Antibody drug conjugates comprising TCR-vbeta specific therapeutic molecules and uses thereof

Abstract

Provided are immunoconjugates comprising an antibody or antigen binding fragment to a Vβ region of a T cell receptor and a chemotherapeutic drug or cytotoxic agent, and composition thereof. Also provided are methods for treating a disease such as cancer or an autoimmune disease using immunoconjugates of the present disclosure.

Description

ANTIBODY DRUG CONJUGATES COMPRISING TCR-VBETA SPECIFIC THERAPEUTIC MOEECUEES AND USES THEREOFREFERENCE TO SEQUENCE LISTING SUBMITTED ELECTRONICALLY

[0001] The content of the electronically submitted sequence listing (Name:2681_160PC02_Sequencelisting_ST26.xml; Size: 611,981 bytes; and Date of Creation: July 2, 2025), filed with the application, is incorporated herein by reference in its entirety.CROSS REFERENCE TO RELATED APPLICATIONS

[0002] The present application claims the priority benefit of U.S. Provisional Application No. 63 / 667,646, filed July 3, 2024, and U.S. Provisional Application No. 63 / 799,639, filed May 4, 2025, each of which are hereby incorporated by reference in their entirety.FIELD

[0003] According to various aspects, the present disclosure relates to an antibody drug conjugate (i.e., immunoconjugate) comprising an antibody or antigen-binding fragment comprising a domain that binds to a VP region of a T-cell receptor. The disclosure also relates to methods of treating a disease in a subject using such binding molecules.BACKGROUND

[0004] Autoimmune diseases are caused by dysfunctional T cells (Haroon N et al., Arthritis Rheum. 2013 October; 65(10):2645-54, Duarte J. et al., PloS One 2010 May 10; 5(5):el 0558; Konig M. et al., Front Immunol 2016 Jan. 25; 7: 11). Dysfunctional T cells afflict a larger population than those solely affected by autoimmune diseases and encompass individuals having cancer and related T cell malignancies. Lymphocyte malignancies, including lymphocytic leukemias and lymphomas, can largely be divided into those which are derived from either T cells or B cells. T cell malignancies are a clinically and biologically heterogeneous group of disorders, together comprising 10-20% of non-Hodgkin's lymphomasand 20% of acute leukemia (see, e.g., cancer.org / cancer / non-hodgkin-lymphoma / about / t-cell- lymphoma.html).

[0005] A difficulty in the development of a treatment for T cell disorders and T cell malignancies is the considerable overlap in marker expression of clonal and normal T-cells, with no single antigen clearly able to identify clonal (malignant) cells. Because T cell disorders and T cell malignancies typically have no single antigen to clearly identify clonal (malignant) T cells, use of an immunconjugate comprising a chemotherapeutic drug / cytotoxic agent and a TCRVB antibody or antigen-binding fragments thereof should allow for specific targeting and eradicatation of the clonal (malignant) T cells..

[0006] A need exists for targeting T cell mediated diseases and T cell malignancies, with high specificity and efficacy in the elimination of abnormal T cells.BRIEF SUMMARY

[0007] The present disclosure provides an immunoconjugate having the formula (A) - (L) - (C), wherein:(A) is an antibody or antigen binding fragment thereof that specifically binds to TCRVP; (L) is a linker; and (C) is a cytotoxic agent, wherein said linker (L) links (A) to (C).

[0008] In some aspects, the (A) antibody or antigen binding fragment comprises (a) (i) a variable chain (VH) comprising CDR1, CDR2, and CDR3 according to SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, respectively; (b) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO: 370, SEQ ID NO: 681, and SEQ ID NO: 372, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:418, SEQ ID NO:419, SEQ ID NO:420, respectively, SEQ ID NO: 682, SEQ ID NO: 419, SEQ ID NO: 420, respectively, SEQ ID NO: 682, SEQ ID NO: 683, SEQ ID NO: 420, respectively, or SEQ ID NO: 418, SEQ ID NO: 684, SEQ ID NO: 420, respectively; (c) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:373, SEQ ID NO:374, and SEQ ID NO:375 respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:421, SEQ ID NO:422, SEQ ID NO:423, respectively; (d) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:376, SEQ ID NO:377, and SEQ ID NO:378,respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:424, SEQ ID NO:425, SEQ ID NO:426, respectively; (e) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:379, SEQ ID NO:380, and SEQ ID NO:381 respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:427, SEQ ID NO:428, SEQ ID NO:429, respectively; (f) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:382, SEQ ID NO:383, and SEQ ID NO:384, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:430, SEQ ID NO:431, SEQ ID NO:432, respectively; (g) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:385, SEQ ID NO:386, and SEQ ID NO:387, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:433, SEQ ID NO:434, SEQ ID NO:435, respectively; (h) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:388, SEQ ID NO:389, and SEQ ID NO:390, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:436, SEQ ID NO:437, SEQ ID NO:438, respectively; (i) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:391, SEQ ID NO:392, and SEQ ID NO:393 respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:439, SEQ ID NO:440, SEQ ID NO:441, respectively; (j) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:394, SEQ ID NO:395, and SEQ ID NO:396, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:442, SEQ ID NO:443, SEQ ID NO:444, respectively; (k) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:397, SEQ ID NO:398, and SEQ ID NO:399, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:445, SEQ ID NO:446, SEQ ID NO:447, respectively; (1) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:400, SEQ ID NO:401, and SEQ ID NO:402, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:448, SEQ ID NO:449, SEQ ID NO:450, respectively; (m) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:403, SEQ ID NO:404, and SEQ ID NO:405 respectively, and / or (ii) a variable light chain(VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:451, SEQ ID NO:452, SEQ ID NO:453, respectively; (n) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:406, SEQ ID NO:407, and SEQ ID NO:408, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:454, SEQ ID NO:455, SEQ ID NO:456, respectively; (o) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:409, SEQ ID NO:410, and SEQ ID NO:411, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:457, SEQ ID NO:458, SEQ ID NO:459, respectively; (p) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:412, SEQ ID NO:413, and SEQ ID NO:414, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:460, SEQ ID NO:461, SEQ ID NO:462, respectively; (q) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:415, SEQ ID NO:416, and SEQ ID NO:417, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:463, SEQ ID NO:464, SEQ ID NO:465, respectively; (r) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:584, SEQ ID NO:585, and SEQ ID NO:586, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:596, SEQ ID NO:597, SEQ ID NO:598, respectively; (s) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:587, SEQ ID NO:588, and SEQ ID NO:589, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:599, SEQ ID NO:600, SEQ ID NO:601, respectively; (t) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:590, SEQ ID NO:591, and SEQ ID NO:592, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:602, SEQ ID NO:603, SEQ ID NO:604, respectively; (u) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:593, SEQ ID NO:594, and SEQ ID NO:595, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:605, SEQ ID NO: 606, SEQ ID NO: 607, respectively, or SEQ ID NO: 608, SEQ ID NO: 609, SEQ ID NO: 610, respectively; or (v) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:675, SEQ ID NO:676, and SEQ ID NO:677, respectively, and / or(ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO: 678, SEQ ID NO:679, SEQ ID NO:680, respectively.

[0009] The present disclosure also provides an immunoconjugate having the formula (Al) - (A2) - (L) - (C), wherein (Al) is an antibody or antigen binding fragment thereof that specifically binds to TCRVP, (A2) is an antibody or antigen binding fragment thereof that specifically binds to TCRVP; (L) is a linker; and (C) is a cytotoxic agent, wherein said linker (L) links (A2) to (C).

[0010] In some aspects, the (A2) antibody or antigen binding fragment comprises (a) (i) a variable chain (VH) comprising CDR1, CDR2, and CDR3 according to SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, respectively; (b) (i) a vailable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO: 370, SEQ ID NO: 681, and SEQ ID NO: 372, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:418, SEQ ID NO:419, SEQ ID NO:420, respectively, SEQ ID NO: 682, SEQ ID NO: 419, SEQ ID NO: 420, respectively, SEQ ID NO: 682, SEQ ID NO: 683, SEQ ID NO: 420, respectively, or SEQ ID NO: 418, SEQ ID NO: 684, SEQ ID NO: 420, respectively; (c) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:373, SEQ ID NO:374, and SEQ ID NO:375 respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:421, SEQ ID NO:422, SEQ ID NO:423, respectively; (d) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:376, SEQ ID NO:377, and SEQ ID NO:378, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:424, SEQ ID NO:425, SEQ ID NO:426, respectively; (e) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:379, SEQ ID NO:380, and SEQ ID NO:381 respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:427, SEQ ID NO:428, SEQ ID NO:429, respectively; (f) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:382, SEQ ID NO:383, and SEQ ID NO:384, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:430, SEQ ID NO:431, SEQ ID NO:432, respectively; (g) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ IDNO:385, SEQ ID NO:386, and SEQ ID NO:387, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:433, SEQ ID NO:434, SEQ ID NO:435, respectively; (h) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:388, SEQ ID NO:389, and SEQ ID NO:390, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:436, SEQ ID NO:437, SEQ ID NO:438, respectively; (i) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:391, SEQ ID NO:392, and SEQ ID NO:393 respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:439, SEQ ID NO:440, SEQ ID NO:441, respectively; (j) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:394, SEQ ID NO:395, and SEQ ID NO:396, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:442, SEQ ID NO:443, SEQ ID NO:444, respectively; (k) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:397, SEQ ID NO:398, and SEQ ID NO:399, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:445, SEQ ID NO:446, SEQ ID NO:447, respectively; (1) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:400, SEQ ID NO:401, and SEQ ID NO:402, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:448, SEQ ID NO:449, SEQ ID NO:450, respectively; (m) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:403, SEQ ID NO:404, and SEQ ID NO:405 respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:451, SEQ ID NO:452, SEQ ID NO:453, respectively; (n) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:406, SEQ ID NO:407, and SEQ ID NO:408, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:454, SEQ ID NO:455, SEQ ID NO:456, respectively; (o) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:409, SEQ ID NO:410, and SEQ ID NO:411, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:457, SEQ ID NO:458, SEQ ID NO:459, respectively; (p) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:412, SEQ ID NO:413, and SEQ IDNO:414, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:460, SEQ ID NO:461, SEQ ID NO:462, respectively; (q) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:415, SEQ ID NO:416, and SEQ ID NO:417, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:463, SEQ ID NO:464, SEQ ID NO:465, respectively; (r) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:584, SEQ ID NO:585, and SEQ ID NO:586, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:596, SEQ ID NO:597, SEQ ID NO:598, respectively; (s) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:587, SEQ ID NO:588, and SEQ ID NO:589, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:599, SEQ ID NO:600, SEQ ID NO:601, respectively; (t) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:590, SEQ ID NO:591, and SEQ ID NO:592, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:602, SEQ ID NO:603, SEQ ID NO:604, respectively; (u) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:593, SEQ ID NO:594, and SEQ ID NO:595, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:605, SEQ ID NO: 606, SEQ ID NO: 607, respectively, or SEQ ID NO: 608, SEQ ID NO: 609, SEQ ID NO: 610, respectively; or (v) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:675, SEQ ID NO:676, and SEQ ID NO:677, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO: 678, SEQ ID NO:679, SEQ ID NO:680, respectively..

[0011] In some aspects, the invention provides an immunoconjugate, wherein (a) the variable heavy chain (VH) comprises any one of SEQ ID NOs: 228-295, 559-569, 632-650, and 685-700; and / or (b) the variable heavy light chain (VL) comprises any one of SEQ ID NOs: 296-369, 570-583, 652-671, and 701-716. In some aspects, the antibody or antigen binding fragment thereof that specifically binds to VP2 comprises: (a) the variable heavy chain (VH) comprises CDR1, CDR2 and CDR3 according to SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12; and / or (b) the variable light chain (VL) comprises CDR1, CDR2 and CDR3 according to SEQ ID NO: 13, SEQ ID NO: 14, and SEQ ID NO: 15.

[0012] In some aspects, the invention provides an immunoconjugate, wherein the antibody or antigen fragment thereof that specifically binds to TCRVP binds to VP2 comprises: (a) the variable heavy chain (VH) comprises SEQ ID NO: 230; and (b) the variable light chain (VL) comprises SEQ ID NO: 299.

[0013] In some aspects, the linker (L) is selected from the group consisting of a cleavable linker, a non-cleavable linker, a hydrophilic linker, and a dicarboxylic acid based linker. In some aspects, the linker is selected from the group consisting: 7V-succinimidyl 4-(2- pyridyldithiojpentanoate (SPP) or -succinimidyl 4-(2-pyridyldithio)-2-sulfopentanoate (sulfo-SPP); 7V-succinimidyl 4-(2-pyridyldithio)butanoate (SPDB) or 7V-succinimidyl 4-(2- pyridyldithio)-2-sulfobutanoate (sulfo-SPDB); 7V-succinimidyl 4-(maleimidomethyl) cyclohexanecarboxylate (SMCC); 7V-sulfosuccinimidyl 4-(maleimidomethyl) cyclohexanecarboxylate (sulfoSMCC); 7V-succinimidyl-4-(iodoacetyl)-aminobenzoate (SIAB); A-succinimidyl-[(N-maleimidopropionamido)-tetraethyleneglycol] ester (NHS- PEG4-maleimide); or Azido-PEG24-TFP-Ester.In some aspects, the cytotoxic agent (C) is selected from the group consisting of: a JAK inhibitor, a BET inhibitor, a BCL2 inhibitor, a MEK inhibitor, a PI3K inhibitor, a MAPK inhibitor, am alkylating agent, a cytoskeletal disruptor, a histone deacetylase inhibitor, a topoisomerase I inhibitor, a topoisomerase II inhibitor, nucleotide analogs or precursors thereof, peptide antibiotics, a protein degrader, platinum-based agents, retinoids, vinka alkaloids and derivatives thereof, and combinations thereof. In some aspects, the cytotoxic agent is selected from the group consisting of Exatecan, Deruxtecan, Monomethyl auristatin F (MMAF), and Monomethyl auristatin E (MMAE). In some aspects, the PI3K inhibitor is selected from the group consisting of: PI103; PI828; LY294002; wortmannin; demethoxy viri din; IC486068; IC87114; GDC-0941; GDC- 0980; perifosine; CAL101; PX-866; IPI-145; BAY 80-6946; BEZ235; P6503; TGR1202; SF1126; INK1117; BKM120; IL147; XL765; Palomid 529; GSK1059615; ZSTK474; PWT33597; TG100-115; CAL263; GNE-447; CUDC-907; and AEZS-136.

[0014] In some aspects, the antibody or antigen binding fragment that specifically binds to TCRVP is a full-length antibody. In some aspects, the antibody or antigen binding fragment that specifically binds to TCRVP is an antigen binding fragment thereof. In some aspects, the antibody or antigen binding fragment thereof that specifically binds to TCRVP is a full-length antibody. In some aspects, the antibody or antigen binding fragment thereof that specifically binds to the antibody or antigen binding fragment that specifically binds toTCRVP is an antigen binding fragment thereof. In some aspects, the antigen binding fragment comprises a Fab, a Fab', a F(ab')2, a Fd, a single chain Fv or scFv, a disulfide linked Fv, a V NAR domain, a IgNar, an intrabody, an IgG-CH2, a minibody, a F(ab')3, a tetrabody, a triabody, a diabody, a single-domain antibody, DVD-Ig, Fcab, mAb2, a (scFv)2, DARPin, or a scFv-Fc. In some aspects, the antigen binding fragment comprises a Fab fragment.

[0015] The present disclosure provides an immunoconjugate comprising (Al) an antibody that specifically binds to VP2 comprising the heavy chain variable domain of SEQ ID NO: 230, and the light chain variable domain of SEQ ID NO: 299; (A2) a Fab fragment comprising an anti-human IgG Fc Antibody; (L) with Non-Cleavable Linker; and (C) Exatecan, Deruxtecan, MMAF, or MMAE; wherein (L) links (A2) to (C), and (A2) binds to (Al).

[0016] In some aspects, the immunoconjugate described herein comprises an antibody or antigen binding fragment, wherein the antibody or antigen binding fragments comprises a Fc domain. In some aspects, the Fc domain comprises a mutation. In some aspects, the mutation reduces effector function. In some aspects, the mutation is L234A / L235A.

[0017] The present disclosure also provides a pharmaceutical composition comprising the immunoconjugate of the invention and a pharmaceutically acceptable carrier.

[0018] The present disclosure also provides a kit comprising the immunoconjugate of the invention.

[0019] The present disclosure also provides a method of treating cancer in a subject, comprising administering a therapeutically effective amount of the immunoconjugate or the pharmaceutical composition of the invention to the subject.

[0020] The present disclosure also provides a method of increasing cancer cell cytotoxicity comprising contacting a cancer cell with the immunoconjugate or the pharmaceutical composition of the invention.

[0021] In some aspects, the cancer is selected from the group consisting of T- cell Lymphoma, T-cell Leukemia, Cutaneous T-cell Lymphoma, Peripheral T-cell Lymphoma (PTCL), Not Otherwise Specified PTCL (PTCL-NOS), Angioimmunoblastic T-cell Lymphoma (AITL), Anaplastic Large-cell Lymphoma (ALCL), Enteropathy -Associated T- cell Lymphoma (EATL), Adult T-cell Leukemia / Lymphoma (ATLL), Hepatosplenic T- cell Lymphoma (HSTL), Subcutaneous Panniculitis-Like T-cell Lymphoma (SPTCL), T-cell Acute Lymphoblastic Leukemia (T-ALL), T-cell Chronic Lymphocytic Leukemia, LargeGranular Lymphocyte Leukemia, T-cell Prolymphocytic Leukemia, Lympomatoid Papulosis, Small Medium Pleiomorphic T-cell Lymphoma, Mycosis Fungoides, Sezary Syndrome, and Cytotoxic T-cell Lymphoma.

[0022] The present disclosure also provides a method of treating a T-cell mediated disease in a subject, comprising administering a therapeutically effective amount of the immunoconjugate or the pharmaceutical composition of the invention to the subject.

