSS (SEQ ID NO: 160), and QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSQYMHWVRQAPGQGLEWMGRIIPLLGIVNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDKNYYGMDVWGQGTTVTVSS (SEQ ID NO: 161).

[0127] 25. The isolated ABP according to any one of items 12 - 24, wherein the ABP comprises a VL sequence selected from: DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYYSYPFTFGPGTKVDIK (SEQ ID NO: 162), DIQMTQSPSSLSASVGDRVTITCRASQSISTWLAWYQQKPGKAPKLLIYAASSLRSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYNTPYTFGQGTKLEIK (SEQ ID NO: 163), DIQMTQSPSSLSASVGDRVTITCRASQSISRWLAWYQQKPGKAPKLLIYAASTVQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK (SEQ ID NO:164), DIQMTQSPSSLSASVGDRVTITCRASQDISRWLAWYQQKPGKAPKLLIYAASRLQAGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYSFGQGTKLEIK (SEQ ID NO: 165), DIQMTQSPSSLSASVGDRVTITCRASQTISSWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPFTFGPGTKVDIK (SEQ ID NO: 166), DIQMTQSPSSLSASVGDRVTITCRASQTISSWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYGVPYTFGQGTKVEIK (SEQ ID NO: 167), DIQMTQSPSSLSASVGDRVTITCRASQSISNWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSAPYTFGPGTKVDIK (SEQ ID NO:168)、DIQMTQSPSSLSASVGDRVTITCRASQSVGNWLAWYQQKPGKAPKLLIYGASSLQTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSAPYTFGQGTKVEIK (SEQ ID NO: 169)、DIQMTQSPSSLSASVGDRVTITCRASQNIGNWLAWYQQKPGKAPKLLIYAASTLQTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSAPYSFGQGTKLEIK (SEQ ID NO: 170)、DIQMTQSPSSLSASVGDRVTITCRASQSISRWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK (SEQ ID NO: 171)、DIQMTQSPSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYGASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSVPYSFGQGTKLEIK(SEQ ID NO: 172)、DIQMTQSPSSLSASVGDRVTITCRASQSISKWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSAPYTFGQGTKVEIK (SEQ ID NO: 173)、DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSVPYSFGQGTKLEIK (SEQ ID NO: 174)、DIQMTQSPSSLSASVGDRVTITCRASQTISNYLNWYQQKPGKAPKLLIYAASNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPQTFGQGTKVEIK (SEQID NO: 175)、DIQMTQSPSSLSASVGDRVTITCRASRDIGRAVGWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQLDSYPFTFGPGTKVDIK (SEQ ID NO:176)、DIQMTQSPSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSSPYTFGPGTKVDIK (SEQ ID NO: 177)、DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKLEIK (SEQ ID NO:178)、DIQMTQSPSSLSASVGDRVTITCRASQSIGRWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYSFGQGTKVEIK (SEQ ID NO: 179)、DIQMTQSPSSLSASVGDRVTITCRASQSISTWLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFAQGTKLEIK (SEQ ID NO: 180)、DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYGASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK (SEQ ID NO: 181)、DIQMTQSPSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPFTFGPGTKVDIK (SEQ ID NO: 182)、DIQMTQSPSSLSASVGDRVTITCRASQSVSNWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPTFGQGTKLEIK (SEQ ID NO: 183)、DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYAIPLTFGGGTKVEIK (SEQ ID NO:184)、DIQMTQSPSSLSASVGDRVTITCQASQDIGSWLAWYQQKPGKAPKLLIYATSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK (SEQ ID NO: 185). ID NO: 187)、DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYGVSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSNPTFGQGTKVEIK (SEQ ID NO: 188)、DIQMTQSPSSLSASVGDRVTITCRASQSISSWVAWYQQKPGKAPKLLIYGASNLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYSFGQGTKLEIK (SEQ ID NO: 189)、DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSDQWTFGQGTKVEIK (SEQ ID NO: 190)、DIQMTQSPSSLSASVGDRVTITCRASQSISRWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYLPPYSFGQGTKVEIK (SEQ ID NO: 191)、DIQMTQSPSSLSASVGDRVTITCRASQSISNWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTYFTLTISSLQPEDFATYYCQQSYSSPYTFGQGTKLEIK (SEQ ID NO: 192)NO:192),DIQMTQSPSSSLSASVGDRVTITCRASQSISHYLNWYQQKPGKAPKLLIYGASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYTTPWTFGQGTRLEIK (SEQ ID NO: 193),DIQMTQSPSSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYLPPYSFGQGTKLEIK (SEQ ID NO: 194), DIQMTQSPSSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYGASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQEGITYTFGQGTKVEIK (SEQ ID NO: 195) and EIVMTQSPATLSVSPGERATLSCRASQSVSRNLAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQHYGYSPVTFGQGTKLEIK (SEQ ID NO: 196).

[0128] 26. The isolated ABP as described in any one of claims 12-25, wherein the ABP comprises a VH sequence and a VL sequence from an scFv named G2-P1H11, G2-P2E07, G2-P2E03, G2-P2A11, G2-P2C06, G2-P1G01, G2-P1C02, G2-P1H01, G2-P1B12, G2-P1B06, G2-P2H10, G2-P1H10, G2-P2C11, G2-P1C09, G2 -P1A10, G2-P1B10, G2-P1D07, G2-P1E05, G2-P1D03, G2-P1G12, G2-P2H11, G2-P1C03, G2-P1G07, G2-P1F12, G2-P1G03, G2-P2B08, G2-P2A10, G2-P2D04, G2-P1C06, G2-P2A09, G2-P1B08, G2-P1E03, G2-P2A03, G2-P2F01 or G2-P1D06.

[0129] 27. The isolated ABP as described in item 26, wherein the ABP comprises a VH sequence and a VL sequence from an scFv named G2-P1H11.

[0130] 28. An isolated antigen-binding protein (ABP) that specifically binds to a human leukocyte antigen (HLA)-peptide target, wherein the HLA-peptide target comprises an HLA-restricted peptide complexed with an HLA class I molecule, wherein the HLA-restricted peptide is located in the peptide-binding groove of the α1 / α2 heterodimeric portion of the HLA class I molecule, wherein the HLA class I molecule is an HLA subtype A. 02:01 (Reference sequence: MGSHSMRYFFTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYWDGETRKVKAHSQTHRVDLGTLRGYYNQSEAGSHTVQRMYGCDVGSDWRFLRGYHQYAYDGKDYIALKEDLRSWTAADMAAQTTKHKWEAAHVAEQLRAYLEGTCVEWLRRYLENGKETLQRTDAPKTHMTHHAVSDHEATLRCWALSFYPAEITLTWQRDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGQEQRYTCHVQHEGLPKPLTLR (SEQ ID NO: 197)), and the HLA-restricted peptide comprises the sequence AIFPGAVPAA (SEQ ID NO: 198), and wherein the ABP binds to any one or more of the following: a. Any one or more of amino acid positions 1-6 of the restriction peptide AIFPGAVPAA (SEQ ID NO: 198), b. The HLA subtype A The amino acid positions of the α1 helix at positions 46, 49, 55, 61, 74, 76, 77, 78, 81, and 84 are all among the given positions. c. The HLA subtype A The amino acid positions of the α1 helix in 02:01 are any one or more of positions 45-60, 66, 67, and 73. d. The HLA subtype A The amino acid positions of the α2 helix of 02:01 are any one or more of 138, 145, 147, 152-156, 164, and 167, and e. The HLA subtype A The amino acid positions of 02:01 are any one or more of the following: 56, 59, 60, 63, 64, 66, 67, 70, 73, 74, 132, 150-153, 155, 156, 158-160, 162-164, 166-168, 170, and 171.

[0131] 29. The isolated ABP as described in item 28, wherein the ABP is bound to any one or more of amino acid positions 1-5 of the restriction peptide AIFPGAVPAA (SEQ ID NO: 198).

[0132] 30. The isolated ABP as described in item 29, wherein the ABP is bound to one or both of amino acid positions 4 and 5 of the restriction peptide AIFPGAVPAA (SEQ ID NO: 198).

[0133] 31. The isolated ABP as described in item 28, wherein the ABP is bound to one or both of amino acid positions 5 and 6 of the restriction peptide AIFPGAVPAA (SEQ ID NO: 198).

[0134] 32. The isolated ABP as described in item 28, wherein the ABP binds to amino acid position 6 of the restriction peptide AIFPGAVPAA (SEQ ID NO: 198).

[0135] 33. The isolated ABP as described in any one of items 28-32, wherein the ABP is associated with HLA subtype A The amino acid positions 46, 49, 55, 66, 67 and 73 of the α1 helix of 02:01 are bound together.

[0136] 34. The isolated ABP as described in any one of claims 28-33, the ABP comprising a VH region containing a complementary site, the complementary site comprising at least one, two, three, or four residues of the following residues in the VH region as shown in the sequence QVQLVQSGAEVKKPGASVKVSCKASGGTLSSYPINWVRQAPGQGLEWMGWISTYSGHADYAQKLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSYDYGDYLNFDYWGQGTLVTVSS (SEQ ID NO: 199)

[0137] 35. The isolated ABP as described in any one of claims 28-34, the ABP comprising a VH region containing complementary sites, the complementary sites comprising residues of the VH region as shown in the Kabat numbering system sequence QVQLVQSGAEVKKPGASVKVSCKASGGTLSSYPINWVRQAPGQGLEWMGWISTYSGHADYAQKLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSYDYGDYLNFDYWGQGTLVTVSS (SEQ ID NO: 199): Thr28, Leu 29, Ser 30, Ser 31, Tyr 32, Pro 33, Trp 47, Trp 50, Ser 52, Tyr 53, Ser 54, His 56, Asp 58, Tyr 59, Gln 61, Gln 64, Asp 97, Tyr At least one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty, twenty, twelve, or twenty-two residues from 98, Gly, 99, Asp100, Tyr100A, Leu100B, and Asn100C.

[0138] 36. The isolated ABP as described in item 35, wherein the complementary site comprises at least one, two, three, four, five, six, or seven residues selected from the VH region as numbered according to the Kabat numbering system: Ser 30, Ser 31, Tyr 32, Tyr 98, Gly 99, Asp 100, and Tyr 100A.

[0139] 37. The isolated ABP as described in any one of claims 28-36, the ABP comprising a VL region containing a complementary site, the complementary site comprising at least one, two, or three residues of Tyr32, Ser 91, and Tyr 92 of the VL region as shown in the Kabat numbering sequence DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSIPPTFGGGTKVDIK (SEQ ID NO: 200).

[0140] 38. The isolated ABP as described in any one of claims 28-37, the ABP comprising a VL region containing a complementary site, the complementary site comprising at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or 13 residues of the VL region as shown in the Kabat numbering sequence DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSIPPTFGGGTKVDIK (SEQ ID NO: 200) as selected from Asp1, Ser30, Asn31, Tyr32, Tyr49, Ala50, Ser53, Ser67, Ser91, Tyr92, Ser93, Ile94 and Pro95.

[0141] 39. The isolated ABP as described in item 38, wherein the complementary site comprises at least one, two, three, four, five, or six residues from the VL region as numbered according to the Kabat numbering system, namely Asp1, Asn31, Tyr32, Ser91, Tyr92, and Ile94.

[0142] 40. The isolated ABP as described in any one of items 28-39, wherein the HLA class I molecule is an HLA subtype A. 02:01, and the HLA-restricted peptide consists of the sequence AIFPGAVPAA (SEQ ID NO: 198).

[0143] 41. The isolated ABP as described in any one of claims 28-40, wherein the ABP comprises CDR-H3, the CDR-H3 comprising a sequence selected from: CARDDYGDYVAYFQHW (SEQ ID NO: 201), CARDLSYYYGMDVW (SEQ ID NO: 202), CARVYDFWSVLSGFDIW (SEQ ID NO: 203), CARVEQGYDIYYYYYMDVW (SEQ ID NO: 204), CARSYDYGDYLNFDYW (SEQ ID NO: 205), CARASGSGYYYYYGMDVW (SEQ ID NO: 206), CAASTWIQPFDYW (SEQ ID NO: 207), CASNGNYYGSGSYYNYW (SEQ ID NO: 208), CARAVYYDFWSGPFDYW (SEQ ID NO: 209), CAKGGIYYGSGSYPSW (SEQ ID NO: 200). 210), CARGLYYMDVW (SEQ ID NO: 211), CARGLYGDYFLYYGMDVW (SEQ ID NO: 212), CARGLLGFGEFLTYGMDVW (SEQ ID NO: 213), CARDRDSSWTYYYYGMDVW (SEQ ID NO: 214), CARGLYGDYFLYYGMDVW (SEQ ID NO: 212), CARGDYYDSSGYYFPVYFDYW (SEQ ID NO: 215) and CAKDPPFWSGHYYYYGMDVW (SEQ ID NO: 216).

[0144] 42. The isolated ABP as described in any one of claims 28-41, wherein the ABP comprises CDR-L3, the CDR-L3 comprising a sequence selected from: CQQNYNSVTF (SEQ ID NO: 217), CQQSYNTPWTF (SEQ ID NO: 218), CGQSYSTPPTF (SEQ ID NO: 219), CQQSYSAPYTF (SEQ ID NO: 111), CQQSYSIPPTF (SEQ ID NO: 220), CQQSYSAPYTF (SEQ ID NO: 111), CQQHNSYPPTF (SEQ ID NO: 221), CQQYSTYPITI (SEQ ID NO: 222), CQQANSFPWTF (SEQ ID NO: 223), CQQSHSTPQTF (SEQ ID NO: 224), CQQSYSTPLTF (SEQ ID NO: 30), CQQSYSTPLTF (SEQ ID NO: 30), CQQTYSTPWTF (SEQ ID NO: 224), CQQSYSTPLTF (SEQ ID NO: 30), CQQTYSTPWTF (SEQ ID NO: 225), CQQSYSTPLTF (SEQ ID NO: 226), CQQSYSTPLTF (SEQ ID NO: 227), CQQSYSTPLTF (SEQ ID NO: 228), CQQSYSTPLTF (SEQ ID NO: 229), CQQSYSTPLTF (SEQ ID NO: 220 ...0), CQQSYSTPLTF (SEQ ID NO: 220), CQQSYSTPLTF (SEQ ID NO: 2 225), CQQYGSSPYTF (SEQ ID NO: 226), CQQSHSTPLTF (SEQ ID NO: 227), CQQANGFPLTF (SEQ ID NO: 228) and CQQSYSTPLTF (SEQ ID NO: 30).

[0145] 43. The isolated ABP as described in any one of items 28-42, wherein the ABP comprises CDR-H3 and CDR-L3 from scFv, the scFv being named G8-P1A03, G8-P1A04, G8-P1A06, G8-P1B03, G8-P1C11, G8-P1D02, G8-P1H08, G8-P2B05, G8-P2E06, R3G8-P2C10, R3G8-P2E04, R3G8-P4F05, R3G8-P5C03, R3G8-P5F02, R3G8-P5G08, G8-P1C01, or G8-P2C11.

[0146] 44. The isolated ABP as described in any one of items 28-43, wherein the ABP comprises all three heavy chain CDRs and all three light chain CDRs from scFv, wherein the scFv is named G8-P1A03, G8-P1A04, G8-P1A06, G8-P1B03, G8-P1C11, G8-P1D02, G8-P1H08, G8-P2B05, G8-P2E06, R3G8-P2C10, R3G8-P2E04, R3G8-P4F05, R3G8-P5C03, R3G8-P5F02, R3G8-P5G08, G8-P1C01, or G8-P2C11.

[0147] 45. The isolated ABP according to any one of items 28 - 44, wherein the ABP comprises a VH sequence selected from: QVQLVQSGAEVKKPGASVKVSCKASGGTFSRSAITWVRQAPGQGLEWMGWINPNSGATNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDDYGDYVAYFQHWGQGTLVTVSS (SEQ ID NO: 229), QVQLVQSGAEVKKPGASVKVSCKASGYPFIGQYLHWVRQAPGQGLEWMGIINPSGDSATYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDLSYYYGMDVWGQGTTVTVSS (SEQ ID NO: 230), QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYYMHWVRQAPGQGLEWMGWMNPIGGGTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARVYDFWSVLSGFDIWGQGTLVTVSS (SEQ ID NO: 231), EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMSWVRQAPGKGLEWVSGINWNGGSTGYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVEQGYDIYYYYYMDVWGKGTTVTVSS (SEQ ID NO: 232), QVQLVQSGAEVKKPGASVKVSCKASGGTLSSYPINWVRQAPGQGLEWMGWISTYSGHADYAQKLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSYDYGDYLNFDYWGQGTLVTVSS (SEQ ID NO: 199), EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYWMSWVRQAPGKGLEWVSSISGRGDNTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARASGSGYYYYYGMDVWGQGTTVTVSS (SEQ IDNO:233)、QVQLVQSGAEVKKPGASVKVSCKASGYTFGNYFMHWVRQAPGQGLEWMGMVNPSGGSETFAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAASTWIQPFDYWGQGTLVTVSS (SEQ ID NO: 234)、EVQLLESGGGLVQPGGSLRLSCAASGFDFSIYSMNWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASNGNYYGSGSYYNYWGQGTLVTVSS (SEQ ID NO: 235)、QVQLVQSGAEVKKPGASVKVSCKASGYTLTTYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARAVYYDFWSGPFDYWGQGTLVTVSS (SEQ ID NO: 236)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGWINPYSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKGGIYYGSGSYPSWGQGTLVTVSS (SEQ ID NO: 237)、QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYGVSWVRQAPGQGLEWMGWISPYSGNTDYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGLYYMDVWGKGTTVTVSS (SEQID NO: 238)、QVQLVQSGAEVKKPGASVKVSCKASGYTFSNMYLHWVRQAPGQGLEWMGWINPNTGDTNYAQTFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGLYGDYFLYYGMDVWGQGTKVTVSS (SEQ ID NO: 239)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGLLGFGEFLTYGMDVWGQGTLVTVSS (SEQ ID NO:240), QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYIHWVRQAPGQGLEWMGVINPSGGSTTYAQKLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDRDSSWTYYYYGMDVWGQGTTVTVSS (SEQ ID NO: 241), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSNYMHWVRQAPGQGLEWMGWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGLYGDYFLYYGMDVWGQGTTVTVSS (SEQ ID NO: 242), QVQLVQSGAEVKKPGASVKVSCKASGGTFSSHAISWVRQAPGQGLEWMGVIIPSGGTSYTQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGDYYDSSGYYFPVYFDYWGQGTLVTVSS (SEQ ID NO: 243), and QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYAMNWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDPFWSGHYYYYGMDVWGQGTTVTVSS (SEQ ID NO: 244).

[0148] 46. The isolated ABP according to any one of items 28 - 45, wherein the ABP comprises a VL sequence selected from: DIQMTQSPSSLSASVGDRVTITCRASQSITSYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQNYNSVTFGQGTKLEIK (SEQ ID NO: 245), DIQMTQSPSSLSASVGDRVTITCWASQGISSYLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYNTPWTFGPGTKVDIK (SEQ ID NO: 246), DIQMTQSPSSLSASVGDRVTITCRASQAISNSLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCGQSYSTPPTFGQGTKLEIK (SEQ ID NO: 247), DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSAPYTFGPGTKVDIK (SEQ ID NO: 248), DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSIPPTFGGGTKVDIK (SEQ ID NO: 200), DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSAPYTFGGGTKVEIK (SEQ ID NO: 249), DIQMTQSPSSLSASVGDRVTITCRASQGINSYLAWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHNSYPPTFGQGTKLEIK (SEQ ID NO:250)、DIQMTQSPSSLSASVGDRVTITCRASQSISRWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYSTYPITIGQGTKVEIK(SEQ ID NO: 251)、DIQMTQSPSSLSASVGDRVTITCRASQGISNSLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPWTFGQGTKLEIK (SEQ ID NO: 252)、DIQMTQSPSSLSASVGDRVTITCRASQDVSTWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSHSTPQTFGQGTKVEIK (SEQ ID NO: 253)、DIQMTQSPSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKLEIK (SEQID NO: 254)、DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ ID NO: 255)、DIQMTQSPSSLSASVGDRVTITCRASQGISNWLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSTPWTFGQGTKLEIK (SEQ ID NO: 256)、EIVMTQSPATLSVSPGERATLSCRASQSVGNSLAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYGSSPYTFGQGTKVEIK (SEQ ID NO:257)、DIQMTQSPSSLSASVGDRVTITCRASQSISGYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSHSTPLTFGQGTKVEIK (SEQ ID NO:258), DIQMTQSPSSSLSASVGDRVTITCRASQNIYTYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANGFPLTFGGGTKVEIK (SEQ ID NO: 259) and DIQMTQSPSSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ ID NO: 71).

[0149] 47. The isolated ABP as described in any one of claims 28-46, wherein the ABP comprises a VH sequence and a VL sequence from an scFv, the scFv being named G8-P1A03, G8-P1A04, G8-P1A06, G8-P1B03, G8-P1C11, G8-P1D02, G8-P1H08, G8-P2B05, G8-P2E06, R3G8-P2C10, R3G8-P2E04, R3G8-P4F05, R3G8-P5C03, R3G8-P5F02, R3G8-P5G08, G8-P1C01, or G8-P2C11.

[0150] 48. An isolated antigen-binding protein (ABP) that specifically binds to a human leukocyte antigen (HLA)-peptide target, wherein the HLA-peptide target comprises an HLA-restricted peptide complexed with an HLA class I molecule, wherein the HLA-restricted peptide is located in the peptide-binding groove of the α1 / α2 heterodimeric portion of the HLA class I molecule, wherein the HLA class I molecule is an HLA subtype A. 01:01 (Reference sequence: MGSHSMRYFFTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQKMEPRAPWIEQEGPEYWDQETRNMKAHSQTDRANLGTLRGYYNQSEDGSHTIQIMYGCDVGPDGRFLRGYRQDAYDGKDYIALNEDLRSWTAADMAAQITKRKWEAVHAAEQRRVYLEGRCVDGLRRYLENGKETLQRTDPPKTHMTHHPISDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLR (SEQ ID NO: 72)), and the HLA-restricted peptide comprises the sequence ASSLPTTMNY (SEQ ID NO: 260), and wherein the ABP binds to any one or more of the following: a. The amino acid positions 4, 6, 7, 8, and 9 of the restricted peptide ASSLPTTMNY (SEQ ID NO: 260), b. HLA subtype A The amino acid at position 49-56 of 01:01 c. HLA subtype A The amino acid at position 59-66 of 01:01 d. HLA subtype A 01:01 amino acid positions 136-147 of any one or more, and e. HLA subtype A 01:01 refers to any one or more amino acids at positions 157-160.

[0151] 49. The isolated ABP as described in item 48, wherein the ABP is bound to any one or more of amino acid positions 6-9 of the restriction peptide ASSLPTTMNY (SEQ ID NO: 260).

[0152] 50. The isolated ABP as described in item 49, wherein the ABP is bound to any one or more of amino acids 6-7 of the restriction peptide ASSLPTTMNY (SEQ ID NO: 260).

[0153] 51. The isolated ABP as described in claim 49, wherein the ABP is bound to amino acid 6 of the restriction peptide ASSLPTTMNY (SEQ ID NO: 260).

[0154] 52. The isolated ABP as described in any one of items 48-51, wherein the ABP is combined with: a. HLA subtype A The amino acid at position 52-54 of 01:01 b. HLA subtype A The amino acid at position 136-139 of 01:01 c. HLA subtype A 01:01 amino acid positions 141-147 or any one or more of them, or d. HLA subtype A 01:01 contains any one or more amino acids at positions 136-139 and HLA subtype A. 01:01 any one or more of the amino acid positions 141-147.

[0155] 53. The isolated ABP as described in any one of items 48-52, wherein the HLA class I molecule is an HLA subtype A. 01:01, and the HLA-restricted peptide consists of the sequence ASSLPTTMNY (SEQ ID NO: 260).

[0156] 54. The isolated ABP as described in any one of claims 48-53, wherein the ABP comprises CDR-H3, the CDR-H3 comprising a sequence selected from: CARDQDTIFGVVITWFDPW (SEQ ID NO: 261), CARDKVYGDGFDPW (SEQ ID NO: 262), CARDEDDSMDVW (SEQ ID NO: 263), CARDSSGLDPW (SEQ ID NO: 264), CARGVGNLDYW (SEQ ID NO: 265), CARDHAHQYYDFWSGYYSGTYYYGMDVW (SEQ ID NO: 266), CARGQWPSYWYFDLW (SEQ ID NO: 267), CARDRGYSYGYFDYW (SEQ ID NO: 268), CARGSGDPNYYYYYGLDVW (SEQ ID NO: 269), CARDTGDHFDYW (SEQ ID NO: 270), CARAENGMDVW (SEQ ID NO: 271), CARDPGGYMDVW (SEQ ID NO: 272), CARDGDAFDIW (SEQ ID NO: 273), CARDMGDAFDIW (SEQ ID NO: 274), CAREEDGMDVW (SEQ ID NO: 275), CARDTGDHFDYW (SEQ ID NO: 270), CARGEYSSGFFFVGWFDLW (SEQ ID NO: 276) and CARETGDDAFDIW (SEQ ID NO: 277).

[0157] 55. The isolated ABP as described in any one of claims 48-54, wherein the ABP comprises CDR-L3, the CDR-L3 comprising a sequence selected from: CQQYFTTPYTF (SEQ ID NO: 278), CQQAEAFPYTF (SEQ ID NO: 279), CQQSYSTPITF (SEQ ID NO: 280), CQQSYIIPYTF (SEQ ID NO: 281), CHQTYSTPLTF (SEQ ID NO: 282), CQQAYSFPWTF (SEQ ID NO: 283), CQQGYSTPLTF (SEQ ID NO: 284), CQQANSFPRTF (SEQ ID NO: 285), CQQANSLPYTF (SEQ ID NO: 286), CQQSYSTPFTF (SEQ ID NO: 109), CQQSYSTPFTF (SEQ ID NO: 109), CQQSYGVPTF (SEQ ID NO: 287), CQQSYSTPLTF (SEQ ID NO: 288), CQQSYGVPTF (SEQ ID NO: 289), CQQSYSTPLTF (SEQ ID NO: 289 ...SYGVPTF (SEQ ID NO: NO: 30), CQQSYSTPLTF (SEQ ID NO: 30), CQQYYSYPWTF (SEQ ID NO: 288), CQQSYSTPFTF (SEQ ID NO: 109), CMQTLKTPLSF (SEQ ID NO: 289) and CQQSYSTPLTF (SEQ ID NO: 30).

[0158] 56. A separate ABP as described in any one of claims 48-55, wherein the ABP comprises CDR-H3 and CDR-L3 from scFv, the scFv being named R3G10-P1A07, R3G10-P1B07, R3G10-P1E12, R3G10-P1F06, R3G10-P1H01, R3G10-P1H08, R3G10 -P2C04, R3G10-P2G11, R3G10-P3E04, R3G10-P4A02, R3G10-P4C05, R3G10-P4D04, R3G10-P4D10, R3G10-P4E07, R3G10-P4E12, R3G10-P4G06, R3G10-P5A08 or R3G10-P5C08.

[0159] 57. The isolated ABP as described in any one of items 48-56, wherein the ABP comprises all three heavy chain CDRs and all three light chain CDRs from scFv, wherein the scFv is named R3G10-P1A07, R3G10-P1B07, R3G10-P1E12, R3G10-P1F06, R3G10-P1H01, R3G10-P1H08, R3 G10-P2C04, R3G10-P2G11, R3G10-P3E04, R3G10-P4A02, R3G10-P4C05, R3G10-P4D04, R3G10-P4D10, R3G10-P4E07, R3G10-P4E12, R3G10-P4G06, R3G10-P5A08 or R3G10-P5C08.

[0160] 58. The isolated ABP according to any one of items 48 - 57, wherein the ABP comprises a VH sequence selected from: EVQLLESGGGLVKPGGSLRLSCAASGFTFSSYWMSWVRQAPGKGLEWVSGISARSGRTYYADSVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCARDQDTIFGVVITWFDPWGQGTLVTVSS (SEQ ID NO: 290), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGIIHPGGGTTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDKVYGDGFDPWGQGTLVTVSS (SEQ ID NO: 291), QVQLVQSGAEVKKPGASVKVSCKASGYIFTGYYMHWVRQAPGQGLEWMGMIGPSDGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREDDSMDVWGKGTTVTVSS (SEQ ID NO: 292), QVQLVQSGAEVKKPGASVKVSCKASGYTFIGYYMHWVRQAPGQGLEWMGMIGPSDGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDSSGLDPWGQGTLVTVSS (SEQ ID NO: 293), QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGMIGPSDGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGVGNLDYWGQGTLVTVSS (SEQ ID NO:294), QVQLVQSGAEVKKPGASVKVSCKASGVTFSTSAISWVRQAPGQGLEWMGWISPYNGNTDYAQMLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDAHQYYDFWSGYYSGTYYYGMDVWGQGTTVTVSS (SEQ ID NO:295), QVQLVQSGAEVKKPGASVKVSCKASGGTFSNSIINWVRQAPGQGLEWMGWMNPNSGNTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREQWPSYWYFDLWGRGTLVTVSS(SEQ ID NO: 296)、QVQLVQSGAEVKKPGASVKVSCKASGGTFSTHDINWVRQAPGQGLEWMGVINPSGGSAIYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYCARDRGYSYGYFDYWGQGTLVTVSS (SEQ ID NO: 297). 298)、QVQLVQSGAEVKKPGASVKVSCKASGYTLSYYYMHWVRQAPGQGLEWMGMIGPSDGSTSYAQRFQGRVTMTRDTSTGTVYMELSSLRSEDTAVYCARDTGDHFDYWGQGTLVTVSS (SEQ ID NO: 299), QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGIIGPSDGSTTYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARAENGMDVWGQGTTVTVSS (SEQ ID NO: 300), QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQGLEWMGIIAPSDGSTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDPGGYMDVWGKGGTTVTVSS (SEQ ID NO: 301), QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYLHWVRQAPGQGLEWMGMIGPSDGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGDAFDIWGQGTMVTVSS (SEQ ID NO: 302)、QVQLVQSGAEVKKPGSSVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGRISPSDGSTTYAPKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDMGDAFDIWGQGTTVTVSS (SEQ ID NO:303), QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGMIGPSDGSTSYAQRFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREEDGMDVWGQGTTVTVSS (SEQ ID NO: 304), QVQLVQSGAEVKKPGASVKVSCKASGYTLSYYYMHWVRQAPGQGLEWMGMIGPSDGSTSYAQRFQGRVTMTRDTSTGTVYMELSSLRSEDTAVYYCARDTGDHFDYWGQGTLVTVSS (SEQ ID NO: 299), QVQLVQSGAEVKKPGSSVKVSCKASGGTFNNFAISWVRQAPGQGLEWMGGIIPIFDATNYAQKFQGRVTFTADESTSTAYMELSSLRSEDTAVYYCARGEYSSGFFFVGWFDLWGRGTQVTVSS (SEQ ID NO: 305) and QVQLVQSGAEVKKPGASVKVSCKASGYNFTGYYMHWVRQAPGQGLEWMGIIAPSDGSTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARETGDDAFDIWGQGTMVTVSS (SEQ ID NO: 306).