[0023] In some aspects, the T-cell mediated disease is selected from the group consisting of Atherosclerosis, Parkinson’s disease, Alzheimer’s disease, Type 1 Diabetes Mellitus, Grave’s Disease, Hashimoto’s Thyroiditis, Addison's Disease, Rheumatoid Arthritis (RA), Multiple Sclerosis (MS), Psoriasis, Psoriatic Arthritis, Lichen Planus, Lichen Planopilaris, Morphea, Scleroderma, Systemic Sclerosis, acute or chronic Graft- Versus-Host Disease (GVHD), Cardiac Organ Transplant Rejection, Pulmonary Organ Transplant Rejection, Renal Organ Transplant Rejection, Interstitial Lung Disease, Scleroderma, Alopecia Areata, Vitiligo, Celiac Disease (Sprue), Myasthenia Gravis, Pernicious Anemia, Sjogren’s Syndrome, Systemic Lupus Erythematosus, Chronic Inflammatory Demyelinating Polyneuropathy, Guillain-Barre Syndrome, Inflammatory Bowel Disease, Crohn’s Disease, and Ulcerative Colitis.DESCRIPTION OF FIGURES

[0024] FIG. 1 shows charts which illustrate the expression of Lens Culinaris Agglutinin (LCA) on the surface of parental expiCHO antibody producing cells (see left chart), presorted expiCHO cells post Fut8 knockout (KO) (see middle chart), and post-sorted (purified) expiCHO cells post Fut8 KO (see right chart), as quantified by flow cytometry.

[0025] FIG. 2 is a chart which shows an anti-VB2 antibody competition assay between 1.25 pg / ml mouse and humanized anti-VB2-FITC antibody as quantified by flow cytometry.

[0026] FIG. 3 is a chart which shows the functional antibody-dependent cellular cytotoxicity (ADCC) assay of humanized anti-VB2 antibody and mouse anti-VB2 antibody.

[0027] FIG. 4 is a chart which depicts the live Jurkat-TRBV20-l target cell count, following an overnight co-culture with effector NK cells from a healthy donor at different E:T ratios without an antibody addition, 100 ng / ml of mouse anti-VB2 antibody, and humanized anti-VB2 antibody, as determined by flow cytometry.

[0028] FIGs. 5A-5B are charts which show the results of live CTCL cell counts as determined by flow cytometry of PBMC, from VB2+ CTCL patient 1 (FIG. 5A), or from VB2+ CTCL patient 2 (FIG. 5B), following an overnight culture with NK effector cells from a healthy donor at different E:T ratios, without an antibody addition, without the addition of mouse anti-VB2 antibody, and with humanized anti-VB2 antibody.

[0029] FIGs. 6A-6B are charts which show the results of live VB2 -negative normal T cell counts, as quantified by flow cytometry, from the the PBMC of VB2+ CTCL patient 1 (FIG. 6A) or from VB2+ CTCL patient 2 (FIG. 6B), which were cultured overnight with natural killer (NK) effector cells from a healthy donor at different E:T ratios without antibody addition, mouse anti-VB2 antibody, and humanized anti-VB2 antibody.

[0030] FIGs. 7A-7B are charts which show the results of live non-T cell counts, as quantified by flow cytometry, from the PBMC of VB2+ CTCL patient 1 (FIG. 7A) or from VB2+ CTCL patient 2 (FIG. 7B), which were cultured overnight with NK effector cells from a healthy donor at different E:T ratios without antibody addition, with addition of mouse anti- VB2 antibody, and humanized anti-VB2 antibody.

[0031] FIG. 8 are images which show the successful treatment of T cell lymphoma via an anti-VB2 humanized therapeutic antibody treatment in NSG mice across the time period of 7, 14, and 16 days between control antibody and NK cells (see top row), followed by anti-VB2 antibody and NK cells (see middle row), and solely anti-VB2 antibody administration (see bottom row).

[0032] FIG. 9 is a graph that shows staining of VP2+ or TCR knockout Jurkat cells stained with 1 pg / mL (top row) or 0.1 pg / mL (bottom row) of each antibody (columns) followed by staining with secondary antibody (anti-protein L) used for detection.

[0033] FIG. 10 is a chart that shows treatment of both target (vP2+) or non-target (vP2-) Jurkat cells with (1) anti-vP2 H3-L4, (2) Fab anti-human IgG Fc-Monomethyl auristatin F (MMAF), (3) anti-vP2 H3-L4 conjugated to Fab anti-human IgG Fc-MMAF, or (4) no antibody control. Treatments were performed in triplicate. The expression of mCherry is higher in the non-target cells when compared to that of the target cells. The gating strategy was as follows: lymphocyte gate -> singlets -> viability vs mCherry.

[0034] FIG. 11 is a chart quantified by flow cytometry showing the reduction in cell viability of target (vP2+) or non-target (vP2-) Jurkat cells after 48 h treatment with (1) anti-vP2 H3-L4, (2) Fab anti-human IgG Fc-Monomethyl auristatin F (MMAF), (3) anti-vP2 H3- L4 conjugated to Fab anti-human IgG Fc-MMAF, or (4) no antibody control.

[0035] FIG. 12 is a chart which shows treatment of both target (yP2+) or non-target (yP2- ) Jurkat cells with (1) anti-vP2 H3-L4, (2) anti-human IgG Fc-DX8951 antibody (Exatecan), (3) anti-vP2 H3-L4 conjugated to anti-human IgG Fc-DX8951 antibody (Exatecan) with a cleavable linker, or (4) no antibody control. Treatments were performed in triplicate. The expression of mCherry is higher in the non-target cells when compared to that of the target cells. The gating strategy was as follows: lymphocyte gate -> singlets -> viability vs mCherry.

[0036] FIG. 13 is a chart quantified by flow cytometry showing the reduction in cell viability of vP2+ or vP2- cells after 72 h treatment with (1) anti-vP2 H3-L7, (2) anti-human IgG Fc-DX8951 antibody (Exatecan), (3) anti-vP2 H3-L4 conjugated to anti-human IgG Fc- DX8951 antibody (Exatecan) with a cleavable linker, or (4) no antibody control.

[0037] FIG. 14 is a chart that shows the internalization of Lysolight-conjugated humanized anti-Vpi IgGl (wild-type Fc) antibody in Vpi -positive Jurkat cells.

[0038] FIG. 15 is a chart that shows the internalization of lysolight-conjugated humanized anti-Vp2 IgGlantibody with a LALA Fc mutation in Vp2-positive or Vpi- positive Jurkat cells.

[0039] FIG. 16 is a chart that shows the internalization of lysolight-conjugated humanized anti-Vp3 IgGl antibody with a LALA Fc mutation in VP3 -positive or Vpi- positive Jurkat cells.

[0040] FIG.17 is a chart that shows the internalization of lysolight-conjugated humanized anti-Vp7.1 IgGl (wild-type Fc) antibody in VP7.1 -positive Jurkat cells.

[0041] FIG. 18 is a chart that shows the internalization of Lysolight-conjugated humanized anti-Vp7.2 IgGl (LALA Fc) antibody in VP7.2-positive or Vpi-positive Jurkat cells.

[0042] FIG. 19 is a chart that shows the internalization of lysolight-conjugated humanized anti-Vpi3.1 IgGl (LALA Fc) antibody in VP 13.1 -positive or Vpi-positive Jurkat cells.

[0043] FIG. 20 is a chart that shows the internalization of lysolight-conjugated humanized anti-Vpi3.2 IgGl (wild-type Fc) antibody in VP 13.2-positive Jurkat cells.

[0044] FIG. 21 is a chart that shows the internalization of lysolight-conjugated humanized anti-Vpi3.6 IgGl (enhanced Fc) antibody in VP 13.6-positive or VP 13.2-positive non-target Jurkat cells.

[0045] FIG. 22 is a chart that shows the internalization of lysolight-conjugated humanized anti-Vpi7 IgGl (wild-type Fc) antibody in Vpi7-positive Jurkat cells.

[0046] FIGs. 23A-23B are charts that shows the effect of LALA Fc mutation (Fc-LALA) on Fc-mediated antibody dependent cytotoxicity (ADCC) when included in the humanized anti-Vp2 H3-L4 antibody compared to Fc wildtype (Fc-WT), Fc enhanced (Fc-enhanced) and isotype antibody with LALA Fc mutation (Fc-LALA). FIG. 23A shows the ADCC activity when each antibody is incubated with target VP2+ Jurkat cells. FIG. 23B shows the ADCC activity when each antibody is incubated with non-target VP2+ Jurkat cells.

[0047] FIGs. 24A-B are graphs that show staining of VP2+ Jurkat cells with humanized anti-Vp2-Dxd Fc-LALA ADCs with linker-payload:antibody ratios of 12.5: 1 (high or “H”) or 6.25: 1 (low or “L”) or no drug (“naked”) compared to isotype control. The linker- payload:antibody ratios of 12.5: 1 and 6.25: 1 correspond to an average drug:antibody ratio (DAR) of 2.5: 1 and 2.3: 1, respectively. FIG. 24A is a graph showing the staining of VP2+ Jurkat cells with the humanized anti- Vp2-Dxd Fc-LALA antibodies. FIG. 24B is a graph showing the staining of VP2+ Jurkat cells using the isotype controls.

[0048] FIGs. 25A-B are graphs that show in vitro cytotoxicity of target VP2+ or non- target Vpi+ Jurkat cells when incubated with humanized anti-Vp2-Dxd Fc-LALA ADCs or controls for 72h. FIG. 25A is a graph that shows the in vitro cytotoxicity of target VP2+ or non-target Vpi+ Jurkat cells when treated with ADCs or controls having a linker- payload:antibody ratio of 12.5 : 1 (high or “H”), corresponding to an average DAR of 2.5 : 1. FIG. 25B is a graph that shows the in vitro cytotoxicity of target VP2+ or non-target Vpi+ Jurkat cells when treated with ADCs or controls having a linker-payload:antibody ratio of 6.25:1 (low or “L”), corresponding to an average DAR of 2.3 : 1.

[0049] FIG. 26 is a chart that shows in vitro cytotoxicity assay of VP2+ Jurkat cells treated with deruxtecan (Dxd)-conjugated LALA variants of anti-Vp2, anti-Vp3, and anti- VP7.2 antibody-drug conjugates (ADCs).

[0050] FIG. 27 is a chart that shows in vitro cytotoxicity assay of VP3+ Jurkat cells treated with Dxd-conjugated LALA variants of anti-Vp2, anti-Vp3, and anti-Vp7.2 antibodydrug conjugates (ADCs).

[0051] FIG. 28 is a chart that shows in vitro cytotoxicity assay of VP7.2+ Jurkat cells treated with Dxd-conjugated LALA variants of anti-Vp2, anti-Vp3, and anti-Vp7.2 antibodydrug conjugates (ADCs).

[0052] FIGs. 29A-B show the treatment of VP2+ Jurkat tumor cells via a humanized anti-Vp2 antibody drug conjugate treatment (2 mg / kg, i.p.) administered at days 15, 22, and 29 in NSG mice across the time period of 50 days. FIG. 29A is an image that shows IVIS bioluminescence imaging of VP2+ Jurkat retro-orbitally injected into NSG mice that were untreated (cntl) or anti-VB2-Dxd ADC (ADC). FIG.29B is a chart quantifying the total flux tumor burden over time shown in FIG. 29A.

[0053] FIGs. 30A-B show the treatment of VP2+ Jurkat tumor cells via a humanized anti-Vp2 antibody drug conjugate (1 mg / kg, i.p.) administered at days 8, 15, and 22 in NSG mice across the time period of 40 days. FIG. 30A is an image that shows IVIS bioluminescence imaging of VP2+ Jurkat subcutaneously injected into NSG mice that were untreated (cntl) or anti-VB2-Dxd ADC (ADC). FIG.30B is a chart quantifying the total flux tumor burden over time shown in FIG. 30 A.

[0054] FIGs. 31A-C show the treatment of VP2+ Jurkat tumor cells via humanized anti- VP2-MMAE and anti-Vp2-Dxd ADCs (1-4 mg / kg, i.p.) administered at various time points in NSG mice across the time period of 36 days. FIG. 31A is an image that shows IVIS bioluminescence imaging of VP2+ Jurkat subcutaneously injected into NSG mice that were untreated; treated with anti-Vp2-MMAE ADC on days 4, 7, and 10; or treated with anti-Vp2- Dxd ADC on days 4, 7, 10, 16, 19, and 23. FIG. 31B is a chart quantifying the total flux tumor burden over time for mice treated with anti-Vp2-MMAE ADC shown in FIG. 31 A. FIG. 31C is a chart quantifying the total flux tumor burden over time for mice treated with anti-Vp2-Dxd ADC shown in FIG. 31 A.DETAILED DESCRIPTIONDefinitions

[0055] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. In case of conflict, the present application including the definitions will control. Unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular. All publications, patents and other referencesmentioned herein are incorporated by reference in their entireties for all purposes as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference.

[0056] Although methods and materials similar or equivalent to those described herein can be used in practice or testing of the present disclosure, suitable methods and materials are described below. The materials, methods and examples are illustrative only and are not intended to be limiting. Other features and advantages of the disclosure will be apparent from the detailed description and from the claims.

[0057] In order to further define this disclosure, the following terms and definitions are provided.

[0058] The singular forms "a," "an" and "the" include plural referents unless the context clearly dictates otherwise. The terms "a" (or "an"), as well as the terms "one or more," and "at least one" can be used interchangeably herein. As described herein, the term "a" or "an" means "single." As disclosed herein, the term "a" or "an" includes "two or more" or "multiple."

[0059] The term "about" is used herein to mean approximately, roughly, around, or in the regions of. When the term "about" is used in conjunction with a numerical range, it modifies that range by extending the boundaries above and below the numerical values set forth. In general, the term "about" is used herein to modify a numerical value above and below the stated value by a variance of 10 percent, up or down (higher or lower).

[0060] As disclosed herein, the language "comprising" constitutes otherwise analogous aspects disclosed in the terms "consisting of' and / or "consisting essentially of.

[0061] Throughout this disclosure, various aspects of this disclosure are presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the disclosure. Accordingly, the description of a range should be considered to have specifically disclosed all the possible sub-ranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed sub-ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.Numeric ranges recited are inclusive of the numbers defining the range and include each integer within the defined range.

[0062] Units, prefixes, and symbols are denoted in their Systeme International de Unites (SI) accepted form. Numeric ranges are inclusive of the numbers defining the range. Where a range of values is recited, it is to be understood that each intervening integer value, and each fraction thereof, between the recited upper and lower limits of that range is also specifically disclosed, along with each subrange between such values. The upper and lower limits of any range can independently be included in or excluded from the range, and each range where either, neither or both limits are included is also encompassed within the disclosure. Thus, ranges recited herein are understood to be shorthand for all of the values within the range, inclusive of the recited endpoints. For example, a range of 1 to 10 is understood to include any number, combination of numbers, or sub-range from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10.

[0063] Where a value is explicitly recited, it is to be understood that values which are about the same quantity or amount as the recited value are also within the scope of the disclosure. Thus, any value recited herein is inclusive of a precise value, as well as values which are about the same as the precise value. Where a combination is disclosed, each subcombination of the elements of that combination is also specifically disclosed and is within the scope of the disclosure. Conversely, where different elements or groups of elements are individually disclosed, combinations thereof are also disclosed. Where any element of a disclosure is disclosed as having a plurality of alternatives, examples of that disclosure in which each alternative is excluded singly or in any combination with the other alternatives are also hereby disclosed; more than one element of a disclosure can have such exclusions, and all combinations of elements having such exclusions are hereby disclosed.

[0064] The term "and / or" where used herein is to be taken as specific disclosure of each of the two specified features or components with or without the other. Thus, the term "and / or" as used in a phrase such as "A and / or B" herein is intended to include "A and B," "A or B," "A" (alone), and "B" (alone). Likewise, the term "and / or" as used in a phrase such as "A, B, and / or C" is intended to encompass each of the following aspects: A, B, and C; A, B, or C; A or C; A or B; B or C; A and C; A and B; B and C; A (alone); B (alone); and C (alone).

[0065] The term "effective amount" or "pharmaceutically effective amount" or "therapeutically effective amount" as used herein refers to the amount or quantity of atherapeutic described herein which is sufficient to elicit the required or desired therapeutic response, or in other words, the amount which is sufficient to elicit an appreciable biological response when administered to a patient.

[0066] The term "unit dosage form" or "unit dose composition" as used herein refers to a device containing a quantity of a therapeutic described herein, said quantity being such that one or more predetermined units may be provided as a single therapeutic administration.

[0067] As used herein, the term "administration" refers to the administration to a subject. Administration to an animal subject (e.g., to a human) can be by any appropriate route. "Administering" refers to the physical introduction of a composition comprising a therapeutic agent into a subject, using any of the various methods and delivery systems known to those skilled in the art. In some aspects of the present disclosure, administration can be enteral administration, including oral and aboral administration, administration via endoscopic delivery system, administration via a nasogastric tube, administration via a nasojejunal tube, administration via esophagogastroduodenoscopy, administration via colonoscopy, or administration via retention enema, via parenteral administration (e.g., intramuscular, subdermal, subcutaneous, intravenous, and intradermal injection), or administration via any other suitable route of administration known to the skilled in the art, or any combination thereof. Administering can also be performed, for example, once, a plurality of times, and / or over one or more extended periods.

[0068] As used herein, the terms “treat,” “treated,” and “treating” mean both therapeutic and prophylactic treatment or preventative measures wherein the object is to reverse, alleviate, ameliorate, lessen, inhibit, slow down progression, development, severity or recurrence of an undesired symptom, complication, condition, biochemical indicia of a disorder, or disease, or obtain beneficial or desired clinical results. Beneficial or desired clinical results include, but are not limited to, alleviation of symptoms; diminishment of the extent of a condition, disorder, or disease; stabilized (i.e., not worsening) state of condition, disorder, or disease; delay in onset or slowing of condition, disorder, or disease progression; amelioration of the condition, disorder, or disease state or remission (whether partial or total), whether detectable or undetectable; an amelioration of at least one measurable physical parameter, not necessarily discernible by the patient; or enhancement or improvement of condition, disorder, or disease. Treatment includes eliciting a clinically significant responsewithout excessive levels of side effects. In some instances, treatment includes prolonging survival as compared to expected survival if not receiving treatment.

[0069] A “complete response” or “complete remission” is defined for any given cancer type as the absence of cancer cells detectable by imaging or molecular methods conventionally used for detection of that type of cancer. A “complete response” does not necessarily mean that all cancer cells are absent from the patient. For cancers in which multiple conventional imaging or molecular methods are conventionally used for detection, the absence of detectable cancer cells using any one of such multiple methods is sufficient to indicate a “complete response” for purposes of the present dislcosure.

[0070] A “partial response” or “partial remission” is defined for any given cancer type as at least a 50% reduction in estimated number of cancer cells or tumor burden detectable by imaging or molecular methods conventionally used for detection of that type of cancer. For cancers in which multiple conventional imaging or molecular methods are conventionally used for detection, a 50% reduction of detectable cancer cells using any one of such multiple methods is sufficient to indicate a “partial response” for purposes of the present disclosure.

[0071] A “poor response” is any response to an antibody or antigen binding fragment, or of the composition of the disclosure, treatment that is not a “complete response” or a “partial response.” A poor response can include an increase in cancer cells or tumor burden as detectable using conventional imaging or molecular methods for detection of that type of cancer. A poor response can also include a minimal decrease in cancer cells that is still not sufficient to be considered “partial remission.”

[0072] As used herein, the term “amelioration” or “ameliorating” refers to a lessening of severity of at least one indicator of a condition or disease. As used herein, the term “preventing” or “prevention” refers to delaying or forestalling the onset, development or progression of a condition or disease for a period of time, including weeks, months, or years. As used herein, the term “prophylactic” (e.g., “prophylactic agent”, “prophylactic treatment”, “prophylactically effective amount”), refers to any complete or partial prevention of a disease or symptom thereof and / or can be therapeutic in terms of a partial or complete cure for a disease and / or adverse effect and / or symptom attributable to the disease.

[0073] A “disease” is a state of health of an animal or subject wherein the subject cannot maintain homeostasis (e.g., cancer and autoimmune diseases, T cell mediated diseases, etc. . .), and wherein if the disease is not ameliorated then the subject’s health continues todeteriorate. In contrast, a “disorder” in a subject is a state of health in which the subject is able to maintain homeostasis, but in which the subject’s state of health is less favorable than it would be in the absence of the disorder. Left untreated, a disorder does not necessarily cause a further decrease in the subject’s state of health.

[0074] Cancer” as used herein can encompass all types of oncogenic processes and / or cancerous growths. In this disclosure, cancer can include, but is not limited to primary tumors as well as metastatic tissues or malignantly transformed cells, tissues, or organs. Cancer can encompasse histopathologies and stages, e.g., stages of invasiveness / severity, of a cancer. Cancer can include relapsed and / or resistant cancer. The terms “cancer” and “tumor” can be used interchangeably. For example, both terms encompass solid and liquid tumors. As used herein, the term “cancer” or “tumor” includes premalignant, as well as malignant cancers and tumors.

[0075] Exemplary T-cell-associated cancer or T-cell malignancies include but are not limited to T-cell Lymphoma, T-cell Leukemia, Cutaneous T-cell Lymphoma, Peripheral T- cell Lymphoma (PTCL), Not Otherwise Specified PTCL (PTCL-NOS), Angioimmunoblastic T-cell Lymphoma (AITL), Anaplastic Large-cell Lymphoma (ALCL), Enteropathy- Associated T-cell Lymphoma (EATL), Adult T-cell Leukemia / Lymphoma (ATLL), Hepatosplenic T- cell Lymphoma (HSTL), Subcutaneous Panniculitis-Like T-cell Lymphoma (SPTCL), T-cell Acute Lymphoblastic Leukemia (T-ALL), T-cell Chronic Lymphocytic Leukemia, Large Granular Lymphocyte Leukemia, T-cell Prolymphocytic Leukemia, Lympomatoid Papulosis, Small Medium Pleiomorphic T-cell Lymphoma, Mycosis Fungoides, Sezary Syndrome, and Cytotoxic T-cell Lymphoma.

[0076] The term “autoimmune” in relation to TCR means that such TCR is involved in the development of an autoimmune disease.

[0077] The term “autoimmune disease” for example, as used herein is defined as a disorder that results from an autoimmune response. An autoimmune disease can result from an inappropriate and excessive response to a self-antigen. Exemplary autoimmune diseases that can be treated include, but are not limited to, Type 1 Diabetes Mellitus, Grave’s Disease, Hashimoto’s Thyroiditis, Addison's Disease, Rheumatoid Arthritis (RA), Multiple Sclerosis (MS), Psoriasis, Psoriatic Arthritis, Lichen Planus, Lichen Planopilaris, Morphea, Scleroderma, Systemic Sclerosis, acute or chronic Graft- Versus-Host Disease (GVHD), Cardiac Organ Transplant Rejection, Pulmonary Organ Transplant Rejection, Renal OrganTransplant Rejection, Interstitial Lung Disease, Stiff Man Syndrome, Scleroderma, Alopecia Areata, Vitiligo, Celiac Disease (Sprue), Myasthenia Gravis, Pernicious Anemia, Sjogren’s Syndrome, Systemic Lupus Erythematosus, Chronic Inflammatory Demyelinating Polyneuropathy, Guillain-Barre Syndrome, Inflammatory Bowel Disease, Crohn’s Disease, and Ulcerative Colitis. In addition, there are other inflammatory disorders that may not historically have been considered autoimmune, but where reactive T cells are nonetheless drivers of inflammation that is fundamental to the disease pathogenesis. Indeed, chronic inflammatory diseases have been recognized as the most significant cause of death in the world today, with more than 50% of all deaths being attributable to inflammation-related diseases such as ischemic heart disease, stroke, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease (NAFLD) and autoimmune and neurodegenerative conditions [GBD 2017 Causes of Death Collaborators. Global, regional, and national age- sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 392, 1736-1788 (2018).]. These include atherosclerosis and resultant cardiovascular disease, neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease, chronic obstructive pulmonary disease, which are encompassed within the term autoimmune disease.

[0078] As used herein “plasma cells” refer to a type of white blood cells which can produce and secrete antibodies. Plasma cells are also referred to as plasmocytes, plasmacytes, or effector B cells.

[0079] As used herein, the terms “therapeutically effective amount”, “therapeutically effective”, “effective amount” or “in an effective amount” are used interchangeably herein and refer to the amount of a compound, preparation, substance or composition that is effective to achieve a specific biological result as described herein, such as but not limited to treating or reducing the count of a cancer or tumor, or to lessen or alleviate a autoimmune disease.

[0080] As used herein, the terms "subject" and "patient" are used interchangeably. The subject can be an animal. The subject can be a mammal such as a non-human animal (e.g., cow, pig, horse, cat, dog, rat, mouse, monkey or other primate, etc.). The subject can be a human.

[0081] The term “cytotoxicity” as used in this specification, refers to an unintended or undesirable alteration in the normal state of a cell. The normal state of a cell can refer to astate that is manifested or exists prior to the cell's exposure to a cytotoxic composition, agent and / or condition. Generally, a cell that is in a normal state is one that is in homeostasis. An unintended or undesirable alteration in the normal state of a cell can be manifested in the form of, for example, cell death (e.g., programmed cell death), a decrease in replicative potential, a decrease in cellular integrity such as membrane integrity, a decrease in metabolic activity, a decrease in developmental capability, or any of the cytotoxic effects disclosed in the present application.

[0082] The phrase “reducing cytotoxicity” or “reduce cytotoxicity” refers to a reduction in degree or frequency of unintended or undesirable alterations in the normal state of a cell upon exposure to a cytotoxic composition, agent and / or condition. The phrase can refer to reducing the degree of cytotoxicity in an individual cell that is exposed to a cytotoxic composition, agent and / or condition, or to reducing the number of cells of a population that exhibit cytotoxicity when the population of cells is exposed to a cytotoxic composition, agent and / or condition.

[0083] The term “disrupting” and its grammatical equivalents as used herein can refer to a process of altering a gene, e.g., by deletion, insertion, mutation, rearrangement, or any combination thereof. For example, a gene can be disrupted by “knockout” (KO). Disrupting a gene can be partially reducing or completely suppressing expression of the gene. Disrupting a gene can also cause activation of a different gene, for example, a downstream gene. As described herein, exemplary KO of the endogenous TCR in T cells strongly ablated alloreactivity in comparison to TCR-expressing T cells (Stenger, D., et al., Blood 136(12): 1407-1418, Sept, 2020).

[0084] As used herein, the terms "nucleic acid" or "polynucleotides" refers to nucleotides and / or polynucleotides, such as deoxyribonucleic acid (DNA) or ribonucleic acid (RNA), oligonucleotides, fragments generated by the polymerase chain reaction (PCR), and fragments generated by any of ligation, scission, endonuclease action, and exonuclease action.

[0085] The terms "polypeptide," "peptide," and "protein" are used interchangeably herein to refer to polymers of amino acids of any length. The polymer can be linear or branched, it can comprise modified amino acids, and it can be interrupted by non-amino acids. The terms also encompass an amino acid polymer that has been modified naturally or by intervention; for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation,or any other manipulation or modification, such as conjugation with a labeling component. Also included within the definition are, for example, polypeptides containing one or more analogs of an amino acid (including, for example, unnatural amino acids, etc.), as well as other modifications known in the art.

[0086] As used herein, the term “conservative sequence modifications” is intended to refer to amino acid modifications that do not significantly affect or alter the binding characteristics of the antibody containing the amino acid sequence. Such conservative modifications include amino acid substitutions, additions and deletions. Modifications can be introduced into an antibody of the disclosure by standard techniques known in the art, such as site-directed mutagenesis and PCR-mediated mutagenesis. Conservative amino acid substitutions are ones in which the amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined in the art. These families include amino acids with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine, tryptophan), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). Thus, for example, one or more amino acid residues within the extracellular regions of the antibodies of the disclosure can be replaced with other amino acid residues having a similar side chain or charge and the altered antibodies can be tested for the ability to bind their targets using the functional assays described herein.

[0087] The term “variant” refers to a polypeptide that has a substantially identical amino acid sequence to a reference amino acid sequence, or is encoded by a substantially identical nucleotide sequence. In aspects described herein, the variant can be a functional variant. The term “functional variant” refers to a polypeptide that has a substantially identical amino acid sequence to a reference amino acid sequence, or is encoded by a substantially identical nucleotide sequence, and is capable of having one or more activities of the reference amino acid sequence.

[0088] A polypeptide, antibody, polynucleotide, vector, cell, or composition which is "isolated" refers to a polypeptide, antibody, polynucleotide, vector, cell, or composition which is in a form not found in nature. Isolated polypeptides, antibodies, polynucleotides,vectors, cell or compositions include those which have been purified to a degree that they are no longer in a form in which they are found in nature.

[0089] As disclosed herein, an antibody, polynucleotide, vector, cell, or composition which is isolated is substantially pure. As used herein, "substantially pure" refers to material which is at least 50% pure (i.e., free from contaminants), at least 90% pure, at least 95% pure, at least 98% pure, or at least 99% pure.

[0090] "Percent identity" refers to the extent of identity between two sequences (e.g., amino acid sequences or nucleic acid sequences). Percent identity can be determined by aligning two sequences, introducing gaps to maximize identity between the sequences. Alignments can be generated using programs known in the art. For non-limiting purposes herein, alignment of nucleotide sequences can be performed with the blastn program set at default parameters, and alignment of amino acid sequences can be performed with the blastp program set at default parameters (see National Center for Biotechnology Information (NCBI) on the worldwide web, ncbi.nlm.nih.gov).

[0091] Human “T cell receptor”, also referred to as “TCR”, “T receptor”, is a heterodimeric protein complex found on the surface of a T lymphocyte. The T receptor is present only on T lymphocytes. The main function of TCR is to specifically recognize processed antigens bound to the molecules of major histocompatibility complex (HLA). Human TCR comprises two subunits, a and P chains, or y and 5 chains, connected through a disulfide bond and docked onto the cell membrane. Each of the TCR chains has an N- terminal variable (V) domain, a connecting domain, and a constant (C) domain connected to a transmembrane domain that anchors the receptor in the T lymphocyte plasma membrane. The T receptor reacts with the MHC / antigen complex via six regions determining complementarity thereof (CDRs): three alpha chain regions and three beta-chain regions.

[0092] A small fraction of T lymphocytes has the y / 5 type T receptors. They are arranged similar to the a / p receptors, but differ in their primary structure and have a number of functional features. They exhibit a much lower variability (limited clone specificity), they recognize antigens in the complex with “non-classical” (non-MHC) antigen-presenting molecules or even free antigens.

[0093] As used herein, the terms “T cell receptor beta variable chain,” “TCRVP,” “TCRVb,” and “TCRPV” are used interchangeably to refer to an extracellular region of the T cell receptor beta chain which comprises the antigen recognition domain of the T cellreceptor. The term “VB,” “VB,” “variable beta,” “variable B,” and “v beta” and any grammatical equivalents are interchangeably used to refer to the variable beta chain of a T cell receptor. The term TCRVP or TCRPV includes isoforms, mammalian, e.g., human TCRPV, species homologs of human and analogs comprising at least one common epitope with TCRPV. Isoforms of TCRVB can be identified by integers or letters of the alphabet, e.g., 1, 2, 3, 4 or A, B, C. Human TCRPV comprises a gene family comprising subfamilies including, but not limited to: a TCRP VI subfamily, a TCRP V2 subfamily, a TCRP V3 subfamily, a TCRP V4 subfamily, a TCRP V5 subfamily, a TCRP V6 subfamily, a TCRP V7 subfamily, a TCRP V8 subfamily, a TCRP V9 subfamily, a TCRP VI 0 subfamily, a TCRP VI 1 subfamily, a TCRP V12 subfamily, a TCRP V13 subfamily, a TCRP V14 subfamily, a TCRP V15 subfamily, a TCRP V16 subfamily, a TCRP V17 subfamily, a TCRP V18 subfamily, a TCRP VI 9 subfamily, a TCRP V20 subfamily, a TCRP V21 subfamily, a TCRP V22 subfamily, a TCRP V23 subfamily, TCRP V24 subfamily, or a TCRP V25 subfamily. An exemplary list of TCRVP and subfamilies is provided in Table 1 (below).Table 1. TCRVB Subfamily

[0094] The term “accession number” or “accession code” and all grammatical equivalents, means an identifiable or searchable number or code, referring to a peptide or nucleotide sequence. Methods of searching the accession number are can be achieved via numerous methods, including but not limited to IMGT (imgt.org), GenBank (ncbi.nlm.nih.gov / genbank), and The Kabat Database (G. Johnson and T. T.Wu, 2002; kabatdatabase.com).

[0095] The term "antibody" means an immunoglobulin molecule that recognizes and specifically binds to a target, such as a protein, polypeptide, peptide, carbohydrate, polynucleotide, lipid, or combinations of the foregoing through at least one antigen recognition site within the variable region of the immunoglobulin molecule. As used herein, the term "antibody" encompasses intact polyclonal antibodies, intact monoclonal antibodies, chimeric antibodies, humanized antibodies, human antibodies, fusion proteins comprising anantibody, and any other modified immunoglobulin molecule so long as the antibodies exhibit the desired biological activity.

[0096] An antibody can be of any of the five major classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, or subclasses (isotypes) thereof (e.g., IgGl, IgG2, IgG3, IgG4, IgAl and IgA2), based on the identity of their heavy-chain constant domains referred to as alpha, delta, epsilon, gamma, and mu, respectively. The different classes of immunoglobulins have different and well-known subunit structures and three-dimensional configurations. Antibodies can be naked or conjugated to other molecules such as toxins, radioisotopes, etc.

[0097] The term "antibody fragment" refers to a portion of an intact antibody. An "antigen-binding fragment," "antigen-binding domain," or "antigen-binding region," refers to a portion of an intact antibody that binds to an antigen. An antigen-binding fragment can contain an antigen recognition site of an intact antibody (e.g., complementarity determining regions (CDRs) sufficient to bind antigen). Examples of antigen-binding fragments of antibodies include, but are not limited to Fab, Fab', F(ab')2, and Fv fragments, linear antibodies, and single chain antibodies. An antigen-binding fragment of an antibody can be derived from any animal species, such as rodents (e.g., mouse, rat, or hamster) and humans or can be artificially produced.

[0098] The term “intrabody” refers to an antibody or antibody binding fragment” that works within the cell to bind to an intracellular protein.

[0099] “Antigen” (Ag) as used herein refers to a molecule that can provoke an immune response, e.g., involving activation of certain immune cells and / or antibody generation. Any natural or synthetic immunogenic substance, including but not limited to a hapten, or any macromolecule, including but not limited to almost all proteins or peptides, can be an antigen. Antigens can also be derived from genomic recombinant or DNA. For example, any DNA comprising a nucleotide sequence or a partial nucleotide sequence that encodes a protein capable of eliciting an immune response encodes an “antigen.” An antigen does not need to be encoded solely by a full-length nucleotide sequence of a gene, nor does an antigen need to be encoded by a gene at all. An antigen can be synthesized or can be derived from a biological sample, e.g., a tissue sample, a tumor sample, a cell, or a fluid with other biological components. As used, herein a “tumor antigen” or interchangeably, a “cancer antigen” includes any molecule present on, or associated with, a cancer, e.g., a cancer cell or a tumor microenvironment that can provoke an immune response. As used, herein an“immune cell antigen” includes any molecule present on, or associated with, an immune cell that can provoke an immune response.

[0100] As used herein, an “immune cell” refers to any of various cells that function in the immune system, e.g., to protect against agents of infection and foreign matter. This term includes leukocytes, e.g., neutrophils, eosinophils, basophils, lymphocytes, and monocytes. Innate leukocytes include phagocytes (e.g., macrophages, neutrophils, and dendritic cells), mast cells, eosinophils, basophils, and natural killer cells. Innate leukocytes identify and eliminate pathogens, either by attacking larger pathogens through contact or by engulfing and then killing microorganisms, and are mediators in the activation of an adaptive immune response. The cells of the adaptive immune system are special types of leukocytes, called lymphocytes. B cells and T cells are important types of lymphocytes and are derived from hematopoietic stem cells in the bone marrow. B cells are involved in the humoral immune response, whereas T cells are involved in cell-mediated immune response. The term “immune cell” includes immune effector cells.

[0101] As used herein, the term “specifically binds” refers to an antigen binding molecule that recognizes and binds a protein of a binding partner (such as a variable 13 region) present in a sample, but the antigen binding molecule does not substantially recognize or bind to other molecules in the sample.

[0102] The term “high affinity” as used herein refers to high specificity in binding or interacting or attraction of one molecule to a target molecule.