[0161] 59. The isolated ABP according to any one of items 48 - 58, wherein the ABP comprises a VL sequence selected from: DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYAASSLQGGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYFTTPYTFGQGTKLEIK (SEQ ID NO: 307), DIQMTQSPSSLSASVGDRVTITCRASQSISRWLAWYQQKPGKAPKLLIFDASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAEAFPYTFGQGTKVEIK (SEQ ID NO: 308), DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPITFGQGTRLEIK (SEQ ID NO:309), DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYIIPYTFGQGTKLEIK (SEQ ID NO: 310), DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCHQTYSTPLTFGQGTKVEIK (SEQ ID NO: 311), DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYSASNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAYSFPWTFGQGTKVEIK (SEQ ID NO: 312), DIQMTQSPSSLSASVGDRVTITCRASQNISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGYSTPLTFGQGTRLEIK (SEQ ID NO:313)、DIQMTQSPSSLSASVGDRVTITCRASQDISRYLAWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPRTFGQGTKVEIK (SEQ ID NO: 314)、DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSLPYTFGQGTKVEIK (SEQ ID NO: 315)、DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASTLQNGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQSYSTPTFGPGTKVDIK (SEQ ID NO: 315) ID NO: 316)、DIQMTQSPSSLSASVGDRVTITCRASQRISSYLNWYQQKPGKAPCLLIYSASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPTFGPGTKVDIK(SEQ ID NO: 317), DIQMTQSPSSLSASVGDRVTITCRASQSISSYLAWYQQKPGKAPKLLIYDASKLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYGVPTFGQGTKLEIK (SEQ ID NO: 318), DIQMTQSPSSLSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ ID NO: 319), DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ ID NO: 71), DIQMTQSPSSLSASVGDRVTITCRASQGISTYLAWYQQKPGKAPKLLIYDASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYYSYPWTFGQGTRLEIK (SEQ ID NO:320), DIQMTQSPSSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASTLQNGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPFTFGPGTKVDIK (SEQ ID NO: 316), DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQTLKTPLSFGGTKVEIK (SEQ IDNO: 321) and DIQMTQSPSSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ ID NO: 71).

[0162] 60. The isolated ABP as described in any one of claims 48-59, wherein the ABP comprises a VH sequence and a VL sequence from an scFv named: R3G10-P1A07, R3G10-P1B07, R3G10-P1E12, R3G10-P1F06, R3G10-P1H01, R3G10-P1H08, R3G10- P2C04, R3G10-P2G11, R3G10-P3E04, R3G10-P4A02, R3G10-P4C05, R3G10-P4D04, R3G10-P4D10, R3G10-P4E07, R3G10-P4E12, R3G10-P4G06, R3G10-P5A08 or R3G10-P5C08.

[0163] 61. An isolated antigen-binding protein (ABP) that specifically binds to a human leukocyte antigen (HLA)-peptide target, wherein the HLA-peptide target comprises an HLA-restricted peptide complexed with an HLA class I molecule, wherein the HLA-restricted peptide is located in the peptide-binding groove of the α1 / α2 heterodimeric portion of the HLA class I molecule, wherein the HLA class I molecule is an HLA subtype A. 02:01 (Reference sequence: MGSHSMRYFFTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYWDGETRKVKAHSQTHRVDLGTLRGYYNQSEAGSHTVQRMYGCDVGSDWRFLRGYHQYAYDGKDYIALKEDLRSWTAADMAAQTTKHKWEAAHVAEQLRAYLEGTCVEWLRRYLENGKETLQRTDAPKTHMTHHAVSDHEATLRCWALSFYPAEITLTWQRDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGQEQRYTCHVQHEGLPKPLTLR (SEQ ID NO: 197)), and the HLA-restricted peptide comprises the sequence LLASSILCA (SEQ ID NO: 322), and wherein the ABP binds to any one or more of the following: a. Any one or more of residues 1-5 of the restricted peptide LLASSILCA (SEQ ID NO: 322), b. The HLA-A 02:01 Any one or more of residues 49-85 of the α1 helix, and c. The HLA-A 02:01 Any one or more of residues 57-67 of the α1 helix.

[0164] 62. The isolated ABP as described in item 61, wherein the HLA class I molecule is an HLA subtype A. 02:01, and the HLA-restricted peptide consists of the sequence LLASSILCA (SEQ ID NO: 322).

[0165] 63. The isolated ABP as described in claim 61 or 62, wherein the ABP comprises CDR-H3, the CDR-H3 comprising a sequence selected from the following: CARDGYDFWSGYTSDDYW (SEQ ID NO: 323), CASDYGDYR (SEQ ID NO: 324), CARDLMTTVVTPGDYGMDVW (SEQ ID NO: 325), CARQDGGAFAFDIW (SEQ ID NO: 326), CARELGYYYGMDVW (SEQ ID NO: 327), CAALIFGVPLLPYGMDVW (SEQ ID NO: 328), CAKDLATVGEPYYYYGMDVW (SEQ ID NO: 329), and CARLWFGELHYYYYYGMDVW (SEQ ID NO: 330).

[0166] 64. The isolated ABP as described in any one of claims 61-63, wherein the ABP comprises CDR-L3, the CDR-L3 comprising a sequence selected from the group consisting of: CHHYGRSHTF (SEQ ID NO: 331), CQQANAFPPTF (SEQ ID NO: 332), CQQYYSIPLTF (SEQ ID NO: 333), CQQSYSTPPTF (SEQ ID NO: 334), CQQSYSFPYTF (SEQ ID NO: 335), CMQALQTPLTF (SEQ ID NO: 31), CQQGNTFPLTF (SEQ ID NO: 336), and CMQGSHWPPSF (SEQ ID NO: 337).

[0167] 65. The isolated ABP as described in any one of claims 61-64, wherein the ABP comprises CDR-H3 and CDR-L3 from scFv, the scFv being named G7R3-P1C6, G7R3-P1G10, 1-G7R3-P1B4, 2-G7R4-P2C2, 3-G7R4-P1A3, 4-G7R4-B5-P2E9, 5-G7R4-B10-P1F8 or B7 (G7R3-P3A9).

[0168] 66. The isolated ABP as described in any one of items 61-65, wherein the ABP comprises all three heavy chain CDRs and all three light chain CDRs from scFv, wherein the scFv is named G7R3-P1C6, G7R3-P1G10, 1-G7R3-P1B4, 2-G7R4-P2C2, 3-G7R4-P1A3, 4-G7R4-B5-P2E9, 5-G7R4-B10-P1F8 or B7 (G7R3-P3A9).

[0169] 67. The isolated ABP according to any one of items 61 - 66, wherein the ABP comprises a VH sequence selected from the following: QVQLVQSGAEVKKPGASVKVSCKASGGTFSNYGISWVRQAPGQGLEWMGIINPGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGYDFWSGYTSDDYWGQGTLVTVSS (SEQ ID NO: 338), EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVSGISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASDYGDYRGQGTLVTVSS (SEQ ID NO: 339), QVQLVQSGAEVKKPGASVKVSCKASGYTFSNYYIHWVRQAPGQGLEWMGWLNPNSGNTGYAQRFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDLMTTVVTPGDYGMDVWGQGTTVTVSS (SEQ ID NO: 340), QVQLVQSGAEVKKPGASMKVSCKASGYTFTTDGISWVRQAPGQGLEWMGRIYPHSGYTEYAKKFKGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARQDGGAFAFDIWGQGTMVTVSS (SEQ ID NO: 341), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSQYMHWVRQAPGQGLEWMGWISPNNGDTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARELGYYYGMDVWGQGTTVTVSS (SEQ IDNO: 342), QVQLVQSGAEVKKPGSSVKVSCKASRYTFTSYDINWVRQAPGQGLEWMGRIIPMLNIANYAPKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARALIFGVPLLPYGMDVWGQGTTVTVSS (SEQ ID NO: 343), EVQLLQSGGGLVQPGGSLRLSCAASGFTFSSSWMHWVRQAPGKGLEWVSFISTSSGYIYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDLATVGEPYYYYGMDVWGQGTTVTVSS(SEQ ID NO: 344) and QVQLVQSGAEVKKPGSSVKVSCKASGDTFNTYALSWVRQAPGQGLEWMGWMNPNSGNAGYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARLWFGELHYYYYYGMDVWGQGTMVTVSS (SEQ ID NO: 345).

[0170] 68. The isolated ABP according to any one of items 61 - 67, wherein the ABP comprises a VL sequence selected from the following: EIVMTQSPATLSVSPGERATLSCRASQSVSSSNLAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCHHYGRSHTFGQGTKVEIK (SEQ ID NO: 346), DIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANAFPPTFGQGTKVEIK (SEQ ID NO: 347), DIVMTQSPDSLAVSLGERATINCKSSQSVFYSSNNKNQLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSIPLTFGQGTKLEIK (SEQ ID NO:348), DIQMTQSPSSLSASVGDRVTITCQASQDIFKYLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPTFGQGTRLEIK (SEQ ID NO: 349), DIQMTQSPSSLSASVGDRVTITCRASQSISTWLAWYQQKPGKAPKLLIYYASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPYTFGQGTKVEIK (SEQ ID NO: 350), DIVMTQSPLSLPVTPGEPASISCSSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPLTFGGGTKVEIK (SEQ ID NO:351), DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYSASNLRSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGNTFPLTFGQGTKVEIK (SEQ ID NO:352) and DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGTDFTLKISRVEAEDVGVYYCMQGSHWPPSFGQGTRLEIK (SEQ ID NO: 353).

[0171] 69. The isolated ABP as described in any one of claims 61-68, wherein the ABP comprises a VH sequence and a VL sequence from an scFv, the scFv being named G7R3-P1C6, G7R3-P1G10, 1-G7R3-P1B4, 2-G7R4-P2C2, 3-G7R4-P1A3, 4-G7R4-B5-P2E9, 5-G7R4-B10-P1F8 or B7 (G7R3-P3A9).

[0172] 70. The isolated ABP as described in any of the preceding claims, wherein the ABP comprises an antibody or an antigen-binding fragment thereof.

[0173] 71. The antigen-binding protein as described in any of the preceding claims, wherein the antigen-binding protein is linked to a scaffold, optionally wherein the scaffold comprises serum albumin or Fc, optionally wherein the Fc is a human Fc and is an isotype of IgG (IgG1, IgG2, IgG3, IgG4), IgA (IgA1, IgA2), IgD, IgE, or IgM.

[0174] 72. The antigen-binding protein as described in any of the preceding claims, wherein the antigen-binding protein is connected to a scaffold via a connector, optionally wherein the connector is a peptide connector, optionally wherein the peptide connector is a hinge region of a human antibody.

[0175] 73. The antigen-binding protein as described in any of the preceding claims, wherein the antigen-binding protein comprises an Fv fragment, a Fab fragment, an F(ab')2 fragment, a Fab' fragment, a scFv fragment, a scFv-Fc fragment, and / or a single-domain antibody or an antigen-binding fragment thereof.

[0176] 74. The antigen-binding protein as described in any of the preceding claims, wherein the antigen-binding protein comprises an scFv fragment.

[0177] 75. The antigen-binding protein as described in any of the preceding claims, wherein the antigen-binding protein comprises one or more antibody complementarity-determining regions (CDRs), optionally, six antibody CDRs.

[0178] 76. The antigen-binding protein as described in any of the preceding claims, wherein the antigen-binding protein includes an antibody.

[0179] 77. The antigen-binding protein as described in any of the preceding claims, wherein the antigen-binding protein is a monoclonal antibody.

[0180] 78. The antigen-binding protein as described in any of the preceding claims, wherein the antigen-binding protein is a humanized antibody, a human antibody, or a chimeric antibody.

[0181] 79. The antigen-binding protein as described in any of the preceding claims, wherein the antigen-binding protein is multispecific, optionally bispecific.

[0182] 80. The antigen-binding protein as described in any of the preceding claims, wherein the antigen-binding protein binds to more than one antigen or more than one epitope on a single antigen.

[0183] 81. The antigen-binding protein as described in any of the preceding claims, wherein the antigen-binding protein comprises a heavy chain constant region selected from the classes of IgG, IgA, IgD, IgE and IgM.

[0184] 82. The antigen-binding protein as described in any of the preceding claims, wherein the antigen-binding protein comprises a heavy chain constant region of class human IgG and a subclass selected from IgG1, IgG4, IgG2 and IgG3.

[0185] 83. The antigen-binding protein as described in any of the preceding claims, wherein the antigen-binding protein comprises a modification that extends its half-life.

[0186] 84. The antigen-binding protein as described in any of the preceding claims, wherein the antigen-binding protein comprises a modified Fc, optionally wherein the modified Fc comprises one or more mutations that extend the half-life, optionally wherein the one or more mutations that extend the half-life are YTE.

[0187] 85. The isolated ABP as described in any of the preceding claims, wherein the ABP comprises a T cell receptor (TCR) or its antigen-binding portion.

[0188] 86. The antigen-binding protein as described in item 85, wherein the TCR or its antigen-binding portion comprises a TCR variable region.

[0189] 87. The antigen-binding protein as described in item 85 or 86, wherein the TCR or its antigen-binding portion comprises one or more TCR complementarity-determining regions (CDRs).

[0190] 88. The antigen-binding protein of any one of claims 85-87, wherein the TCR comprises an α chain and a β chain.

[0191] 89. The antigen-binding protein of any one of claims 85-88, wherein the TCR comprises a γ chain and a δ chain.

[0192] 90. The antigen-binding protein as described in any of the preceding claims, wherein the antigen-binding protein is part of a chimeric antigen receptor (CAR), the chimeric antigen receptor comprising: an extracellular portion containing the antigen-binding protein; and an intracellular signal transduction domain.

[0193] 91. The antigen-binding protein of claim 90, wherein the antigen-binding protein comprises scFv and the intracellular signal transduction domain comprises ITAM.

[0194] 92. The antigen-binding protein as described in claim 90 or 91, wherein the intracellular signal transduction domain comprises the signal transduction domain of the ζ chain of the CD3-ζ (CD3) chain.

[0195] 93. The antigen-binding protein of any one of claims 90-92, further comprising a transmembrane domain connecting the extracellular domain and the intracellular signal transduction domain.

[0196] 94. The antigen-binding protein as described in claim 93, wherein the transmembrane domain comprises the transmembrane portion of CD28.

[0197] 95. The antigen-binding protein as described in any one of items 90-94, further comprising an intracellular signal transduction domain of a T-cell co-stimulatory molecule.

[0198] 96. The antigen-binding protein as described in item 95, wherein the T-cell co-stimulatory molecule is CD28, 4-1BB, OX-40, ICOS, or any combination thereof.

[0199] 97. An isolated polynucleotide encoding the isolated ABP of any one of the preceding claims.

[0200] 98. The ABP as described in any of the preceding claims, wherein the antigen-binding protein binds to the HLA-peptide target via a contact site with the HLA class I molecule and via a contact site with the HLA-restricted peptide of the HLA-peptide target.

[0201] 99. The ABP as described in any of the preceding claims, wherein the binding of the ABP to the amino acid position or contact point on the restricted peptide or HLA subtype is determined by position scanning, hydrogen-deuterium exchange, or protein crystallography.

[0202] 100. The antigen-binding protein as described in any of the preceding items, which is used as a medicine.

[0203] 101. An antigen-binding protein as described in any of the preceding claims, used for the treatment of cancer, optionally wherein the cancer expresses or is expected to express the HLA-peptide target.

[0204] 102. The antigen-binding protein as described in any of the preceding claims, for the treatment of cancer, wherein the cancer is selected from solid tumors and hematologic malignancies.

[0205] 103. An ABP that is a conservatively modified variant of the ABP as described in any of the preceding items.

[0206] 104. An antigen-binding protein (ABP) that competes with the antigen-binding protein as described in any of the preceding claims.

[0207] 105. An antigen-binding protein (ABP) that binds to the same HLA-peptide epitope as the antigen-binding protein of any of the preceding claims.

[0208] 106. An engineered cell that expresses a receptor comprising an antigen-binding protein as described in any one of the preceding claims.

[0209] 107. The engineered cell as described in item 106 is a T cell, optionally a cytotoxic T cell (CTL).

[0210] 108. The engineered cell as described in item 106 or 107, wherein the antigen-binding protein is expressed from a heterologous promoter.

[0211] 109. An isolated polynucleotide or polynucleotide group encoding an antigen-binding protein, or an antigen-binding portion thereof, as described in any of the preceding claims.

[0212] 110. A vector or set of vectors comprising a polynucleotide or set of polynucleotides as described in claim 109.

[0213] 111. A host cell comprising a polynucleotide or group of polynucleotides as described in any of the preceding claims, or a vector or group of vectors as described in claim 110, wherein the host cell is optionally CHO or HEK293, or wherein the host cell is optionally a T cell.

[0214] 112. A method for producing an antigen-binding protein, comprising: expressing the antigen-binding protein in a host cell as described in claim 111, and isolating the expressed antigen-binding protein.

[0215] 113. A pharmaceutical composition comprising an antigen-binding protein as described in any of the preceding claims, and a pharmaceutically acceptable excipient.

[0216] 114. A method of treating a subject with cancer, comprising administering to the subject an effective amount of an antigen-binding protein as described in any of the preceding claims, or a pharmaceutical composition as described in claim 113, optionally wherein the cancer is selected from solid tumors and hematologic malignancies.

[0217] 115. The method as described in item 114, wherein the cancer expresses or is expected to express the HLA-peptide target.

[0218] 116. A kit comprising an antigen-binding protein as described in any of the preceding claims, or a pharmaceutical composition as described in claim 113, and instructions for use.

[0219] 117. A virus comprising isolated polynucleotides or polynucleotide groups as described in any of the preceding claims.

[0220] 118. The virus as described in item 117, wherein the virus is a filamentous bacteriophage.

[0221] 119. A yeast cell comprising isolated polynucleotides or groups of polynucleotides as described in any of the preceding claims. Attached Figure Description

[0222] The following description and accompanying drawings will help to better understand these and other features, aspects and advantages of the invention, wherein: Figure 1 This image shows the general structure of a human leukocyte antigen (HLA) class I molecule. A personal work by user atropos235 published via en.wikipedia, CC BY 2.5, https: / / commons.wikimedia.org / w / index.php?curid=1805424 Figure 2 An exemplary construct element for cloning TCRs into an expression system for therapeutic development is depicted.

[0223] Figure 3 The design of the target and micro-collection negative control for the HLA-peptide target “G5” is shown.

[0224] Figure 4 The design of the HLA-peptide targets “G8” and “G10” and the micro-collection negative control are shown.

[0225] Figure 5 A and Figure 5B shows the HLA stability results of the G5 reverse screening "micro-assembly" and the G5 target. Figure 5 A discloses SEQ ID NOS 2, 358 and 378-379, Figure 5 B discloses SEQ ID NOS 2, 358, 378-379 and 636, all of which are disclosed in the order of their appearance.

[0226] Figure 6 A- Figure 6 E shows the HLA stability results of reverse-screening peptides from the “complete” G5 set. Figure 6 A discloses SEQ IDNOS 368-369 and 359, Figure 6 B disclosed SEQ ID NOS 370-371 and 360, Figure 6 C discloses SEQ ID NOS 380-381 and 637, Figure 6 D disclosed SEQ ID NOS 372-374, Figure 6 E disclosed SEQ ID NOS 375-377, and the above disclosures are made in the order of their appearance.

[0227] Figure 7 A and Figure 7 B shows the HLA stability results for the reverse screening peptide and the G8 target. Figure 7 A discloses SEQ ID NOS198 and 638-640, which are disclosed in the order of their appearance.

[0228] Figure 8 A and Figure 8 B shows the HLA stability results of the G10 reverse screening "micro-assembly" and the G10 target. Figure 8 A discloses SEQ ID NOS 260, 370-371, and 360. Figure 8 B discloses SEQ ID NOS 260, 370-371, 360 and 641, all of which are disclosed in the order of their appearance.

[0229] Figure 9 A- Figure 9 D shows the HLA stability results of the reverse screening peptides from the additional G8 and G10 “complete” set. Figure 9 A disclosed SEQ ID NOS 368-369 and 359, Figure 9 B disclosed SEQ ID NOS 383-385, Figure 9 C discloses SEQ IDNOS 372-374, Figure 9D disclosed SEQ ID NOS 380-382, and the above disclosures are made in the order of their appearance.

[0230] Figure 10 A- Figure 10 C shows the ELISA results of the phage supernatant, indicating that G5-, G8-, and G10-binding phages were gradually enriched as the panning wheel progressed.

[0231] Figure 11 A flowchart describing the antibody selection process is shown, including the standards and intended applications for scFv, Fab, and IgG forms.

[0232] Figure 12 A, Figure 12 B and Figure 12 C depicts the Fab clone G5-P7A05 to the HLA peptide target B. 35:01-EVDPIGHVY (SEQ ID NO: 2), Fab clones R3G8-P2C10 and G8-P1C11 to HLA peptide target A 02:01-AIFPGAVPAA (SEQ ID NO: 198) and Fab clone R3G10-P1B07 to HLA peptide target A Biolayer Interferometry (BLI) results of 01:01-ASSLPTTMNY (SEQ ID NO: 260).

[0233] Figure 13 The general experimental design for a position scanning experiment is shown.

[0234] Figure 14 A shows the stability results for the G5 position variant-HLA. Figure 14 A disclosed SEQ ID NO: 2.

[0235] Figure 14 B shows the binding affinity of Fab clone G5-P7A05 to G5 position variant-HLA. Figure 14 B disclosed SEQ ID NO: 2.

[0236] Figure 15 A shows the stability results for the G8 positional variants HLAs. Figure 15 A disclosed SEQ ID NO: 198.

[0237] Figure 15 B shows the binding affinity of Fab clone G8-P2C10 to the G8 position variant HLA. Figure 15 B disclosed SEQ ID NO: 198.

[0238] Figure 16 A shows the stability results for the G10 position variant-HLA. Figure 16 A disclosed SEQ ID NO: 260.

[0239] Figure 16 B shows the binding affinity of Fab clone G10-P1B07 to the G10 position variant HLA. Figure 16 B disclosed SEQ ID NO: 260.

[0240] Figure 17 A, Figure 17 B and Figure 17 C shows a representative example of antibodies that bind to G5-, G8-, or G10-presenting K562 cells, as detected by flow cytometry.

[0241] Figure 18 A- Figure 18 C shows a histogram of K562 cells binding to the generated target-specific antibodies.

[0242] Figure 19 A- Figure 19 C shows a histogram of cell binding assays using tumor cell lines expressing HLA subtypes and target genes of selected HLA-peptide targets.

[0243] Figure 20A and Figure 20B The number of target-specific T cells from the tested donors is shown in (A) and the number of target-specific unique TCR clones is shown in (B). Figure 20A SEQ ID NOS 260 and 367 have been disclosed. Figure 20B SEQ IDs NOS260 and 367 have been disclosed, and the disclosures are made in the order of their appearance.

[0244] Figure 21 A shows an exemplary heatmap of scFv G8-P1H08, which uses a comprehensive perturbation view to visualize the entire HLA portion of the HLA-peptide target G8. Figure 21 A disclosed SEQ ID NO: 642. Figure 21 B shows an example of HDX data from scFv G8-P1H08 plotted on the crystal structure PDB5bs0 (1jf1.pd, available at http: / / www.rcsb.org / structure / 1JF1).

[0245] Figure 22 A shows the target HLA-peptide G8 (HLA-A). The thermal map of HLA α1 helix of all ABPs tested by 02:01_AIFPGAVPAA (SEQ ID NO: 198). Figure 22 A disclosed SEQ ID NO: 643. Figure 22 B shows the target HLA-peptide G8 (HLA-A). The thermal map of HLA α2 helix of all ABPs tested by 02:01_AIFPGAVPAA (SEQ ID NO: 198)). Figure 22 B disclosed SEQ ID NO: 644. Figure 22 C shows the resulting heatmap of the restricted peptide AIFPGAVPAA (SEQ ID NO: 198) of ABP for all tests. Figure 22 C disclosed SEQ ID NO: 198.

[0246] Figure 23 A shows an exemplary heatmap of scFv R3G10-P2G11, which uses a comprehensive perturbation view to visualize the entire HLA portion of the HLA-peptide target G10. Figure 23 A disclosed SEQ ID NO: 645.

[0247] Figure 23 B shows an example of HDX data from scFv R3G10-P2G11 plotted on the crystal structure PDB5bs0.

[0248] Figure 23 C shows an example of HDX data from scFv G10-P5A08 plotted on the crystal structure PDB5bs0. Figure 23 C discloses "RRVY" as SEQ ID NO: 646.

[0249] Figure 24 A shows the target HLA-peptide G10 (HLA-A). The resulting thermograms of the HLA α1 helix of all ABPs tested by 01:01_ASSLPTTMNY (SEQ ID NO:260). Figure 24 A disclosed SEQ ID NO: 647. Figure 24 B shows the target HLA-peptide G10 (HLA-A). The resulting heatmap of all ABP HLAα2 helices tested by 01:01_ASSLPTTMNY (SEQ ID NO: 260)). Figure 24 B disclosed SEQ ID NO: 648. Figure 24C shows the resulting heatmap of the restricted peptide ASSLPTTMNY (SEQ ID NO: 260) of ABP for all tests.

[0250] Figure 25 Exemplary spectral data for the peptide EVDPIGHVY (SEQ ID NO: 2) are depicted. This plot includes peptide fragmentation information and patient-sample-related information, including HLA type.

[0251] Figure 26 Exemplary spectral data for the peptide AIFPGAVPAA (SEQ ID NO: 198) are depicted. This plot includes peptide fragmentation information and patient-sample-related information, including HLA type.

[0252] Figure 27 Exemplary spectral data for the peptide ASSLPTTMNY (SEQ ID NO: 260) are depicted. This plot includes peptide fragmentation information and patient-sample-related information, including HLA type.

[0253] Figure 28 A and 28B depict size exclusion chromatographic fractions (A) and SDS-PAGE analysis of chromatographic fractions under reducing conditions (B).

[0254] Figure 29 The map depicts the Fab clone G8-P1C11 and HLA-peptide target A. Micrograph of an exemplary crystal of the composite of 02:01_AIFPGAVPAA (SEQ IDNO: 198) (“G8”).

[0255] Figure 30 The process of cloning G8-P1C11 via Fab and targeting the HLA peptide A was described. The overall structure of the complex formed by combining 02:01_AIFPGAVPAA (SEQ IDNO: 198) (“G8”).

[0256] Figure 31 Depicting the interaction with HLA-peptide target A Fine electron density region of the crystal structure of Fab clone G8-P1C11 of 02:01_AIFPGAVPAA (SEQ ID NO: 198) (“G8”) complex, the region depicted corresponds to the restriction peptide AIFPGAVPAA (SEQ ID NO: 198).

[0257] Figure 32 LigPlot was used to depict the interaction between HLA and the restriction peptide. The crystal structure corresponds to the interaction with HLA-peptide target A. 02:01_AIFPGAVPAA (SEQ ID NO: 198) (“G8”) composite Fab clone G8-P1C11.

[0258] Figure 33 A diagram depicting the interacting residues between the Fab VH and VL chains and the restriction peptide is provided. The crystal structure corresponds to the HLA-peptide target A. 02:01_AIFPGAVPAA (SEQ ID NO: 198) (“G8”) composite Fab clone G8-P1C11.

[0259] Figure 34 LigPlots depicting the interaction between the restriction peptide chain and the Fab chain were used. The crystal structure corresponds to the interaction with the HLA-peptide target A. 02:01_AIFPGAVPAA (SEQ ID NO: 198) (“G8”) composite Fab clone G8-P1C11.

[0260] Figure 35 LigPlot was used to depict the interaction between the Fab VH chain and HLA. The crystal structure corresponds to the interaction with the HLA-peptide target A. 02:01_AIFPGAVPAA (SEQ ID NO: 198) (“G8”) composite Fab clone G8-P1C11.

[0261] Figure 36 LigPlot was used to depict the interaction between the Fab VL chain and HLA. The crystal structure corresponds to the interaction with the HLA-peptide target A. 02:01_AIFPGAVPAA (SEQ ID NO: 198) (“G8”) composite Fab clone G8-P1C11.