[0103] As used herein, the terms "variable region" or "variable domain" are used interchangeably and are common in the art. The variable region typically refers to a portion of an antibody, generally, a portion of a light or heavy chain, typically about the aminoterminal 110 to 120 amino acids or 110 to 125 amino acids in the mature heavy chain and about 90 to 115 amino acids in the mature light chain, which differ in sequence among antibodies and are used in the binding and specificity of a particular antibody for its particular antigen. The variability in sequence is concentrated in those regions called complementarity determining regions (CDRs) while the more highly conserved regions in the variable domain are called framework regions (FR). Without wishing to be bound by any particular mechanism or theory, it is believed that CDRs of the light and heavy chains are primarily responsible for the interaction and specificity of the antibody with antigen.

[0104] The terms "VH" and " VH domain" are used interchangeably to refer to the heavy chain variable region of an antibody or antigen-binding fragment thereof.

[0105] The terms "VL" and "VL domain" are used interchangeably to refer to the light chain variable region of an antibody or antigen-binding fragment thereof.

[0106] The “hypervariable regions” in each chain are held together in close proximity by FRs, and with the hypervariable regions from the other chain, contribute to the formation of the antigen-binding site of antibodies (see Kabat et al, Sequences of Proteins of Immunological Interest, 1992). The term "hypervariable region" as used herein refers to the amino acid residues of an antibody, which are responsible for antigen binding. The hypervariable region generally comprises amino acid residues from a "complementary determining region" or "CDR", the latter being of highest sequence variability and / or involved in antigen recognition. A number of CDR definitions are in use and are encompassed herein. The Kabat definition is based on sequence variability and is the most commonly used (Kabat EA et al., supra). Chothia refers instead to the location of the structural loops (Chothia C & LeskAM (1987) J. Mol. Biol. 196: 901-917). The AbM definition is a compromise between the Kabat and the Chothia definitions and is used by Oxford Molecular's AbM antibody modelling software (Martin AC R et al., (1989) Proc. Natl Acad. Sci. USA, 86: 9268-72; Martin AC R et al., (1991) Methods Enzymol. 203: 121-153; Pedersen J T et al., (1992) Immunomethods, 1 : 126-136; Rees AR et al., (1996) In Sternberg M. J. E. (ed.), Protein Structure Prediction. Oxford University Press, Oxford, 141-172). The contact definition has been recently introduced (Maccallum RM et al., (1996) J. Mol. Biol. 262: 732-7 45) and is based on an analysis of the complex structures available in the Protein Databank. The definition of the CDR by IMGT®, the international ImMunoGeneTics information System® (imgt.org) is based on the IMGT numbering for all immunoglobulin and T cell receptor V-REGIONs of all species (IMGT®, the international ImMunoGeneTics information System®; Lefranc MP et al., (1991) Nucleic Acids Res. 27(1): 209-12; Ruiz M et al., (2000) Nucleic Acids Res. 28(1): 219-21; Lefranc M P (2001) Nucleic Acids Res. 29(1): 207-9; Lefranc M P (2003) Nucleic Acids Res. 31(1): 307-10; Lefranc M P et al., (2005) Dev. Comp. Immunol. 29(3): 185-203; Kaas Q et al., (2007) Briefings in Functional Genomics & Proteomics, 6(4): 253-64).

[0107] The Complementarity Determining Regions (CDRs) disclosed herein can be defined according to IMGT®. The CDRs can be defined according to Chothia. The CDRs canbe defined according to Kabat. For example, for the light chains, the variable domain residues for each of the CDRs can be (numbering according to Kabat E A, et al., supra): LCDR1 : 27- 32, LCDR2: 50-52, LCDR3: 89-97. The "non-CDR region" of the VL region as used herein comprise the amino acid sequences: 1-26 (FRI), 33-49 (FR2), 53-88 (FR3), and 98- approximately 107 (FR4). For the heavy chains, the variable domain residues for each of the three CDRs can be HCDR1 : 26-35, HCDR2: 51-57 and HCDR3: 93-102.

[0108] Different software can be used to generate alternate CDR sequences for the framework sequences of a variable region with different CDR sequences resulting from the use of the different software programs. The use of alternate CDR sequences can improve binding affinities of an antibody to at least one antigen. Alternate CDR sequences are used for affinity optimization of one or both antigen binding sites of an antibody according to the present disclosure. The alternate CDRs are defined according to Kabat, Chothia, Paratome, AbM, Contact and / or IMGT annotations. The CDRs are defined according to more than one annotation.

[0109] As used herein, the term "Fab region" refers to VH and CHI domains of a heavy chain ("Fab heavy chain"), or VL and CL domains of a light chain ("Fab light chain") of an immunoglobulin.

[0110] As used herein, the term "scFv" or "single chain antibody fragment" refers to a single chain consisting of a heavy chain variable region and a light chain variable region of an antibody being linearly linked together by a linker (e.g., a short peptide of 10-25 amino acids), which exhibits specific binding to an antigen. The scFv can be refer to a single chain comprising a signal peptide, a heavy chain variable region and a light chain variable region of an antibody being linearly linked together by a linker.[OHl] As used herein, the terms "constant region" and "constant domain" are interchangeable and have their meaning common in the art. The constant region is an antibody portion, e.g., a carboxyl terminal portion of a light and / or heavy chain which is not directly involved in binding of an antibody to antigen but which can exhibit various effector functions, such as interaction with the Fc receptor. The constant region of an immunoglobulin molecule generally has a more conserved amino acid sequence relative to an immunoglobulin variable domain.

[0112] As used herein, the term "heavy chain" when used in reference to an antibody can refer to any distinct type, e.g. , alpha (a), delta (d), epsilon (e), gamma (g), and mu (m), basedon the amino acid sequence of the constant domain, which give rise to IgA, IgD, IgE, IgG, and IgM classes of antibodies, respectively, including subclasses of IgG, e.g., IgGl, IgG2, IgG3, and IgG4. Heavy chain amino acid sequences are well known in the art. The heavy chain can be a human heavy chain.

[0113] As used herein, the term "light chain" when used in reference to an antibody can refer to any distinct type, e.g. , kappa (K) or lambda (1) based on the amino acid sequence of the constant domains. Light chain amino acid sequences are well known in the art. The light chain can be a human light chain.

[0114] The term "chimeric" antibodies or antigen-binding fragments thereof refers to antibodies or antigen-binding fragments thereof wherein the amino acid sequence is derived from two or more species. Typically, the variable region of both light and heavy chains corresponds to the variable region of antibodies or antigen-binding fragments thereof derived from one species of mammals (e.g. mouse, rat, rabbit, etc.) with the desired specificity, affinity, and capability while the constant regions are homologous to the sequences in antibodies or antigen-binding fragments thereof derived from another (usually human) to avoid eliciting an immune response in that species.

[0115] The term "humanized" antibody or antigen-binding fragment thereof refers to forms of non-human (e.g. murine) antibodies or antigen-binding fragments that are specific immunoglobulin chains, chimeric immunoglobulins, or fragments thereof that contain minimal non-human (e.g., murine) sequences. Typically, humanized antibodies or antigenbinding fragments thereof are human immunoglobulins in which residues from the complementary determining region (CDR) are replaced by residues from the CDR of a non- human species (e.g. mouse, rat, rabbit, hamster) that have the desired specificity, affinity, and capability ("CDR grafted") (Jones et al., Nature 321 :522-525 (1986); Riechmann et al., Nature 332:323-327 (1988); Verhoeyen et al., Science 239: 1534-1536 (1988)). In some instances, the Fv framework region (FR) residues of a human immunoglobulin are replaced with the corresponding residues in an antibody or fragment from a non-human species that has the desired specificity, affinity, and capability. The humanized antibody or antigenbinding fragment thereof can be further modified by the substitution of additional residues either in the Fv framework region and / or within the non-human CDR residues to refine and optimize the specificity, affinity, and / or capability of the antibody or antigen-binding fragment thereof. In general, the humanized antibody or antigen-binding fragment thereofwill comprise substantially all of at least one, and typically two or three, variable domains containing all or substantially all of the CDR regions that correspond to the non-human immunoglobulin whereas all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence. The humanized antibody or antigen-binding fragment thereof can also comprise at least a portion of an immunoglobulin constant region or domain (Fc), typically that of a human immunoglobulin. Examples of methods used to generate humanized antibodies are described in U.S. Pat. 5,225,539; Roguska et al., Proc. Natl. Acad. Sci., USA, 91(3):969- 973 (1994), and Roguska et al., Protein Eng. 9(10):895-904 (1996). A "humanized antibody" can be a resurfaced antibody.

[0116] The term "human" antibody or antigen-binding fragment thereof means an antibody or antigen-binding fragment thereof having an amino acid sequence derived from a human immunoglobulin gene locus, where such antibody or antigen-binding fragment is made using any technique known in the art. This definition of a human antibody or antigenbinding fragment thereof includes intact or full-length antibodies and fragments thereof.

[0117] The term “ADCC” or “antibody dependent cell-mediated cytotoxicity” as used herein is the cell-mediated reaction wherein nonspecific cytotoxic cells that express FcyRs recognize bound antibody on a target cell and subsequently cause lysis of the target cell. ADCC is correlated with binding to FcyRIIIa; increased binding to FcyRIIIa leads to an increase in ADCC activity.

[0118] The term “ADCP” or antibody dependent cell-mediated phagocytosis as used herein is meant the cell-mediated reaction wherein nonspecific cytotoxic cells that express FcyRs recognize bound antibody on a target cell and subsequently cause phagocytosis of the target cell.

[0119] In some aspects the humanized antibody heavy chain Fc region with ADCC enhancing mutations comprises, but is not limited to, one or more, of the following mutations H268F, S324T, S239D, and I332E and any combination thereof.

[0120] In vitro and / or in vivo cytotoxicity assays can be conducted to confirm the reduction / depletion of CDC and / or ADCC activities. For example, Fc receptor (FcR) binding assays can be conducted to ensure that the antibody lacks FcyR binding (hence likely lacking ADCC activity), but retains FcRn binding ability. The primary cells for mediating ADCC, NK cells, express FcyRIII only, whereas monocytes express FcyRI, FcyRII and FcyRIII FcR expression on hematopoietic cells is summarized in Table 3 on page 464 of Ravetch, J. V.and Kinet, J. P., Annu. Rev. Immunol. 9 (1991) 457-492. Non-limiting examples of in vitro assays to assess ADCC activity of a molecule of interest is described in U.S. Pat. No.5,500,362 (see, e.g. Hellstrom, I. et al., Proc. Natl. Acad. Sci. USA 83 (1986) 7059-7063; and Hellstrom, I. et al., Proc. Natl. Acad. Sci. USA 82 (1985) 1499-1502); U.S. Pat. No.5,821,337 (see Bruggemann, M. et al., J. Exp. Med. 166 (1987) 1351-1361). Alternatively, non-radioactive assays methods may be employed (see, for example, ACTI™ non-radioactive cytotoxicity assay for flow cytometry (CellTechnology, Inc. Mountain View, Calif.; and CytoTox 96® non-radioactive cytotoxicity assay (Promega, Madison, Wis.). Useful effector cells for such assays include peripheral blood mononuclear cells (PBMC) and Natural Killer (NK) cells.

[0121] Alternatively, or additionally, ADCC activity of the molecule of interest may be assessed in vivo, e.g., in an animal model such as that disclosed in Clynes, R. et al., Proc. Natl. Acad. Sci. USA 95 (1998) 652-656. Clq binding assays may also be carried out to confirm that the antibody is unable to bind Clq and hence lacks CDC activity. See, e.g., Clq and C3c binding ELISA in WO 2006 / 029879 and WO 2005 / 100402. To assess complement activation, a CDC assay may be performed (see, for example, Gazzano- Santoro, H. et al., J. Immunol. Methods 202 (1996) 163-171; Cragg, M. S. et al., Blood 101 (2003) 1045-1052; and Cragg, M. S. and M. J. Glennie, Blood 103 (2004) 2738-2743). FcRn binding and in vivo clearance / half-life determinations can also be performed using methods known in the art (see, e.g., Petkova, S. B. et al., Int. Immunol. 18 (2006) 1759-1769).

[0122] Antibodies with reduced effector function include those with substitution of one or more of Fc-region residues 238, 265, 269, 270, 297, 327 and 329 (U.S. Pat. No. 6,737,056). Such Fc mutants include Fc mutants with substitutions at two or more of amino acid positions 265, 269, 270, 297 and 327, including the so-called “DANA” Fc mutant with substitution of residues 265 and 297 to alanine (U.S. Pat. No. 7,332,581).By “effector function” as used herein is meant a biochemical event that results from the interaction of an antibody Fc region with an Fc receptor or ligand. Effector functions include but are not limited to ADCC, ADCP, and CDC.

[0123] Certain antibody variants with improved or diminished binding to FcRs are described in, e.g., U.S. Pat. No. 6,737,056; WO 2004 / 056312, and Shields, R. L. et al., J. Biol. Chem. 276 (2001) 6591-6604.

[0124] In certain aspects, an antibody variant comprises an Fc-region with one or more amino acid substitutions which improve ADCC, e.g., substitutions at positions 298, 333, and / or 334 of the Fc-region (EU numbering of residues).

[0125] "Binding affinity" generally refers to the strength of the sum total of non-covalent interactions between a single binding site of a molecule (e.g., an antibody or antigen binding fragment thereof) and its binding partner (e.g., an antigen). Unless indicated otherwise, as used herein, "binding affinity" refers to intrinsic binding affinity which reflects a 1 : 1 interaction between members of a binding pair (e.g., antibody or antigen binding fragment thereof and antigen). The affinity of a molecule X for its partner Y can generally be represented by the dissociation constant (KD). Affinity can be measured and / or expressed in a number of ways known in the art, including, but not limited to, equilibrium dissociation constant (KD), and equilibrium association constant (KA). The KD is calculated from the quotient of k0ff / k0n, whereas KA is calculated from the quotient of k0n / k0ff. konrefers to the association rate constant of, e.g., an antibody or antigen binding fragment thereof to an antigen, and koirrefers to the dissociation of, e.g., an antibody or antigen-binding fragment thereof from an antigen. The konand koir can be determined by techniques known to one of ordinary skill in the art, such as BIAcore® or KinExA.

[0126] As used herein, an "epitope" is a term in the art and refers to a localized region of an antigen to which an antibody or antigen-binding fragment thereof can specifically bind. An epitope can be, for example, contiguous amino acids of a polypeptide (linear or contiguous epitope) or an epitope can, for example, come together from two or more noncontiguous regions of a polypeptide or polypeptides (conformational, non-linear, discontinuous, or non-contiguous epitope).

[0127] The epitope to which an antibody or antigen-binding fragment thereof binds can be determined by, e.g., NMR spectroscopy, X-ray diffraction crystallography studies, ELISA assays, hydrogen / deuterium exchange coupled with mass spectrometry (e.g., liquid chromatography electrospray mass spectrometry), array-based oligo-peptide scanning assays, and / or mutagenesis mapping (e.g., site-directed mutagenesis mapping).

[0128] As used herein, an antibody is to "competitively inhibit" binding of a reference antibody to a given epitope if it preferentially binds to that epitope or an overlapping epitope to the extent that it blocks, to some degree, binding of the reference antibody to the epitope. Competitive inhibition can be determined by any method known in the art, for example,competition ELISA assays. An antibody can be said to competitively inhibit binding of the reference antibody to a given epitope by at least 90%, at least 80%, at least 70%, at least 60%, or at least 50%.

[0129] As used herein, the term “promoter / regulatory sequence” refers to a nucleic acid sequence required to express a gene product operably linked to a promoter / regulatory sequence. The term “constitutive” promoter refers to a nucleotide sequence that, when operably linked to a polynucleotide encoding or specifying a gene product, results in the production of a gene product in the cell under most or all physiological conditions of the cell. The term “inducible” promoter means that when operably linked to a polynucleotide encoding a specified gene product, it basically results in the production of a gene in the cell only when the inducer corresponding to the promoter is present in the cell The nucleotide sequence of the product.

[0130] As used herein, the term “expression” refers to a process by which a gene produces a biochemical, for example, a polypeptide. The process includes any manifestation of the functional presence of the gene within the cell including, without limitation, gene knockdown as well as both transient expression and stable expression. It includes without limitation transcription of the gene into messenger RNA (mRNA), and the translation of such mRNA into polypeptide(s). Expression of a gene produces a “gene product.” As used herein, a gene product can be either a nucleic acid, e.g., a messenger RNA produced by transcription of a gene, or a polypeptide which is translated from a transcript. Gene products described herein further include nucleic acids with post transcriptional modifications, e.g., polyadenylation, or polypeptides with post translational modifications, e.g., methylation, glycosylation, the addition of lipids, association with other protein subunits, proteolytic cleavage, and the like.

[0131] The nucleic acid molecule can be cloned into any number of different types of vectors. For example, the nucleic acid molecule can be cloned into a vector including, but not limited to a plasmid, a phagemid, a phage derivative, an animal virus, and a cosmid. Vectors of particular interest include expression vectors, replication vectors, probe generation vectors, and sequencing vectors.

[0132] The term "vector" as used herein, includes, but is not limited to, a viral vector, a plasmid, an RNA vector or a linear or circular DNA or RNA molecule which can include chromosomal, non-chromosomal, semi -synthetic or synthetic nucleic acids. In some cases,the vectors are those capable of autonomous replication (episomal vector) and / or expression of nucleic acids to which they are linked (expression vectors). Large numbers of suitable vectors are known to those of skill in the art and are commercially available. Viral vectors include retrovirus, adenovirus, parvovirus (e.g., adenoassociated viruses), coronavirus, negative strand RNA viruses such as orthomyxovirus (e.g., influenza virus), rhabdovirus (e.g., rabies and vesicular stomatitis virus), paramyxovirus (e.g. measles and Sendai), positive strand RNA viruses such as picornavirus and alphavirus, and double-stranded DNA viruses including adenovirus, herpesvirus (e.g., Herpes Simplex virus types 1 and 2, Epstein-Barr virus, cytomegalovirus), and poxvirus (e.g., vaccinia, fowlpox and canarypox). Other viruses include Norwalk virus, togavirus, flavivirus, reoviruses, papovavirus, hepadnavirus, and hepatitis virus, for example. Examples of retroviruses include: avian leukosis-sarcoma, mammalian C-type, B-type viruses, D type viruses, HTLV-BLV group, and lentivirus.

[0133] As used herein, the term “expression vector” refers to a vector comprising a recombinant polynucleotide comprising an expression control sequence operably linked to the nucleotide sequence to be expressed. The expression vector contains sufficient cis-acting elements for expression; other elements for expression can be provided by the host cell or in an in vitro expression system. Expression vectors include expression vectors known in the art, including cosmids, plasmids (for example, naked or contained in liposomes), and viruses incorporating recombinant polynucleotides (for example, lentivirus, retrovirus, adenovirus, and adeno-associated virus).

[0134] The expression vector may be provided to a cell in the form of a viral vector. Viral vector technology is well known in the art and is described, for example, in Sambrook et ak, 2012, MOLECULAR CLONING: A LABORATORY MANUAL, volumes 1-4, Cold Spring Harbor Press, NY), and in other virology and molecular biology manuals. Viruses, which are useful as vectors include, but are not limited to, retroviruses, adenoviruses, adeno- associated viruses, herpes viruses, and lentiviruses. In general, a suitable vector contains an origin of replication functional in at least one organism, a promoter sequence, convenient restriction endonuclease sites, and one or more selectable markers, (e.g., WO 01 / 96584; WO 01 / 29058; and U.S. Pat. No. 6,326,193).

[0135] Additional promoter elements, e.g., enhancers, regulate the frequency of transcriptional initiation. Typically, these are located in the region 30-110 bp upstream of the start site, although a number of promoters have recently been shown to contain functionalelements downstream of the start site as well. The spacing between promoter elements frequently is flexible, so that promoter function is preserved when elements are inverted or moved relative to one another. In the thymidine kinase (tk) promoter, the spacing between promoter elements can be increased to 50 bp apart before activity begins to decline. Depending on the promoter, individual elements can function either cooperatively or independently to activate transcription.

[0136] As used herein, the term “transfer vector” refers to a composition containing an isolated nucleic acid and a substance that can be used to deliver the isolated nucleic acid to the inside of a cell. Many vectors are known in the art, including but not limited to linear polynucleotides, polynucleotides associated with ionic or amphiphilic compounds, plasmids, and viruses. Therefore, a transfer vector can include autonomously replicating plasmids or viruses. The term transfer vector should also be interpreted to further include non-plasmid and non-viral compounds that facilitate the transfer of nucleic acids into cells, such as polylysine compounds, liposomes, and the like. Examples of virus transfer vectors include, but are not limited to, adenoviral vectors, adeno-associated virus vectors, retroviral vectors, lentiviral vectors, and the like.

[0137] A “lentivirus” as used herein refers to a genus of the Retroviridae family. Lentiviruses are unique among the retroviruses in being able to infect non-dividing cells; they can deliver a significant amount of genetic information into the DNA of the host cell, so they are one of the most efficient methods of a gene delivery vector. HIV, SIV, and FIV are all examples of lentiviruses. Vectors derived from lentiviruses offer the means to achieve significant levels of gene transfer in vivo.

[0138] As used herein, the term “operably linked” or “transcription control” refers to a functional linkage between a regulatory sequence and a heterologous nucleic acid sequence, which results in the expression of the latter. For example, when the first nucleic acid sequence and the second nucleic acid sequence are arranged in a functional relationship, the first nucleic acid sequence and the second nucleic acid sequence are operably linked. For example, if a promoter affects the transcription or expression of a coding sequence, the promoter is operably linked to the coding sequence. The operably linked DNA sequences may be adjacent to each other, and for example, in the case where two protein coding regions need to be linked, the DNA sequences are in the same reading frame.

[0139] Methods of introducing and expressing genes into a cell are known in the art. In the context of an expression vector, the vector can be readily introduced into a host cell, e.g., mammalian, bacterial, yeast, or insect cell by any method in the art. For example, the expression vector can be transferred into a host cell by physical, chemical, or biological means.

[0140] As used herein, the term “host cell” can be any type of cell, e.g., a primary cell, a cell in culture, or a cell from a cell line. The term “host cell” refers to a cell transfected with a nucleic acid molecule and the progeny or potential progeny of such a cell. Progeny of such a cell may not be identical to the parent cell transfected with the nucleic acid molecule, e.g., due to mutations or environmental influences that may occur in succeeding generations or integration of the nucleic acid molecule into the host cell genome.

[0141] Physical methods for introducing a polynucleotide into a host cell include calcium phosphate precipitation, lipofection, particle bombardment, microinjection, electroporation, and the like. Methods for producing cells comprising vectors and / or exogenous nucleic acids are well-known in the art. See, for example, Sambrook et al., 2012, MOLECULAR CLONING: A LABORATORY MANUAL, volumes 1 -4, Cold Spring Harbor Press, NY).

[0142] Biological methods for introducing a polynucleotide of interest into a host cell include the use of DNA and RNA vectors. RNA vectors include vectors having a RNA promoter and / other relevant domains for production of a RNA transcript. Viral vectors, and especially retroviral vectors, have become the most widely used method for inserting genes into mammalian, e.g., human cells. Other viral vectors may be derived from lentivirus, poxviruses, herpes simplex virus, adenoviruses and adeno-associated viruses, and the like. See, for example, U.S. Pat. Nos. 5,350,674 and 5,585,362.

[0143] Chemical means for introducing a polynucleotide into a host cell include colloidal dispersion systems, such as macromolecule complexes, nanocapsules, microspheres, beads, and lipid-based systems including oil-in-water emulsions, micelles, mixed micelles, and liposomes. An exemplary colloidal system for use as a delivery vehicle in vitro and in vivo is a liposome (e.g. , an artificial membrane vesicle). In the case where a non-viral delivery system is utilized, an exemplary delivery vehicle is a liposome. The use of lipid formulations is contemplated for the introduction of the nucleic acids into a host cell (in vitro, ex vivo or in vivo). In another aspect, the nucleic acid may be associated with a lipid. The nucleic acid associated with a lipid may be encapsulated in the aqueous interior of a liposome,interspersed within the lipid bilayer of a liposome, attached to a liposome via a linking molecule that is associated with both the liposome and the oligonucleotide, entrapped in a liposome, complexed with a liposome, dispersed in a solution containing a lipid, mixed with a lipid, combined with a lipid, contained as a suspension in a lipid, contained or complexed with a micelle, or otherwise associated with a lipid. Lipid, lipid / DNA or lipid / expression vector associated compositions are not limited to any particular structure in solution. For example, they may be present in a bilayer structure, as micelles, or with a “collapsed” structure. They may also simply be interspersed in a solution, possibly forming aggregates that are not uniform in size or shape. Lipids are fatty substances, which may be naturally occurring or synthetic lipids. For example, lipids include the fatty droplets that naturally occur in the cytoplasm as well as the class of compounds which contain long-chain aliphatic hydrocarbons and their derivatives, such as fatty acids, alcohols, amines, amino alcohols, and aldehydes.

[0144] As used herein, the terms, “transfection” and “transduction,” refer to the processes by which an exogenous nucleic acid sequence is introduced into a host cell. The nucleic acid can be integrated into the host cell DNA or can be maintained extrachromosomally. The nucleic acid can be maintained transiently or can be a stable introduction. Transfection can be accomplished by a variety of means known in the art including but not limited to calcium phosphate-DNA co-precipitation, DEAE-dextran-mediated transfection, polybrene-mediated transfection, electroporation, microinjection, liposome fusion, lipofection, protoplast fusion, retroviral infection, and biolistics.

[0145] The term "drug" or "payload" as used herein means any chemical or biological substance that causes a change in an organism's physiology (e.g., a chemotherapeutic drug).

[0146] The terms "anticancer drug", "chemotherapeutic drug", and "cytotoxic agent", refer to drugs (i.e., chemical compounds) or prodrugs known to, or suspected of being able to treat a cancer (e.g., to kill cancer cells, prohibit proliferation of cancer cells, or treat a symptom related to cancer).

[0147] A "linker" is any chemical moiety that is capable of linking a compound, usually a drug to an agent in a stable, covalent manner. Linkers can be susceptible to or be substantially resistant to acid-induced cleavage, light-induced cleavage, peptidase-induced cleavage, esterase-induced cleavage, and disulfide bond cleavage, at conditions under which the compound or the agent remains active. In some aspects disclosed herein, the linker is acleavable linker or dissociable linker. In some aspects disclosed herein, the linker is an amino acid linker.

[0148] It is to be understood that headers are provided solely for ease of reading, and are not intended to be limiting. Aspects disclosed under one or more headers can be applicable to or combinable with aspects disclosed under one or more other headers.

[0149] It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as "solely", "only" and the like in connection with the recitation of claim elements, or the use of a "negative" limitation.I. Anti-TCRVB Antibodies and Antigen-Binding Fragments Thereof

[0150] In some aspects, provided herein are antibodies (e.g. monoclonal antibodies) and antigen-binding fragments thereof which specifically bind to VB region of a TCR (e.g., human VB region of a TCR).

[0151] In some aspects described herein, the antibody or antigen-binding fragment, for example, comprises (i) a variable heavy chain (VH) which comprises: (a) CDR1, CDR2 and CDR3 according to SEQ ID NOTO, SEQ ID NO: 11, and SEQ ID NO: 12, respectively; or (b) CDR1, CDR2 and CDR3 according to SEQ ID NO:370, SEQ ID NO:371, and SEQ ID NO:372, respectively; or (c) CDR1, CDR2 and CDR3 according to SEQ ID NO:373, SEQ ID NO: 374, and SEQ ID NO: 375 respectively; or (d) CDR1, CDR2 and CDR3 according to SEQ ID NO:376, SEQ ID NO:377, and SEQ ID NO:378, respectively; or (e) CDR1, CDR2 and CDR3 according to SEQ ID NO:379, SEQ ID NO:380, and SEQ ID NO:381 respectively; or (f) CDR1, CDR2 and CDR3 according to SEQ ID NO: 382, SEQ ID NO: 383, and SEQ ID NO:384, respectively; or (g) CDR1, CDR2 and CDR3 according to SEQ ID NO:385, SEQ ID NO:386, and SEQ ID NO:387, respectively; or (h) CDR1, CDR2 and CDR3 according to SEQ ID NO:388, SEQ ID NO:389, and SEQ ID NO:390, respectively; or (i) CDR1, CDR2 and CDR3 according to SEQ ID NO:391, SEQ ID NO: 392, and SEQ ID NO:393, respectively; or (j) CDR1, CDR2 and CDR3 according to SEQ ID NO:394, SEQ ID NO:395, and SEQ ID NO:396, respectively; or (k) CDR1, CDR2 and CDR3 according to SEQ ID NO: 397, SEQ ID NO: 398, and SEQ ID NO: 399, respectively; or (1) CDR1, CDR2 and CDR3 according to SEQ ID NO:400, SEQ ID NO:401, and SEQ ID NO:402, respectively; or (m) CDR1, CDR2 and CDR3 according to SEQ ID NO:403, SEQ ID NO:404, and SEQ ID NO:405, respectively; or (n) CDR1, CDR2 and CDR3 according toSEQ ID NO:406, SEQ ID NO:407, and SEQ ID NO:408, respectively; or (o) CDR1, CDR2 and CDR3 according to SEQ ID NO:409, SEQ ID NO:410, and SEQ ID NO:411, respectively; or (p) CDR1, CDR2 and CDR3 according to SEQ ID NO:412, SEQ ID NO:413, and SEQ ID NO:414, respectively; or (q) CDR1, CDR2 and CDR3 according to SEQ ID NO:415, SEQ ID NO:416, and SEQ ID NO:417, respectively; or (r) CDR1, CDR2 and CDR3 according to SEQ ID NO:584, SEQ ID NO:585, and SEQ ID NO:586, respectively; or (s) CDR1, CDR2 and CDR3 according to SEQ ID NO:587, SEQ ID NO:588, and SEQ ID NO:589, respectively; or (t) CDR1, CDR2 and CDR3 according to SEQ ID NO:590, SEQ ID NO:591, and SEQ ID NO:592, respectively; (u) CDR1, CDR2 and CDR3 according to SEQ ID NO:593, SEQ ID NO:594, and SEQ ID NO:595, respectively; (v) CDR1, CDR2 and CDR3 according to SEQ ID NO:370, SEQ ID NO:681, and SEQ ID NO:372, respectively; or (w) CDR1, CDR2 and CDR3 according to SEQ ID NO:675, SEQ ID NO:676, and SEQ ID NO:677; and / or (ii) a variable light chain (VL) which comprises: (a) CDR1, CDR2 and CDR3 according to SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, respectively; or (b) CDR1, CDR2 and CDR3 according to SEQ ID NO:418, SEQ ID NO:419, SEQ ID NO:420, respectively; or (c) CDR1, CDR2 and CDR3 according to SEQ ID NO:421, SEQ ID NO:422, SEQ ID NO:423, respectively; or (d) CDR1, CDR2 and CDR3 according to SEQ ID NO:424, SEQ ID NO:425, SEQ ID NO:426, respectively; or (e) CDR1, CDR2 and CDR3 according to SEQ ID NO:427, SEQ ID NO:428, SEQ ID NO:429, respectively; or (f) CDR1, CDR2 and CDR3 according to SEQ ID NO:430, SEQ ID NO:431, SEQ ID NO:432, respectively; or (g) CDR1, CDR2 and CDR3 according to SEQ ID NO:433, SEQ ID NO:434, SEQ ID NO:435, respectively; or (h) CDR1, CDR2 and CDR3 according to SEQ ID NO:436, SEQ ID NO:437, SEQ ID NO:438, respectively; or (i) CDR1, CDR2 and CDR3 according to SEQ ID NO:439, SEQ ID NO:440, SEQ ID NO:441, respectively; or (j) CDR1, CDR2 and CDR3 according to SEQ ID NO:442, SEQ ID NO:443, SEQ ID NO:444, respectively; or (k) CDR1, CDR2 and CDR3 according to SEQ ID NO:445, SEQ ID NO:446, SEQ ID NO:447, respectively; or (1) CDR1, CDR2 and CDR3 according to SEQ ID NO:448, SEQ ID NO:449, SEQ ID NO:450, respectively; or (m) CDR1, CDR2 and CDR3 according to SEQ ID NO:451, SEQ ID NO:452, SEQ ID NO:453, respectively; or (n) CDR1, CDR2 and CDR3 according to SEQ ID NO:454, SEQ ID NO:455, SEQ ID NO:456, respectively; or (o) CDR1, CDR2 and CDR3 according to SEQ ID NO:457, SEQ ID NO:458, SEQ ID NO:459, respectively; or (p) CDR1, CDR2 and CDR3 according to SEQ ID NO:460, SEQ ID NO:461, SEQ ID NO:462,respectively; or (q) CDR1, CDR2 and CDR3 according to SEQ ID NO:463, SEQ ID NO:464, SEQ ID NO:465, respectively; or (r) CDR1, CDR2 and CDR3 according to SEQ ID NO:596, SEQ ID NO:597, SEQ ID NO:598, respectively; or (s) CDR1, CDR2 and CDR3 according to SEQ ID NO:599, SEQ ID NO:600, SEQ ID NO:601, respectively; or (t) CDR1, CDR2 and CDR3 according to SEQ ID NO: 602, SEQ ID NO: 603, SEQ ID NO: 604, respectively; (u) CDR1, CDR2 and CDR3 according to SEQ ID NO:605, SEQ ID NO:606, SEQ ID NO:607, respectively, or SEQ ID NO: 608, SEQ ID NO: 609, SEQ ID NO: 610, respectively; (v) CDR1, CDR2 and CDR3 according to SEQ ID NO: 682, SEQ ID NO: 419, SEQ ID NO: 420, respectively, SEQ ID NO: 682, SEQ ID NO: 683, SEQ ID NO: 420, respectively, or SEQ ID NO: 418, SEQ ID NO: 684, SEQ ID NO: 420, respectively; or (w) CDR1, CDR2 and CDR3 according to SEQ ID NO: 678, SEQ ID NO:679, SEQ ID NO:680, respectively.

[0152] In some aspects described herein, an antibody or antigen-binding fragment thereof, is capable of specifically binding to a TCR VB region, comprising a heavy chain variable region (VH) having an amino acid sequence according to any of SEQ ID NOs: 228- 295, 559-569, and 632-650. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 85% sequence identity to any one of SEQ ID NOs: 228-295 and 559-569. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 86% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, and 650. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 87% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, and 650. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 88% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, and 650. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 89% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, 639, 641, 642, and 650. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, 632, 638, 639, 641, 642, and 650. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 91% sequence identity to any one of SEQ ID NOs: 228- 295, 559-569, 632, 633, 638-642, 648, and 650. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 92% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, 632, 633, 638-642, and 648-650. Insome aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 93% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, 632, 633, 638-642, and 648-650. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 94% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, 632, 633, 638-642, and 648-650. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, 632, 633, 638-643, and 648- 650. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 96% sequence identity to any one of SEQ ID NOs: 228-295, 559- 569, 632, 633, 635, 637-643, and 647-650. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 97% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, 632-643, and 646-650. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 98% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, and 632-650. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 99% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, and 632-650.In some aspects described herein, the variable heavy chain comprises an amino acid sequence according to any one of SEQ ID NOs: 228-295, 559-569, and 632-650.

[0153] In some aspects described herein, an antibody or antigen-binding fragment thereof, is capable of specifically binding to a TCR VB region, comprising a heavy chain variable region (VH) having an amino acid sequence according to any of SEQ ID NOs: 685- 700. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 92% sequence identity to SEQ ID NO: 687. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 93% sequence identity to SEQ ID NO: 687 or 698. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 94% sequence identity to SEQ ID NO: 687 or 698. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 685, 687, 697, and 698. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 96% sequence identity to any one of SEQ ID NOs: 685, 687, 688, 697, and 698. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 97% sequence identity to anyone of SEQ ID NOs: 685, 687, 688, 693, and 697-700. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 98% sequence identity to any one of SEQ ID NOs: 685-689, 693, and 697-700. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 99% sequence identity to any one of SEQ ID NOs: 685-689, 691, and 693-700.

[0154] In some aspects described herein, the antibody or antigen-binding fragment comprising a heavy chain variable region (VH) as described above, further comprises a light chain variable region (VL) having an amino acid sequence according to any of SEQ ID NOs: 296-369, 570-583, 652-671.

[0155] In some aspects described herein, the antibody or antigen-binding fragment comprising a heavy chain variable region (VH) as described above, further comprises a light chain variable region (VL) having an amino acid sequence according to any of SEQ ID NOs: 701-716.