[0262] Figure 37 An overview of the interfaces depicted by PISA analysis for the interaction between HLA and the restriction peptide is provided. The crystal structure corresponds to the interaction with HLA-peptide target A. 02:01_AIFPGAVPAA (SEQ ID NO: 198) (“G8”) composite Fab clone G8-P1C11.

[0263] Figure 38 PISA analysis depicted the interaction residues between HLA and the restriction peptide. The crystal structure corresponds to the HLA-peptide target A. 02:01_AIFPGAVPAA (SEQ ID NO: 198) (“G8”) composite Fab clone G8-P1C11.

[0264] Figure 39 The Fab VH chain and the PISA analysis depicting the interacting residues with the restriction peptide are described. The crystal structure corresponds to the HLA-peptide target A. 02:01_AIFPGAVPAA (SEQ ID NO: 198) (“G8”) composite Fab clone G8-P1C11.

[0265] Figure 40 PISA analysis depicted the interaction residues between the Fab VL chain and the restriction peptide. The crystal structure corresponds to the HLA-peptide target A. 02:01_AIFPGAVPAA (SEQ ID NO: 198) (“G8”) composite Fab clone G8-P1C11.

[0266] Figure 41 An overview of the interface depicted by PISA analysis illustrates the interaction between the Fab VH chain and HLA. The crystal structure corresponds to the interaction with the HLA-peptide target A. 02:01_AIFPGAVPAA (SEQ ID NO: 198) (“G8”) composite Fab clone G8-P1C11.

[0267] Figure 42 PISA analysis depicted the interaction residues between the Fab VH chain and HLA. The crystal structure corresponds to the HLA-peptide target A. 02:01_AIFPGAVPAA (SEQ ID NO: 198) (“G8”) composite Fab clone G8-P1C11.

[0268] Figure 43 An overview of the interface depicted by PISA analysis illustrates the interaction between the Fab VL chain and HLA. The crystal structure corresponds to the interaction with the HLA-peptide target A. 02:01_AIFPGAVPAA (SEQ ID NO: 198) (“G8”) composite Fab clone G8-P1C11.

[0269] Figure 44 PISA analysis depicted the interaction residues between the Fab VL chain and HLA. The crystal structure corresponds to the HLA-peptide target A. 02:01_AIFPGAVPAA (SEQ ID NO: 198) (“G8”) composite Fab clone G8-P1C11.

[0270] Figure 45A depicts an exemplary heatmap of the HLA portion of the G8 HLA-peptide complex when incubated with the scFv clone G8-P1C11, which visualizes the whole using a comprehensive perturbation. Figure 45 A disclosed SEQ ID NO: 642.

[0271] Figure 45 B depicts the mapping on HLA-peptide target A. 02:01_AIFPGAVPAA (SEQ ID NO: 198) (“G8”) composite Fab clone G8-P1C11 crystal structure scFv G8-P1C11 HDX data instance.

[0272] Figure 46 The binding affinity of Fab clone G8-P1C11 to the G8 position variant HLA was depicted. Figure 46 SEQ ID NO: 198 has been disclosed.

[0273] Figure 47 It showed compatibility with G8-P1C11 (targeting HLA-peptide A) Histogram of K562 cells bound to the target-specific antibody of AIFPGAVPAA (SEQ ID NO:198) (“G8”).

[0274] Figure 48 An exemplary construct backbone sequence for cloning TCRs into an expression system for therapeutic development is depicted. Figure 48 SEQ ID NO: 650 has been disclosed.

[0275] Figure 49 Describing the use of A 0201_LLASSILCA (SEQ ID NO: 322) is an exemplary construct sequence of a specific TCR cloned into an expression system for therapeutic development. Figure 49 SEQ ID NO: 651 was also disclosed.

[0276] Figure 50 Describing the use of A 0101_EVDPIGHLY (SEQ ID NO: 354) is an exemplary construct sequence of a specific TCR cloned into an expression system for therapeutic development. Figure 50 SEQ ID NO: 652 was also disclosed.

[0277] Figure 51The spectral data for peptide EVDPIGHLY (SEQ ID NO: 354) are displayed. This figure includes peptide fragmentation information and patient-sample-related information, including HLA type.

[0278] Figure 52 The spectral data for peptide GVHGGILNK (SEQ ID NO: 355) are shown. This figure includes peptide fragmentation information and patient-sample-related information, including HLA type.

[0279] Figure 53 The spectral data of peptide GVYDGEEHSV (SEQ ID NO: 356) are shown.

[0280] Figure 54 The spectral data of peptide NTDNLAVY (SEQ ID NO: 73) are shown.

[0281] Figures 55-63 The spectral data for other peptides disclosed in Table A are shown. Figure 55 SEQ ID NO: 653, 653, and 653 have been disclosed. Figure 56 SEQ ID NOS 654, 654 and 654 have been disclosed. Figure 57 SEQ ID NOS 655, 655 and 655 have been disclosed. Figure 58 SEQ ID NOS 656, 656 and 656 have been disclosed. Figure 59 SEQ ID NOS 656, 656 and 656 have been disclosed. Figure 60 SEQ ID NOS 657, 657 and 657 have been disclosed. Figure 61 SEQ ID NOS 658, 658 and 658 have been disclosed. Figure 62 SEQ IDNOS 659, 659 and 659 are disclosed. Figure 63 SEQ ID NO 355, 355 and 355 are disclosed, and the disclosures are made in the order of their appearance.

[0282] Figure 64 The G2 target HLA-A was shown. Design of target screening 1 for 01:01_NTDNNLAVY (SEQ ID NO: 73).

[0283] Figure 65 A shows the target and micro-collection negative control design for the G2 target. Figure 65 A discloses SEQ ID NOS 73, 370-371 and 360 in the order of their appearance.

[0284] Figure 65 B shows the stability ELISA results for the G2 reverse screening "mini-set" and the G2 target. Figure 65 B discloses SEQ ID NOS 73, 370-371, 360 and 641 in the order of their appearance.

[0285] Figure 66 The stability ELISA results for the additional G2 “complete” set of reverse-screening peptides are shown. Figure 66 SEQ ID NOS 368-369, 359, 372-377, 358 and 378-382 are disclosed in the order of their appearance.

[0286] Figure 67 The G7 target HLA-A was shown. Design of target screening 2 for 02:01_LLASSILCA (SEQ ID NO: 322).

[0287] Figure 68 The stability ELISA results for the additional G7 “complete set” reverse screening peptides are shown. Figure 68 SEQ ID NOS 372-374, 380-382, 638-640, 383-385, 370-371 and 360 are disclosed in the order of their appearance.

[0288] Figure 69 A shows the target and micro-collection negative control design for the G7 target. Figure 69 A discloses SEQ ID NOS 322, 368-369 and 359 in the order of their appearance.

[0289] Figure 69 B shows the stability ELISA results for the G7 reverse screening "mini-set" and the G7 target. Figure 69 B discloses SEQ ID NOS 322, 368-369, 359 and 375 in the order of their appearance.

[0290] Figure 70 A and Figure 70 B shows the phage panning results for targets G2 and G7, respectively.

[0291] Figure 71 A and Figure 71 B shows the biolayer interferometry (BLI) results for the G2 target Fab clone G-2P1H11 and the G7 target G7R4-B5-P2E9, respectively.

[0292] Figure 72 The amino acid substitution map of the position scanning experiment described in this paper is shown. Figure 72SEQ ID NOS 73 and 322 are disclosed in the order of their appearance.

[0293] Figure 73 A shows a stability heatmap of the G2 position variant - HLA. Figure 73 A disclosed SEQ ID NO: 73.

[0294] Figure 73 B shows an affinity heatmap of Fab clone G2-P1H11. Figure 73 B disclosed SEQ ID NO: 73.

[0295] Figure 74 A shows a stability heatmap of the G7 position variant. Figure 74 A disclosed SEQ ID NO: 322.

[0296] Figure 74 B shows an affinity heatmap of Fab clone G7R4-B5-P2E9. Figure 74 B disclosed SEQ ID NO: 322.

[0297] Figure 75 The results show the cell binding of Fab clones G2-P1H11 and G7R4-B5-P2E9 to HLA-transduced K562 cells bombarded with the target or negative control peptides.

[0298] Figure 76 The results show the cell binding of Fab clones G2-P1H11 and G7R4-B5-P2E9 to HLA-transduced K562 cells bombarded with the target or negative control peptides.

[0299] Figure 77 An example of hydrogen-deuterium exchange (HDX) data plotted on the crystal structure PDB 5bs0 is shown.

[0300] Figure 78 An exemplary HDX heatmap of scFv clone G2-P1G07 is shown, which is visualized as a whole using a comprehensive perturbation view. Figure 78 SEQ ID NO: 660 has been disclosed.

[0301] Figure 79 HDX heatmaps of the tested G2 scFv and Fab clones across the HLA α1 and α2 helices are shown. Figure 79 SEQ ID NOS 661-662 are disclosed in the order of their appearance.

[0302] Figure 80HDX heatmaps of the tested G2 scFv and Fab clone restricted peptide NTDNNLAVY (SEQ ID NO: 73) are shown.

[0303] Figure 81 An experimental workflow is described, which allows for the isolation of TCRs that specifically bind to HLA-peptide targets.

[0304] Figure 82 The flow cytometry sorting procedure for sorting MHC target-specific CD8+ T cells is shown. Figure 82 "GEMSSNSTAL" is disclosed as SEQ ID NO: 357 and "EVDPIGHLY" is disclosed as SEQ ID NO: 354.

[0305] Figure 83 An example HLA-peptide target B is shown. 44:02_GEMSSNSTAL(SEQ ID NO: 357) and A Flow cytometry results of 01:01_EVDPIGHLY (SEQ ID NO: 354).

[0306] Figure 84 HLA-peptide target A was shown. Flow cytometry results of 03:01_GVHGGILNK (SEQ ID NO: 355). Figure 84 "EVDPIGHVY" was also disclosed as SEQ ID NO: 2.

[0307] Figure 85 A shows the total number of isolated CD8+ T cells for each HLA-peptide target across all tested donors. Figure 85 A discloses SEQ ID NO 73, 414, 322, 356, 355, 357, 2 and 354 in the order of their appearance.

[0308] Figure 85 B shows the frequency of isolated CD8+ T cells for each HLA-peptide target across all tested donors. Figure 85 B discloses SEQ ID NO 354, 322, 414, 355, 2, 357, 356 and 73 in the order of their appearance.

[0309] Figure 86 A describes the number of unique TCR clones for each HLA-peptide target from each donor for each test. Figure 86A discloses SEQ ID NO 73, 322, 356, 355, 357, 2 and 354 in the order of their appearance.

[0310] Figure 86 B depicts the total number of unique clones for each HLA-peptide target across all tested donors. Figure 86 B discloses SEQ ID NO 73, 322, 356, 355, 357, 2 and 354 in the order of their appearance.

[0311] Figure 87 The expression A was shown. 0201_LLASSILCA (SEQ ID NO: 322), A 0201_GVYDGEEHSV (SEQ ID NO: 356), B 4402_GEMSSNSTAL (SEQ ID NO: 357) and A 0101_EVDPIGHLY (SEQ ID NO: 354) - An example of Jurkat cells with specific TCRs that bind to their respective HLA-peptide targets but not to control peptide tetramers.

[0312] Figure 88 The gating strategy and flow data are shown, which demonstrate that human CD8+ cells transduced with the TCR identified in this paper bind to their specific HLA-peptide targets. Figure 88 "LLASSILCA" is disclosed as SEQ ID NO: 322.

[0313] Figure 89 An exemplary lentiviral vector that can be used to transduce recipient cells using the TCR disclosed herein is shown.

[0314] Figure 90 This shows the BLI results for the G2 target Fab clone G2-P2C06. Figure 90 SEQ ID NO: 73 has been disclosed.

[0315] Figure 91 A depicts the stability results of a second experiment from the G2 position variant HLA. Figure 91 A disclosed SEQ ID NO: 73.

[0316] Figure 91 B depicts the binding affinity of Fab clone G2-P2C06 to the G2 position variant HLA. Figure 91 B disclosed SEQ ID NO: 73.

[0317] Figure 92 HDX heatmaps of the second round of HDX experiments are shown for the HLA α1 helix, HLA α2 helix, and restriction peptide ASSLPTTMNY (SEQ ID NO: 260) of G10 ABP from various tests. Figure 92 The amino acid sequence beginning with “KMEPR…” is also disclosed as SEQ ID NO: 647 and the amino acid sequence beginning with “AADMA…” is disclosed as SEQ ID NO: 648.

[0318] Figure 93 HDX heatmaps from the second round of HDX experiments are shown for the HLAα1 helix, HLAα2 helix, and the restriction peptide NTDNNLAVY (SEQ ID NO: 73) from the tested G2 ABP. Figure 93 The amino acid sequence beginning with “KMEPR…” is also disclosed as SEQ ID NO: 647 and the amino acid sequence beginning with “AADMA…” is disclosed as SEQ ID NO: 648.

[0319] Figure 94 An example of HDX data from scFv G2-P2C11 plotted on crystal structure PDB 5bs0 is shown. Figure 94 "RRVY" is disclosed as SEQ ID NO: 646.

[0320] Figure 95 High-resolution HDX data plotted on the PDB 5bs0 crystal structure are shown. As described in the experimental procedure, peptide fragmentation was performed via electron transfer dissociation (ETD) to obtain data for G2 binding to four different scFvs. Peptide fragments with high-resolution data (at approximately single amino acid resolution) and residues 157–160 are shown circled. Figure 95 "RRVY" is disclosed as SEQ ID NO: 646. Figure 95 The amino acid sequence beginning with “TDRAN…” is also disclosed as SEQ ID NO: 663 and the amino acid sequence beginning with “LRSWT…” is disclosed as SEQ ID NO: 664.

[0321] Figure 96 The image shows the result from targeting the HLA-PEPTIDE target G5 (HLA-B). Color thermograms of HDX experiments on all ABPs tested in 35:01_EVDPIGHVY (SEQ ID NO: 2), including HLAα1 helices, HLAα2 helices, and the restriction peptide EVDPIGHVY (SEQ ID NO: 2). Figure 96The amino acid sequence beginning with “RTEPR…” is also disclosed as SEQ ID NO: 665 and the amino acid sequence beginning with “AADTA…” is disclosed as SEQ ID NO: 649.

[0322] Figure 97 Showing Figure 96 The digital representation of a color heatmap. Figure 97 "EVDPIGHVY" is disclosed as SEQ ID NO:2. Figure 97 The amino acid sequence beginning with “RTEPR…” is also disclosed as SEQ ID NO: 665 and the amino acid sequence beginning with “AADTA…” is disclosed as SEQ ID NO: 649.

[0323] Figure 98 Showing the data plotted in HLA-B An example of data for the scFv clone G5-P1C12 on a crystal structure of 35:01 (5xos.pdb; https: / / www.rcsb.org / structure / 5XOS).

[0324] Figure 99 It shows the effect of targeting the HLA-peptide target G8 (HLA-A) Color thermograms of the second round of HDX experiments on all ABPs, HLAα1 helices, HLAα2 helices, and restriction peptides within AIFPGAVPAA (SEQ ID NO: 198) tested at 02:01_AIFPGAVPAA (SEQ ID NO: 198). Figure 99 The amino acid sequence beginning with “RMEPR…” is also disclosed as SEQ ID NO:643 and the amino acid sequence beginning with “AADMA…” is disclosed as SEQ ID NO:364.

[0325] Figure 100 Showing Figure 99 The digital representation of a color heatmap. Figure 100 "AIFPGAVPAA" is disclosed as SEQ ID NO: 198. Figure 100 The amino acid sequence beginning with “RMEPR…” is also disclosed as SEQ ID NO: 643 and the amino acid sequence beginning with “AADMA…” is disclosed as SEQ ID NO: 364.

[0326] Figure 101 The image shows the result of plotting on HLA-PEPTIDE target A. 02:01_AIFPGAVPAA (SEQ ID NO:198) (“G8”) is an example of high-resolution HDX data of scFv G8-P1H08 on the crystal structure of Fab clone G8-P1C11.

[0327] Figure 102 The results of flow cytometry experiments are shown, in which HLA-B was shocked with 50 µM of the target peptide EVDPIGHVY (SEQ ID NO: 2) (“EVD”) or the negative control peptide IPSINVHHY (SEQ ID NO: 358) (“IPS”). K562 cells were transduced at 35:01, and pHLA-specific antibodies were detected by flow cytometry.

[0328] Figure 103 The results of flow cytometry experiments are shown, in which HLA-A was bombarded with 50 μM of the target peptide AIFPGAVPAA (SEQ ID NO: 198) (“AIF”) or the negative control peptide FLLTRILTI (SEQ ID NO: 359) (“FLL”). K562 cells were transduced at 02:01, and pHLA-specific antibodies were detected by flow cytometry.

[0329] Figure 104 The results of flow cytometry experiments are shown, in which HLA-A was shocked with 50 μM of the target peptide ASSLPTTMNY (SEQ ID NO: 260) (“ASSL”) or the negative control peptide ATDALMTGY (SEQ ID NO: 360) (“ATDA”). K562 cells were transduced at 01:01, and pHLA-specific antibodies were detected by flow cytometry.

[0330] Figure 105 The G8 target Fab clones G8-P4F05, G8-P1B03, and G8-P5G08 were shown to interact with the HLA-peptide target A. 02:01-BLI results of AIFPGAVPAA (SEQ ID NO: 198); and G5 target Fab clone G5-P1C12 and HLA-PEPTIDE target B BLI results for 35:01-EVDPIGHVY (SEQ ID NO: 2). Detailed Implementation

[0331] Unless otherwise defined, all technical terms, symbols, and other scientific terms used herein are intended to have the meanings commonly understood by those skilled in the art. In some instances, for clarity and / or ease of reference, terms are defined herein with their commonly understood meanings, and such definitions included herein are not necessarily construed as indicating a difference from their commonly understood meanings in the art. The methods and procedures described or referenced herein are methods and procedures that are commonly understood by those skilled in the art and are typically applied using conventional methodologies, such as, for example, those described by Sambrook et al. Molecular Cloning: A Laboratory Manual The widely used molecular cloning methods described in the 4th edition (2012) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. Appropriately, unless otherwise stated, procedures regarding the use of commercially available kits and reagents should generally be performed according to the manufacturer's defined protocols and conditions.

[0332] Unless the context clearly indicates otherwise, the singular forms “a,” “an,” and “the” used herein include the plural indicator. Unless otherwise clearly indicated, the terms “comprising,” “such as,” etc., are intended to convey a meaning that includes but is not limiting.

[0333] Unless otherwise specifically stated, the term "comprising" as used herein also specifically includes embodiments that "comprise the listed elements" and "comprise substantially the listed elements." For example, a multispecific ABP that "comprising a bifunctional antibody" includes a multispecific ABP that "comprises a bifunctional antibody" and a multispecific ABP that "comprises substantially a bifunctional antibody."

[0334] The term "about" refers to and covers both the indicated value and the range greater than and less than the value. In some embodiments, the term "about" means ±10%, ±5%, or ±1% of the specified value. In some embodiments, if applicable, the term "about" means the specified value ± one standard deviation of the value.

[0335] The term "immunoglobulin" refers to a class of structurally related proteins, typically consisting of two pairs of polypeptide chains: a pair of light chains (L) and a pair of heavy chains (H). In a "complete immunoglobulin," all four chains are interconnected by disulfide bonds. The structure of immunoglobulins has been well characterized. See, for example, Paul, Fundamental Immunology 7th Edition, Chapter 5 (2013) Lippincott Williams & Wilkins, Philadelphia, PA. In short, each heavy chain typically contains a heavy chain variable region (V... H ) and heavy chain constant region (C HThe heavy-chain constant region typically contains three structural domains, abbreviated as C. H1 C H2 and C H3 Each light chain typically contains a light chain variable region (V). L ( ) and the light chain constant region. The light chain constant region typically contains a structural domain, abbreviated as C. L .

[0336] The term “antigen-binding protein” or “ABP” as used herein is used in its broadest sense and includes certain types of molecules that contain one or more antigen-binding domains that specifically bind to an antigen or epitope.

[0337] In some embodiments, the ABP comprises an antibody. In some embodiments, the ABP is composed of an antibody. In some embodiments, the ABP is substantially composed of an antibody. Specifically, the ABP comprises an intact antibody (e.g., an intact immunoglobulin), an antibody fragment, an ABP fragment, and a multispecific antibody. In some embodiments, the ABP comprises an alternative scaffold. In some embodiments, the ABP is composed of an alternative scaffold. In some embodiments, the ABP is substantially composed of an alternative scaffold. In some embodiments, the ABP comprises an antibody fragment. In some embodiments, the ABP is substantially composed of an antibody fragment. In some embodiments, the ABP comprises a TCR or its antigen-binding portion. In some embodiments, the ABP is composed of a TCR or its antigen-binding portion. In some embodiments, the ABP is substantially composed of a TCR or its antigen-binding portion. In some embodiments, the CAR comprises the ABP. As provided herein, “HLA-peptide ABP,” “anti-HLA-peptide ABP,” or “HLA-peptide-specific ABP” is an ABP that specifically binds to the antigen HLA-peptide. ABP includes proteins containing one or more antigen-binding domains that specifically bind to antigens or epitopes via variable regions, such as variable regions derived from B cells (e.g., antibodies) or T cells (e.g., TCRs).

[0338] The term "antibody" in this article is used in its broadest sense and includes both polyclonal and monoclonal antibodies, encompassing complete antibodies and functional (antigen-binding) antibody fragments, including fragment antigen-binding (Fab) fragments, F(ab')2 fragments, Fab' fragments, Fv fragments, recombinant IgG (rIgG) fragments, and variable heavy chains (V) capable of specifically binding antigens. HThis term encompasses single-chain antibody fragments (including single-chain variable fragments (scFv)) and single-domain antibody fragments (e.g., sdAb, sdFv, nanobodies). The term covers genetically engineered and / or otherwise modified forms of immunoglobulins, such as intracellular antibodies, peptide bodies, chimeric antibodies, fully human antibodies, humanized antibodies and conjugated antibodies, multispecific antibodies (e.g., bispecific antibodies), biantibodies, triantibodies and tetraantibodies, tandem bivalent scFv, and tandem trivalent scFv. Unless otherwise stated, the term "antibody" should be understood to encompass its functional antibody fragment. The term also covers complete or full-length antibodies, including antibodies of any class or subclass, including IgG and its subclasses, IgM, IgE, IgA, and IgD.

[0339] As used in this article, “variable region” refers to a variable nucleotide sequence resulting from a recombination event, which may include, for example, the V, J, and / or D regions of an immunoglobulin or T cell receptor (TCR) sequence from a B cell or T cell (such as an activated T cell or an activated B cell).

[0340] The term "antigen-binding domain" refers to the portion of an ABP that can specifically bind to an antigen or epitope. An example of an antigen-binding domain is an antibody V against an ABP. H -V L The antigen-binding domain is formed by the dimer. Another example of an antigen-binding domain is an antigen-binding domain formed by diversifying certain loops from the tenth fibronectin type III domain of adnectin. The antigen-binding domain may sequentially contain antibody CDR1, CDR2, and CDR3 from the heavy chain; and antibody CDR1, CDR2, and CDR3 sequentially from the light chain. The antigen-binding domain may contain TCR CDRs, such as αCDR1, αCDR2, αCDR3, βCDR1, βCDR2, and βCDR3. TCR CDRs are described herein.

[0341] antibody V H District and V L The region can be further subdivided into highly variable regions (“HVR”; also known as “complementary determinant regions” (CDR)), interspersed with more conservative regions. The more conservative regions are called framing regions (FR). Each V H and V L Typically, it contains three antibody CDRs and four antibody FRs, arranged in the following order (from N-terminus to C-terminus): FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4. Antibody CDRs participate in antigen binding and influence antigen specificity and binding affinity of ABP. See Kabat et al. Sequences of Proteins of Immunological Interest5th edition (1991) Public Health Service, National Institutes of Health, Bethesda, MD, which is incorporated in its entirety by reference.

[0342] Based on the sequence of constant structural domains in vertebrates, light chains from any vertebrate can be divided into two types, called κ-kappa and λ-lambda.

[0343] Heavy chains in any vertebrate can be classified into one of five distinct classes (or isotypes): IgA, IgD, IgE, IgG, and IgM. These classes are also referred to as α, δ, ε, γ, and µ, respectively. Based on sequence and functional differences, IgG and IgA are further subdivided into subclasses. Humans express the following subclasses: IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2.

[0344] Those skilled in the art can use any of the many known numbering schemes to determine the amino acid sequence boundaries of antibody CDRs. Known numbering schemes include those described in the following literature: Kabat et al., see above (“Kabat” numbering scheme); Al-Lazikani et al., 1997, J. Mol. Biol. , 273:927-948 (“Chothia” numbering scheme); MacCallum et al., 1996, J. Mol. Biol. 262:732-745 (“Contact” numbering scheme); Lefran et al., Dev. Comp. Immunol. , 2003, 27:55-77 (“IMGT” numbering scheme) and Honegge and Plückthun, J. Mol. Biol. , 2001, 309:657-70 (“AHo” numbering scheme); each of them is incorporated in whole by reference.

[0345] Table 20 provides the positions of antibodies CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR-H2, and CDR-H3 identified using the Kabat and Chothia schemes. For CDR-H1, residue numbers are provided using both the Kabat and Chothia numbering schemes.

[0346] For example, ABP numbering software (such as Abnum) can be used to assign antibody CDRs. Abnum is available from www.bioinf.org.uk / abs / abnum / and is also used by Abhinandan and Martin. Immunology It is described in , 2008, 45:3832-3839 (which is incorporated in its entirety by reference).

[0347] When using the Kabat numbering convention, the C end of CDR-H1 varies between H32 and H34 depending on the length of the CDR.

[0348] When referring to residues in the constant region of the ABP heavy chain, the “EU numbering scheme” is generally used (e.g., as reported by Kabat et al., see above). Unless otherwise stated, the EU numbering scheme is used to refer to residues in the constant region of the ABP heavy chain as described herein.

[0349] The terms “full-length antibody,” “intact antibody,” and “whole antibody” used herein are interchangeable and refer to antibodies that have a structure substantially similar to that of naturally occurring antibodies and that contain a heavy chain including an Fc region. For example, when used to refer to IgG molecules, a “full-length antibody” is an antibody that consists of two heavy chains and two light chains.

[0350] Those skilled in the art can use any of the many known numbering schemes to determine the amino acid sequence boundaries of TCR CDRs, including but not limited to the unique IMGT numbering described in the following references: LeFranc, M.-P, Immunol Today. Nov. 1997;18(11):509; Lefranc, M.-P., "IMGTLocus on Focus: A new section of Experimental and Clinical Immunogenetics",Exp. Clin. Immunogenet., 15, 1-7 (1998); Lefranc and Lefranc, The T Cell Receptor FactsBook; and M.-P. Lefranc / Developmental and Comparative Immunology 27 (2003) 55–77; all of which are incorporated herein by reference.

[0351] "ABP fragment" includes a portion of the complete ABP, such as the antigen-binding or variable region of the complete ABP. ABP fragments include, for example, Fv fragments, Fab fragments, F(ab')2 fragments, Fab' fragments, scFv((sFv)) fragments, and scFv-Fc fragments. ABP fragments also include antibody fragments. Antibody fragments can include Fv fragments, Fab fragments, F(ab')2 fragments, Fab' fragments, scFv((sFv)) fragments, scFv-Fc fragments, and TCR fragments.

[0352] The “Fv” fragment is a non-covalently linked dimer consisting of a heavy chain variable domain and a light chain variable domain.

[0353] In addition to the variable domains of the heavy chain and the light chain, the "Fab" fragment also contains a constant domain of the light chain and a first constant domain ((CH1)) of the heavy chain. The Fab fragment can be produced, for example, by recombinant methods or by papain digestion of a full-length ABP.

[0354] The “F(ab’)2” fragment contains two Fab’ fragments linked by disulfide bonds near the hinge region. The F(ab’)2 fragment can be produced, for example, by recombinant methods or by pepsin digestion of the intact ABP. The F(ab’) fragment can be dissociated, for example, by treatment with β-mercaptoethanol.

[0355] The "single-chain Fv" or "sFv" or "scFv" fragment contains a VH domain and a VL domain within a single polypeptide chain. The VH and VL domains are typically linked by a peptide linker. See Plückthun A. (1994). Any suitable linker can be used. In some embodiments, the linker is (GGGGS). n (SEQ ID NO: 361). In some embodiments, n = 1, 2, 3, 4, 5, or 6. See ABP derived from Escherichia coli. Rosenberg M. & Moore GP (edited) The Pharmacology of Monoclonal ABPs Volume 113 (pp. 269-315). Springer-Verlag, New York, which is incorporated in its entirety by reference.

[0356] The “scFv-Fc” fragment contains an scFv attached to an Fc domain. For example, the Fc domain may be attached to the C-terminus of the scFv. Depending on the orientation of the variable domains in the scFv (i.e., VH-VL or VL-VH), the Fc domain may be after VH or VL. Any suitable Fc domain known in the art or described herein may be used. In some cases, the Fc domain includes the IgG4Fc domain.

[0357] The term "single-domain antibody" refers to a molecule in which one variable domain of an ABP specifically binds to an antigen while the other variable domain is absent. Single-domain ABPs and their fragments are described by Arabi Ghahroudi et al. FEBS Letters , 1998, 414:521-526 and Muyldermans et al., Trends in Biochem. Sci. , 2001, 26:230-245, each of which is incorporated in its entirety by reference. Single-domain ABPs are also known as sdAbs or nanobodies.