[0156] In some aspects described herein, an antibody or antigen-binding fragment thereof, is capable of specifically binding to a TCR VB region, comprising a light chain variable region (VL) having an amino acid sequence according to any of SEQ ID NOs: 296- 369, 570-583, and 652-671. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 85% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, and 671. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 86% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 662, and 671. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 87% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 662, and 671. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 88% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 662, 670, and 671. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 89% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 662, 670, and 671. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 662, 670, and 671. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 91% sequence identity to any one of SEQ ID NOs: 296-369, 570- 583, 662, 670, and 671. In some aspects described herein, the variable light chain comprisesan amino acid sequence having at least 92% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 662, and 669-671. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 93% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 652, 662, and 669-671. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 94% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 652, 661, 662, and 669-671. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 652-654, 657, 659, 661, 662, and 669-671. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 96% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 652-659, 661, 662, 664, 667, and 669-671. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 97% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 652-662, 664, 665, 667, and 669-671. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 98% sequence identity to any one of SEQ ID NOs: 296- 369, 570-583, 652-665, 667, and 669-671. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 99% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 652-665, and 667-671. In some aspects described herein, the variable light chain comprises an amino acid sequence according to any one of SEQ ID NOs: 296-369, 570-583, and 652-671.

[0157] In some aspects described herein, an antibody or antigen-binding fragment thereof, is capable of specifically binding to a TCR VB region, comprising a light chain variable region (VL) having an amino acid sequence according to any of SEQ ID NOs: 701- 716. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 82% sequence identity to SEQ ID NOs: 714 or 715. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 83% sequence identity to SEQ ID NOs: 714 or 715. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 84% sequence identity to any one of SEQ ID NOs: 713-715. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 85% sequence identity to any one of SEQ ID NOs: 713-715. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 86% sequence identity to any one of SEQ ID NOs:713-715. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 87% sequence identity to any one of SEQ ID NOs: 713-715. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 88% sequence identity to any one of SEQ ID NOs: 713-715. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 89% sequence identity to any one of SEQ ID NOs: 713-715. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOs: 713-715. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 91% sequence identity to any one of SEQ ID NOs: 713-715. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 92% sequence identity to any one of SEQ ID NOs: 711 and 713-715. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 93% sequence identity to any one of SEQ ID NOs: 709, 711, and 713-715. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 94% sequence identity to any one of SEQ ID NOs: 709, 711, and 713-715. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 709, 711, and 713-716. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 96% sequence identity to any one of SEQ ID NOs: 703- 706, 709-711, and 713-716. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 97% sequence identity to any one of SEQ ID NOs: 701, 703-707, 709-711, and 713-716. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 98% sequence identity to any one of SEQ ID NOs: 701-711, and 713-716. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 99% sequence identity to any one of SEQ ID NOs: 701-716.

[0158] In some aspects described herein the antibody or antigen-binding fragment comprising a light chain variable region (VL) as described above, further comprises a heavy chain variable region (VH) having an amino acid sequence according to any of SEQ ID NOs: 228-295, 559-569, and 632-650.

[0159] In some aspects described herein the antibody or antigen-binding fragment comprising a light chain variable region (VL) as described above, further comprises a heavychain variable region (VH) having an amino acid sequence according to any of SEQ ID NOs: 685-700.

[0160] In some aspects described herein, the variable heavy chain comprises an amino acid sequence having any percent identity described above to any one of SEQ ID NOs: 228- 295, 559-569, and 632-650, and the variable light chain comprises an amino acid sequence having any percent identity described above to any one of SEQ ID NOs: 296-369, 570-583, and 652-671. To illustrate, a non-limiting example pairing of variable heavy and light chains includes a variable heavy chain comprising an amino acid sequence having at least 88% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, and 632-650, and a variable light chain comprising an amino acid sequence having at least 93% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 652, 662, and 669-671. In other aspects decribed herein, pairing of variable heavy and light chains includes a variable heavy chain comprising an amino acid sequence having any percent identity described above to any one of SEQ ID NOs: 228-295, 559-569, and 632-650, and a variable light chain comprising an amino acid sequence according to any one of SEQ ID NOs: 296-369, 570-583, and 652-671. In other aspects described herein, pairing of variable heavy and light chains includes a variable heavy chain comprising an amino acid sequence according to any one of SEQ ID NOs: 228-295, 559-569, and 632-650, and a variable light chain comprising an amino acid sequence having any percent identity described above to any one of SEQ ID NOs: 296-369, 570-583, and 652- 671. To illustrate, a non-limiting example pairing of variable heavy and light chains includes a variable heavy chain comprising an amino acid sequence having at least 92% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, 632, 633, 638-642, and 648-650, and a variable light chain comprising an amino acid sequence according to any one of SEQ ID NOs: 296-369, 570-583, 652-671. In yet other aspects described herein, the variable heavy chain comprises an amino acid sequence according to any one of SEQ ID NOs: 228-295, 559-569, and 632-650, and the variable light chain comprises an amino acid sequence according to any one of SEQ ID NOs: 296-369, 570-583, and 652-671.

[0161] In some aspects described herein, the variable heavy chain comprises an amino acid sequence having any percent identity described above to any one of SEQ ID NOs: 228- 295, 559-569, 632-650, and 685-700, and the variable light chain comprises an amino acid sequence having any percent identity described above to any one of SEQ ID NOs: 296-369, 570-583, 652-671, and 701-716. To illustrate, a non-limiting example pairing of variableheavy and light chains includes a variable heavy chain comprising an amino acid sequence having at least 92% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, 632- 650, and 685-700, and a variable light chain comprising an amino acid sequence having at least 93% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 652, 662, 669- 671, 709, 711, and 713-715. In other aspects described herein, pairing of variable heavy and light chains includes a variable heavy chain comprising an amino acid sequence having any percent identity described above to any one of SEQ ID NOs: 228-295, 559-569, 632-650, and 685-700, and a variable light chain comprising an amino acid sequence according to any one of SEQ ID NOs: 296-369, 570-583, 652-671, and 701-716. In other aspects described herein, pairing of variable heavy and light chains includes a variable heavy chain comprising an amino acid sequence according to any one of SEQ ID NOs: 228-295, 559-569, 632-650, and 685-700, and a variable light chain comprising an amino acid sequence having any percent identity described above to any one of SEQ ID NOs: 296-369, 570-583, 652-671, and 701- 716. To illustrate, a non-limiting example pairing of variable heavy and light chains includes a variable heavy chain comprising an amino acid sequence having at least 92% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, 632, 633, 638-642, 648-650, and 687, and a variable light chain comprising an amino acid sequence according to any one of SEQ ID NOs: 296-369, 570-583, 652-671, and 701-716. In yet other aspects described herein, the variable heavy chain comprises an amino acid sequence according to any one of SEQ ID NOs: 228-295, 559-569, 632-650, and 685-700, and the variable light chain comprises an amino acid sequence according to any one of SEQ ID NOs: 296-369, 570-583, 652-671, and 701-716.