[0358] The term "Fc region" or "Fc" refers to the C-terminal region of the immunoglobulin heavy chain, which interacts with Fc receptors and certain proteins of the complement system in naturally occurring antibodies. The structure of the Fc regions of various immunoglobulins and the glycosylation sites they contain are known in the art. See Schroeder and Cavacini. J. Allergy Clin. Immunol. , 2010, 125:S41-52, which is incorporated in its entirety by reference. The Fc region can be a naturally occurring Fc region or an Fc region modified as described in the art or elsewhere in this disclosure.

[0359] The term "alternative scaffold" refers to a molecule in which one or more regions can be diversified to generate one or more antigen-binding domains that specifically bind to an antigen or epitope. In some embodiments, the antigen-binding domains bind to the antigen or epitope with a specificity and affinity similar to that of ABP. Exemplary alternative scaffolds include those derived from fibronectin (e.g., Adnectins). TM ), β-sandwich (e.g., iMab), lipid transport proteins (e.g., Anticalins®), EETI-II / AGRP, BPTI / LACI-D1 / ITI-D2 (e.g., Kunitz domain), thioredoxin peptide aptamers, protein A (e.g., Affibody®), ankyrin repeat sequences (e.g., DARPins), γ-β-crystallins / ubiquitous proteins (e.g., Affilins), CTLD3 (e.g., Tetranectins), Fynomers, and (LDLR-A modules) (e.g., Avimers). Further information on alternative scaffolds is provided in the following literature: Binz et al., Nat.Biotechnol. , 200523:1257-1268; Skerra, Current Opinion in Biotech. , 2007 18:295-304; and Silacci et al., J. Biol. Chem. , 2014, 289:14392-14398; each of these is incorporated in its entirety by reference. An alternative stent is a type of ABP.

[0360] A "multispecific ABP" is an ABP comprising two or more distinct antigen-binding domains that collectively and specifically bind to two or more distinct epitopes. The two or more distinct epitopes can be epitopes on the same antigen (e.g., a single HLA-peptide molecule expressed by a cell) or epitopes on different antigens (e.g., different HLA-peptide molecules expressed by the same cell, or HLA-peptide and non-HLA-peptide molecules). In some aspects, a multispecific ABP binds to two distinct epitopes (i.e., a "bispecific ABP"). In some aspects, a multispecific ABP binds to three distinct epitopes (i.e., a "trispecific ABP").

[0361] A "monospecific ABP" is an ABP that contains one or more binding sites that specifically bind to a single epitope. An example of a monospecific ABP is the naturally occurring IgG molecule, which, although bivalent (i.e., having two antigen-binding domains), recognizes the same epitope on each of the two antigen-binding domains. Binding specificity can exist at any suitable valence.

[0362] The term "monoclonal antibody" refers to an antibody derived from a substantially homogeneous population of antibodies. A substantially homogeneous population of antibodies contains broadly similar antibodies that bind to the same epitopes, except for variants that may typically occur during monoclonal antibody production. Typically, only a small number of such variants are present. Monoclonal antibodies are usually obtained by methods involving the selection of a single antibody from a plurality of antibodies. For example, the selection method may be to choose a unique clone from a plurality of clones, such as a hybridoma clone, a phage clone, a yeast clone, a bacterial clone, or a collection of other recombinant DNA clones. The selected antibody may be further modified, for example, to improve affinity for the target ("affinity maturation"), to humanize the antibody, to improve its production in cell cultures, and / or to reduce its immunogenicity in subjects.

[0363] The term "chimeric antibody" refers to an antibody in which a portion of the heavy chain and / or light chain originates from a specific source or species, while the remainder of the heavy chain and / or light chain originates from a different source or species.

[0364] A “humanized” form of a nonhuman antibody is a chimeric antibody containing a minimal sequence derived from a nonhuman antibody. Humanized antibodies are typically human antibodies (recipient antibodies) in which one or more CDR residues are replaced by residues of one or more CDRs of a nonhuman antibody (donor antibody). The donor antibody can be any suitable nonhuman antibody, such as mouse, rat, rabbit, chicken, or nonhuman primate antibodies with the desired specificity, affinity, or biological effect. In some cases, selected frame region residues of the recipient antibody are replaced by corresponding frame region residues of the donor antibody. Humanized antibodies may also contain residues not found in either the recipient or donor antibody. This modification can be made to further improve antibody function. For more details, see Jones et al. Nature , 1986, 321:522-525; Riechmann et al., Nature , 1988, 332:323-329; and Presta, Curr. Op. Struct. Biol. , 1992, 2:593-596, each of the references is incorporated in its entirety by reference.

[0365] "Human antibody" is an antibody having an amino acid sequence that corresponds to the amino acid sequence of an antibody produced by a human or human cell, or derived from a non-human source (e.g., obtained from a human source or designed de novo) using a human antibody library or a human antibody encoding sequence. Human antibodies specifically exclude humanized antibodies.

[0366] “Affinity” refers to the strength of the sum of non-covalent interactions between a single binding site of a molecule (e.g., ABP) and its binding mate (e.g., an antigen or epitope). Unless otherwise stated, “affinity” as used herein refers to intrinsic binding affinity, which reflects a 1:1 interaction between members of the binding pair (e.g., ABP and an antigen or epitope). The affinity of molecule X for its mate Y can be expressed using the dissociation equilibrium constant (K0). D The following describes the kinetic elements relating to the dissociation equilibrium constant in more detail. Affinity can be measured by conventional methods known in the art, including those described herein, such as surface plasmon resonance (SPR) techniques (e.g., BIACORE®) or biolayer interferometry (e.g., FORTEBIO®).

[0367] Regarding the binding of ABP to target molecules, the terms "binding to a specific antigen (e.g., a peptide target) or an epitope on a specific antigen," "specifically binding to a specific antigen (e.g., a peptide target) or an epitope on a specific antigen," "specifically binding to a specific antigen (e.g., a peptide target) or an epitope on a specific antigen," "specific to a specific antigen (e.g., a peptide target) or an epitope on a specific antigen," "selectively binding to a specific antigen (e.g., a peptide target) or an epitope on a specific antigen," and "selectively binding to a specific antigen (e.g., a peptide target) or an epitope on a specific antigen" refer to binding that is distinctly different from nonspecific or nonselective interactions (e.g., binding to non-target molecules). Specific binding can be measured, for example, by measuring the binding to a target molecule and comparing it to the binding to a non-target molecule. Specific binding can also be determined by competition with a control molecule that mimics the epitope recognized on the target molecule. In that case, if the control molecule competitively inhibits the binding of ABP to the target molecule, it indicates specific binding. In some respects, HLA-peptide ABP has an affinity for non-target molecules that is approximately 50% less than its affinity for HLA-peptides. In some respects, HLA-peptide ABP has an affinity for non-target molecules that is approximately 40% less than its affinity for HLA-peptides. In some respects, HLA-peptide ABP has an affinity for non-target molecules that is approximately 30% less than its affinity for HLA-peptides. In some respects, HLA-peptide ABP has an affinity for non-target molecules that is approximately 20% less than its affinity for HLA-peptides. In some respects, HLA-peptide ABP has an affinity for non-target molecules that is approximately 10% less than its affinity for HLA-peptides. In some respects, HLA-peptide ABP has an affinity for non-target molecules that is approximately 1% less than its affinity for HLA-peptides. In some respects, HLA-peptide ABP has an affinity for non-target molecules that is approximately 0.1% less than its affinity for HLA-peptides.

[0368] The term "k" used in this article d (sec) -1 () refers to the dissociation rate constant of a specific ABP-antigen interaction. This value is also known as k. off value.

[0369] The term "k" used in this article a (M) -1 ×sec -1 () refers to the association rate constant of a specific ABP-antigen interaction. This value is also known as k. on value.

[0370] The term "K" used in this article D (M) refers to the dissociation equilibrium constant of a specific ABP-antigen interaction. K D = k d / k aIn some implementations, the affinity of ABP is based on the K-axis against the interaction between the ABP and its antigen. D Described. For clarity, as is known in the art, the smaller K... D A higher K value indicates a stronger affinity interaction, while a larger K value indicates a weaker affinity interaction. D The value indicates a lower affinity interaction.

[0371] The term "K" used in this article A (M) -1 K refers to the association equilibrium constant of a specific ABP-antigen interaction. A =k a / k d .

[0372] "Immune conjugate" is an ABP conjugated with one or more heterologous molecules, such as therapeutic agents (e.g., cytokines) or diagnostic agents.

[0373] "Fc effector function" refers to biological activities mediated by the Fc region of an ABP containing an Fc region, and these activities can vary by subtype. Examples of ABP effector functions include C1q binding to activate complement-dependent cytotoxicity (CDC), Fc receptor binding to activate ABP-dependent cytotoxicity (ADCC), and ABP-dependent phagocytosis (ADCP).

[0374] When used in the context of two or more ABPs, the terms "competing with" or "cross-competing with" mean that two or more ABPs compete to bind to an antigen (e.g., an HLA-peptide). In one exemplary assay, an HLA-peptide is coated onto a surface and brought into contact with a first HLA-peptide ABP, and then a second HLA-peptide ABP is added. In another exemplary assay, a first HLA-peptide ABP is coated onto a surface and brought into contact with an HLA-peptide, and then a second HLA-peptide ABP is added. If, in either assay, the presence of the first HLA-peptide ABP reduces the binding of the second HLA-peptide ABP, then the ABPs compete with each other. The term "competing with" also includes combinations of ABPs where one ABP reduces the binding of another ABP, but no competition is observed when the ABPs are added in reverse order. However, in some embodiments, the first and second ABPs inhibit each other's binding regardless of their order of addition. In some embodiments, one ABP reduces the binding of another ABP to its antigen by at least 25%, at least 50%, at least 60%, at least 70%, at least 80%, at least 85%, at least 90%, or at least 95%. A technician can select the concentration of the ABP used for the competitive assay based on the ABP's affinity for the HLA-peptide and the ABP's valence. The assays described in this definition are illustrative, and a technician can use any suitable assay to determine whether ABPs compete with each other. Suitable assays are described in the following literature: e.g., Cox et al., updated December 24, 2014. Assay Guidance Manual [Internet] See “Immunoassay Methods” (www.ncbi.nlm.nih.gov / books / NBK92434 / ; accessed September 29, 2015); Silman et al. Cytometry , 2001, 44:30-37; and Finco et al., J. Pharm. Biomed. Anal. , 2011, 54:351-358; each of them is incorporated in whole by reference.

[0375] The term "epitope" refers to a portion of an antigen that specifically binds to ABP. Epitopes typically consist of surface-accessible amino acid residues and / or sugar side chains and may possess specific three-dimensional structural characteristics and specific charge properties. The difference between conformational and non-conformational epitopes is that binding to the former, but not the latter, may be lost in the presence of denaturing solvents. Epitopes may contain amino acid residues that directly participate in binding and other amino acid residues that do not directly participate in binding. Known techniques for identifying epitopes can be used to determine epitopes that bind to ABP, such as, for example, testing the binding of ABP to HLA-peptide variants with different point mutations or to chimeric HLA-peptide variants.

[0376] The percentage of “identity” between a polypeptide sequence and a reference sequence is defined as the percentage of amino acid residues in the polypeptide sequence that are identical to those in the reference sequence after sequence alignment and the introduction of gaps (if necessary) to obtain the maximum percentage of sequence identity. Alignment used to determine the percentage of amino acid sequence identity can be performed in various ways within the scope of the art, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN, MEGALIGN (DNASTAR), CLUSTALW, CLUSTAL OMEGA, or MUSCLE software. Those skilled in the art can determine suitable parameters for sequence alignment, including any algorithm required to achieve maximum alignment across the full length of the sequences being compared.

[0377] "Conservative substitution" or "conservative amino acid substitution" refers to the substitution of one amino acid by another amino acid that is chemically or functionally similar to it. Conservative substitution of similar amino acids is well known in the art. For example, in some embodiments, the amino acid groups provided in Tables 21-23 are considered to be conservative substitutions of each other.

[0378] Table 21. Selected amino acid groups that are considered to be conservatively substituted for each other in some embodiments.

[0379] Table 22. In some embodiments, other selected amino acid groups are considered to be conservatively substituted for each other.

[0380] Table 23. Further selected amino acids considered as conservative substitutions of each other in some embodiments. Group .

[0381] Other conservative substitutions can be seen, for example, Creighton. Proteins: Structures and Molecular Properties 2nd edition (1993) WH Freeman & Co., New York, NY. ABPs produced by making one or more conserved substitutions of amino acid residues in the parental ABP are called "conservatively modified variants".

[0382] The term "amino acid" refers to twenty common, naturally occurring amino acids. These include alanine (Ala; A), arginine (Arg; R), asparagine (Asn; N), aspartic acid (Asp; D), cysteine (Cys; C), glutamic acid (Glu; E), glutamine (Gln; Q), glycine (Gly; G), histidine (His; H), isoleucine (Ile; I), leucine (Leu; L), lysine (Lys; K), methionine (Met; M), phenylalanine (Phe; F), proline (Pro; P), serine (Ser; S), threonine (Thr; T)), tryptophan (Trp; W), tyrosine (Tyr; Y), and valine (Val; V).

[0383] As used herein, the term "vector" refers to a nucleic acid molecule capable of replicating another nucleic acid linked to it. This term includes vectors that function as self-replicating nucleic acid structures, as well as vectors incorporated into the host cell genome. Some vectors are capable of directing the expression of nucleic acids operatively linked to them. Such vectors are referred to herein as "expression vectors."

[0384] The terms "host cell," "host cell line," and "host cell culture" are used interchangeably and refer to cells into which exogenous nucleic acids have been introduced and their progeny. Host cells include "transformants" (or "transformed cells") and "transfectants" (or "transfected cells"), each comprising primary transformed or transfected cells and their derived progeny. These progeny may not be identical to the parent cells in terms of nucleic acid content and may contain mutations.

[0385] The term "treating" (and its variations, such as "treat" or "treatment") refers to a clinical intervention that attempts to alter the natural course of a disease or symptom in a subject in need. Treatment can be aimed at prevention and at addressing clinicopathological processes. Ideal therapeutic outcomes include preventing the onset or recurrence of disease, alleviating symptoms, reducing any direct or indirect pathological consequences of the disease, preventing metastasis, slowing the rate of disease progression, improving or mitigating the disease state, and alleviating or improving prognosis.

[0386] As used herein, the term "therapeutic effective amount" or "effective amount" refers to the amount of ABP or pharmaceutical composition provided herein that, when administered to a subject, is effective in treating a disease or condition.

[0387] As used herein, the term "subject" refers to a mammalian subject. Exemplary subjects include humans, monkeys, dogs, cats, mice, rats, cattle, horses, camels, goats, rabbits, and sheep. In some embodiments, the subject is a human. In some embodiments, the subject suffers from a disease or condition that can be treated with the ABP provided herein. In some aspects, the disease or condition is cancer. In some aspects, the disease or condition is a viral infection.

[0388] The term "instructions for use" is used to refer to instructions typically included in the commercial packaging of a therapeutic or diagnostic product (e.g., a test kit), which contain information about the indications, usage, dosage, administration, combination therapy, contraindications, and / or warnings for using such a therapeutic or diagnostic product.

[0389] The term "tumor" refers to the growth and proliferation of all proliferative cells (whether malignant or benign), as well as all precancerous and cancerous cells and tissues. The terms "cancer," "carcinoma," "cellular proliferative disorder," "proliferative lesion," and "tumor" are not mutually exclusive herein. The terms "cellular proliferative disorder" and "proliferative lesion" refer to conditions associated with some degree of abnormal cell proliferation. In some implementations, a cellular proliferative disorder is cancer. In some respects, a tumor is a solid tumor. In some respects, a tumor is a hematologic malignancy.

[0390] The term "pharmaceutical composition" refers to a formulation which exists in a form that allows the biological activity of the active ingredient contained therein to effectively treat a subject, and which does not contain any additional components provided in the pharmaceutical composition that would have unacceptable toxicity to the subject.

[0391] The terms “modulate” and “modulation” refer to reducing or suppressing, or alternatively, activating or increasing, the listed variables.

[0392] The terms “increase” and “activation” refer to an increase of 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 100%, 2 times, 3 times, 4 times, 5 times, 10 times, 20 times, 50 times, 100 times or more in the listed variables.

[0393] The terms “reduction” and “suppression” refer to the reduction of the listed variables by 10%, 20%, 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 95%, 2 times, 3 times, 4 times, 5 times, 10 times, 20 times, 50 times, 100 times or more.

[0394] The term "agonist" refers to the activation of receptor signaling to induce a biological response associated with receptor activation. An "agonist" is an entity that binds to and activates receptors.

[0395] The term "antagonist" refers to the inhibition of receptor signaling to suppress biological responses associated with receptor activation. An "antagonist" is an entity that binds to and antagonizes a receptor.

[0396] The terms "nucleic acid" and "polynucleotide" are used interchangeably in this document and refer to a polymer of nucleotides of any length, namely deoxyribonucleotides or ribonucleotides or their analogues. Polynucleotides may include, but are not limited to, coding or non-coding regions of genes or gene fragments, loci as defined from the perspective of linkage analysis, exons, introns, messenger RNA (mRNA), cDNA, recombinant polynucleotides, branched polynucleotides, plasmids, vectors, isolated DNA, isolated RNA, nucleic acid probes, and primers. Polynucleotides may include modified nucleotides, such as methylated nucleotides and nucleotide analogues. Exemplary modified nucleotides include, for example, 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xanthine, 4-acetylcytosine, 5-(carboxyhydroxymethyl)uracil, 5-carboxymethylaminomethyl-2-thiouridine, 5-carboxymethylaminomethyluracil, dihydrouracil, β-D-galactosylinosine, inosine, N6-isopentene adenine, 1-methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 3-methylcytosine, 5-methylcytosine, N6-substituted adenine, 7-methylguanine. 5-Methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, β-D-mannosyl queosine, 5'-methoxycarboxymethyluracil, 5-methoxyuracil, 2-methylthioN6-isopentene adenine, uracil-5-oxyacetic acid (v), wybutoxosine, pseudouracil, queosine, 2-thiocytosine, 5-methyl-2-thiouracil, 2-thiouracil, 4-thiouracil, 5-methyluracil, methyl uracil-5-oxyacetic acid, 3-(3-amino-3-N-2-carboxypropyl)uracil, and 2,6-diaminopurine.

[0397] Isolated HLA-peptide targets The major histocompatibility complex (MHC) is a complex of antigens encoded by a set of linked loci. These antigens are collectively referred to as H-2 in mice and HLA in humans. MHC antigens have two main classes, class I and class II, each comprising a group of cell surface glycoproteins that play a role in determining tissue type and transplant compatibility. In transplant response, cytotoxic T cells (CTLs) primarily respond to class I glycoproteins, while helper T cells primarily respond to class II glycoproteins.

[0398] Human major histocompatibility complex (MHC) class I molecules (which may be interchangeably referred to herein as HLA class I molecules) are expressed on the surface of almost all cells. These molecules function to present peptides, primarily derived from endogenously synthesized proteins, to cells such as CD8+ T cells through interaction with α-β T cell receptors. MHC class I molecules consist of a heterodimer consisting of a 46 kDa α chain that is non-covalently associated with a 12 kDa light chain β-2 microglobulin. The α chain typically contains α1 and α2 domains that form the groove for presenting HLA-restricted peptides, and an α3 transmembrane domain that interacts with the CD8 co-receptor on T cells. Figure 1 (Prior art) describes the general structure of HLA class I molecules. Some TCRs can bind to MHC class I molecules independently of the CD8 co-receptor (see, e.g., Kerry SE, Buslepp J, Cramer LA et al. Interplay between TCR Affinity and Necessity of Coreceptor Ligation: High-Affinity Peptide-MHC / TCR Interaction Overcomes Lack of CD8 Engagement. Journal of Immunology (Baltimore, Md:1950). 2003;171(9):4493-4503).

[0399] Class I MHC-restricted peptides (which may also be referred to interchangeably herein as HLA-restricted antigens, HLA-restricted peptides, MHC-restricted antigens, restricted peptides, or peptides) generally bind to the α1-α2 groove of the heavy chain via about two or three anchoring residues that interact with the corresponding binding pockets in the MHC molecule. The β-2-microglobulin chain plays a crucial role in intracellular transport, peptide binding, and conformational stability of MHC class I molecules. For most class I molecules, the formation of a heterotrimeric complex of the MHC class I heavy chain, peptide (self, non-self, and / or antigenic), and β-2-microglobulin leads to protein maturation and export to the cell surface.

[0400] The binding of a given HLA subtype to an HLA-restricted peptide forms a complex with a unique and novel surface, which can be specifically recognized by ABPs (e.g., TCRs on T cells or their antibody or antigen-binding fragments). The HLA complexed with the HLA-restricted peptide is referred to herein as an HLA-peptide, pHLA, or HLA-peptide target. In some cases, the restriction peptide is located in the α1 / α2 groove of the HLA molecule. In other cases, the restriction peptide binds to the α1 / α2 groove of the HLA molecule via about two or three anchoring residues that interact with the corresponding binding pocket in the HLA molecule.

[0401] Therefore, this article provides antigens containing HLA-peptide targets. HLA-peptide targets may contain specific HLA-restricted peptides with a defined amino acid sequence that complexes with a specific HLA subtype.

[0402] The HLA-peptide targets identified in this paper can be used for cancer immunotherapy. In some embodiments, the HLA-peptide targets identified in this paper are present on the surface of tumor cells. The HLA-peptide targets identified in this paper can be expressed by tumor cells in human subjects. The HLA-peptide targets identified in this paper can be expressed by tumor cells in a human subject population. For example, the HLA-peptide targets identified in this paper can be common antigens that are typically expressed in human subject populations with cancer.

[0403] The HLA-peptide targets identified in this study exhibit varying prevalence rates depending on the individual tumor type. The prevalence rates for different tumor types may be approximately 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 4 4%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%. The prevalence varies depending on the individual tumor type, ranging from approximately 0.1% to 100%, 0.2% to 50%, 0.5% to 25%, or 1% to 10%.

[0404] Preferably, HLA-peptide targets are not typically expressed in most normal tissues. For example, in some cases, HLA-peptide targets may not be expressed in tissues included in a Genotype Tissue Expression (GTEx) project, or in some cases, they may only be expressed in immune-privileged or non-essential tissues. Exemplary immune-privileged or non-essential tissues include the testes, minor salivary glands, cervical endometrium, and thyroid gland. In some cases, an HLA-peptide target may be considered not expressed in essential or non-immune-privileged tissues if the median expression of the gene for which the restriction peptide is derived is less than 0.5 RPKM (number of reads per kilobase transcript per million mapped reads) in a GTEx sample, if the gene expression in a GTEx sample does not exceed 10 RPKM, if the gene is expressed at ≥5 RPKM in no more than two samples across all essential tissue samples, or any combination thereof.

[0405] Exemplary HLA class I subtypes of HLA-peptide targets Many MHC haplotypes exist in humans (which may be interchangeably referred to herein as MHC subtypes, HLA subtypes, MHC types, and HLA types). Exemplary HLA subtypes include (by way of example only) HLA-A2, HLA-A1, HLA-A3, HLA-A11, HLA-A23, HLA-A24, HLA-A25, HLA-A26, HLA-A28, HLA-A29, HLA-A30, HLA-A31, HLA-A32, HLA-A33, HLA-A34, HLA-68, HLA-B7, HLA-B8, HLA-B40, HL... A-B44, HLA-B13, HLA-B15, HLA-B-18, HLA-B27, HLA-B35, HLA-B37, HLA-B38, HLA-B39, HLA -B45, HLA-B46, HLA-B49, HLA-B51, HLA-B54, HLA-B55, HLA-B56, HLA-B57, HLA-B58, HLA-C 01. HLA-C 02. HLA-C 03. HLA-C 04. HLA-C 05. HLA-C 06. HLA-C 07. HLA-C 12. HLA-C 14. HLA-C 16. HLA-Cw8, HLA-A 01:01, HLA-A 02:01, HLA-A 02:03, HLA-A 02:04, HLA-A 02:07, HLA-A 03:01, HLA-A 03:02, HLA-A 11:01, HLA-A 23:01, HLA-A 24:02, HLA-A 25:01, HLA-A 26:01, HLA-A 29:02, HLA-A 30:01, HLA-A 30:02, HLA-A 31:01, HLA-A 32:01, HLA-A 33:01、HLA-A 33:03、HLA-A 68:01、HLA-A 68:02、HLA-B 07:02、HLA-B 08:01、HLA-B 13:02, HLA-B 15:01、HLA-B 15:03、HLA-B 18:01、HLA-B 27:02、HLA-B 27:05、HLA-B 35:01、HLA-B 35:03、HLA-B 37:01、HLA-B 38:01、HLA-B 39:01、HLA-B 40:01、HLA-B 40:02、HLA-B 44:02、HLA-B 44:03、HLA-B 46:01、HLA-B 49:01、HLA-B 51:01、HLA-B 54:01、HLA-B 55:01、HLA-B 56:01、HLA-B 57:01、HLA-B 58:01、HLA-C 01:02、HLA-C 02:02、HLA-C 03:03、HLA-C 03:04、HLA-C 04:01、HLA-C 05:01、HLA-C 06:02、HLA-C 07:01、HLA-C 07:02、HLA-C 07:04、HLA-C 07:06、HLA-C 12:03, HLA-C 14:02, HLA-C 16:01, HLA-C 16:02, HLA-C 16:04 and all its subtypes, including, for example, 4-position, 6-position, and 8-position subtypes. It is known to those skilled in the art that allele variants of the above-described HLA types exist, and this invention covers all such allele variants. A complete list of HLA class alleles can be found at http: / / hla.alleles.org / alleles / . For example, a complete list of HLA class I alleles can be found at http: / / hla.alleles.org / alleles / class1.html.

[0406] HLA-restricted peptide HLA-restricted peptides (which may be referred to interchangeably herein) "restricted peptides" can be peptide fragments of tumor-specific genes (e.g., cancer-specific genes). Preferably, the cancer-specific gene is expressed in a cancer sample. Genes aberrantly expressed in cancer samples can be identified using databases. Exemplary databases, illustrated only by way of enumeration, include: The Cancer Genome Atlas (TCGA) Research Network: http: / / cancergenome.nih.gov / ; International Cancer Genome Association: https: / / dcc.icgc.org / . In some embodiments, the cancer-specific gene is observed to have at least 10 RPKMs expressed in at least 5 samples from the TCGA database. The cancer-specific gene may have an observable bimodal distribution.

[0407] The cancer-specific gene may have observed expression levels greater than 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 transcripts per million (TPM) in at least one TCGA tumor tissue. In a preferred embodiment, the cancer-specific gene has observed expression levels greater than 100 TPM in at least one TCGA tumor tissue. In some cases, the cancer-specific gene exhibits an observed bimodal expression distribution in TCGA samples. Where it is not desired to be bound by theory, this bimodal expression pattern is consistent with biological models in which expression levels are minimum at baseline across all tumor samples, with higher expression levels in a subset of tumors that have undergone epigenetic dysregulation.

[0408] Preferably, cancer-specific genes are not typically expressed in most normal tissues. For example, in some cases, cancer-specific genes may not be expressed in tissues included in a Genotype Tissue Expression (GTEx) project, or in some cases, they may be expressed in immune-privileged or non-essential tissues. Exemplary immune-privileged or non-essential tissues include the testes, minor salivary glands, cervical endometrium, and thyroid gland. In some cases, a cancer-specific gene may be considered not expressed in an essential or non-immune-privileged tissue if the median expression of the cancer-specific gene in a GTEx sample is less than 0.5 RPKM (number of reads per kilobase transcript per million mapped reads), if the gene expression in a GTEx sample does not exceed 10 RPKM, if the gene is expressed at ≥5 RPKM in no more than two samples across all essential tissue samples, or any combination thereof.

[0409] In some implementations, cancer-specific genes are evaluated to meet the following criteria: (1) median GTEx expression in the brain, heart or lung is less than 0.1 transcripts per million (TPM), with no sample exceeding 5 TPM; (2) median GTEx expression in other essential organs (excluding the testes, thyroid gland and minor salivary glands) is less than 2 TPM, with no sample exceeding 10 TPM.

[0410] In some implementations, cancer-specific genes are generally unlikely to be expressed in immune cells; for example, they are not interferon family genes, not eye-related genes, not olfactory or gustatory receptor genes, and not genes associated with circadian rhythms (e.g., not CLOCK, PERIOD, CRY genes).

[0411] The restricted peptide is preferably present on the surface of the tumor.

[0412] The size of the restricted peptide can be about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, or about 15 amino acid residues, and any range that can be derived therefrom. In a particular embodiment, the size of the restricted peptide is about 8, about 9, about 10, about 11, or about 12 amino acid residues. The length of the restricted peptide can be about 5 to 15 amino acids, preferably about 7 to 12 amino acids, or more preferably about 8 to 11 amino acids.

[0413] Exemplary HLA-peptide targets Exemplary HLA-peptide targets are shown in Tables A, A1, and A2. Each row in Tables A, A1, and A2 shows the HLA allele and the corresponding HLA-restricted peptide sequence for each complex. The peptide sequence may consist of the corresponding sequence shown in any row of Tables A, A1, or A2. Alternatively, the peptide sequence may comprise the corresponding sequence shown in any row of Tables A, A1, or A2. Alternatively, the peptide sequence may consist substantially of the corresponding sequence shown in any row of Tables A, A1, or A2.

[0414] In some implementations, the HLA-peptide target is the target shown in Table A, Table A1, or Table A2.

[0415] In some implementations, the HLA-peptide target is the target shown in Table A, Table A1, or Table A2, provided that the isolated HLA-peptide target is not any of target numbers 6364-6369, 6386-6389, 6500, 6521-6524, or 6578, and is not an HLA-peptide target present in Table B or Table C.

[0416] In some implementations, the HLA-restricted peptide is not derived from a gene selected from WT1 or MART1.

[0417] HLA class I molecules that do not associate with restriction peptide ligands are generally unstable. Therefore, association of the restriction peptide with the α1 / α2 groove of the HLA molecule can stabilize the non-covalent association between the β2-microglobulin subunit of the HLA isotype and the α-subunit of the HLA isotype.

[0418] The stability of the nonvalent association between the β2-microglobulin subunit and the α-subunit of the HLA isotype can be determined using any suitable method. For example, this stability can be assessed by dissolving the insoluble aggregates of the HLA molecule in a high concentration of urea (e.g., about 8 M urea) and determining the ability of the HLA molecule to refold in the presence of the restriction peptide during urea removal (e.g., by dialysis). This refolding method is described, for example, in Proc. Natl. Acad. Sci. USA, Vol. 89, pp. 3429-3433, April 1992, which is hereby incorporated by reference.

[0419] For other examples, conditional HLA class I ligands can be used to assess this stability. Conditional HLA class I ligands are typically designed as short restriction peptides that stabilize the association between the β2 and α subunits of an HLA class I molecule by binding to the α1 / α2 groove, and contain one or more amino acid modifications that cause the restriction peptide to cleave upon exposure to a conditional stimulus. Once the conditional ligand cleaves, the β2 and α subunits of the HLA molecule dissociate unless the conditional ligand is replaced with a restriction peptide that binds to the α1 / α2 groove and stabilizes the HLA molecule. Conditional ligands can be designed by introducing amino acid modifications into known HLA peptide ligands or predicted high-affinity HLA peptide ligands. For HLA alleles with available structural information, the water accessibility of the side chains can also be used to select the site for introducing amino acid modifications. The use of conditional HLA ligands may be advantageous by allowing the batch production of stable HLA-peptide complexes that can be used to query and test restriction peptides in a high-throughput manner.Conditional HLA class I ligands and their production methods are described in, for example, Proc Natl Acad Sci U SA. 2008 Mar 11; 105(10): 3831–3836; Proc Natl Acad Sci US A. 2008 Mar 11; 105(10): 3825–3830; J Exp Med. 2018 May 7; 215(5): 1493–1504; Choo, JAL et al. Bioorthogonal cleavage and exchange of major histocompatibility complex ligands by employing azobenzene-containing peptides. Angew Chem Int Ed Engl53, 13390–13394 (2014); Amore, A. et al. Development of a Hypersensitive Periodont-Cleavable Amino Acid that is Methionine- and Disulfide-Compatible and Its Application in MHC Exchange Reagents for T Cell Characterisation. ChemBioChem 14, 123–131 (2012); Rodenko, B. et al. Class I Major Histocompatibility Complexes Loaded by a Periodate Trigger. J Am Chem Soc 131, 12305–12313 (2009); and Chang, CXL et al. Conditional ligands for Asian HLA variants facilitate the definition of CD8+ T-cell responses inacute and chronic viral diseases. Eur J Immunol 43, 1109–1120 (2013). These references are incorporated in their entirety by citation.

[0420] Therefore, in some embodiments, the ability of the HLA-restricted peptides described herein (e.g., those described in Table A, Table A1, or Table A2) to stabilize the association of the β2- and α-subunits of an HLA molecule is assessed by performing conditional ligand-mediated exchange reactions and HLA stability assays. HLA stability can be determined using any suitable method, including, for example, mass spectrometry, immunoassays (e.g., ELISA), size exclusion chromatography, and HLA multimer staining, followed by flow cytometry evaluation of T cells.

[0421] Other exemplary methods for assessing the stability of non-covalent association between the β2-microglobulin subunit of an HLA isotype and the α-subunit of an HLA isotype include peptide exchange using dipeptides. Peptide exchange using dipeptides is described, for example, in ProcNatl Acad Sci US A. 2013 Sep 17; 110(38):15383-8; Proc Natl Acad Sci US A. 2015 Jan 6; 112(1):202-7, which are incorporated herein by reference.

[0422] This article provides useful antigens containing HLA-peptide targets. HLA-peptide targets can contain specific HLA-restricted peptides with well-defined amino acid sequences that are complexed with specific HLA subtype alleles.

[0423] HLA-peptide targets can be isolated and / or in substantially pure form. For example, HLA-peptide targets can be isolated from their natural environment or produced by technical methods. In some cases, HLA-peptide targets are provided in a form that is substantially free of other peptides or proteins.

[0424] HLA-peptide targets may exist in soluble form and, optionally, may be recombinant HLA-peptide target complexes. Those skilled in the art can use any suitable method to generate and purify recombinant HLA-peptide targets. Suitable methods include, for example, using Escherichia coli expression systems, insect cells, etc. Other methods include synthetic generation, for example using cell-free systems. WO2017089756 describes exemplary suitable cell-free systems, which are hereby incorporated in their entirety by reference.

[0425] This article also provides compositions containing HLA-peptide targets.

[0426] In some cases, the composition comprises an HLA-peptide target attached to a solid support. Exemplary solid supports include, but are not limited to, beads, pores, membranes, tubes, columns, plates, agarose gels, magnetic beads, and fragments. Exemplary solid supports are described, for example, in Catalysts 2018, 8, 92; doi:10.3390 / catal8020092, which is hereby incorporated herein by reference in its entirety.

[0427] HLA-peptide targets can be attached to solid supports using any suitable method known in the art. In some cases, HLA-peptide targets are covalently attached to solid supports.

[0428] In some cases, HLA-peptide targets are attached to solid supports via affinity binding pairs. Affinity binding pairs typically involve specific interactions between two molecules. Ligands with affinity for their binding chaperone molecules can be covalently attached to solid supports and thus used as decoys to immobilize common affinity binding pairs, including, for example, streptavidin and biotin, avidin and biotin; and multihistidine tags with metal ions (such as copper, nickel, zinc, and cobalt).

[0429] HLA-peptide targets can contain detectable markers.

[0430] A pharmaceutical composition containing HLA-peptide targets.

[0431] Compositions containing HLA-peptide targets can be pharmaceutical compositions. Such compositions may contain multiple HLA-peptide targets. Exemplary pharmaceutical compositions are described herein. These compositions may be able to elicit an immune response. The compositions may contain adjuvants. Suitable adjuvants include, but are not limited to: 1018 ISS, alum, aluminum salts, Amplivax, AS15, BCG, CP-870893, CpG7909, CyaA, dSLIM, GM-CSF, IC30, IC31, imiquimod, ImuFact IMP321, IS Patch, ISS, ISCMATRIX, JuvImmune, LipoVac, MF59, monophospholipid A, Montanide IMS 1312, Montanide ISA 206, Montanide ISA 50V, Montanide... ISA-51, OK-432, OM-174, OM-197-MP-EC, ONTAK, PepTel vector system, PLG microparticles, Remiquimod, SRL172, viral particles and other virus-like particles, YF-17D, VEGFtrap, R848, β-glucan, Pam3Cys, saponin-derived Aquila QS21 stimulant (Aquila Biotech, Worcester, Mass., USA), mycobacterial extracts and synthetic bacterial cell wall mimics, and other proprietary adjuvants such as Ribi's Detox. Quil or Superfos. Adjuvants (such as incomplete Freund's or GM-CSF) are useful. Several adjuvants specific to dendritic cells (e.g., MF59) and their preparation have been described previously (Dupuis M, et al., Cell Immunol. 1998; 186(1):18-27; Allison AC; Dev Biol Stand. 1998; 92:3-11). Cytokines may also be used. Several cytokines have been directly linked to influence the migration of dendritic cells to lymphoid tissues (e.g., TNF-α), accelerate the maturation of dendritic cells into effective antigen-presenting cells (e.g., GM-CSF, IL-1, and IL-4) (US Patent No. 5,849,589, which is incorporated herein by reference in its entirety), and act as adjuvants (e.g., IL-12) (Gabrilovich DI et al., J Immunother Emphasis Tumor Immunol. 1996(6):414-418). HLA surface expression and intracellular protein processing into peptides to be presented on HLA can also be enhanced by interferon-γ (IFN-γ).See, for example, York IA, Goldberg AL, Mo XY, Rock KL. Proteolysis and class I major histocompatibility complex antigen presentation. Immunol Rev. 1999;172:49-66; and Rock KL, Goldberg AL. Degradation of cell proteins and the generation of MHC class I-presented peptides. Ann Rev Immunol. 1999;17: 12. 739-779, which are incorporated herein by reference in their entirety.

[0432] HLA-peptide ABP This article also provides ABPs that specifically bind to the HLA-peptide targets described herein.

[0433] HLA-peptide targets can be expressed on the surface of any suitable target cells, including tumor cells.

[0434] The ABP can specifically bind to human leukocyte antigen (HLA)-peptide targets, wherein the HLA-peptide targets include HLA-restricted peptides complexed with HLA class I molecules, wherein the HLA-restricted peptides are located in the peptide-binding groove of the α1 / α2 heterodimer portion of the HLA class I molecule.

[0435] In some respects, ABP does not bind to HLA class I in the absence of an HLA-restricted peptide. In some respects, ABP does not bind to an HLA-restricted peptide in the absence of human MHC class I. In some respects, ABP binds to tumor cells presenting human MHC class I complexed with an HLA-restricted peptide, optionally wherein the HLA-restricted peptide is a tumor antigen characterizing cancer.

[0436] ABPs can bind to each part of an HLA-peptide complex (i.e., HLA and a peptide representing each part of the complex). When bound together, they form new targets and protein surfaces that interact with and are bound by the ABP, unlike the surfaces presented by individual peptides or individual HLA subtypes. Generally, in the absence of each part of the HLA-peptide complex, there are no new targets and protein surfaces formed by HLA binding to peptides.

[0437] ABP can specifically bind to a complex containing HLA and an HLA-restricted peptide (HLA-peptide), for example, derived from a tumor. In some aspects, ABP does not bind to HLA in the absence of a tumor-derived HLA-restricted peptide. In other aspects, ABP does not bind to tumor-derived HLA-restricted peptides in the absence of HLA. In other aspects, ABP binds to a complex containing HLA and an HLA-restricted peptide when the HLA-restricted peptide is naturally present on cells (such as tumor cells).

[0438] In some implementations, the ABP provided herein regulates the binding of HLA-peptides to one or more ligands of the HLA-peptides.

[0439] ABP can specifically bind to any of the HLA-peptide targets disclosed in Table A, Table A1, or Table A2. In some embodiments, the HLA-restricted peptide is not derived from a gene selected from WT1 or MART1. In some embodiments, the ABP does not specifically bind to any of the target numbers 6364-6369, 6386-6389, 6500, 6521-6524, or 6578, and does not specifically bind to the HLA-peptide targets present in Table B or Table C.

[0440] In a more specific embodiment, ABP specifically binds to an HLA-peptide target selected from any of the following: HLA subtype A complexed with an HLA-restricted peptide containing the sequence LLASSILCA (SEQ ID NO: 322). 02:01, HLA subtype A complexed with an HLA-restricted peptide containing the sequence EVDPIGHLY (SEQ ID NO: 354). 01:01, HLA subtype B complexed with an HLA-restricted peptide containing the sequence GEMSSNSTAL (SEQ ID NO: 357). 44:02, HLA subtype A complexed with an HLA-restricted peptide containing the sequence GVYDGEEHSV (SEQ ID NO: 356). 02:01, HLA subtypes complexed with an HLA-restricted peptide containing the sequence EVDPIGHVY (SEQ ID NO: 2) 01:01, HLA subtype HLA-A complexed with an HLA-restricted peptide containing the sequence NTDNLAVY (SEQ ID NO: 73). 01:01 HLA subtype B complexed with an HLA-restricted peptide containing the sequence EVDPIGHVY (SEQ ID NO: 2) 35:01, HLA subtype HLA-A complexed with an HLA-restricted peptide containing the sequence AIFPGAVPAA (SEQ ID NO: 198). 02:01 and HLA subtype A complexed with an HLA-restricted peptide containing the sequence ASSLPTTMNY (SEQ ID NO: 260). 01:01.

[0441] In a more specific implementation, ABP specifically binds to an HLA-peptide target selected from any of the following: HLA subtype A that is complexed with an HLA-restricted peptide consisting essentially of the sequence LLASSILCA (SEQ ID NO: 322). 02:01, HLA subtype A, which is complexed with an HLA-restricted peptide consisting essentially of the sequence EVDPIGHLY (SEQ ID NO: 354). 01:01, HLA subtype B containing an HLA-restricted peptide complex consisting essentially of the sequence GEMSSNSTAL (SEQ ID NO: 357). 44:02, HLA subtype A complexed with an HLA-restricted peptide consisting essentially of the sequence GVYDGEEHSV (SEQ ID NO: 356). 02:01, HLA subtypes that are complexed with an HLA-restricted peptide consisting essentially of the sequence EVDPIGHVY (SEQ ID NO: 2). 01:01, HLA subtype HLA-A, which is essentially composed of an HLA-restricted peptide consisting of the sequence NTDNLAVY (SEQ ID NO: 73). 01:01, HLA subtype B complexed with an HLA-restricted peptide consisting essentially of the sequence EVDPIGHVY (SEQ ID NO: 2). 35:01, HLA subtype A, which is essentially composed of an HLA-restricted peptide consisting of the sequence AIFPGAVPAA (SEQ ID NO: 198). 02:01 and HLA subtype A, which is essentially composed of an HLA-restricted peptide consisting of the sequence ASSLPTTMNY (SEQ ID NO: 260). Any of the HLA-peptide targets in 01:01.

[0442] In a more specific implementation, ABP specifically binds to an HLA-peptide target selected from any of the following: HLA subtype A complexed with an HLA-restricted peptide consisting of the sequence LLASSILCA (SEQ ID NO: 322). 02:01, HLA subtype A complexed with an HLA-restricted peptide composed of the sequence EVDPIGHLY (SEQ ID NO: 354). 01:01, HLA subtype B complexed with an HLA-restricted peptide composed of the sequence GEMSSNSTAL (SEQ ID NO: 357). 44:02, HLA subtype A complexed with an HLA-restricted peptide composed of the sequence GVYDGEEHSV (SEQ ID NO: 356). 02:01, HLA subtypes complexed with an HLA-restricted peptide composed of the sequence EVDPIGHVY (SEQ ID NO: 2). 01:01, HLA subtype HLA-A complexed with an HLA-restricted peptide composed of the sequence NTDNLAVY (SEQ ID NO: 73). 01:01 subtype, HLA subtype B complexed with an HLA-restricted peptide composed of the EVDPIGHVY (SEQ ID NO: 2) sequence. 35:01, HLA subtype A complexed with an HLA-restricted peptide composed of the AIFPGAVPAA (SEQ ID NO: 198) sequence. 02:01 and HLA subtype A complexed with an HLA-restricted peptide consisting of the sequence ASSLPTTMNY (SEQ ID NO: 260). 01:01.

[0443] In some implementations, the ABP is a competing ABP with the illustrative ABP provided herein. In some aspects, the competing ABP and the illustrative ABP provided herein combine with the same epitope.

[0444] In some embodiments, the ABP described herein is referred to herein as a “variant.” In some embodiments, such a variant is derived from the sequence provided herein, for example, by affinity maturation, site-directed mutagenesis, random mutagenesis, or any other method known in the art or described herein. In some embodiments, such a variant is not derived from the sequence provided herein, but can be de novo isolated, for example, according to the methods provided herein for obtaining an ABP. In some embodiments, the variant is derived from any sequence provided herein, wherein one or more conserved amino acid substitutions are performed. In some embodiments, the variant is derived from any sequence provided herein, wherein one or more non-conserved amino acid substitutions are performed. Conserved amino acid substitutions are described herein. Exemplary non-conserved amino acid substitutions include those described in the following literature: J Immunol. 2008 May 1;180(9):6116-31, which is incorporated herein by reference in its entirety. In a preferred embodiment, the non-conserved amino acid substitution does not interfere with or inhibit the biological activity of the functional variant. In a more preferred embodiment, the non-conserved amino acid substitution enhances the biological activity of the functional variant, thereby enhancing the biological activity of the functional variant relative to the parental ABP.

[0445] ABP containing an antibody or its antigen-binding fragment ABP may contain antibodies or their antigen-binding fragments.

[0446] In some implementations, the ABP provided herein comprises a light chain. In some aspects, the light chain is a κ light chain. In other aspects, the light chain is a λ light chain.

[0447] In some embodiments, the ABP provided herein comprises a heavy chain. In some aspects, the heavy chain is IgA. In some aspects, the heavy chain is IgD. In some aspects, the heavy chain is IgE. In some aspects, the heavy chain is IgG. In some aspects, the heavy chain is IgM. In some aspects, the heavy chain is IgG1. In some aspects, the heavy chain is IgG2. In some aspects, the heavy chain is IgG3. In some aspects, the heavy chain is IgG4. In some aspects, the heavy chain is IgA1. In some aspects, the heavy chain is IgA2.

[0448] In some embodiments, the ABP provided herein comprises an antibody fragment. In some embodiments, the ABP provided herein consists of an antibody fragment. In some embodiments, the ABP provided herein consists primarily of an antibody fragment. In some aspects, the ABP fragment is an Fv fragment. In some aspects, the ABP fragment is a Fab fragment. In some aspects, the ABP fragment is an F(ab')2 fragment. In some aspects, the ABP fragment is a Fab' fragment. In some aspects, the ABP fragment is an scFv (sFv) fragment. In some aspects, the ABP fragment is an scFv-Fc fragment. In some aspects, the ABP fragment is a fragment of a single-domain ABP.

[0449] In some implementations, the ABP fragments provided herein are derived from the illustrative ABPs provided herein. In other implementations, the ABP fragments provided herein are not derived from the illustrative ABPs provided herein, but can be extracted from scratch, for example, according to the methods provided herein for obtaining ABP fragments.

[0450] In some embodiments, the ABP fragments provided herein retain the ability to bind to HLA-peptide targets, such as by one or more assays or biological effects described herein. In some embodiments, the ABP fragments provided herein retain the ability to prevent HLA-peptides from interacting with one or more ligands, as described herein.

[0451] In some implementations, the ABP provided herein is a monoclonal ABP. In some implementations, the ABP provided herein is a polyclonal ABP.

[0452] In some embodiments, the ABP provided herein includes a chimeric ABP. In some embodiments, the ABP provided herein consists of a chimeric ABP. In some embodiments, the ABP provided herein consists primarily of a chimeric ABP. In some embodiments, the ABP provided herein includes a humanized ABP. In some embodiments, the ABP provided herein consists of a humanized ABP. In some embodiments, the ABP provided herein consists primarily of a humanized ABP. In some embodiments, the ABP provided herein includes a human ABP. In some embodiments, the ABP provided herein consists of a human ABP. In some embodiments, the ABP provided herein consists primarily of a human ABP.

[0453] In some embodiments, the ABP provided herein includes a replacement stent. In some embodiments, the ABP provided herein consists of a replacement stent. In some embodiments, the ABP provided herein consists essentially of a replacement stent. Any suitable replacement stent can be used. In some aspects, the replacement stent is selected from: Adnectin TM iMab, Anticalin ® EETI-II / AGRP, Kunitz domain, thioredoxin peptide aptamer, Affibody ® , DARPin, Affilin, Tetranectin, Fynomer and Avimer.

[0454] This article also discloses isolated humanized, human or chimeric ABPs that compete with the ABPs disclosed herein for binding to HLA-peptides.

[0455] This article also discloses isolated humanized, human or chimeric ABPs that bind to the HLA-peptide epitopes of the ABPs described herein.

[0456] In some respects, ABP contains a human Fc region containing at least one modification that reduces binding to human Fc receptors.

[0457] It is known that when ABP is expressed in cells, it is post-translationally modified. Examples of post-translational modifications include: cleavage of lysine at the C-terminus of the heavy chain by carboxypeptidase; modification of the N-terminus of the heavy and light chains with glutamine or glutamate via pyroglutamylmethylation, glycosylation, oxidation, deamidation, and glycosylation, and such post-translational modifications are known to occur in various ABPs (see Journal of Pharmaceutical Sciences, 2008, Vol. 97, pp. 2426-2447, which is incorporated herein by reference in its entirety). In some embodiments, the ABP is a post-translational modified ABP or its antigen-binding fragment thereof. Examples of post-translational modified ABPs or their antigen-binding fragments thereof include ABPs or their antigen-binding fragments that have undergone pyroglutamylmethylation at the N-terminus of the variable region of the heavy chain and / or have lysine absent at the C-terminus of the heavy chain. It is known in the art that such post-translational modifications, resulting from N-terminal pyroglutamyl methylation and C-terminal lysine deletion, have no effect on the activity of ABP or fragments thereof (Analytical Biochemistry, 2006, Vol. 348, pp. 24-39, which is incorporated herein by reference in its entirety). Single-specific and multi-specific HLA-peptide ABP In some implementations, the ABP provided herein is a single-specific ABP.

[0458] In some implementations, the ABP provided herein is a multispecific ABP.

[0459] In some embodiments, the multispecific ABP provided herein binds to more than one antigen. In some embodiments, the multispecific ABP binds to two antigens. In some embodiments, the multispecific ABP binds to three antigens. In some embodiments, the multispecific ABP binds to four antigens. In some embodiments, the multispecific ABP binds to five antigens.

[0460] In some embodiments, the multispecific ABP provided herein binds to more than one epitope on the HLA-peptide antigen. In some embodiments, the multispecific ABP binds to two epitopes on the HLA-peptide antigen. In some embodiments, the multispecific ABP binds to three epitopes on the HLA-peptide antigen.

[0461] Many multispecific ABP constructs are known in the art, and the ABPs provided herein can be provided in any suitable form of multispecific construct.

[0462] In some embodiments, the multispecific ABP comprises an immunoglobulin containing at least two distinct heavy chain variable regions, each heavy chain variable region pairing with a common light chain variable region (i.e., the "common light chain ABP"). The common light chain variable region forms a distinct antigen-binding domain with each of the two distinct heavy chain variable regions. See Merchant et al. Nature Biotechnol. , 1998, 16:677-681, which is incorporated in its entirety by reference.

[0463] In some embodiments, the multispecific ABP comprises an immunoglobulin, wherein the immunoglobulin comprises one or more fragments of the ABP linked to the N-terminus or C-terminus of the heavy or light chain of the immunoglobulin. See Coloma and Morrison. Nature Biotechnol. , 1997, 15:159-163, which is incorporated in its entirety by reference. In some respects, this ABP includes a tetravalent bispecific ABP.

[0464] In some embodiments, the multispecific ABP comprises a hybrid immunoglobulin containing at least two distinct heavy chain variable regions and at least two distinct light chain variable regions. See Milstein and Cuello. Nature , 1983, 305:537-540; and Staerz and Bevan, Proc. Natl. Acad. Sci. USA , 1986, 83:1453-1457, each of which is incorporated in its entirety by reference.

[0465] In some embodiments, the multispecific ABP comprises a modified immunoglobulin chain to reduce the formation of non-multispecific byproducts. In some aspects, the ABP comprises one or more "mortar and pestle" modifications, as described in U.S. Patent No. 5,731,168, which is incorporated herein by reference in its entirety.

[0466] In some embodiments, the multispecific ABP comprises an immunoglobulin chain having one or more electrostatic modifications to facilitate the assembly of Fc heteromultimers. See WO 2009 / 089004, which is incorporated herein by reference in its entirety.

[0467] In some implementations, multispecific ABPs comprise bispecific single-chain molecules. See Traunecker et al. EMBO J. , 1991, 10:3655-3659; and Gruber et al., J. Immunol., 1994, 152:5368-5374, each of which is incorporated in whole by reference.

[0468] In some embodiments, a multispecific ABP comprises a heavy chain variable domain and a light chain variable domain linked via a peptide linker, wherein the linker length is selected to facilitate the assembly of a multispecific ABP with the desired multispecificity. For example, when the heavy chain variable domain and the light chain variable domain are linked via a peptide linker having more than 12 amino acid residues, a monospecific scFv is typically formed. See U.S. Patents 4,946,778 and 5,132,405, both incorporated herein by reference in their entirety. In some embodiments, reducing the peptide linker length to less than 12 amino acid residues prevents the pairing of heavy chain and light chain variable domains on the same polypeptide chain, thereby allowing the heavy chain and light chain variable domains from one chain to pair with complementary domains on the other chain. Thus, the resulting ABP is multispecific, with the specificity at each binding site contributed by more than one polypeptide chain. Polypeptide chains comprising heavy chain and light chain variable domains linked by linkers of 3 to 12 amino acid residues primarily form dimers (called biantibodies). Linkers with 0 to 2 amino acid residues, i.e., trimers (called triantibodies) and tetramers (called tetraantibodies), are advantageous. However, apart from the length of the linker, the exact type of oligomerization appears to depend on the composition of the amino acid residues and the order of variable domains in each polypeptide chain (e.g., V...). H -Connector-V L With V L -Connector-V H Technicians can select the appropriate connector length based on the required multispecificity.

[0469] Fc region and variants In some embodiments, the ABP provided herein comprises an Fc region. The Fc region may be wild-type or a variant thereof. In some embodiments, the ABP provided herein comprises an Fc region having one or more amino acid substitutions, insertions, or deletions compared to a naturally occurring Fc region. In some aspects, such substitutions, insertions, or deletions produce an ABP with altered stability, glycosylation, or other characteristics. In some aspects, such substitutions, insertions, or deletions produce a glycosylated ABP.

[0470] The “variant Fc region” or “engineered Fc region” comprises an amino acid sequence that differs from the native Fc region due to modification of at least one amino acid, preferably one or more amino acid substitutions. Preferably, the variant Fc region has at least one amino acid substitution, for example, about one to about ten amino acid substitutions, compared to the native Fc region or the Fc region of the parent polypeptide, and more preferably, about one to about five amino acid substitutions in the native Fc region or the Fc region of the parent polypeptide. The variant Fc region herein preferably has at least about 80% homology with the native Fc region and / or with the Fc region of the parent polypeptide, and most preferably, at least about 90% homology, and more preferably, at least about 95% homology.

[0471] The term "ABP containing the Fc region" refers to an ABP that includes the Fc region. The C-terminal lysine (residue 447, according to the EU numbering system) of the Fc region can be removed, for example, during ABP purification or by recombinant engineering of the nucleic acid encoding the ABP. Therefore, an ABP with the Fc region can include ABPs with or without K447.

[0472] In some respects, the Fc region of the ABP provided herein is modified to produce an ABP with altered affinity for the Fc receptor, or to produce a more immune-inert ABP. In some embodiments, the ABP variants provided herein have some, but not all, effector functions. For example, such an ABP may be useful when the half-life of the ABP is important in vivo, but when certain effector functions (e.g., complement activation and ADCC) are unnecessary or harmful.

[0473] In some implementations, the Fc region of the ABP provided herein is the human IgG4 Fc region, which contains one or more hinge-stabilizing mutations S228P and L235E. See Aalberse et al. Immunology , 2002, 105:9-19, which is incorporated in its entirety by reference. In some implementations, the IgG4 Fc region contains one or more of the following mutations: E233P, F234V, and L235A. See Armour et al., Mol. Immunol. , 2003, 40:585-593, which is incorporated in its entirety by reference. In some implementations, the IgG4 Fc region includes a deletion at the G236 position.

[0474] In some embodiments, the Fc region of the ABP provided herein is the human IgG1 Fc region, which contains one or more mutations that reduce Fc receptor binding. In some aspects, said one or more mutations are in residues selected from S228 (e.g., S228A), L234 (e.g., L234A), L235 (e.g., L235A), D265 (e.g., D265A), and N297 (e.g., N297A). In some aspects, the ABP contains the PVA236 mutation. PVA236 refers to the substitution of PVA for the amino acid sequence ELLG (SEQ ID NO: 362) of IgG1 from amino acid positions 233 to 236 or for the EFLG (SEQ ID NO: 363) of IgG4. See U.S. Patent No. 9,150,641, which is incorporated herein by reference in its entirety.

[0475] In some implementations, the Fc region of the ABP provided herein is modified, as described in the following literature: Armour et al. Eur. J. Immunol. , 1999, 29:2613-2624; WO 1999 / 058572; and / or UK Patent Application No. 98099518, each of which is incorporated herein by reference in its entirety.

[0476] In some implementations, the Fc region of the ABP provided herein is the human IgG2 Fc region, which contains one or more mutations A330S and P331S.

[0477] In some embodiments, the Fc region of the ABP provided herein has amino acid substitutions at one or more of the following positions: 238, 265, 269, 270, 297, 327, and 329. See U.S. Patent No. 6,737,056, which is incorporated herein by reference in its entirety. Such Fc mutants comprise Fc mutants having substitutions at two or more of the amino acid positions 265, 269, 270, 297, and 327, including the so-called “DANA” Fc mutant, which has alanine substitutions at residues 265 and 297. See U.S. Patent No. 7,332,581, which is incorporated herein by reference in its entirety. In some embodiments, the ABP comprises alanine at amino acid position 265. In some embodiments, the ABP comprises alanine at amino acid position 297.

[0478] In some embodiments, the ABP provided herein comprises an Fc region having one or more amino acid substitutions that improve ADCC, such as substitutions at one or more positions of Fc region 298, 333, and 334. In some embodiments, the ABP provided herein comprises an Fc region having one or more amino acid substitutions at positions 239, 332, and 330, as described in the following literature: Lazar et al. Proc. Natl. Acad. Sci. USA, 2006, 103:4005-4010, which is incorporated in its entirety by reference.

[0479] In some implementations, the ABP provided herein includes one or more modifications that improve or reduce C1q binding and / or CDC. See U.S. Patent No. 6,194,551; WO 99 / 51642; and Idusogie et al. J. Immunol., 2000, 164:4178-4184; all are incorporated in their entirety by reference.