[0162] In some aspects described herein, the antibody or antigen-binding fragment thereof is capable of specifically binding to TCR VB2 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 228, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 296; SEQ ID NO: 297; SEQ ID NO: 298; SEQ ID NO: 299; SEQ ID NO: 300; SEQ ID NO: 301; SEQ ID NO: 302; or SEQ ID NO: 303. In some aspects, the VB2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 229, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 296; SEQ ID NO: 297; SEQ ID NO: 298; SEQ ID NO: 299; SEQ ID NO: 300; SEQ ID NO: 301;SEQ ID NO: 302; or SEQ ID NO: 303. In some aspects, the VB2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 230, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 296; SEQ ID NO: 297; SEQ ID NO: 298; SEQ ID NO: 299; SEQ ID NO: 300; SEQ ID NO: 301; SEQ ID NO: 302; or SEQ ID NO: 303. In some aspects, the VB2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 231, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 296; SEQ ID NO: 297; SEQ ID NO: 298; SEQ ID NO: 299; SEQ ID NO: 300; SEQ ID NO: 301; SEQ ID NO: 302; or SEQ ID NO: 303. In some aspects, the VB2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 232, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 296; SEQ ID NO: 297; SEQ ID NO: 298; SEQ ID NO: 299; SEQ ID NO: 300; SEQ ID NO: 301; SEQ ID NO: 302; or SEQ ID NO: 303. In some aspects, the VB2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 233, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 296; SEQ ID NO: 297; SEQ ID NO: 298; SEQ ID NO: 299; SEQ ID NO: 300; SEQ ID NO: 301; SEQ ID NO: 302; or SEQ ID NO: 303. In some aspects, the VB2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 234, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 296; SEQ ID NO: 297; SEQ ID NO: 298; SEQ ID NO: 299; SEQ ID NO: 300; SEQ ID NO: 301; SEQ ID NO: 302; or SEQ ID NO: 303. In some aspects, the VB2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 235, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 296; SEQ ID NO: 297; SEQ ID NO: 298; SEQ ID NO: 299; SEQ ID NO: 300; SEQ ID NO: 301; SEQ ID NO: 302; or SEQ ID NO: 303. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0163] In some aspects described herein, the antibody or antigen binding fragment thereof is capable of specifically binding to VB7.2 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB7.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 236, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 304;SEQ ID NO: 305; SEQ ID NO: 306; or SEQ ID NO: 307. In some aspects, the VB7.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 237, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 304; SEQ ID NO: 305; SEQ ID NO: 306; or SEQ ID NO: 307. In some aspects, the VB7.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 238, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 304; SEQ ID NO: 305; SEQ ID NO: 306; or SEQ ID NO: 307. In some aspects, the VB7.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 638, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 656; SEQ ID NO: 657; SEQ ID NO: 658; SEQ ID NO: 659; or SEQ ID NO: 660. In some aspects, the VB7.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 639, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 656; SEQ ID NO: 657; SEQ ID NO: 658; SEQ ID NO: 659; or SEQ ID NO: 660. In some aspects, the VB7.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 640, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 656; SEQ ID NO: 657; SEQ ID NO: 658; SEQ ID NO: 659; or SEQ ID NO: 660. In some aspects, the VB7.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 641, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 656; SEQ ID NO: 657; SEQ ID NO: 658; SEQ ID NO: 659; or SEQ ID NO: 660. In some aspects, the VB7.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 642, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 656; SEQ ID NO: 657; SEQ ID NO: 658; SEQ ID NO: 659; or SEQ ID NO: 660. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0164] In some aspects described herein, the antibody or antigen binding fragment thereof is capable of specifically binding to VB4, and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB4 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 239, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 308; orSEQ ID NO: 309. In some aspects, the VB4 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 240, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 308; or SEQ ID NO: 309. In some aspects, the VB4 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 241, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 308; or SEQ ID NO: 309. In some aspects, the VB4 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 242, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 308; or SEQ ID NO: 309. In some aspects, the VB4 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 243, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 308; or SEQ ID NO: 309. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0165] In some aspects described herein, the antibody or antigen binding fragment thereof is capable of specifically binding to VB13.2 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL), In some aspects described herein, the antibody or antigen binding fragment thereof is capable of specifically binding to VB13.2 and, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 244, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 310; SEQ ID NO: 311; SEQ ID NO: 312; SEQ ID NO: 313; SEQ ID NO: 314; SEQ ID NO: 315; SEQ ID NO: 316; or SEQ ID NO: 317. In some aspects, the VB13.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 245, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 310; SEQ ID NO: 311; SEQ ID NO: 312; SEQ ID NO: 313; SEQ ID NO: 314; SEQ ID NO: 315; SEQ ID NO: 316; or SEQ ID NO: 317. In some aspects, the VB13.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 246, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 310; SEQ ID NO: 311; SEQ ID NO: 312; SEQ ID NO: 313; SEQ ID NO: 314; SEQ ID NO: 315; SEQ ID NO: 316; or SEQ ID NO: 317. In some aspects, the VB13.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 247, and / or (ii) avariable light chain (VL) according to SEQ ID NO: 310; SEQ ID NO: 311; SEQ ID NO: 312; SEQ ID NO: 313; SEQ ID NO: 314; SEQ ID NO: 315; SEQ ID NO: 316; or SEQ ID NO: 317. In some aspects, the VB13.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 248, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 310; SEQ ID NO: 311; SEQ ID NO: 312; SEQ ID NO: 313; SEQ ID NO: 314; SEQ ID NO: 315; SEQ ID NO: 316; or SEQ ID NO: 317. In some aspects, the VB13.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 249, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 310; SEQ ID NO: 311; SEQ ID NO: 312; SEQ ID NO: 313; SEQ ID NO: 314; SEQ ID NO: 315; SEQ ID NO: 316; or SEQ ID NO: 317. In some aspects, the VB13.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 250, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 310; SEQ ID NO: 311; SEQ ID NO: 312; SEQ ID NO: 313; SEQ ID NO: 314; SEQ ID NO: 315; SEQ ID NO: 316; or SEQ ID NO: 317. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0166] In some aspects described herein, the antibody or antigen binding fragment thereof is capable of specifically binding to VB14 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB14 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 251, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 318; or SEQ ID NO: 319. SEQ ID NO: 320; SEQ ID NO: 321; SEQ ID NO: 322; or SEQ ID NO: 323. In some aspects, the VB14 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 252, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 318; or SEQ ID NO: 319. SEQ ID NO: 320; SEQ ID NO: 321; SEQ ID NO: 322; or SEQ ID NO: 323. In some aspects, the VB14 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 253, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 318; or SEQ ID NO: 319. SEQ ID NO: 320; SEQ ID NO: 321; SEQ ID NO: 322; or SEQ ID NO: 323. In some aspects, the VB14 antibody or antigen binding fragment, for example, comprises(i) a variable heavy chain (VH) according to SEQ ID NO: 254, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 318; or SEQ ID NO: 319. SEQ ID NO: 320; SEQ ID NO: 321; SEQ ID NO: 322; or SEQ ID NO: 323. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0167] In some aspects described herein, the antibody or antigen binding fragment thereof is capable of specifically binding to VB22 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB22 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 255, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 324; SEQ ID NO: 325; SEQ ID NO: 326; or SEQ ID NO: 327. In some aspects, the VB22 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 256, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 324; SEQ ID NO: 325; SEQ ID NO: 326; or SEQ ID NO: 327. In some aspects, the VB22 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 257, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 324; SEQ ID NO: 325; SEQ ID NO: 326; or SEQ ID NO: 327. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0168] In some aspects described herein, the antibody or antigen binding fragment thereof is capable of specifically binding to VB11 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB11 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 258, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 328; SEQ ID NO: 329; SEQ ID NO: 330; or SEQ ID NO: 331. In some aspects, the VB11 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 259, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 328; SEQ ID NO: 329; SEQ ID NO: 330; or SEQ ID NO: 331, In some aspects, the VB11 antibody or antigen binding fragment, for example, comprises (i) a variable heavychain (VH) according to SEQ ID NO: 260, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 328; SEQ ID NO: 329; SEQ ID NO: 330; or SEQ ID NO: 331. In some aspects, the VB11 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 261, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 332; SEQ ID NO: 333; SEQ ID NO: 334; SEQ ID NO: 335; or SEQ ID NO: 336. In some aspects, the VB11 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 262, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 332; SEQ ID NO: 333; SEQ ID NO: 334; SEQ ID NO: 335; or SEQ ID NO: 336. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0169] In some aspects described herein, the antibody or antigen binding fragment thereof is capable of specifically binding to VB12 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB12 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 263, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 337; SEQ ID NO: 338; SEQ ID NO: 339; SEQ ID NO: 340; or SEQ ID NO: 341. In some aspects, the VB12 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 264, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 337; SEQ ID NO: 338; SEQ ID NO: 339; SEQ ID NO: 340; or SEQ ID NO: 341. In some aspects, the VB12 antibody or antigen binding fragment, for example, comprises(i) a variable heavy chain (VH) according to SEQ ID NO: 265, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 337; SEQ ID NO: 338; SEQ ID NO: 339; SEQ ID NO: 340; or SEQ ID NO: 341. In some aspects, the VB12 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 266, and / or(ii) a variable light chain (VL) according to SEQ ID NO: 337; SEQ ID NO: 338; SEQ ID NO: 339; SEQ ID NO: 340; or SEQ ID NO: 341. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0170] In some aspects described herein, the antibody or antigen binding fragment thereof is capable of specifically binding to VB8 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB8 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 267, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 342; SEQ ID NO: 343; or SEQ ID NO: 344. In some aspects, the VB8 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 268, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 342; SEQ ID NO: 343; or SEQ ID NO: 344. In some aspects, the VB8 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 269, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 342; SEQ ID NO: 343; or SEQ ID NO: 344. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0171] In some aspects described herein, the antibody or antigen binding fragment thereof is capable of specifically binding to VB13.1 and, for example comprises (i) a variable heavy chain (VH), and / or a vailable light chain (VL). In some aspects, the VB13.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 270, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 345; SEQ ID NO: 346; or SEQ ID NO: 347. In some aspects, the VB13.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 271, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 345; SEQ ID NO: 346; or SEQ ID NO: 347. In some aspects, the VB13.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 272, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 345; SEQ ID NO: 346; or SEQ ID NO: 347. In some aspects, the VB13.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 273, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 345; SEQ ID NO: 346; or SEQ ID NO: 347. In some aspects, the VB13.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 643, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 661; SEQ ID NO: 662; or SEQ IDNO: 663; or SEQ ID NO: 664. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0172] In some aspects described herein, the antibody or antigen binding fragment thereof is capable of specifically binding to VB13.1 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB13.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 270, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 345; SEQ ID NO: 346; SEQ ID NO: 347; SEQ ID NO: 709; SEQ ID NO: 710; SEQ ID NO: 711; or SEQ ID NO: 712. In some aspects, the VB13.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 271, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 345; SEQ ID NO: 346; SEQ ID NO: 347; SEQ ID NO: 709; SEQ ID NO: 710; SEQ ID NO: 711; or SEQ ID NO: 712. In some aspects, the VB13.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 272, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 345; SEQ ID NO: 346; SEQ ID NO: 347; SEQ ID NO: 709; SEQ ID NO: 710; SEQ ID NO: 711; or SEQ ID NO: 712. In some aspects, the VB13.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 273, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 345; SEQ ID NO: 346; SEQ ID NO: 347; SEQ ID NO: 709; SEQ ID NO: 710; SEQ ID NO: 711; or SEQ ID NO: 712. In some aspects, the VB13.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 643, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 661; SEQ ID NO: 662; SEQ ID NO: 663; SEQ ID NO: 664; SEQ ID NO: 709; SEQ ID NO: 710; SEQ ID NO: 711; or SEQ ID NO: 712. In some aspects, the VB13.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 693, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 345; SEQ ID NO: 346; SEQ ID NO: 347; SEQ ID NO: 709; SEQ ID NO: 710; SEQ ID NO: 711; or SEQ ID NO: 712. In some aspects, the VB13.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 694, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 345; SEQ ID NO: 346; SEQ ID NO: 347;SEQ ID NO: 709; SEQ ID NO: 710; SEQ ID NO: 711; or SEQ ID NO: 712. In some aspects, the VB13.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 695, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 345; SEQ ID NO: 346; SEQ ID NO: 347; SEQ ID NO: 709; SEQ ID NO: 710; SEQ ID NO: 711; or SEQ ID NO: 712. In some aspects, the VB13.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 696, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 345; SEQ ID NO: 346; SEQ ID NO: 347; SEQ ID NO: 709; SEQ ID NO: 710; SEQ ID NO: 711; or SEQ ID NO: 712. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0173] In some aspects described herein, the antibody or antigen binding fragment thereof is capable of specifically binding to VB5.1 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB5.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 274, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 348; SEQ ID NO: 349; or SEQ ID NO: 350. In some aspects, the VB5.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 275, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 348; SEQ ID NO: 349; or SEQ ID NO: 350. In some aspects, the VB5.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 276, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 348; SEQ ID NO: 349; or SEQ ID NO: 350. In some aspects, the VB5.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 277, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 348; SEQ ID NO: 349; or SEQ ID NO: 350. In some aspects, the VB5.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 278, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 348; SEQ ID NO: 349; or SEQ ID NO: 350. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, atleast 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0174] In some aspects described herein, the antibody or antigen binding fragment thereof is capable of specifically binding to VB9 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB9 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 279, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 351; SEQ ID NO: 352; SEQ ID NO: 353; SEQ ID NO: 354. In some aspects, the VB9 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 280, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 351; SEQ ID NO: 352; SEQ ID NO: 353; or SEQ ID NO: 354, In some aspects, the VB9 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 281, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 351; SEQ ID NO: 352; SEQ ID NO: 353; or SEQ ID NO: 354. In some aspects, the VB9 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 282, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 351; SEQ ID NO: 352; SEQ ID NO: 353; or SEQ ID NO: 354. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0175] In some aspects described herein, the antibody or antigen binding fragment thereof is capable of specifically binding to VB17 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB17 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 283, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 355; SEQ ID NO: 356; or SEQ ID NO: 357. In some aspects, the VB17 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 284, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 355; SEQ ID NO: 356; or SEQ ID NO: 357. In some aspects, the VB17 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 285, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 355; SEQ ID NO: 356;or SEQ ID NO: 357. In some aspects, the VB17 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 644, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 665; SEQ ID NO: 666; or SEQ ID NO: 667; or SEQ ID NO: 668. In some aspects, the VB17 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 645, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 665; SEQ ID NO: 666; or SEQ ID NO: 667; or SEQ ID NO: 668. In some aspects, the VB17 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 646, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 665; SEQ ID NO: 666; or SEQ ID NO: 667; or SEQ ID NO: 668. In some aspects, the VB17 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 647, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 665; SEQ ID NO: 666; or SEQ ID NO: 667; or SEQ ID NO: 668. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0176] In some aspects described herein, the antibody or antigen binding fragment thereof is capable of specifically binding to VB3 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 286, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 358; SEQ ID NO: 359; or SEQ ID NO: 360. In some aspects, the VB3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 287, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 358; SEQ ID NO: 359; or SEQ ID NO: 360. In some aspects, the VB3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 289, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 358; SEQ ID NO: 359; or SEQ ID NO: 360. In some aspects, the VB3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 634, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 652; SEQ ID NO: 653; SEQ ID NO: 654; or SEQ ID NO: 655. In some aspects, the VB3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 635, and / or(ii) a variable light chain (VL) according to SEQ ID NO: 652; SEQ ID NO: 653; SEQ ID NO: 654; or SEQ ID NO: 655. In some aspects, the VB3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO:636, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 652; SEQ ID NO: 653; SEQ ID NO: 654; or SEQ ID NO: 655. In some aspects, the VB3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO:637, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 652; SEQ ID NO: 653; SEQ ID NO: 654; or SEQ ID NO: 655. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0177] In some aspects described herein, the antibody or antigen binding fragment thereof is capable of specifically binding to VB7.1 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB7.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 290, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 361; SEQ ID NO: 362; SEQ ID NO: 363; SEQ ID NO: 364; SEQ ID NO: 365; SEQ ID NO: 366; or SEQ ID NO: 367. In some aspects, the VB7.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 291, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 361; SEQ ID NO: 362; SEQ ID NO: 363; SEQ ID NO: 364; SEQ ID NO: 365; SEQ ID NO: 366; or SEQ ID NO: 367. In some aspects, the VB7.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 292, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 361; SEQ ID NO: 362; SEQ ID NO: 363; SEQ ID NO: 364; SEQ ID NO: 365; SEQ ID NO: 366; or SEQ ID NO: 367. In some aspects, the VB7.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 293, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 361; SEQ ID NO: 362; SEQ ID NO: 363; SEQ ID NO: 364; SEQ ID NO: 365; SEQ ID NO: 366; or SEQ ID NO: 367. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0178] In some aspects described herein, the antibody or antigen binding fragment thereof is capable of specifically binding to VB7.1 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB7.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 290, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 361; SEQ ID NO: 362; SEQ ID NO: 363; SEQ ID NO: 364; SEQ ID NO: 365; SEQ ID NO: 366; SEQ ID NO: 367; SEQ ID NO: 705; SEQ ID NO: 706; SEQ ID NO: 707; or SEQ ID NO: 708. In some aspects, the VB7.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 291, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 361; SEQ ID NO: 362; SEQ ID NO: 363; SEQ ID NO: 364; SEQ ID NO: 365; SEQ ID NO: 366; SEQ ID NO: 367; SEQ ID NO: 705; SEQ ID NO: 706; SEQ ID NO: 707; or SEQ ID NO: 708. In some aspects, the VB7.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 292, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 361; SEQ ID NO: 362; SEQ ID NO: 363; SEQ ID NO: 364; SEQ ID NO: 365; SEQ ID NO: 366; SEQ ID NO: 367; SEQ ID NO: 705; SEQ ID NO: 706; SEQ ID NO: 707; or SEQ ID NO: 708. In some aspects, the VB7.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 293, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 361; SEQ ID NO: 362; SEQ ID NO: 363; SEQ ID NO: 364; SEQ ID NO: 365; SEQ ID NO: 366; SEQ ID NO: 367; SEQ ID NO: 705; SEQ ID NO: 706; SEQ ID NO: 707; or SEQ ID NO: 708. In some aspects, the VB7.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 689, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 361; SEQ ID NO: 362; SEQ ID NO: 363; SEQ ID NO: 364; SEQ ID NO: 365; SEQ ID NO: 366; SEQ ID NO: 367; SEQ ID NO: 705; SEQ ID NO: 706; SEQ ID NO: 707; or SEQ ID NO: 708. In some aspects, the VB7.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 690, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 361; SEQ ID NO: 362; SEQ ID NO: 363; SEQ ID NO: 364; SEQ ID NO: 365; SEQ ID NO: 366; SEQ ID NO: 367; SEQ ID NO: 705; SEQ ID NO: 706; SEQ ID NO: 707; or SEQ ID NO: 708. In some aspects, the VB7.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 691, and / or (ii) a variable light chain (VL) according to SEQ IDNO: 361; SEQ ID NO: 362; SEQ ID NO: 363; SEQ ID NO: 364; SEQ ID NO: 365; SEQ ID NO: 366; SEQ ID NO: 367; SEQ ID NO: 705; SEQ ID NO: 706; SEQ ID NO: 707; or SEQ ID NO: 708. In some aspects, the VB7.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 692, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 361; SEQ ID NO: 362; SEQ ID NO: 363; SEQ ID NO: 364; SEQ ID NO: 365; SEQ ID NO: 366; SEQ ID NO: 367; SEQ ID NO: 705; SEQ ID NO: 706; SEQ ID NO: 707; or SEQ ID NO: 708. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0179] In some aspects described herein, the antibody or antigen binding fragment thereof is capable of specifically binding to VB5.3 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB5.3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 294, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 368 or SEQ ID NO: 369. In some aspects, the VB5.3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 295, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 368 or SEQ ID NO: 369. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0180] In some aspects described herein, the antibody or antigen binding fragment thereof is capable of specifically binding to VB20 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB20 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 559, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 570; SEQ ID NO: 571; or SEQ ID NO: 572. In some aspects, the VB20 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 560, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 570; SEQ ID NO: 571; or SEQ ID NO: 572. In some aspects, the VB20 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO:561, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 570; SEQ ID NO: 571; or SEQ ID NO: 572. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0181] In some aspects described herein, the antibody or antigen binding fragment thereof is capable of specifically binding to VB18 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB18 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 562, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 573; SEQ ID NO: 574; SEQ ID NO: 575. In some aspects, the VB18 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 563, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 573; SEQ ID NO: 574; SEQ ID NO: 575. In some aspects, the VB18 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 564, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 573; SEQ ID NO: 574; SEQ ID NO: 575. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0182] In some aspects described herein, the antibody or antigen binding fragment thereof is capable of specifically binding to VB13.6 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB13.6 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 565, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 576; SEQ ID NO: 577. In some aspects, the VB13.6 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 566, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 576; SEQ ID NO: 577. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0183] In some aspects described herein, the antibody or antigen binding fragment thereof is capable of specifically binding to VB16 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB16 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 567, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 578; SEQ ID NO: 579; SEQ ID NO: 580; SEQ ID NO: 581; SEQ ID NO: 582; or SEQ ID NO: 583. In some aspects, the VB16 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 568, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 578; SEQ ID NO: 579; SEQ ID NO: 580; SEQ ID NO: 581; SEQ ID NO: 582; or SEQ ID NO: 583. In some aspects, the VB16 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 569, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 578; SEQ ID NO: 579; SEQ ID NO: 580; SEQ ID NO: 581; SEQ ID NO: 582; or SEQ ID NO: 583. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0184] In some aspects described herein, the antibody or antigen binding fragment thereof is capable of specifically binding to VB21.3 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB21.3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 648, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 669; SEQ ID NO: 670; or SEQ ID NO: 671. In some aspects, the VB21.3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 649, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 669; SEQ ID NO: 670; or SEQ ID NO: 671. In some aspects, the VB21.3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 650, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 669; SEQ ID NO: 670; or SEQ ID NO: 671. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0185] In some aspects described herein, the antibody or antigen binding fragment thereof is capable of specifically binding to VB21.3 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB21.3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 648, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 669; SEQ ID NO: 670; SEQ ID NO: 671; SEQ ID NO: 713; SEQ ID NO: 714; SEQ ID NO: 715; or SEQ ID NO: 716. In some aspects, the VB21.3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 649, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 669; SEQ ID NO: 670; SEQ ID NO: 671; SEQ ID NO: 713; SEQ ID NO: 714; SEQ ID NO: 715; or SEQ ID NO: 716. In some aspects, the VB21.3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 650, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 669; SEQ ID NO: 670; SEQ ID NO: 671; SEQ ID NO: 713; SEQ ID NO: 714; SEQ ID NO: 715; or SEQ ID NO: 716. In some aspects, the VB21.3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 697, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 669; SEQ ID NO: 670; SEQ ID NO: 671; SEQ ID NO: 713; SEQ ID NO: 714; SEQ ID NO: 715; or SEQ ID NO: 716. In some aspects, the VB21.3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 698, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 669; SEQ ID NO: 670; SEQ ID NO: 671; SEQ ID NO: 713; SEQ ID NO: 714; SEQ ID NO: 715; or SEQ ID NO: 716. In some aspects, the VB21.3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 699, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 669; SEQ ID NO: 670; SEQ ID NO: 671; SEQ ID NO: 713; SEQ ID NO: 714; SEQ ID NO: 715; or SEQ ID NO: 716. In some aspects, the VB21.3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 700, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 669; SEQ ID NO: 670; SEQ ID NO: 671; SEQ ID NO: 713; SEQ ID NO: 714; SEQ ID NO: 715; or SEQ ID NO: 716. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0186] In some aspects described herein, the antibody or antigen binding fragment thereof is capable of specifically binding to VB1 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 632, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 333; SEQ ID NO: 334; SEQ ID NO: 335; or SEQ ID NO: 336. In some aspects, the VB1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 633, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 333; SEQ ID NO: 334; SEQ ID NO: 335; or SEQ ID NO: 336. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0187] In some aspects described herein, the antibody or antigen binding fragment thereof is capable of specifically binding to VB1 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 632, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 333; SEQ ID NO: 334; SEQ ID NO: 335; SEQ ID NO: 336; SEQ ID NO: 701; SEQ ID NO: 702; SEQ ID NO: 703; or SEQ ID NO: 704. In some aspects, the VB1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 633, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 333; SEQ ID NO: 334; SEQ ID NO: 335; SEQ ID NO: 336; SEQ ID NO: 701; SEQ ID NO: 702; SEQ ID NO: 703; or SEQ ID NO: 704. In some aspects, the VB1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 685, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 333; SEQ ID NO: 334; SEQ ID NO: 335; SEQ ID NO: 336; SEQ ID NO: 701; SEQ ID NO: 702; SEQ ID NO: 703; or SEQ ID NO: 704. In some aspects, the VB1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 686, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 333; SEQ ID NO: 334; SEQ ID NO: 335; SEQ ID NO: 336; SEQ ID NO: 701; SEQ ID NO: 702; SEQ ID NO: 703; or SEQ ID NO: 704. In some aspects, the VB1 antibody or antigen binding fragment, for example, comprises(i) a variable heavy chain (VH) according to SEQ ID NO: 687, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 333; SEQ ID NO: 334; SEQ ID NO: 335; SEQ ID NO: 336; SEQ ID NO: 701; SEQ ID NO: 702; SEQ ID NO: 703; or SEQ ID NO: 704. In some aspects, the VB1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 688, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 333; SEQ ID NO: 334; SEQ ID NO: 335; SEQ ID NO: 336; SEQ ID NO: 701; SEQ ID NO: 702; SEQ ID NO: 703; or SEQ ID NO: 704. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0188] In some aspects described herein, the antibody or antigen-binding fragment thereof, is human, humanized, or chimeric. In a preferred aspect, the antibody or antigenbinding fragment thereof, is humanized.

[0189] In some aspects described herein, the antibody or antigen-binding fragment thereof, is an IgG antibody. In some aspects described herein, the IgG antibody, is an IgGl, IgG2, IgG3, or an IgG4 antibody. In some aspects described herein, the IgG antibody, is an IgGl antibody or an IgG4 antibody. In some aspects described herein, the IgG antibody is an IgGl antibody.

[0190] In some aspects described herein, the antibody, is an antigen-binding fragment of an antibody. In some aspects described herein, the antigen-binding fragment, is selected from the group consisting of Fab, F(ab’)2, Fv, scFv, scFv-Fc, dsFv and a single domain molecule. In some aspects described herein, the antigen-binding fragment, is an scFv. In some aspects described herein, the antigen-binding fragment, is a Fab. In some aspects described herein, the antigen-binding fragment, is an intrabody. In some aspects described herein, the antigenbinding fragment, is devoid of an Fc region.

[0191] In some aspects, the antibody or antigen-binding fragment comprises a Fc domain, wherein the Fc domain comprises a mutation. In some aspects, the Fc mutant is a modified IgGl Fc comprising one or more modifications. For example, in some aspects, the IgGl modified Fc comprises one or more amino acid substitutions (e.g., relative to a wild-type Fc region of the same isotype). In some aspects, the one or more amino acid substitutions are selected from N297A (Bolt S et al. (1993) Eur J Immunol 23:403-411), D265A (Shields et al.(2001) R. J. Biol. Chem. 276, 6591-6604), L234A, L235A (Hutchins et al. (1995) Proc Natl Acad Sci USA, 92: 11980-11984; Alegre et al., (1994) Transplantation 57: 1537-1543. 31; Xu et al., (2000) Cell Immunol, 200: 16-26), G237A (Alegre et al. (1994) Transplantation 57: 1537-1543. 31; Xu et al. (2000) Cell Immunol, 200: 16-26), C226S, C229S, E233P, L234V, L234F, L235E (McEarchem et al., (2007) Blood, 109: 1185-1192), P331S (Sazinsky et al., (2008) Proc Natl Acad Sci USA 2008, 105:20167-20172), S267E, L328F, A330L, M252Y, S254T, E430G, and / or T256E, where the amino acid position is according to the EU numbering convention. In some aspects, the antibody comprises the amino acid substitutions L234A and L235A (LALA) according to EU numbering. In some aspects, the antibody comprises the amino acid substitutions L234A, L235A, and P331S (LALAPS) accordingly to EU numbering. In some aspects of any of the modified IgGl Fc, the Fc comprises N325S and L328F mutations according to EU numbering. In some aspects of any of the modified IgGl Fc, the Fc comprises P329G or P329S according to EU numbering.

[0192] In some instances, the the heavy chain-hole and the heavy chain-knob also included mutations to reduce effector function, such as L234A / L235A / P331S (LALAPS) or N325S / L328 (NSLF). In some aspects described herein, the antibody or antigen-binding fragment, comprises a VH and a VL on the same polypeptide chain. In some aspects described herein, the antibody or antigen-binding fragment, comprises a VH and a VL on separate polypeptide chains.

[0193] In some aspects described herein, the antibody or antigen-binding fragment VH and VL are connected by a linker.

[0194] In some aspects described herein, the TCR VP region is selected from the group consisting of Vpi, Vp2, Vp3, Vp4, VP5.1, VP5.3, Vp6, VP7.1, VP7.2, Vp8, Vp9, VpiO, Vpi l, VP12, VP13.1, VP13.2, VP14, Vpi5, Vpi6, Vpi7, Vpi8, Vpi9, VP20, VP21, VP21.3, VP22, VP23, VP24, VP25, VP26, VP27, VP28, VP29, VP30, VpA, VpB, and VpC. It will be understood that a combination of variable heavy and light chains described herein that specifically bind to the same TCR VP region are capable of providing increased in vitro and / or in vivo activity compared to a combination of variable heavy and light chains described herein that specifically bind to different TCR VP regions.

[0195] In some aspects described herein, the antibody or antigen-binding fragment TCR VP region is selected from the group consisting of Vpi, VP2, VP3, VP4, VP5.1, VP5.3, VP7.1, VP7.2, VP8, VP9, Vpi l, Vpi2, Vpi3.1, Vpi3.2, Vpi4, Vpi7, VP21.3, and VP22.