[0480] In some implementations, the ABPs provided herein include one or more modifications to increase the half-life. ABPs with increased half-life and improved binding to the neonatal Fc receptor (FcRn) are described, for example, by Hinton et al. J. Immunol. References , 2006, 176:346-356; and U.S. Patent Publication No. 2005 / 0014934; are all incorporated herein by reference in their entirety. Such Fc variants include Fc variants having substituted Fc residues at one or more of the following Fc regions of IgG: 238, 250, 256, 265, 272, 286, 303, 305, 307, 311, 312, 314, 317, 340, 356, 360, 362, 376, 378, 380, 382, 413, 424, 428, and 434. In some embodiments, the ABP comprises one or more non-Fc modifications that extend half-life. Exemplary non-Fc modifications that extend half-life are described, for example, in US20170218078, which is hereby incorporated herein by reference in its entirety.

[0481] In some implementations, the ABP provided herein includes one or more Fc region variants, as described in the following documents: U.S. Patent Nos. 7,371,826, 5,648,260, and 5,624,821; Duncan and Winter; Nature , 1988,322:738-740; and WO 94 / 29351; each of which is incorporated in its entirety by reference.

[0482] For B 35:01 _EVDPIGHVY (SEQ ID NO: 2) (HLA-peptide target "G5") specific antibody In some respects, this article provides an ABP comprising an antibody or antigen-binding fragment thereof that specifically binds to an HLA-peptide target, wherein the HLA-peptide target is an HLA class I molecule that is HLA subtype B. 35:01, and the HLA-restricted peptide of the HLA-peptide target comprises or is composed of or substantially comprises the sequence EVDPIGHVY (SEQ ID NO: 2) (“G5”).

[0483] CDR For B 35:01_EVDPIGHVY (SEQ ID NO: 2) Specific ABP may contain one or more antibody complementarity-determining region (CDR) sequences, for example, it may contain three heavy chain CDRs (CDR-H1, CDR-H2, CDR-H3) and three light chain CDRs (CDR-L1, CDR-L2, CDR-L3).

[0484] For B 35:01_EVDPIGHVY (SEQ ID NO: 2) has a specific ABP that may contain the CDR-H3 sequence. The CDR-H3 sequence can be selected from CARDGVRYYGMDVW (SEQ ID NO: 3), CARGVRGYDRSAGYW (SEQ ID NO: 4), CASHDYGDYGEYFQHW (SEQ ID NO: 5), CARVSWYCSSTSCGVNWFDPW (SEQ ID NO: 6), CAKVNWNDGPYFDYW (SEQ ID NO: 7), CAPTNSGYYGPYYYYGMDVW (SEQ ID NO: 8), CARDVMDVW (SEQ ID NO: 9), CAREGYGMDVW (SEQ ID NO: 10), CARDNGVGVDYW (SEQ ID NO: 11), CARGIADSGSYYGNGRDYYYGMDVW (SEQ ID NO: 12), CARGDYYFDYW (SEQ ID NO: 12) ID NO: 13), CARDGTRYYGMDVW (SEQ ID NO: 14), CARDVVANFDYW (SEQ ID NO: 15), CARGHSSGWYYYYGMDVW (SEQ ID NO: 16), CAKDLGSYGGYYW (SEQ ID NO: 17), CARSWFGGFNYHYYGMDVW (SEQ ID NO: 18), CARELPIGYGMDVW (SEQ ID NO: 19) and CARGGSYYYYGMDVW (SEQ ID NO: 20).

[0485] For B 35:01_EVDPIGHVY (SEQ ID NO: 2) has a specific ABP that may contain the CDR-L3 sequence. The CDR-L3 sequence can be selected from CMQGLQTPITF (SEQ ID NO: 21), CMQALQTPPTF (SEQ ID NO: 22), CQQAISFPLTF (SEQ ID NO: 23), CQQANSFPLTF (SEQ ID NO: 24), CQQANSFPLTF (SEQ ID NO: 24), CQQSYSIPLTF (SEQ ID NO: 25), CQQTYMMPYTF (SEQ ID NO: 26), CQQSYITPWTF (SEQ ID NO: 27), CQQSYITPYTF (SEQ ID NO: 28), CQQYYTTPYTF (SEQ ID NO: 29), CQQSYSTPLTF (SEQ ID NO: 30), CMQALQTPLTF (SEQ ID NO: 31), CQQYGSWPRTF (SEQ ID NO: 32), CQQSYSTPVTF (SEQ ID NO: 33), CMQALQTPYTF (SEQ ID NO: 34), CQQANSFPFTF (SEQ ID NO: 35), CMQALQTPLTF (SEQ ID NO: 31) and CQQSYSTPLTF (SEQ ID NO: 30).

[0486] For B 35:01 _ EVDPIGHVY (SEQ ID NO: 2) A specific ABP may contain a specific heavy chain CDR3 (CDR-H3) sequence and a specific light chain CDR3 (CDR-L3) sequence. In some implementations, the ABP comprises CDR-H3 and CDR-L3 from scFv, which are named G5_P7_E7, G5_P7_B3, G5_P7_A5, G5_P7_F6, G5-P1B12, G5-P1C12, G5-P1-E05, G5-P3G01, G5-P3G08, G5-P4B02, G5-P4E04, G5R4-P1D06, G5R4-P1H11, G5R4-P2B10, G5R4-P2H8, G5R4-P3G05, G5R4-P4A07, or G5R4-P4B01. Table 5 shows the identified specific binding B. 35:01 _ EVDPIGHVY (SEQ ID NO: 2) CDR sequence of scFv. For clarity, each identified scFv is named with a clone name, and each line contains the CDR sequence for that specific clone name. For example, the scFv identified by clone name G5_P7_E7 scFv It contains the heavy chain CDR3 sequence CARDGVRYYGMDVW (SEQ ID NO: 3) and the light chain CDR3 sequence CMQGLQTPITF (SEQ ID NO: 21).

[0487] For B 35:01_EVDPIGHVY (SEQ ID NO: 2) The specific ABP may contain all 6 CDRs from scFv, which are named G5_P7_E7, G5_P7_B3, G5_P7_A5, G5_P7_F6, G5-P1B12, G5-P1C12, G5-P1-E05, G5-P3G01, G5-P3G08, G5-P4B02, G5-P4E04, G5R4-P1D06, G5R4-P1H11, G5R4-P2B10, G5R4-P2H8, G5R4-P3G05, G5R4-P4A07 or G5R4-P4B01.

[0488] VH For B 35:01_ An ABP specific to EVDPIGHVY (SEQ ID NO: 2) may contain a VH sequence. The VH sequence may be selected from QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGIINPRSGSTKYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGVRYYGMDVWGQGTTVTVSS (SEQ ID NO: 36), QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSHDINWVRQAPGQGLEWMGWMNPNSGDTGYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGVRGYDRSAGYWGQGTLVIVSS (SEQ ID NO: 37), EVQLLESGGGLVKPGGSLRLSCAASGFSFSSYWMSWVRQAPGKGLEWISYISGDSGYTNYADSVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCASHDYGDYGEYFQHWGQGTLVTVSS (SEQ ID NO: 38), EVQLLQSGGGLVQPGGSLRLSCAASGFTFSNSDMNWVRQAPGKGLEWVAYISSGSSTIYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVSWYCSSTSCGVNWFDPWGQGTLVTVSS (SEQ ID NO: 39), EVQLLESGGGLVQPGGSLRLSCAASGFTFSNSDMNWVRQAPGKGLEWVASISSSGGYINYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKVNWNDGPYFDYWGQGTLVTVSS(SEQ ID NO: 40), QVQLVQSGAEVKKPGSSVKVSCKASGGTFSNFGVSWLRQAPGQGLEWMGGIIPILGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCATPTNSGYYGPYYYYGMDVWGQGTTVTVSS (SEQ IDNO:41)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYNMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDVMDVWGQGTTVTVSS (SEQ ID NO: 42)、QVQLVQSGAEVKKPGASVKVSCKASGGTFSGYLVSWVRQAPGQGLEWMGWINPNSGGTNTAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREGYGMDVWGQGTTVTVSS (SEQ ID NO: 43)、QVQLVQSGAEVKKPGASVKVSCKASGYIFRNYPMHWVRQAPGQGLEWMGWINPDSGGTKYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDNGVGVDYWGQGTLVTVSS (SEQ ID NO: 44)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWMNPNIGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGIADSGSYYGNGRDYYYGMDVWGQGTTVTVSS (SEQ ID NO: 45)、QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYGISWVRQAPGQGLEWMGWINPNSGVTKYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGDYYFDYWGQGTLVTVSS (SEQ ID NO:46)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGWINPNSGDTKYSQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGTRYYGMDVWGQGTTVTVSS (SEQ ID NO: 47)、EVQLLESGGGLVKPGGSLRLSCAASGFTFSDYYMSWVRQAPGKGLEWVSYISSSSSYTNYADSVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCARDVVANFDYWGQGTLVTVSS (SEQ ID NO:48) QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWMNPDSGSTGYAQRFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGHSSGWYYYYGMDVWGQGTTVTVSS (SEQ ID NO: 49), EVQLLESGGGLVQPGGSLRLSCAASGFTFTSYSMHWVRQAPGKGLEWVSSITSFTNTMYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDLGSYGGYYWGQGTLVTVSS(SEQ ID NO: 50), QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYYMHWVRQAPGQGLEWMGIINPSGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSWFGGFNYHYYGMDVWGQGTTVTVSS (SEQ ID NO:51), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARELPIGYGMDVWGQGTTVTVSS (SEQ ID NO: 52) and QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIVGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGGSYYYYGMDVWGQGTTVTVSS (SEQ ID NO: 53).

[0489] VL For B The ABP specific to 35:01_EVDPIGHVY (SEQ ID NO: 2) may contain a VL sequence. The VL sequence may be selected from DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSYRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGLQTPITFGQGTRLEIK (SEQ ID NO: 54), DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSSRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPPTFGPGTKVDIK (SEQ ID NO: 55), DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAISFPLTFGQSTKVEIK (SEQID NO: 56), DIQMTQSPSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYSASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPLTFGGGTKVEIK (SEQ ID NO: 57), DIQMTQSPSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPLTFGGGTKVEIK (SEQ ID NO: 58), DIQMTQSPSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSIPLTFGGGTKVEIK (SEQ ID NO:59), DIQMTQSPSSLSASVGDRVTITCRASQGISNYLNWYQQKPGKAPKLLIYYASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYMMPYTFGQGTKVEIK (SEQ ID NO:60)、DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYGASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYITPWTFGQGTKVEIK (SEQ ID NO: 61)、DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYITPYTFGQGTKLEIK (SEQ ID NO: 62)、DIVMTQSPDSLAVSLGERATINCKTSQSVLYRPNNENYLAWYQQKPGQPPKLLIYQASIREPGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYTTPYTFGQGTKLEIK (SEQ ID NO: 63)、DIQMTQSPSSLSASVGDRVTITCRASQSISRFLNWYQQKPGKAPKLLIYGASRPQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGQGTKVEIK (SEQ ID NO: 64)、DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSHRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPLTFGGGTKVEIK (SEQ ID NO: 65)、EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQKPGQAPRLLIYAASARASGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYGSWPRTFGQGTKVEIK (SEQ ID NO: 66)、DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYGASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPVTFGQGTKVEIK (SEQ ID NO: 67)、DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPYTFGQGTKVEIK (SEQID NO: 68), DIQMTQSPSSSLSASVGDRVTITCQASEDISNHLNWYQQKPGKAPKLLIYDALSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPFTFGPGTKVDIK (SEQ ID NO: 69), DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPLTFGQGTKVEIK (SEQ ID NO: 70) and DIQMTQSPSSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ ID NO: 71).

[0490] VH-VL combination For B 35:01_EVDPIGHVY (SEQ ID NO: 2) A specific ABP may contain a specific VH sequence and a specific VL sequence. In some embodiments, for B... 35:01_EVDPIGHVY (SEQ ID NO: 2) contains specific ABP sequences comprising the VH and VL sequences from scFvs named G5_P7_E7, G5_P7_B3, G5_P7_A5, G5_P7_F6, G5-P1B12, G5-P1C12, G5-P1-E05, G5-P3G01, G5-P3G08, G5-P4B02, G5-P4E04, G5R4-P1D06, G5R4-P1H11, G5R4-P2B10, G5R4-P2H8, G5R4-P3G05, G5R4-P4A07, or G5R4-P4B01. Table 4 shows the specific binding to B. VH and VL sequences of the identified scFv 35:01_EVDPIGHVY (SEQ ID NO: 2). For clarity, each identified scFv hit is named with a clone name, and each line contains the VH and VL sequences for that specific clone name. For example, the scFv identified by the clone name G5_P7_E7 contains the VH sequence QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGIINPRSGSTKYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGVRYYGMDVWGQGTTVTVSS (SEQ ID NO: 36) and the VL sequence DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSYRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGLQTPITFGQGTRLEIK (SEQ ID NO: 54).

[0491] For A 02:01 _AIFPGAVPAA (SEQ ID NO: 198) (HLA-peptide target "G8") has specific anti- body In some respects, this article provides an ABP comprising an antibody or antigen-binding fragment thereof that specifically binds to an HLA-peptide target, wherein the HLA-peptide target is an HLA class I molecule that is HLA subtype A. 02:01, and the HLA-restricted peptide of the HLA-peptide target comprises, or is substantially composed of, the sequence AIFPGAVPAA (SEQ ID NO: 198) (“G8”).

[0492] CDR For A 02:01_ AIFPGAVPAA (SEQ ID NO: 198) The specific ABP may contain one or more antibody complementarity-determining region (CDR) sequences, such as three heavy chain CDRs (CDR-H1, CDR-H2, CDR-H3) and three light chain CDRs (CDR-L1, CDR-L2, CDR-L3).

[0493] For A 02:01_AIFPGAVPAA (SEQ ID NO: 198) A specific ABP may contain a CDR-H3 sequence. The CDR-H3 sequence may be selected from CARDDYGDYVAYFQHW (SEQ ID NO: 201), CARDLSYYYGMDVW (SEQ ID NO: 202), CARVYDFWSVLSGFDIW (SEQ ID NO: 203), CARVEQGYDIYYYYYMDVW (SEQ ID NO:204)、CARSYDYGDYLNFDYW (SEQ ID NO:205)、CARASGSGYYYYYGMDVW (SEQ ID NO:206)、CAASTWIQPFDYW (SEQ ID NO:207)、CASNGNYYGSGSYYNYW (SEQ ID NO:208)、CARAVYDFWSGPFDYW (SEQ ID NO:209)、CAKGGIYYGSGSSYPSW (SEQ ID NO: 210), CARGLYYMDVW (SEQ ID NO: 211), CARGLYGDYFLYYGMDVW (SEQ ID NO: 212), CARGLLGFGEFLTYGMDVW (SEQ ID NO: 213), CARDRDSSWTYYYYGMDVW (SEQ ID NO: 214), CARGLYGDYFLYYGMDVW (SEQ ID NO: 212), CARGDYYDSSGYYFPVYFDYW (SEQ ID NO: 215) and CAKDPFSGHYYYYGMDVW (SEQ ID NO: 215). ID NO: 216).

[0494] A 02:01_AIFPGAVPAA (SEQ ID NO: 198) has a specific ABP that may contain a CDR-L3 sequence. The CDR-L3 sequence may be selected from CQQNYNSVTF (SEQ ID NO: 217), CQQSYNTPWTF (SEQ ID NO: 218), CGQSYSTPPTF (SEQ ID NO: 219), CQQSYSAPYTF (SEQ ID NO: 111), CQQSYSIPPTF (SEQ ID NO: 220), CQQSYSAPYTF (SEQ ID NO: 111), CQQHNSYPPTF (SEQ ID NO: 221), CQQYSTYPITI (SEQ ID NO: 222), CQQANSFPWTF (SEQ ID NO: 223), CQQSHSTPQTF (SEQ ID NO: 224), CQQSYSTPLTF (SEQ ID NO: 30), CQQSYSTPLTF (SEQ ID NO: 30), CQQTYSTPWTF (SEQ ID NO: 225), CQQYGSSPYTF (SEQ ID NO: 226), CQQSHSTPLTF (SEQ ID NO: 227), CQQANGFPLTF (SEQ ID NO: 228) and CQQSYSTPLTF (SEQ ID NO: 30).

[0495] For A 02:01_AIFPGAVPAA (SEQ ID NO: 198) A specific ABP may contain a specific heavy chain CDR3 (CDR-H3) sequence and a specific light chain CDR3 (CDR-L3) sequence. In some implementations, the ABP comprises CDR-H3 and CDR-L3 from scFv, which are named G8-P1A03, G8-P1A04, G8-P1A06, G8-P1B03, G8-P1C11, G8-P1D02, G8-P1H08, G8-P2B05, G8-P2E06, R3G8-P2C10, R3G8-P2E04, R3G8-P4F05, R3G8-P5C03, R3G8-P5F02, R3G8-P5G08, G8-P1C01, or G8-P2C11. Table 7 shows the specific binding of A. The CDR sequence of the identified scFv is 02:01_AIFPGAVPAA (SEQ ID NO: 198). For clarity, each identified scFv match is named with a clone name, and each line contains the CDR sequence for that specific clone name. For example, the scFv identified by clone name G8-P1A03 contains the heavy chain CDR3 sequence CARDDYGDYVAYFQHW (SEQ ID NO: 201) and the light chain CDR3 sequence CQQNYNSVTF (SEQ ID NO: 217).

[0496] For A 02:01_AIFPGAVPAA (SEQ ID NO: 198) has a specific ABP that can contain all 6 CDRs from scFv, which are named G8-P1A03, G8-P1A04, G8-P1A06, G8-P1B03, G8-P1C11, G8-P1D02, G8-P1H08, G8-P2B05, G8-P2E06, R3G8-P2C10, R3G8-P2E04, R3G8-P4F05, R3G8-P5C03, R3G8-P5F02, R3G8-P5G08, G8-P1C01 or G8-P2C11.

[0497] VH For A The ABP specific to 02:01_AIFPGAVPAA (SEQ ID NO: 198) may contain a VH sequence. The VH sequence may be selected from QVQLVQSGAEVKKPGASVKVSCKASGGTFSRSAITWVRQAPGQGLEWMGWINPNSGATNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDDYGDYVAYFQHWGQGTLVTVSS (SEQ ID NO: 229), QVQLVQSGAEVKKPGASVKVSCKASGYPFIGQYLHWVRQAPGQGLEWMGIINPSGDSATYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDLSYYYGMDVWGQGTTVTVSS (SEQ ID NO: 230), QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYYMHWVRQAPGQGLEWMGWMNPIGGGTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARVYDFWSVLSGFDIWGQGTLVTVSS (SEQ ID NO: 231), EVQLLESGGGLVQPGGSLRLSCAASGFTFSDYYMSWVRQAPGKGLEWVSGINWNGGSTGYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVEQGYDIYYYYYMDVWGKGTTVTVSS (SEQ ID NO: 232), QVQLVQSGAEVKKPGASVKVSCKASGGTLSSYPINWVRQAPGQGLEWMGWISTYSGHADYAQKLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSYDYGDYLNFDYWGQGTLVTVSS (SEQ ID NO: 199), EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYWMSWVRQAPGKGLEWVSSISGRGDNTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARASGSGYYYYYGMDVWGQGTTVTVSS (SEQID NO:233)、QVQLVQSGAEVKKPGASVKVSCKASGYTFGNYFMHWVRQAPGQGLEWMGMVNPSGGSETFAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAASTWIQPFDYWGQGTLVTVSS (SEQ ID NO: 234)、EVQLLESGGGLVQPGGSLRLSCAASGFDFSIYSMNWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASNGNYYGSGSYYNYWGQGTLVTVSS (SEQ ID NO: 235)、QVQLVQSGAEVKKPGASVKVSCKASGYTLTTYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARAVYYDFWSGPFDYWGQGTLVTVSS (SEQ ID NO: 236)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGWINPYSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKGGIYYGSGSYPSWGQGTLVTVSS (SEQ ID NO: 237)、QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYGVSWVRQAPGQGLEWMGWISPYSGNTDYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGLYYMDVWGKGTTVTVSS(SEQ ID NO: 238)、QVQLVQSGAEVKKPGASVKVSCKASGYTFSNMYLHWVRQAPGQGLEWMGWINPNTGDTNYAQTFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGLYGDYFLYYGMDVWGQGTKVTVSS (SEQ ID NO:239)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGLLGFGEFLTYGMDVWGQGTLVTVSS (SEQ ID NO:240), QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYIHWVRQAPGQGLEWMGVINPSGGSTTYAQKLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDRDSSWTYYYYGMDVWGQGTTVTVSS (SEQ ID NO: 241), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSNYMHWVRQAPGQGLEWMGWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGLYGDYFLYYGMDVWGQGTTVTVSS (SEQ ID NO: 242), QVQLVQSGAEVKKPGASVKVSCKASGGTFSSHAISWVRQAPGQGLEWMGVIIPSGGTSYTQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGDYYDSSGYYFPVYFDYWGQGTLVTVSS (SEQ ID NO: 243) and QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYAMNWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDPFWSGHYYYYGMDVWGQGTTVTVSS (SEQ ID NO: 244).

[0498] VL A The ABP with specificity of 02:01_AIFPGAVPAA (SEQ ID NO: 198) may contain a VL sequence. The VL sequence may be selected from DIQMTQSPSSLSASVGDRVTITCRASQSITSYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQNYNSVTFGQGTKLEIK (SEQ ID NO: 245), DIQMTQSPSSLSASVGDRVTITCWASQGISSYLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYNTPWTFGPGTKVDIK (SEQ ID NO: 246), DIQMTQSPSSLSASVGDRVTITCRASQAISNSLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCGQSYSTPPTFGQGTKLEIK (SEQ ID NO:247), DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSAPYTFGPGTKVDIK (SEQ ID NO: 248), DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSIPPTFGGGTKVDIK (SEQ ID NO: 200), DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSAPYTFGGGTKVEIK (SEQ ID NO: 249), DIQMTQSPSSLSASVGDRVTITCRASQGINSYLAWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHNSYPPTFGQGTKLEIK (SEQ ID NO:250)、DIQMTQSPSSLSASVGDRVTITCRASQSISRWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYSTYPITIGQGTKVEIK (SEQ ID NO: 251)、DIQMTQSPSSLSASVGDRVTITCRASQGISNSLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPWTFGQGTKLEIK (SEQ ID NO: 252)、DIQMTQSPSSLSASVGDRVTITCRASQDVSTWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSHSTPQTFGQGTKVEIK (SEQ ID NO: 253)、DIQMTQSPSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKLEIK(SEQ ID NO: 254)、DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ ID NO: 255)、DIQMTQSPSSLSASVGDRVTITCRASQGISNWLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYSTPWTFGQGTKLEIK (SEQ ID NO: 256)、EIVMTQSPATLSVSPGERATLSCRASQSVGNSLAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYGSSPYTFGQGTKVEIK (SEQID NO: 257)、DIQMTQSPSSLSASVGDRVTITCRASQSISGYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSHSTPLTFGQGTKVEIK (SEQ ID NO:258), DIQMTQSPSSSLSASVGDRVTITCRASQNIYTYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANGFPLTFGGGTKVEIK (SEQ ID NO: 259) and DIQMTQSPSSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ IDNO: 71).

[0499] VH-VL combination For A 02:01_AIFPGAVPAA (SEQ ID NO: 198) A specific ABP may contain a specific VH sequence and a specific VL sequence. In some embodiments, for A... 02:01_AIFPGAVPAA (SEQ ID NO: 198) Specific ABPs may contain VH and VL sequences from scFvs named G8-P1A03, G8-P1A04, G8-P1A06, G8-P1B03, G8-P1C11, G8-P1D02, G8-P1H08, G8-P2B05, G8-P2E06, R3G8-P2C10, R3G8-P2E04, R3G8-P4F05, R3G8-P5C03, R3G8-P5F02, R3G8-P5G08, G8-P1C01, or G8-P2C11. Table 6 shows the specific binding A... The VH and VL sequences of the identified scFv for 02:01_AIFPGAVPAA (SEQ ID NO: 198). For clarity, each identified scFv hit is named with a clone name, and each line contains the VH and VL sequences for that specific clone name. For example, the scFv identified by clone name G8-P1A03 contains the VH sequence QVQLVQSGAEVKKPGASVKVSCKASGGTFSRSAITWVRQAPGQGLEWMGWINPNSGATNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDDYGDYVAYFQHWGQGTLVTVSS (SEQ ID NO: 229) and the VL sequence DIQMTQSPSSLSASVGDRVTITCRASQSITSYLNWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQNYNSVTFGQGTKLEIK (SEQ ID NO: 245).

[0500] For A 01:01 _ASSLPTTMNY (SEQ ID NO: 260) (HLA-peptide target "G10") has specific anti- body In some respects, this article provides ABPs comprising antibodies or antigen-binding fragments thereof that specifically bind to HLA-peptide targets, wherein the HLA-peptide target HLA class I molecules are HLA subtype A. 01:01, and the HLA-restricted peptide of the HLA-peptide target comprises the sequence ASSLPTTMNY (SEQ ID NO: 260) (“G10”), or is composed of or substantially composed of it.

[0501] CDR For A 01:01_ASSLPTTMNY (SEQ ID NO: 260) Specific ABP may contain one or more antibody complementarity-determining region (CDR) sequences, such as 3 heavy chain CDRs (CDR-H1, CDR-H2, CDR-H3) and 3 light chain CDRs (CDR-L1, CDR-L2, CDR-L3).

[0502] For A 01:01_ASSLPTTMNY (SEQ ID NO: 260) has a specific ABP that may contain the CDR-H3 sequence. The CDR-H3 sequence may be selected from CARDQDTIFGVVITWFDPW (SEQ ID NO: 261), CARDKVYGDGFDPW (SEQ ID NO: 262), CAREDDSMDVW (SEQ ID NO: 263), CARDSSGLDPW (SEQ ID NO: 264), CARGVGNLDYW (SEQ ID NO: 265), CARDAHQYYDFWSGYYSGTYYYGMDVW (SEQ ID NO: 266), CAREQWPSYWYFDLW (SEQ ID NO: 267), CARDRGYSYGYFDYW (SEQ ID NO: 268), CARGSGDPNYYYYYGLDVW (SEQ ID NO: 269), CARDTGDHFDYW (SEQ ID NO: 270), CARAENGMDVW (SEQ ID NO: 271), CARDPGGYMDVW (SEQ ID NO: 272), CARDGDAFDIW (SEQ ID NO: 273), CARDMGDAFDIW (SEQ ID NO: 274), CAREEDGMDVW (SEQ ID NO: 275), CARDTGDHFDYW (SEQ ID NO: 270), CARGEYSSGFFFVGWFDLW (SEQ ID NO: 276) and CARETGDDAFDIW (SEQ ID NO: 277).

[0503] For A 01:01_ASSLPTTMNY (SEQ ID NO: 260) has a specific ABP that may contain a CDR-L3 sequence. The CDR-L3 sequence can be selected from CQQYFTTPYTF (SEQ ID NO: 278), CQQAEAFPYTF (SEQ ID NO: 279), CQQSYSTPITF (SEQ ID NO: 280), CQQSYIIPYTF (SEQ ID NO: 281), CHQTYSTPLTF (SEQ ID NO: 282), CQQAYSFPWTF (SEQ ID NO: 283), CQQGYSTPLTF (SEQ ID NO: 284), CQQANSFPRTF (SEQ ID NO: 285), CQQANSLPYTF (SEQ ID NO: 286), CQQSYSTPFTF (SEQ ID NO: 109), CQQSYSTPFTF (SEQ ID NO: 109), CQQSYGVPTF (SEQ ID NO: 287), CQQSYSTPLTF (SEQ ID NO: 30), CQQSYSTPLTF (SEQ ID NO: 30), CQQYYSYPWTF (SEQ ID NO: 288), CQQSYSTPFTF (SEQ ID NO: 109), CMQTLKTPLSF (SEQ ID NO: 289) and CQQSYSTPLTF (SEQ ID NO: 30).

[0504] For A 01:01_ASSLPTTMNY (SEQ ID NO: 260) A specific ABP may contain a specific heavy chain CDR3 (CDR-H3) sequence and a specific light chain CDR3 (CDR-L3) sequence. In some embodiments, the ABP contains CDR-H3 and CDR-L3 from scFvs named R3G10-P1A07, R3G10-P1B07, R3G10-P1E12, R3G10-P1F06, R3G10-P1H01, R3G10-P1H08, R3G10-P2C04, R3G10-P2G11, R3G10-P3E04, R3G10-P4A02, R3G10-P4C05, R3G10-P4D04, R3G10-P4D10, R3G10-P4E07, R3G10-P4E12, R3G10-P4G06, R3G10-P5A08, or R3G10-P5C08. Table 9 shows the specific binding of A. The CDR sequence of the identified scFv is 01:01_ASSLPTTMNY (SEQ ID NO: 260). For clarity, each identified scFv match is named with a clone name, and each line contains the CDR sequence for that specific clone name. For example, the scFv identified by clone name R3G10-P1A07 contains the heavy chain CDR3 sequence CARDQDTIFGVVITWFDPW (SEQ ID NO: 261) and the light chain CDR3 sequence CQQYFTTPYTF (SEQ ID NO: 278).

[0505] For A 01:01_ASSLPTTMNY (SEQ ID NO: 260) A specific ABP may contain all 6 CDRs from scFv, which are named R3G10-P1A07, R3G10-P1B07, R3G10-P1E12, R3G10-P1F06, R3G10-P1H01, R3G10-P1H08, R3G10-P2C04, R3G10-P2G11, R3G10-P3E04, R3G10-P4A02, R3G10-P4C05, R3G10-P4D04, R3G10-P4D10, R3G10-P4E07, R3G10-P4E12, R3G10-P4G06, R3G10-P5A08, or R3G10-P5C08.

[0506] VH For A The ABP with specificity may contain a VH sequence. The VH sequence may be selected from EVQLLESGGGLVKPGGSLRLSCAASGFTFSSYWMSWVRQAPGKGLEWVSGISARSGRTYYADSVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCARDQDTIFGVVITWFDPWGQGTLVTVSS (SEQ ID NO:290), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGIIHPGGGTTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDKVYGDGFDPWGQGTLVTVSS (SEQ ID NO: 291), QVQLVQSGAEVKKPGASVKVSCKASGYIFTGYYMHWVRQAPGQGLEWMGMIGPSDGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREDDSMDVWGKGTTVTVSS (SEQ ID NO: 292), QVQLVQSGAEVKKPGASVKVSCKASGYTFIGYYMHWVRQAPGQGLEWMGMIGPSDGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDSSGLDPWGQGTLVTVSS (SEQ ID NO: 293), QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGMIGPSDGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGVGNLDYWGQGTLVTVSS (SEQID NO: 294), QVQLVQSGAEVKKPGASVKVSCKASGVTFSTSAISWVRQAPGQGLEWMGWISPYNGNTDYAQMLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDAHQYYDFWSGYYSGTYYYGMDVWGQGTTVTVSS (SEQ IDNO:295)、QVQLVQSGAEVKKPGASVKVSCKASGGTFSNSIINWVRQAPGQGLEWMGWMNPNSGNTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREQWPSYWYFDLWGRGTLVTVSS (SEQ ID NO: 296)、QVQLVQSGAEVKKPGASVKVSCKASGGTFSTHDINWVRQAPGQGLEWMGVINPSGGSAIYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDRGYSYGYFDYWGQGTLVTVSS (SEQ ID NO: 297)、QVQLVQSGAEVKKPGASVKVSCKASGNTFIGYYVHWVRQAPGQGLEWVGIINPNGGSISYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGSGDPNYYYYYGLDVWGQGTTVTVSS (SEQ ID NO: 298)、QVQLVQSGAEVKKPGASVKVSCKASGYTLSYYYMHWVRQAPGQGLEWMGMIGPSDGSTSYAQRFQGRVTMTRDTSTGTVYMELSSLRSEDTAVYYCARDTGDHFDYWGQGTLVTVSS (SEQ ID NO: 299)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGIIGPSDGSTTYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARAENGMDVWGQGTTVTVSS (SEQID NO: 300)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYVHWVRQAPGQGLEWMGIIAPSDGSTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDPGGYMDVWGKGTTVTVSS (SEQ ID NO: 301)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYLHWVRQAPGQGLEWMGMIGPSDGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGDAFDIWGQGTMVTVSS (SEQ ID NO:302), QVQLVQSGAEVKKPGSSVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGRISPSDGSTTYAPKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDMGDAFDIWGQGTTVTVSS (SEQ ID NO: 303), QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGMIGPSDGSTSYAQRFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREEDGMDVWGQGTTVTVSS(SEQ ID NO: 304), QVQLVQSGAEVKKPGASVKVSCKASGYTLSYYYMHWVRQAPGQGLEWMGMIGPSDGSTSYAQRFQGRVTMTRDTSTGTVYMELSSLRSEDTAVYYCARDTGDHFDYWGQGTLVTVSS (SEQ ID NO: 299), QVQLVQSGAEVKKPGSSVKVSCKASGGTFNNFAISWVRQAPGQGLEWMGGIIPIFDATNYAQKFQGRVTFTADESTSTAYMELSSLRSEDTAVYYCARGEYSSGFFFVGWFDLWGRGTQVTVSS (SEQ ID NO: 305) and QVQLVQSGAEVKKPGASVKVSCKASGYNFTGYYMHWVRQAPGQGLEWMGIIAPSDGSTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARETGDDAFDIWGQGTMVTVSS (SEQ ID NO: 306).

[0507] VL For A The ABP with specificity of 01:01_ASSLPTTMNY (SEQ ID NO: 260) may contain a VL sequence. The VL sequence may be selected from DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYAASSLQGGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYFTTPYTFGQGTKLEIK (SEQ ID NO: 307), DIQMTQSPSSLSASVGDRVTITCRASQSISRWLAWYQQKPGKAPKLLIFDASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAEAFPYTFGQGTKVEIK (SEQ ID NO: 308), DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPITFGQGTRLEIK (SEQ ID NO:309), DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYKASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYIIPYTFGQGTKLEIK (SEQ ID NO: 310), DIQMTQSPSSLSASVGDRVTITCRASQSISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCHQTYSTPLTFGQGTKVEIK (SEQ ID NO: 311), DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYSASNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAYSFPWTFGQGTKVEIK (SEQ ID NO: 312), DIQMTQSPSSLSASVGDRVTITCRASQNISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGYSTPLTFGQGTRLEIK (SEQ ID NO:313)、DIQMTQSPSSLSASVGDRVTITCRASQDISRYLAWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPRTFGQGTKVEIK (SEQ ID NO: 314)、DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSLPYTFGQGTKVEIK (SEQ ID NO: 315)、DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASTLQNGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQSYSTPTFGPGTKVDIK (SEQ ID NO: 315) ID NO: 316)、DIQMTQSPSSLSASVGDRVTITCRASQRISSYLNWYQQKPGKAPCLLIYSASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPTFGPGTKVDIK(SEQ ID NO: 317), DIQMTQSPSSLSASVGDRVTITCRASQSISSYLAWYQQKPGKAPKLLIYDASKLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYGVPTFGQGTKLEIK (SEQ ID NO: 318), DIQMTQSPSSLSASVGDRVTITCRASQGISSWLAWYQQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ ID NO: 319), DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ ID NO: 71), DIQMTQSPSSLSASVGDRVTITCRASQGISTYLAWYQQKPGKAPKLLIYDASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYYSYPWTFGQGTRLEIK (SEQ ID NO:320), DIQMTQSPSSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASTLQNGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPFTFGPGTKVDIK (SEQ ID NO: 316), DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQTLKTPLSFGGTKVEIK (SEQ IDNO: 321) and DIQMTQSPSSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ ID NO: 71).

[0508] VH-VL combination For A 01:01_ASSLPTTMNY (SEQ ID NO: 260) ABP with specificity may contain a specific VH sequence and a specific VL sequence. In some embodiments, for A... 01:01_ASSLPTTMNY (SEQ ID NO: 260) A specific ABP contains a VH sequence and a VL sequence from an scFv named R3G10-P1A07, R3G10-P1B07, R3G10-P1E12, R3G10-P1F06, R3G10-P1H01, R3G10-P1H08, R3G10-P2C04, R3G10-P2G11, R3G10-P3E04, R3G10-P4A02, R3G10-P4C05, R3G10-P4D04, R3G10-P4D10, R3G10-P4E07, R3G10-P4E12, R3G10-P4G06, R3G10-P5A08, or R3G10-P5C08. Table 8 shows the specific binding of A. The VH and VL sequences of the identified scFv for 01:01_ASSLPTTMNY (SEQ ID NO: 260). For clarity, each identified scFv hit is named with a clone name, and each line contains the VH and VL sequences for that specific clone name. For example, the scFv identified by clone name R3G10-P1A07 contains the VH sequence EVQLLESGGGLVKPGGSLRLSCAASGFTFSSYWMSWVRQAPGKGLEWVSGISARSGRTYYADSVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCARDQDTIFGVVITWFDPWGQGTLVTVSS (SEQ ID NO: 290) and the VL sequence DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYAASSLQGGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYFTTPYTFGQGTKLEIK (SEQ ID NO: 307).

[0509] For A 02:01 LLASSILCA (SEQ ID NO: 322)(G7) has specific antibodies. In some respects, this article provides ABPs comprising antibodies or antigen-binding fragments thereof that specifically bind to HLA-peptide targets, wherein the HLA-peptide target HLA class I molecules are HLA subtype A. 02:01, and the HLA-restricted peptide of the HLA-peptide target contains the sequence LLASSILCA (SEQ ID NO: 322) (“G7”), is composed of or substantially composed of the sequence.

[0510] Sequence of G7 specific antibody As described in further detail, for A 02:01_ LLASSILCA (SEQ ID NO: 322) A specific ABP may contain one or more sequences.

[0511] CDR For A 02:01_ LLASSILCA (SEQ ID NO: 322) Specific ABPs may contain one or more antibody complementarity-determining region (CDR) sequences, for example, they may contain three heavy chain CDRs (CDR-H1, CDR-H2, CDR-H3) and three light chain CDRs (CDR-L1, CDR-L2, CDR-L3).

[0512] For A 02:01_ LLASSILCA (SEQ ID NO: 322) has a specific ABP that may contain a CDR-H3 sequence. The CDR-H3 sequence may be selected from CARDGYDFWSGYTSDDYW (SEQ ID NO: 323), CASDYGDYR (SEQ ID NO: 324), CARDLMTTVVTPGDYGMDVW (SEQ ID NO: 325), CARQDGGAFAFDIW (SEQ ID NO: 326), CARELGYYYGMDVW (SEQ ID NO: 327), CALAIFGVPLLPYGMDVW (SEQ ID NO: 328), CAKDLATVGEPYYYYGMDVW (SEQ ID NO: 329), and CARLWFGELHYYYYYGMDVW (SEQ ID NO: 330).

[0513] For A 02:01_ LLASSILCA (SEQ ID NO: 322) has a specific ABP that may contain a CDR-L3 sequence. The CDR-L3 sequence may be selected from CHHYGRSHTF (SEQ ID NO: 331), CQQANAFPPTF (SEQ ID NO: 332), CQQYYSIPLTF (SEQ ID NO: 333), CQQSYSTPPTF (SEQ ID NO: 334), CQQSYSFPYTF (SEQ ID NO: 335), CMQALQTPLTF (SEQ ID NO: 31), CQQGNTFPLTF (SEQ ID NO: 336), and CMQGSHWPPSF (SEQ ID NO: 337).

[0514] For A 02:01_ LLASSILCA (SEQ ID NO: 322) A specific ABP may contain a specific heavy chain CDR3 (CDR-H3) sequence and a specific light chain CDR3 (CDR-L3) sequence. In some embodiments, the ABP contains CDR-H3 and CDR-L3 from scFvs named G7R3-P1C6, G7R3-P1G10, 1-G7R3-P1B4, 2-G7R4-P2C2, 3-G7R4-P1A3, 4-G7R4-B5-P2E9, 5-G7R4-B10-P1F8, or B7 (G7R3-P3A9). Table 36 shows the specific binding of A... The CDR sequence of the identified scFv 02:01_ LLASSILCA (SEQ ID NO: 322). For clarity, each identified scFv match is named with a clone name, and each line contains the CDR sequence for that specific clone name. For example, the scFv identified by the clone name G7R3-P1C6 contains the heavy chain CDR3 sequence CARDGYDFWSGYTSDDYW (SEQ ID NO: 323) and the light chain CDR3 sequence CHHYGRSHTF (SEQ ID NO: 331).

[0515] For A 02:01_ LLASSILCA (SEQ ID NO: 322) has a specific ABP that may contain all six CDRs from scFv, which are named G7R3-P1C6, G7R3-P1G10, 1-G7R3-P1B4, 2-G7R4-P2C2, 3-G7R4-P1A3, 4-G7R4-B5-P2E9, 5-G7R4-B10-P1F8 or B7 (G7R3-P3A9).

[0516] VL right The ABP specific to LLASSILCA (SEQ ID NO: 322) may comprise a VL sequence. The VL sequence may be selected from EIVMTQSPATLSVSPGERATLSCRASQSVSSSNLAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCHHYGRSHTFGQGTKVEIK (SEQ ID NO: 346), DIQMTQSPSSLSASVGDRVTITCRASQDIRNDLGWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANAFPPTFGQGTKVEIK (SEQ ID NO: 347), DIVMTQSPDSLAVSLGERATINCKSSQSVFYSSNNKNQLAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYSIPLTFGQGTKLEIK (SEQID NO: 348), DIQMTQSPSSLSASVGDRVTITCQASQDIFKYLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPPTFGQGTRLEIK (SEQ ID NO: 349), DIQMTQSPSSLSASVGDRVTITCRASQSISTWLAWYQQKPGKAPKLLIYYASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSFPYTFGQGTKVEIK (SEQ ID NO: 350), DIVMTQSPLSLPVTPGEPASISCSSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPLTFGGGTKVEIK (SEQID NO: 351), DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYSASNLRSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQGNTFPLTFGQGTKVEIK (SEQ ID NO:352) and DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGSHWPPSFGQGTRLEIK (SEQ ID NO: 353).

[0517] VH For The ABP specific to LLASSILCA (SEQ ID NO: 322) may contain a VH sequence. The VH sequence may be selected from QVQLVQSGAEVKKPGASVKVSCKASGGTFSNYGISWVRQAPGQGLEWMGIINPGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGYDFWSGYTSDDYWGQGTLVTVSS (SEQ ID NO: 338), EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVSGISGSGGSTYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASDYGDYRGQGTLVTVSS (SEQ ID NO: 339), QVQLVQSGAEVKKPGASVKVSCKASGYTFSNYYIHWVRQAPGQGLEWMGWLNPNSGNTGYAQRFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDLMTTVVTPGDYGMDVWGQGTTVTVSS (SEQ ID NO: 340), QVQLVQSGAEVKKPGASMKVSCKASGYTFTTDGISWVRQAPGQGLEWMGRIYPHSGYTEYAKKFKGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARQDGGAFAFDIWGQGTMVTVSS (SEQ ID NO: 341), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSQYMHWVRQAPGQGLEWMGWISPNNGDTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARELGYYYGMDVWGQGTTVTVSS (SEQID NO: 342), QVQLVQSGAEVKKPGSSVKVSCKASRYTFTSYDINWVRQAPGQGLEWMGRIIPMLNIANYAPKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARALIFGVPLLPYGMDVWGQGTTVTVSS (SEQ IDNO: 343), EVQLLQSGGGLVQPGGSLRLSCAASGFTFSSSWMHWVRQAPGKGLEWVSFISTSSGYIYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDLATVGEPYYYYGMDVWGQGTTVTVSS (SEQ ID NO: 344) and QVQLVQSGAEVKKPGSSVKVSCKASGDTFNTYALSWVRQAPGQGLEWMGWMNPNSGNAGYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARLWFGELHYYYYYGMDVWGQGTMVTVSS (SEQ ID NO: 345).

[0518] VH-VL combination For A 02:01_LLASSILCA (SEQ ID NO: 322) ABP with specificity may contain a specific VH sequence and a specific VL sequence. In some embodiments, for A... 02:01_ LLASSILCA (SEQ ID NO: 322) contains specific ABP sequences comprising the VH and VL sequences from scFvs named G7R3-P1C6, G7R3-P1G10, 1-G7R3-P1B4, 2-G7R4-P2C2, 3-G7R4-P1A3, 4-G7R4-B5-P2E9, 5-G7R4-B10-P1F8, or B7 (G7R3-P3A9). Table 35 shows the specific binding to A. VH and VL sequences of the identified scFv of 02:01_ LLASSILCA (SEQ ID NO: 322). For clarity, each identified scFv hit is named with a clone name, and each line contains the VH and VL sequences for that specific clone name. For example, the scFv identified by clone name G7R3-P1C6 contains the VH sequence QVQLVQSGAEVKKPGASVKVSCKASGGTFSNYGISWVRQAPGQGLEWMGIINPGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGYDFWSGYTSDDYWGQGTLVTVSS (SEQ ID NO: 338) and the VL sequence EIVMTQSPATLSVSPGERATLSCRASQSVSSSNLAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCHHYGRSHTFGQGTKVEIK (SEQ ID NO: 346).

[0519] For A 01:01_NTDNNLAVY (SEQ ID NO: 73) (G2) contains a specific antibody. In some respects, this article provides ABPs comprising antibodies or antigen-binding fragments thereof that specifically bind to HLA-PEPTIDE targets, wherein the HLA-peptide target HLA class I molecule is HLA subtype A. 01:01, and the HLA-restricted peptide of the HLA-peptide target comprises the sequence NTDNNLAVY (SEQ ID NO: 73) (“G2”), is composed of or substantially composed of the sequence.

[0520] Sequence of G2-specific antibody As described in further detail, for A 01:01_ NTDNNLAVY (SEQ ID NO: 73) A specific ABP may contain one or more sequences.

[0521] CDR For A 01:01_ NTDNNLAVY (SEQ ID NO: 73) Specific ABP may contain one or more antibody complementarity-determining region (CDR) sequences, for example, it may contain three heavy chain CDRs (CDR-H1, CDR-H2, CDR-H3) and three light chain CDRs (CDR-L1, CDR-L2, CDR-L3).

[0522] For A01:01_ An ABP specific to NTDNNLAVY (SEQ ID NO: 73) may contain a CDR-H3 sequence. The CDR-H3 sequence may be selected from CAATEWLGVW (SEQ ID NO: 74), CARANWLDYW (SEQ ID NO: 75), CARANWLDYW (SEQ ID NO: 75), CARDWVLDYW (SEQ ID NO: 76), CARGEWLDYW (SEQ ID NO:77), CARGWELGYW (SEQ ID NO: 78), CARDFVGYDDW (SEQ ID NO: 79), CARDYGDLDYW (SEQID NO: 80), CARGSYGMDVW (SEQ ID NO: 81), CARDGYSGLDVW (SEQ ID NO: 82), CARDSGVGMDVW (SEQ ID NO: 83), CARDGVAVASDYW (SEQ ID NO: 84), CARGVNVDDFDYW (SEQID NO: 85), CARGDYTGNWYFDLW (SEQ ID NO: 86), CARANWLDYW (SEQ ID NO: 75), CARDQFYGGNSGGHDYW (SEQ ID NO: 87), CAREEDYW (SEQ ID NO: 88), CARGDWFDPW (SEQ IDNO: 89), CARGDWFDPW (SEQ ID NO: 89), CARGEWFDPW (SEQ ID NO: 90), CARSDWFDPW (SEQID NO: 91), CARDSGSYFDYW (SEQ ID NO: 92), CARDYGGYVDYW (SEQ ID NO: 93), CAREGPAALDVW (SEQ ID NO: 94), CARERRSGMDVW (SEQ ID NO: 95), CARVLQEGMDVW (SEQID NO: 96), CASERELPFDIW (SEQ ID NO: 97), CAKGGGGYGMDVW (SEQ ID NO: 98), CAAMGIAVAGGMDVW (SEQ ID NO: 99), CARNWNLDYW (SEQ ID NO: 100), CATYDDGMDVW (SEQID NO: 101), CARGGGGALDYW (SEQ ID NO: 102), CALSGNYYGMDVW (SEQ ID NO:103), CARGNPWELRLDYW (SEQ ID NO: 104), and CARDKNYYGMDVW (SEQ ID NO: 105).

[0523] For A 1:01 (SEQ ID NO: 107)、CQQSYSTPYSF (SEQ ID NO: 108)、CQQSYSTPFTF (SEQ ID NO: 109)、CQQSYGVPYTF (SEQ IDNO: 110)、CQQSYSAPYTF (SEQ ID NO: 111)、CQQSYSAPYTF (SEQ ID NO: 111)、CQQSYSAPYSF (SEQ ID NO: 112)、CQQSYSTPYTF (SEQ ID NO: 107)、CQQSYSVPYSF (SEQ IDNO: 113)、CQQSYSAPYTF (SEQ ID NO: 111)、CQQSYSVPYSF (SEQ ID NO: 113)、CQQSYSTPQTF (SEQ ID NO: 114)、CQQLDSYPFTF (SEQ ID NO: 115)、CQQSYSSPYTF (SEQ IDNO: 116)、CQQSYSTPLTF (SEQ ID NO: 30)、CQQSYSTPYSF (SEQ ID NO: 108). 118). 108)、CQQSYSDQWTF (SEQ ID NO: 121)、CQQSYLPPYSF (SEQ ID NO: 122)、CQQSYSSPYTF (SEQ ID NO: 116)、CQQSYTTPWTF (SEQ IDNO: 123)、CQQSYLPPYSF (SEQ ID NO: 122)、CQEGITYTF (SEQ IDNO: 124), CQQYYSYPFTF (SEQ ID NO: 125) and CQHYGYSPVTF (SEQ ID NO: 126).

[0524] For A 01:01_ NTDNNLAVY (SEQ ID NO: 73) A specific ABP may contain a specific heavy chain CDR3 (CDR-H3) sequence and a specific light chain CDR3 (CDR-L3) sequence. In some embodiments, the ABP contains CDR-H3 and CDR-L3 from scFvs named G2-P2E07, G2-P2E03, G2-P2A11, G2-P2C06, G2-P1G01, G2-P1C02, G2-P1H01, G2-P1B12, G2-P1B06, G2-P2H10, G2-P1H10, G2-P2C11, G2-P1C09, G2-P1A10, G2-P1B10, G2-P1D07, G2-P1E05, G2-P1D03, G2-P1G12, G2-P2H11, G2-P1C03, G2-P1G07, G2-P1F12, G2-P1G03, G2-P2B08, G2-P2A10, G2-P2D04, G2-P1C06, G2-P2A09, G2-P1B08, G2-P1E03, G2-P2A03, G2-P2F01, G2-P1H11, or G2-P1D06. Specifically binds to A. The CDR sequences of the identified scFv 01:01_NTDNNLAVY (SEQ ID NO: 73) are shown in Table 34. For clarity, each identified scFv match is named with a clone name, and each row contains the CDR sequence for that specific clone name. For example, the scFv identified by clone name G2-P2E07 contains the heavy chain CDR3 sequence CAATEWLGVW (SEQ ID NO: 74) and the light chain CDR3 sequence CQQSYNTPYTF (SEQ ID NO: 106).

[0525] For A 01:01_ NTDNNLAVY (SEQ ID NO: 73) ABP with specificity may contain all 6 CDRs from scFv, which are named G2-P2E07, G2-P2E03, G2-P2A11, G2-P2C06, G2-P1G01, G2-P1C02, G2-P1H01, G2-P1B12, G2-P1B06, G2-P2H10, G2-P1H10, G2-P2C11, G2-P1C09, G2-P1A10, G2-P1B10, G2 -P1D07, G2-P1E05, G2-P1D03, G2-P1G12, G2-P2H11, G2-P1C03, G2-P1G07, G2-P1F12, G2-P1G03, G2-P2B08, G2-P2A10, G2-P2D04, G2-P1C06, G2-P2A09, G2-P1B08, G2-P1E03, G2-P2A03, G2-P2F01, G2-P1H11 or G2-P1D06.

[0526] VL For A 01:01_ The ABP specific to NTDNNLAVY (SEQ ID NO: 73) contains a VL sequence. The VL sequence can be selected from DIQMTQSPSSLSASVGDRVTITCRASQSISTWLAWYQQKPGKAPKLLIYAASSLRSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYNTPYTFGQGTKLEIK (SEQ ID NO: 163), DIQMTQSPSSLSASVGDRVTITCRASQSISRWLAWYQQKPGKAPKLLIYAASTVQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK (SEQ ID NO: 164), DIQMTQSPSSLSASVGDRVTITCRASQDISRWLAWYQQKPGKAPKLLIYAASRLQAGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYSFGQGTKLEIK (SEQ ID NO:165), DIQMTQSPSSLSASVGDRVTITCRASQTISSWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPFTFGPGTKVDIK (SEQ ID NO: 166), DIQMTQSPSSLSASVGDRVTITCRASQTISSWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYGVPYTFGQGTKVEIK (SEQ ID NO: 167), DIQMTQSPSSLSASVGDRVTITCRASQSISNWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSAPYTFGPGTKVDIK (SEQ ID NO: 168), DIQMTQSPSSLSASVGDRVTITCRASQSVGNWLAWYQQKPGKAPKLLIYGASSLQTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSAPYTFGQGTKVEIK (SEQ ID NO:169)、DIQMTQSPSSLSASVGDRVTITCRASQNIGNWLAWYQQKPGKAPKLLIYAASTLQTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSAPYSFGQGTKLEIK (SEQ ID NO: 170)、DIQMTQSPSSLSASVGDRVTITCRASQSISRWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK (SEQ ID NO: 171)、DIQMTQSPSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYGASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSVPYSFGQGTKLEIK (SEQ ID NO: 172)、DIQMTQSPSSLSASVGDRVTITCRASQSISKWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSAPYTFGQGTKVEIK(SEQ ID NO: 173)、DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSVPYSFGQGTKLEIK (SEQ ID NO: 174)、DIQMTQSPSSLSASVGDRVTITCRASQTISNYLNWYQQKPGKAPKLLIYAASNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPQTFGQGTKVEIK (SEQ ID NO: 175)、DIQMTQSPSSLSASVGDRVTITCRASRDIGRAVGWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQLDSYPFTFGPGTKVDIK (SEQID NO: 176)、DIQMTQSPSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSSPYTFGPGTKVDIK (SEQ ID NO:177)、DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKLEIK (SEQ ID NO: 178)、DIQMTQSPSSLSASVGDRVTITCRASQSIGRWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYSFGQGTKVEIK (SEQ ID NO:179)、DIQMTQSPSSLSASVGDRVTITCRASQSISTWLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFAQGTKLEIK (SEQ ID NO: 180)、DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYGASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK (SEQ ID NO: 181)、DIQMTQSPSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPFTFGPGTKVDIK (SEQ ID NO: 182)、DIQMTQSPSSLSASVGDRVTITCRASQSVSNWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPTFGQGTKLEIK (SEQ ID NO: 183)、DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYAIPLTFGGGTKVEIK (SEQ ID NO: 184)、DIQMTQSPSSLSASVGDRVTITCQASQDIGSWLAWYQQKPGKAPKLLIYATSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYTFGQGTKLEIK (SEQ ID NO:185)、DIQMTQSPSSLSASVGDRVTITCRASQGISRWLAWYQQKPGKAPKLLIYAASTLQPGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYIAPFTFGPGTKVDIK (SEQ ID NO: 186). ID NO: 188)、DIQMTQSPSSLSASVGDRVTITCRASQSISSWVAWYQQKPGKAPKLLIYGASNLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPYSFGQGTKLEIK (SEQ ID NO: 189)、DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSDQWTFGQGTKVEIK (SEQ ID NO: 190)、DIQMTQSPSSLSASVGDRVTITCRASQSISRWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYLPPYSFGQTGVEIK (SEQ ID NO: 191)、DIQMTQSPSSLSASVGDRVTITCRASQSISNWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTYFTLTISSLQPEDFATYYCQQSYSSPYTFGQGTKLEIK (SEQ ID NO: 192)、DIQMTQSPSSLSASVGDRVTITCRASQSISHYLNWYQQKPGKAPKLLIYGASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYTTPWTFGQGTRLEIK (SEQ IDNO: 193), DIQMTQSPSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYLPPYSFGQGTKLEIK (SEQ ID NO: 194), DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYGASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQEGITYTFGQGTKVEIK (SEQ ID NO: 195), DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYYSYPFTFGPGTKVDIK (SEQ ID NO: 162) and EIVMTQSPATLSVSPGERATLSCRASQSVSRNLAWYQQKPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQHYGYSPVTFGQGTKLEIK (SEQ ID NO: 196).

[0527] VH For A The ABP specific to NTDNNLAVY (SEQ ID NO: 73) may comprise a VH sequence. The VH sequence may be selected from QVQLVQSGAEVKKPGASVKVSCKASGGTFSSATISWVRQAPGQGLEWMGWIYPNSGGTVYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAATEWLGVWGQGTTVTVSS (SEQ ID NO: 128), EVQLLQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWINPNSGGTISAPNFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARANWLDYWGQGTLVTVSS (SEQ ID NO: 129), EVQLLESGAEVKKPGASVKVSCKASGYTFTTYDLAWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARANWLDYWGQGTLVTVSS (SEQ ID NO: 130), QVQLVQSGAEVKKPGASVKVSCKSSGYSFDSYVVNWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDWVLDYWGQGTLVTVSS (SEQID NO: 131), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWMNPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGEWLDYWGQGTLVTVSS (SEQ ID NO: 132), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGWELGYWGQGTLVTVSS (SEQ ID NO: 133), QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYTINWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDFVGYDDWGQGTLVTVSS (SEQ ID NO:134)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGITWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDYGDLDYWGQGTLVTVSS (SEQID NO: 135)、QVQLVQSGAEVKKPGASVKVSCKASGGTFSNYILSWVRQAPGQGLEWMGWINPDSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGSYGMDVWGQGTTVTVSS (SEQ ID NO: 136)、QVQLVQSGAEVKKPGASVKVSCKASGYSFTRYNMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGYSGLDVWGKGTTVTVSS (SEQ ID NO: 137)、QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWINPNNGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDSGVGMDVWGQGTTVTVSS (SEQ ID NO: 138)、QVQLVQSGAEVKKPGASVKVSCKASGGTFNNYAFSWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGVAVASDYWGQGTLVTVSS (SEQ ID NO: 139)、QVQLVQSGAEVKKPGASVKVSCKASGYTFSSYNMHWVRQAPGQGLEWMGWINGNTGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGVNVDDFDYWGQGTLVTVSS (SEQ ID NO:140)、QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAFSWVRQAPGQGLEWMGWINPDTGYTRYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGDYTGNWYFDLWGRGTLVTVSS (SEQ ID NO:141)、EVQLLESGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWINPYSGGTNYAQKLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARANWLDYWGQGTLVTVSS (SEQ ID NO: 142)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGYTNYAQNLQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDQFYGGNSGGHDYWGQGTLVTVSS (SEQ ID NO: 143)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYNMHWVRQAPGQGLEWMGWMNPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREEDYWGQGTLVTVSS(SEQID NO: 144)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTRYTINWVRQAPGQGLEWMGWINPNSGGANYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGDWFDPWGQGTLVTVSS (SEQ ID NO: 145)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYLMHWVRQAPGQGLEWMGWISPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGDWFDPWGQGTLVTVSS (SEQ ID NO: 146)、QVQLVQSGAEVKKPGASVKVSCKASGYTFSDYYVHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGEWFDPWGQGTLVTVSS (SEQ ID NO: 147)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTTYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSDWFDPWGQGTLVTVSS (SEQID NO:148)、QVQLVQSGAEVKKPGASVKVSCKASGGTFSNYAINWVRQAPGQGLEWMGWISPYSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDSGSYFDYWGQGTLVTVSS (SEQ ID NO: 149)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYMHWVRQAPGQGLEWMGWIYPNTGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDYGGYVDYWGQGTLVTVSS (SEQ ID NO: 150)、EVQLLESGAEVKKPGASVKVSCKASGYTFTSYAMNWVRQAPGQGLEWMGWMNPNSGGTKYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREGPAALDVWGQGTLVTVSS (SEQ ID NO: 151)、QVQLVQSGAEVKKPGASVKVSCKASGYTLTSHLIHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARERRSGMDVWGQGTTVTVSS (SEQ ID NO: 152)、EVQLLESGAEVKKPGASVKVSCKASGYSFTDYIVHWVRQAPGQGLEWMGWINPYSGGTKYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARVLQEGMDVWGQGTLVTVSS (SEQ ID NO:153)、QVQLVQSGAEVKKPGASVKVSCKASGYTFSNFLINWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCASERELPFDIWGQGTMVTVSS (SEQ ID NO: 154)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYQMFWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAKGGGGYGMDVWGQGTTVTVSS (SEQ ID NO:155) QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAAMGIAVAGGMDVWGQGTLVTVSS (SEQ ID NO: 156), QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYHMHWVRQAPGQGLEWMGWIHPDSGGTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARNWNLDYWGQGTLVTVSS (SEQ ID NO: 157), QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCATYDDGMDVWGQGTTVTVSS (SEQ ID NO: 158), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYTVNWVRQAPGQGLEWMGWINPNSGGTKYAQNFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGGGGALDYWGQGTLVTVSS (SEQ ID NO: 159), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGMINPRDDTTDYARDFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCALSGNYYGMDVWGQGTTVTVSS (SEQ ID NO: 160), QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYYMHWVRQAPGQGLEWMGMINPSGGGTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGNPWELRLDYWGQGTLVTVSS (SEQ ID NO: 127) and QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSQYMHWVRQAPGQGLEWMGRIIPLLGIVNYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARDKNYYGMDVWGQGTTVTVSS (SEQID NO: 161).

[0528] VH-VL combination For A 01:01_NTDNNLAVY (SEQ ID NO: 73) is a specific ABP containing a specific VH sequence and a specific VL sequence. In some embodiments, for A... 01:01_NTDNNLAVY (SEQ ID NO: 73) has a specific ABP containing VH and VL sequences from scFvs named G2-P2E07, G2-P2E03, G2-P2A11, G2-P2C06, G2-P1G01, G2-P1C02, G2-P1H01, G2-P1B12, G2-P1B06, G2-P2H10, G2-P1H10, G2-P2C11, G2-P1C09, G2-P1A10, G2-P1B10, G2 -P1D07, G2-P1E05, G2-P1D03, G2-P1G12, G2-P2H11, G2-P1C03, G2-P1G07, G2-P1F12, G2-P1G03, G2-P2B08, G2-P2A10, G2-P2D04, G2-P1C06, G2-P2A09, G2-P1B08, G2-P1E03, G2-P2A03, G2-P2F01, G2-P1H11, or G2-P1D06. Specifically binds to A. The VH and VL sequences of the identified scFv of 01:01_NTDNNLAVY (SEQ ID NO: 73) are shown in Table 33. For clarity, each identified scFv hit is named with a clone name, and each row contains the CDR sequence for that specific clone name. For example, the scFv identified by clone name G2-P2E07 contains the VH sequence QVQLVQSGAEVKKPGASVKVSCKASGGTFSSATISWVRQAPGQGLEWMGWIYPNSGGTVYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAATEWLGVWGQGTTVTVSSAS (SEQ ID NO: 365) and the VL sequence DIQMTQSPSSLSASVGDRVTITCRASQSISTWLAWYQQKPGKAPKLLIYAASSLRSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYNTPYTFGQGTKLEIK (SEQ ID NO: 163).

[0529] receptor In the provided ABPs, such as the HLA-peptide ABP, the receptor is used. Receptors may include antigen receptors that specifically bind to the HLA-peptide targets disclosed herein, and other chimeric receptors. The receptor may be a T-cell receptor (TCR). The receptor may be a chimeric antigen receptor (CAR).

[0530] TCRs can be soluble or membrane-bound. Among antigen receptors are functional non-TCR antigen receptors, such as chimeric antigen receptors (CARs). Cells expressing the receptors and their use in adoptive cell therapies, such as those treating diseases and conditions associated with HLA-peptide expression, including cancer, are also provided.

[0531] Exemplary antigen receptors (including CARs) and methods for engineering and introducing such receptors into cells include those described in the following documents: for example, International Patent Application Publications Nos. WO200014257, WO2013126726, WO2012 / 129514, WO2014031687, WO2013 / 166321, WO2013 / 071154, and WO2013 / 123061; and U.S. Patent Application Publications Nos. US2002131960, US2013287748, and US20130. 149337; U.S. Patents 6,451,995, 7,446,190, 8,252,592, 8,339,645, 8,398,282, 7,446,179, 6,410,319, 7,070,995, 7,265,209, 7,354,762, 7,446,191, 8,324,353 and 8,479,118; and European Patent Application EP2537416, and / or those described in the following documents: Sadelain et al., Cancer Discov. April 2013; 3(4): 388-398; Davila et al. (2013) PLoS ONE 8(4): e61338; Turtle et al., Curr. Opin. Immunol., October 2012; 24(5): 633-39; Wu et al., Cancer, March 2012 18(2): 160-75. In some respects, antigen receptors include the CARs described in U.S. Patent No. 7,446,190 and those described in International Patent Application Publication No. WO / 2014055668 A1. Exemplary CARs include any of the CARs described in the aforementioned publications, such as WO2014031687, U.S. Patent No. 8,339,645, U.S. Patent No. 7,446,179, US 2013 / 0149337, U.S. Patent No. 7,446,190, U.S. Patent No. 8,389,282, etc., wherein the antigen-binding portion (e.g., scFv) is replaced by an antibody (e.g., the antibody provided herein).

[0532] Chimeric receptors include chimeric antigen receptors (CARs). Chimeric receptors, such as CARs, generally include an extracellular antigen-binding domain comprising, being, or contained within one of the provided anti-HLA-peptide ABPs (such as anti-HLA-peptide antibodies). Therefore, the extracellular portion of a chimeric receptor (e.g., a CAR) typically contains one or more HLA-peptide-ABPs, such as one or more antigen-binding fragments, domains, or portions, or one or more antibody variable domains, and / or antibody molecules (as described herein). In some embodiments, the CAR contains an HLA-peptide-binding portion or a portion of an ABP (e.g., an antibody) molecule, such as a variable heavy (VH) chain region and / or a variable light (VL) chain region of an antibody, for example, an scFv antibody fragment.

[0533] TCR On the one hand, the ABPs provided herein, such as ABPs that specifically bind to the HLA-peptide targets disclosed herein, contain T-cell receptors (TCRs). TCRs can be isolated and purified.

[0534] In most T cells, the TCR is a heterodimeric polypeptide with alpha (α) and beta (β) chains encoded by TRA and TRB, respectively. The α chain typically contains an α variable region encoded by TRAV, an α linker region encoded by TRAJ, and an α constant region encoded by TRAC. The β chain typically contains a β variable region encoded by TRBV, a β diversity region encoded by TRBD, a β linker region encoded by TRBJ, and a β constant region encoded by TRBC. The TCR-α chain is generated via VJ recombination, while the β chain receptor is generated via V(D)J recombination. Additional diversity in the TCR arises from linker diversity. Several bases can be deleted and several bases added (called N and P nucleotides) at each linker. In most T cells, the TCR contains both γ and δ chains. The TCR γ chain is generated through VJ recombination, while the TCR δ chain is generated through V(D)J recombination (Kenneth Murphy, Paul Travers, and Mark Walport, Janeway's Immunology 7th ed., Garland Science, 2007, which is incorporated herein by reference in its entirety). The antigen-binding site of a TCR typically contains six complementarity-determining regions (CDRs). The α chain contributes three CDRs: αCDR1, αCDR2, and αCDR3. The β chain also provides three CDRs: βCDR1, βCDR2, and βCDR3. αCDR3 and βCDR3 are the regions most affected by V(D)J recombination and are responsible for most variations in the TCR repertoire.

[0535] TCRs can specifically recognize HLA-peptide targets, such as those disclosed in Tables A, A1, or A2; therefore, a TCR can be an ABP that specifically binds to HLA-peptides. TCRs can be soluble, such as antibodies similar to those secreted by B cells. TCRs can also be membrane-bound, for example, binding to cells such as T cells or natural killer (NK) cells. Therefore, TCRs can be used in the context of soluble antibodies and / or membrane-bound CARs.

[0536] Any TCR disclosed herein may include an α-variable region, an α-connection region, optionally an α-constant region, a β-variable region, optionally a β-diversity region, a β-connection region, and optionally a β-constant region.

[0537] In some implementations, the TCR or CAR is a recombinant TCR or CAR. A recombinant TCR or CAR may contain any TCR identified herein, but may contain one or more modifications. Exemplary modifications, such as amino acid substitutions, are described herein. The amino acid substitutions described herein are referred to in the IMGT nomenclature and the amino acid numbers available at www.imgt.org.

[0538] Recombinant TCRs or CARs can be human TCRs or CARs containing complete human sequences, such as natural human sequences. Recombinant TCRs or CARs may retain their natural human variable domain sequences but contain modifications to the α-constant region, β-constant region, or both. Such modifications to the TCR constant region can, for example, drive preferential pairing of exogenous TCR strands to improve TCR assembly and expression in TCR gene therapy.

[0539] In some implementations, the α and β constant regions are modified by replacing the mouse constant region sequence with a whole human constant region sequence. This “mouse-derived” TCR and its preparation method are described in Cancer Res. 2006 Sep 1;66(17):8878-86, which is incorporated herein by reference in its entirety.

[0540] In some embodiments, the α and β constant regions are modified by substituting one or more amino acids into the human TCR α constant (TRAC) region, the TCR β constant (TRBC) region, or the TRAC and TRAB regions, i.e., replacing human residues with mouse residues ((humanmouse amino acid exchange)). One or more amino acid substitutions in the TRAC region may include: a Ser substitution at residue 90, an Asp substitution at residue 91, a Val substitution at residue 92, a Pro substitution at residue 93, or any combination thereof. One or more amino acid substitutions in the human TRBC region may include: a Lys substitution at residue 18, an Ala substitution at residue 22, an Ile substitution at residue 133, a His substitution at residue 139, or any combination thereof. Such targeted amino acid substitutions are described in J Immunol 2010 1 June, 184 (11) 6223-6231, which is incorporated herein by reference in its entirety.

[0541] In some implementations, human TRAC contains an Asp substitution at residue 210, while human TRBC contains a Lys substitution at residue 134. Such substitutions can promote the formation of salt bridges between the α and β chains and disulfide bonds between the TCR chains. These targeted substitutions are described in J Immunol 2010 1 June; 184(11) 6232-6241, which is incorporated herein by reference in its entirety.

[0542] In some implementations, the human TRAC region and the human TRBC region are modified to contain an introduced cysteine residue, which can improve the preferential pairing of exogenous TCR chains by forming additional disulfide bonds. For example, the human TRAC may contain a Cys substitution at residue 48, and the human TRBC may contain a Cys substitution at residue 57, as described in the following references: Cancer Research, April 15, 2007; 67(8):3898-903 and Blood, March 15, 2007; 109(6):2331-8; which are incorporated herein by reference in their entirety.

[0543] Recombinant TCRs or CARs may contain additional modifications to the α and β chains.

[0544] In some implementations, the α and β chains are modified by linking the extracellular domains of the α and β chains to the intact human CD3ζ ((CD3-zeta)) molecule. Such modifications are described in the following references: J Immunol 1 June 2008, 180(11) 7736-7746; Gene Ther. Aug 2000; 7(16): 1369-77; and The Open Gene Therapy Journal, 2011, 4: 11-22 (the references are hereby incorporated in their entirety by reference).

[0545] In some implementations, the α chain is modified by introducing hydrophobic amino acid substitutions into the transmembrane region of the α chain, as described in JImmunol 1 June 2012; 188(11) 5538-5546; Gene Ther. 8 August 2000; 7(16):1369-77; and The Open Gene Therapy Journal, 2011, 4: 11-22 (the entire references are hereby incorporated by reference).

[0546] The α or β chain can be modified by altering any N-glycosylation site in the amino acid sequence, as described in J Exp Med. 2009 Feb 16;206(2): 463–475 (which is hereby incorporated in its entirety by reference).

[0547] The α and β chains may each contain a dimerizing domain, such as a heterodimerizing domain. Such heterodimerizing domains are known in the art to be leucine zippers (5H3 domains), hydrophobic proline-rich inverse domains, or other similar forms. In one instance, the α and β chains can be modified by introducing 30-mer segments into the carboxyl ends of the α and β extracellular domains, wherein said segments selectively associate to form stable leucine zippers. This modification is described in: PNAS November 22, 1994, 91(24) 11408-11412; https: / / doi.org / 10.1073 / pnas.91.24.11408; which is incorporated herein by reference in its entirety.

[0548] The TCRs identified in this paper may be modified to include mutations that result in increased affinity or half-life, such as those described in WO2012 / 013913, which are incorporated herein by reference in their entirety.

[0549] Recombinant TCRs or CARs can be single-stranded TCRs (scTCRs). Such scTCRs may include an α-strand variable region sequence fused to the N-terminus of the extracellular sequence of the α-strand constant region of the TCR, a TCR β-strand variable region fused to the N-terminus of the extracellular sequence of the β-strand constant region of the TCR, and a linker sequence connecting the C-terminus of the α-strand to the N-terminus of the β-strand, or vice versa. In some embodiments, the extracellular sequences of the α-strand and β-strand constant regions of the scTCR are linked by disulfide bonds. In some embodiments, the length of the linker sequence and the position of the disulfide bonds cause the variable region sequences of the α-strand and β-strand to be substantially oriented to each other as in the native αβ T cell receptor. An exemplary scTCR is described in U.S. Patent No. 7,569,664, which is incorporated herein by reference in its entirety.

[0550] In some cases, the variable region of the scTCR can be covalently linked via a short peptide linker, as described in Gene Therapy, Vol. 7, pp. 1369–1377 (2000). The short peptide linker may be serine-rich or glycine-rich. For example, the linker may be (Gly4Ser)3 (SEQ ID NO: 366), as described in Cancer Gene Therapy (2004) 11, 487–496 (which is incorporated herein by reference in its entirety).

[0551] Recombinant TCRs or their antigen-binding fragments can be expressed as fusion proteins. For example, a TCR or its antigen-binding fragment can be fused with a toxin. Such fusion proteins are described in Cancer Res. 2002, March 15; 62(6):1757-60. A TCR or its antigen-binding fragment can also be fused with the Fc region of an antibody. Such fusion proteins are described in J Immunol, May 1, 2017, 198 ((1 Supplement)) 120.9.

[0552] In some embodiments, recombinant receptors such as TCRs or CARs (e.g., their antibody portions) also include a spacer, which may be or contain at least a portion of an immunoglobulin constant region or a variant or modified form thereof, such as a hinge region, for example, the IgG4 hinge region and / or CH1 / CL and / or Fc region. In some embodiments, the constant region or portion is human IgG, such as IgG4 or IgG1. In some aspects, a portion of the constant region serves as a spacer between an antigen recognition component (e.g., scFv) and a transmembrane domain. The length of the spacer can provide increased cellular reactivity after antigen binding compared to the absence of a spacer. In some instances, the length of the spacer is about 12 amino acids, or not more than 12 amino acids. Exemplary spacers comprise those having at least about 10 to 229 amino acids, about 10 to 200 amino acids, about 10 to 175 amino acids, about 10 to 150 amino acids, about 10 to 125 amino acids, about 10 to 100 amino acids, about 10 to 75 amino acids, about 10 to 50 amino acids, about 10 to 40 amino acids, about 10 to 30 amino acids, about 10 to 20 amino acids, or about 10 to 15 amino acids, and those comprising any integer between the endpoints of any of the listed ranges. In some embodiments, the spacer region has about 12 or fewer amino acids, about 119 or fewer amino acids, or about 229 or fewer amino acids. Exemplary spacers comprise individual IgG4 hinges, IgG4 hinges connected to the CH2 and CH3 domains, or IgG4 hinges connected to the CH3 domain. Exemplary spacers include, but are not limited to, those described in the following documents: Hudecek et al. (2013) Clin. Cancer Res., 19:3153, or International Patent Application Publication No. WO2014031687. In some embodiments, the constant region or portion is IgD.

[0553] The antigen recognition domain of a receptor (such as a TCR or CAR) can be linked to one or more intracellular signaling components, such as, in the ca...

Claims

1. An isolated antigen-binding protein (ABP) that specifically binds to a human leukocyte antigen (HLA)-peptide target, wherein the HLA-peptide target comprises an HLA-restricted peptide complexed with an HLA class I molecule, wherein the HLA-restricted peptide is located in the peptide-binding groove of the α1 / α2 heterodimeric portion of the HLA class I molecule, wherein the HLA class I molecule is an HLA subtype B. 35:01 (Reference sequence: MGSHSMRYFYTAMSRPGRGEPRFIAVGYVDDTQFVRFDSDAASPRTEPRAPWIEQEGPEYWDRNTQIFKTNTQTYRESLRNLRGYYNQSEAGSHIIQRMYGCDLGPDGRLLRGHDQSAYDGKDYIALNEDLSSWTAADTAAQITQRKWEAARVAEQLRAYLEGLCVEWLRRYLENGKETLQRADPPKTHVTHHPVSDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDRTFQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLR (SEQ ID NO:1)), and the HLA-restricted peptide comprises the sequence EVDPIGHVY (SEQ ID NO: 2), and wherein the ABP binds to any one or more of the following: a. Any one or more of amino acid positions 2-9 of the restricted peptide EVDPIGHVY (SEQ ID NO: 2); b. HLA subtype B The amino acid positions of the α1 helix of 35:01 are any one or more of 50, 54, 55, 57, 61, 62, 74, 81, 82, and 85; and c. HLA subtype B The amino acid positions 147 and 148 of the α2 helix of 35:

01.

2. The isolated ABP as claimed in claim 1, wherein the ABP is bound to any one or more of amino acid positions 2-8 of the restriction peptide EVDPIGHVY (SEQ ID NO: 2).

3. The isolated ABP as claimed in claim 1, wherein the ABP is bound to any one or more of amino acid positions 5-9 of the restriction peptide EVDPIGHVY (SEQ ID NO: 2).

4. The isolated ABP according to any one of claims 1 to 3, wherein the HLA class I molecule is HLA subtype B. 35:01, and the HLA-restricted peptide consists of the sequence EVDPIGHVY (SEQ ID NO: 2).

5. The isolated ABP according to any one of claims 1-4, wherein the ABP comprises CDR-H3, the CDR-H3 comprising a sequence selected from: CARDGVRYYGMDVW (SEQ ID NO: 3), CARDGVRGYDRSAGYW (SEQ ID NO: 4), CARDHDYGDYGEYFQHW (SEQ ID NO: 5), CARDSWYCSSTSCGVNWFDPW (SEQ ID NO: 6), CARDVNWNDGPYFDYW (SEQ ID NO: 7), CATPTNSGYYGPYYYYGMDVW (SEQ ID NO: 8), CARDVMDVW (SEQ ID NO: 9), CAREGYGMDVW (SEQ ID NO: 10), CARDNGVGVDYW (SEQ ID NO: 11), CARGIADSGSYYGNGRDYYYGMDVW (SEQ ID NO: 12), CARDGDYYFDYW (SEQ ID NO: 13), CARDGVRYYGMDVW (SEQ ID NO: 14), CARDGVRYYGMDVW (SEQ ID NO: 15), CARDGVRYYGMDVW (SEQ ID NO: 16), CARDGVRYYGMDVW (SEQ ID NO: 17), CARDGVRYYGMDVW (SEQ ID NO: 18), CARDGVRYYGMDVW (SEQ ID NO: 19), CARDGVRYYGMDVW (SEQ ID NO: 10), CARDGVRYYGMDVW (SEQ ID NO: 11), CARDGVRYYGMDVW (SEQ ID NO: 12), CARDGVRYYGMDVW (SEQ ID NO: 13), CARDGVRYYGMDVW (SEQ ID NO: 14), CARDGVRYYGMDVW (SEQ ID NO: 15), CARDGVRYYGMDVW (SEQ ID NO: 16), CARDGVRYYGMD 13), CARDGTRYYGMDVW (SEQ ID NO: 14), CARDVVANFDYW (SEQ ID NO: 15), CARGHSSGWYYYYGMDVW (SEQ ID NO: 16), CAKDLGSYGGYYW (SEQ ID NO: 17), CARSWFGGFNYHYYGMDVW (SEQ ID NO: 18), CARELPIGYGMDVW (SEQ ID NO: 19) and CARGGSYYYYGMDVW (SEQ ID NO: 20).

6. The isolated ABP according to any one of claims 1-5, wherein the ABP comprises CDR-L3, the CDR-L3 comprising a sequence selected from: CMQGLQTPITF (SEQ ID NO: 21), CMQALQTPPTF (SEQ ID NO: 22), CQQAISFPLTF (SEQ ID NO: 23), CQQANSFPLTF (SEQ ID NO: 24), CQQANSFPLTF (SEQ ID NO: 24), CQQSYSIPLTF (SEQ ID NO: 25), CQQTYMMPYTF (SEQ ID NO: 26), CQQSYITPWTF (SEQ ID NO: 27), CQQSYITPYTF (SEQ ID NO: 28), CQQYYTTPYTF (SEQ ID NO: 29), CQQSYSTPLTF (SEQ ID NO: 30), CMQALQTPLTF (SEQ ID NO: 31), CQQYGSWPRTF (SEQ ID NO: 32), CQQSYSTPVTF (SEQ ID NO: 33), CMQALQTPYTF (SEQ ID NO: 34), CQQANSFPFTF (SEQ ID NO: 35), CMQALQTPLTF (SEQ ID NO: 31), and CQQSYSTPLTF (SEQ ID NO: 30).

7. The isolated ABP as claimed in any one of claims 1-6, wherein the ABP comprises CDR-H3 and CDR-L3 from scFv, and the scFv is named G5_P7_E7, G5_P7_B3, G5_P7_A5, G5_P7_F6, G5-P1B12, G5-P1C12, G5-P1-E05, G5-P3G01, G5-P3G08, G5-P4B02, G5-P4E04, G5R4-P1D06, G5R4-P1H11, G5R4-P2B10, G5R4-P2H8, G5R4-P3G05, G5R4-P4A07 or G5R4-P4B01.

8. The isolated ABP as claimed in any one of claims 1-7, wherein the ABP comprises all three heavy chain CDRs and all three light chain CDRs from the scFv, the scFv being named G5_P7_E7, G5_P7_B3, G5_P7_A5, G5_P7_F6, G5-P1B12, G5-P1C12, G5-P1-E05, G5-P3G01, G5-P3G08, G5-P4B02, G5-P4E04, G5R4-P1D06, G5R4-P1H11, G5R4-P2B10, G5R4-P2H8, G5R4-P3G05, G5R4-P4A07, or G5R4-P4B01.

9. An isolated ABP according to any one of claims 1 - 8, wherein the ABP comprises a VH sequence selected from QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGIINPRSGSTKYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGVRYYGMDVWGQGTTVTVSS (SEQ ID NO: 36), QVQLVQSGAEVKKPGSSVKVSCKASGYTFTSHDINWVRQAPGQGLEWMGWMNPNSGDTGYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGVRGYDRSAGYWGQGTLVIVSS (SEQ ID NO: 37), EVQLLESGGGLVKPGGSLRLSCAASGFSFSSYWMSWVRQAPGKGLEWISYISGDSGYTNYADSVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCASHDYGDYGEYFQHWGQGTLVTVSS (SEQ ID NO: 38), EVQLLQSGGGLVQPGGSLRLSCAASGFTFSNSDMNWVRQAPGKGLEWVAYISSGSSTIYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARVSWYCSSTSCGVNWFDPWGQGTLVTVSS (SEQ ID NO: 39), EVQLLESGGGLVQPGGSLRLSCAASGFTFSNSDMNWVRQAPGKGLEWVASISSSGGYINYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKVNWNDGPYFDYWGQGTLVTVSS (SEQID NO: 40), QVQLVQSGAEVKKPGSSVKVSCKASGGTFSNFGVSWLRQAPGQGLEWMGGIIPILGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCATPTNSGYYGPYYYYGMDVWGQGTTVTVSS (SEQ ID NO:41), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYNMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDVMDVWGQGTTVTVSS (SEQID NO: 42)、QVQLVQSGAEVKKPGASVKVSCKASGGTFSGYLVSWVRQAPGQGLEWMGWINPNSGGTNTAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREGYGMDVWGQGTTVTVSS (SEQ ID NO: 43)、QVQLVQSGAEVKKPGASVKVSCKASGYIFRNYPMHWVRQAPGQGLEWMGWINPDSGGTKYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDNGVGVDYWGQGTLVTVSS (SEQ ID NO: 44)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWMNPNIGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGIADSGSYYGNGRDYYYGMDVWGQGTTVTVSS(SEQ ID NO: 45)、QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYGISWVRQAPGQGLEWMGWINPNSGVTKYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGDYYFDYWGQGTLVTVSS (SEQ ID NO: 46)、QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQAPGQGLEWMGWINPNSGDTKYSQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARDGTRYYGMDVWGQGTTVTVSS (SEQ ID NO: 47)、EVQLLESGGGLVKPGGSLRLSCAASGFTFSDYYMSWVRQAPGKGLEWVSYISSSSSYTNYADSVKGRFTISRDDSKNTLYLQMNSLKTEDTAVYYCARDVVANFDYWGQGTLVTVSS (SEQ ID NO: 48)、QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWMNPDSGSTGYAQRFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARGHSSGWYYYYGMDVWGQGTTVTVSS (SEQ ID NO:49), EVQLLESGGGLVQPGGSLRLSCAASGFTFTSYSMHWVRQAPGKGLEWVSSITSFTNTMYYADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCAKDLGSYGGYYWGQGTLVTVSS (SEQ ID NO: 50), QVQLVQSGAEVKKPGASVKVSCKASGYTFTNYYMHWVRQAPGQGLEWMGIINPSGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARSWFGGFNYHYYGMDVWGQGTTVTVSS (SEQ ID NO: 51), QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGWMNPNSGNTGYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARELPIGYGMDVWGQGTTVTVSS (SEQ ID NO: 52) and QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIVGTANYAQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCARGGSYYYYGMDVWGQGTTVTVSS (SEQ ID NO: 53).

10. The isolated ABP according to any one of claims 1-9, wherein the ABP comprises a VL sequence selected from DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSYRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQGLQTPITFGQGTRLEIK (SEQ ID NO: 54), DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSSRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPPTFGPGTKVDIK (SEQ ID NO: 55), DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQAISFPLTFGQSTKVEIK (SEQ ID NO:56), DIQMTQSPSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYSASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPLTFGGGTKVEIK (SEQ ID NO: 57), DIQMTQSPSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPLTFGGGTKVEIK (SEQ ID NO: 58), DIQMTQSPSSLSASVGDRVTITCRASQSISSWLAWYQQKPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSIPLTFGGGTKVEIK (SEQ ID NO: 59), DIQMTQSPSSLSASVGDRVTITCRASQGISNYLNWYQQKPGKAPKLLIYYASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQTYMMPYTFGQGTKVEIK (SEQ ID NO:60)、DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYGASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYITPWTFGQGTKVEIK(SEQ ID NO: 61)、DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYITPYTFGQGTKLEIK (SEQ ID NO: 62)、DIVMTQSPDSLAVSLGERATINCKTSQSVLYRPNNENYLAWYQQKPGQPPKLLIYQASIREPGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQYYTTPYTFGQGTKLEIK (SEQ ID NO: 63)、DIQMTQSPSSLSASVGDRVTITCRASQSISRFLNWYQQKPGKAPKLLIYGASRPQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGQGTKVEIK(SEQ ID NO: 64)、DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSHRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPLTFGGGTKVEIK (SEQ ID NO: 65)、EIVMTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQKPGQAPRLLIYAASARASGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQYGSWPRTFGQGTKVEIK (SEQ ID NO: 66)、DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYGASRLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPVTFGQGTKVEIK (SEQID NO: 67)、DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPYTFGQGTKVEIK (SEQ IDNO: 68), DIQMTQSPSSLSASVGDRVTITCQASEDISNHLNWYQQKPGKAPKLLIYDALSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPFTFGPGTKVDIK (SEQ ID NO: 69), DIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYLDWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCMQALQTPLTFGQGTKVEIK (SEQ ID NO: 70) and DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQKPGKAPKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSYSTPLTFGGGTKVEIK (SEQ ID NO: 71).

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Patent Citations

Methods and materials for high gradient magnetic separation of biological materials

Trifunctional antibody-like compounds as a combined diagnostic and therapeutic agent

Identification and expression of insect steroid receptor DNA sequences

Constitutive expression of costimulatory ligands on adoptively transferred T lymphocytes

Halogenated pyranthrone and process of making same