[0196] In some aspects described herein, the antibody or antigen-binding fragment TCR VP region is VP2.

[0197] In some aspects, for the expression of antibodies or antigen-binding fragments thereof, vectors encoding both the heavy and light chains, individually, can be co-expressed in the host cell for expression of the entire immunoglobulin, as detailed below.

[0198] In some aspects, a host cell contains a vector comprising a polynucleotide encoding both the heavy chain and light chain of an antibody disclosed herein or a domain thereof.

[0199] In some aspects, a host cell contains two different vectors, a first vector comprising a polynucleotide encoding a heavy chain or a heavy chain variable region of an antibody or antigen-binding fragment thereof disclosed herein, and a second vector comprising a polynucleotide encoding a light chain or a light chain variable region of an antibody disclosed herein or a domain thereof. In some aspects, a first host cell comprises a first vector comprising a polynucleotide encoding a heavy chain or a heavy chain variable region of an antibody or antigen-binding fragment thereof disclosed herein, and a second host cell comprises a second vector comprising a polynucleotide encoding a light chain or a light chain variable region of an antibody or antigen-binding fragment thereof disclosed herein. In some aspects, a heavy chain / heavy chain variable region expressed by a first cell associated with a light chain / light chain variable region of a second cell to form an anti-TCR VB antibody or antigen-binding fragment thereof disclosed herein. In some aspects, provided herein is a population of host cells comprising such first host cell and such second host cell.

[0200] In some aspects, provided herein is a population of vectors comprising a first vector comprising a polynucleotide encoding a light chain / light chain variable region of an anti- TCR VB antibody or antigen-binding fragment thereof disclosed herein, and a second vector comprising a polynucleotide encoding a heavy chain / heavy chain variable region of an anti- TCR VB antibody or antigen-binding fragment thereof disclosed herein. Alternatively, a single vector can be used which encodes, and is capable of expressing, both heavy and light chain polypeptides.

[0201] A variety of host-expression vector systems can be utilized to express antibodies and antigen-binding fragments thereof disclosed herein (see, e.g., U.S. Patent No. 5,807,715). Such host-expression systems represent vehicles by which the coding sequences of interest can be produced and subsequently purified, but also represent cells which can, whentransformed or transfected with the appropriate nucleotide coding sequences, express an antibody or antigen-binding fragment thereof disclosed herein in situ. These include but are not limited to microorganisms such as bacteria (e.g. ,E. coli and B. subtilis) transformed with recombinant bacteriophage DNA, plasmid DNA or cosmid DNA expression vectors containing antibody coding sequences; yeast (e.g., Saccharomyces Pichia) transformed with recombinant yeast expression vectors containing antibody coding sequences; insect cell systems infected with recombinant virus expression vectors (e.g., baculovirus) containing antibody coding sequences; plant cell systems (e.g., green algae such as Chlamydomonas reinhardtii) infected with recombinant virus expression vectors (e.g., cauliflower mosaic virus, CaMV; tobacco mosaic virus, TMV) or transformed with recombinant plasmid expression vectors (e.g., Ti plasmid) containing antibody coding sequences; or mammalian cell systems (e.g, COS (e g., COS1 or COS), CHO, BHK, MDCK, HEK 293, NSO, PER.C6, VERO, CRL7O3O, HsS78Bst, HeLa, and NIH 3T3, HEK-293T, HepG2, SP210, Rl. l, B-W, L-M, BSC1, BSC40, YB / 20 and BMT10 cells) harboring recombinant expression constructs containing promoters derived from the genome of mammalian cells (e.g., metallothionein promoter) or from mammalian viruses (e.g, the adenovirus late promoter; the vaccinia virus 7.5K promoter). In some aspects, cells for expressing antibodies and antigen-binding fragments thereof disclosed herein are CHO cells, for example CHO cells from the CHO GS System™ (Lonza). In some aspects, cells for expressing antibodies disclosed herein are human cells, e.g, human cell lines. In some aspects, a mammalian expression vector is pOptiVEC™ or pcDNA3.3. In some aspects, bacterial cells such as Escherichia coli, or eukaryotic cells (e.g, mammalian cells), especially for the expression of whole recombinant antibody molecule, are used for the expression of a recombinant antibody molecule. For example, mammalian cells such as Chinese hamster ovary (CHO) cells in conjunction with a vector such as the major intermediate early gene promoter element from human cytomegalovirus is an effective expression system for antibodies (Foecking MK & Hofstetter H (1986) Gene 45: 101-105; and Cockett MI et al, (1990) Biotechnology 8: 662-667). In some aspects, antibodies or antigen-binding fragments thereof disclosed herein are produced by CHO cells or NSO cells.

[0202] In addition, a host cell strain can be chosen which modulates the expression of the inserted sequences, or modifies and processes the gene product in the specific fashion desired. Such modifications (e.g, glycosylation) and processing (e.g, cleavage) of proteinproducts can contribute to the function of the protein. To this end, eukaryotic host cells that possess the cellular machinery for proper processing of the primary transcript, glycosylation, and phosphorylation of the gene product can be used. Such mammalian host cells include but are not limited to CHO, VERO, BHK, HeLa, MDCK, HEK 293, NIH 3T3, W138, BT483, Hs578T, HTB2, BT20 and T47D, NSO (a murine myeloma cell line that does not endogenously produce any immunoglobulin chains), CRL7O3O, COS (e.g., COS1 or COS), PER.C6, VERO, HsS78Bst, HEK-293T, HepG2, SP210, Rl.l, B-W, L-M, BSC1, BSC40, YB / 20, BMT10 and HsS78Bst cells. In some aspects, anti- TCR VB antibodies disclosed herein are produced in mammalian cells, such as CHO cells, e.g., CH0-K1 cells. In some aspects, anti-TCR VB antibodies disclosed herein are produced in mammalian cells, such as HEK-293 cells.

[0203] Once an antibody or antigen-binding fragment thereof disclosed herein has been produced by recombinant expression, it can be purified by any method known in the art for purification of an immunoglobulin molecule, for example, by chromatography (e.g., ion exchange, affinity, particularly by affinity for the specific antigen after Protein A, and sizing column chromatography), centrifugation, differential solubility, or by any other standard technique for the purification of proteins. Further, the antibodies or antigen-binding fragments thereof disclosed herein can be fused to heterologous polypeptide sequences disclosed herein or otherwise known in the art to facilitate purification.

[0204] In some aspects, an antibody or antigen-binding fragment thereof for example, disclosed herein is isolated or purified. Generally, an isolated antibody or antigen-binding fragment thereof is one that is substantially free of other antibodies or antigen-binding fragments thereof with different antigenic specificities than the isolated antibody or antigenbinding fragment thereof. For example, in some aspects, a preparation of an antibody or antigen-binding fragment thereof disclosed herein is substantially free of cellular material and / or chemical precursors.

[0205] In some aspects the antibody or antigen binding fragment is modified to enhance antibody-dependent cell-mediated cytotoxicity (ADCC).

[0206] In some aspects, the ADCC activity of the antibody composition is increased or decreased by about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, about 100%, about 125%, about 150%, about175%, about 200%, about 1-fold, about 2-fold, about 3 -fold, or about 4-fold, or increased or decreased by about 5% to about 400%.

[0207] In some aspects, the antibody or antigen binding fragment has an increased antibody-dependent cell mediated cytotoxicity activity achieved through afucosylation.

[0208] In some aspects, the antibody or antigen binding fragment has an increased antibody-dependent cell mediated cytotoxicity activity achieved through glycosylation.II. Antibody drug conjugates / Immunoconjugates comprising Anti-TCRVfi Antibodies and Antigen-Binding Fragments Thereof

[0209] The present disclosure is directed to immunoconjugates, comprising the anti- TCRVB antibodies and antigen-binding fragments thereof and their aspects as disclosed herein, linked or conjugated to a chemotherapeutic drug or cytotoxic agent. Thus, in a certain aspect, the disclosure provides an immunoconjugate comprising an antibody or antigen binding fragment thereof that specifically binds TCRVB, wherein the antibody comprises (i) a variable heavy chain (VH) which comprises: (a) CDR1, CDR2 and CDR3 according to SEQ ID NOTO, SEQ ID NO: 11, and SEQ ID NO: 12, respectively; or (b) CDR1, CDR2 and CDR3 according to SEQ ID NO:370, SEQ ID NO:371, and SEQ ID NO:372, respectively; or (c) CDR1, CDR2 and CDR3 according to SEQ ID NO:373, SEQ ID NO:374, and SEQ ID NO:375 respectively; or (d) CDR1, CDR2 and CDR3 according to SEQ ID NO:376, SEQ ID NO:377, and SEQ ID NO:378, respectively; or (e) CDR1, CDR2 and CDR3 according to SEQ ID NO:379, SEQ ID NO:380, and SEQ ID NO:381 respectively; or (f) CDR1, CDR2 and CDR3 according to SEQ ID NO:382, SEQ ID NO:383, and SEQ ID NO:384, respectively; or (g) CDR1, CDR2 and CDR3 according to SEQ ID NO:385, SEQ ID NO:386, and SEQ ID NO:387, respectively; or (h) CDR1, CDR2 and CDR3 according to SEQ ID NO:388, SEQ ID NO:389, and SEQ ID NO:390, respectively; or (i) CDR1, CDR2 and CDR3 according to SEQ ID NO:391, SEQ ID NO:392, and SEQ ID NO:393, respectively; or (j) CDR1, CDR2 and CDR3 according to SEQ ID NO:394, SEQ ID NO:395, and SEQ ID NO: 396, respectively; or (k) CDR1, CDR2 and CDR3 according to SEQ ID NO: 397, SEQ ID NO: 398, and SEQ ID NO: 399, respectively; or (1) CDR1, CDR2 and CDR3 according to SEQ ID NO:400, SEQ ID NO:401, and SEQ ID NO:402, respectively; or (m) CDR1, CDR2 and CDR3 according to SEQ ID NO:403, SEQ ID NO:404, and SEQ ID NO:405, respectively; or (n) CDR1, CDR2 and CDR3 according to SEQ ID NO:406, SEQ ID NO:407, and SEQ ID NO:408, respectively; or (o) CDR1, CDR2 and CDR3 according to SEQ IDNO:409, SEQ ID NO:410, and SEQ ID N0:411, respectively; or (p) CDR1, CDR2 and CDR3 according to SEQ ID NO:412, SEQ ID NO:413, and SEQ ID NO:414, respectively; or (q) CDR1, CDR2 and CDR3 according to SEQ ID NO:415, SEQ ID NO:416, and SEQ ID NO:417, respectively; or (r) CDR1, CDR2 and CDR3 according to SEQ ID NO:584, SEQ ID NO:585, and SEQ ID NO:586, respectively; or (s) CDR1, CDR2 and CDR3 according to SEQ ID NO:587, SEQ ID NO:588, and SEQ ID NO:589, respectively; or (t) CDR1, CDR2 and CDR3 according to SEQ ID NO:590, SEQ ID NO:591, and SEQ ID NO:592, respectively; (u) CDR1, CDR2 and CDR3 according to SEQ ID NO:593, SEQ ID NO:594, and SEQ ID NO:595, respectively; (v) CDR1, CDR2 and CDR3 according to SEQ ID NO: 370, SEQ ID NO: 681, and SEQ ID NO: 372, respectively; or (w) CDR1, CDR2 and CDR3 according to SEQ ID NO:675, SEQ ID NO:676, and SEQ ID NO:677; and / or (ii) a variable light chain (VL) which comprises: (a) CDR1, CDR2 and CDR3 according to SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, respectively; or (b) CDR1, CDR2 and CDR3 according to SEQ ID NO:418, SEQ ID NO:419, SEQ ID NO:420, respectively; or (c) CDR1, CDR2 and CDR3 according to SEQ ID NO:421, SEQ ID NO:422, SEQ ID NO:423, respectively; or (d) CDR1, CDR2 and CDR3 according to SEQ ID NO:424, SEQ ID NO:425, SEQ ID NO:426, respectively; or (e) CDR1, CDR2 and CDR3 according to SEQ ID NO:427, SEQ ID NO:428, SEQ ID NO:429, respectively; or (f) CDR1, CDR2 and CDR3 according to SEQ ID NO:430, SEQ ID NO:431, SEQ ID NO:432, respectively; or (g) CDR1, CDR2 and CDR3 according to SEQ ID NO:433, SEQ ID NO:434, SEQ ID NO:435, respectively; or (h) CDR1, CDR2 and CDR3 according to SEQ ID NO:436, SEQ ID NO:437, SEQ ID NO:438, respectively; or (i) CDR1, CDR2 and CDR3 according to SEQ ID NO:439, SEQ ID NO:440, SEQ ID NO:441, respectively; or (j) CDR1, CDR2 and CDR3 according to SEQ ID NO:442, SEQ ID NO:443, SEQ ID NO:444, respectively; or (k) CDR1, CDR2 and CDR3 according to SEQ ID NO:445, SEQ ID NO:446, SEQ ID NO:447, respectively; or (1) CDR1, CDR2 and CDR3 according to SEQ ID NO:448, SEQ ID NO:449, SEQ ID NO:450, respectively; or (m) CDR1, CDR2 and CDR3 according to SEQ ID NO:451, SEQ ID NO:452, SEQ ID NO:453, respectively; or (n) CDR1, CDR2 and CDR3 according to SEQ ID NO:454, SEQ ID NO:455, SEQ ID NO:456, respectively; or (o) CDR1, CDR2 and CDR3 according to SEQ ID NO:457, SEQ ID NO:458, SEQ ID NO:459, respectively; or (p) CDR1, CDR2 and CDR3 according to SEQ ID NO:460, SEQ ID NO:461, SEQ ID NO:462, respectively; or (q) CDR1, CDR2 and CDR3 according to SEQ ID NO:463, SEQ ID NO:464, SEQ ID NO:465, respectively; or (r)CDR1, CDR2 and CDR3 according to SEQ ID NO:596, SEQ ID NO:597, SEQ ID NO:598, respectively; or (s) CDR1, CDR2 and CDR3 according to SEQ ID NO:599, SEQ ID NO:600, SEQ ID NO:601, respectively; or (t) CDR1, CDR2 and CDR3 according to SEQ ID NO:602, SEQ ID NO: 603, SEQ ID NO: 604, respectively; (u) CDR1, CDR2 and CDR3 according to SEQ ID NO:605, SEQ ID NO:606, SEQ ID NO:607, respectively, or SEQ ID NO: 608, SEQ ID NO: 609, SEQ ID NO: 610, respectively; (v) CDR1, CDR2 and CDR3 according to SEQ ID NO: 682, SEQ ID NO: 419, SEQ ID NO: 420, respectively, SEQ ID NO: 682, SEQ ID NO: 683, SEQ ID NO: 420, respectively, or SEQ ID NO: 418, SEQ ID NO: 684, SEQ ID NO: 420, respectively; or (w) CDR1, CDR2 and CDR3 according to SEQ ID NO: 678, SEQ ID NO:679, SEQ ID NO:680, respectively.

[0210] In some aspects described herein, the immunoconjugate comprises an antibody or antigen binding fragment thereof that specifically binds TCRVB, wherein the antibody comprises a heavy chain variable region (VH) having an amino acid sequence according to any of SEQ ID NOs: 228-295, 559-569, and 632-650. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 85% sequence identity to any one of SEQ ID NOs: 228-295 and 559-569. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 86% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, and 650. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 87% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, and 650. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 88% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, and 650. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 89% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, 639, 641, 642, and 650. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOs: 228-295, 559- 569, 632, 638, 639, 641, 642, and 650. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 91% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, 632, 633, 638-642, 648, and 650. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 92% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, 632, 633, 638-642, and 648- 650. In some aspects described herein, the variable heavy chain comprises an amino acidsequence having at least 93% sequence identity to any one of SEQ ID NOs: 228-295, 559- 569, 632, 633, 638-642, and 648-650. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 94% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, 632, 633, 638-642, and 648-650. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, 632, 633, 638-643, and 648- 650. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 96% sequence identity to any one of SEQ ID NOs: 228-295, 559- 569, 632, 633, 635, 637-643, and 647-650. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 97% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, 632-643, and 646-650. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 98% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, and 632-650. In some aspects described herein, the variable heavy chain comprises an amino acid sequence having at least 99% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, and 632-650.In some aspects described herein, the variable heavy chain comprises an amino acid sequence according to any one of SEQ ID NOs: 228-295, 559-569, and 632-650.

[0211] In some aspects described herein, the immunoconjugate comprises an antibody or antigen binding fragment thereof comprising a heavy chain variable region (VH) as described above, further comprises a light chain variable region (VL) having an amino acid sequence according to any of SEQ ID NOs: 296-369, 570-583, 652-671.

[0212] In some aspects described herein, an immunoconjugate comprises an antibody or antigen binding fragment thereof capable of specifically binding to a TCR VB region, comprising a light chain variable region (VL) having an amino acid sequence according to any of SEQ ID NOs: 296-369, 570-583, and 652-671. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 86% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 662, and 671. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 87% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 662, and 671. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 88% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 662, 670, and 671. In some aspects described herein, the variable light chain comprises an amino acidsequence having at least 89% sequence identity to any one of SEQ ID NOs: 296-369, 570- 583, 662, 670, and 671. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 662, 670, and 671. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 91% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 662, 670, and 671. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 92% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 662, and 669-671. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 93% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 652, 662, and 669-671. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 94% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 652, 661, 662, and 669-671. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 652-654, 657, 659, 661, 662, and 669-671. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 96% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 652-659, 661, 662, 664, 667, and 669-671. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 97% sequence identity to any one of SEQ ID NOs: 296- 369, 570-583, 652-662, 664, 665, 667, and 669-671. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 98% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 652-665, 667, and 669-671. In some aspects described herein, the variable light chain comprises an amino acid sequence having at least 99% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 652-665, and 667-671. In some aspects described herein, the variable light chain comprises an amino acid sequence according to any one of SEQ ID NOs: 296-369, 570-583, and 652-671.

[0213] In some aspects described herein the immunoconjugate comprises an antibody or antigen-binding fragment comprising a light chain variable region (VL) as described above, further comprises a heavy chain variable region (VH) having an amino acid sequence according to any of SEQ ID NOs: 228-295, 559-569, and 632-650.

[0214] In some aspects described herein, the variable heavy chain comprises an amino acid sequence having any percent identity described above to any one of SEQ ID NOs: 228-295, 559-569, and 632-650, and the variable light chain comprises an amino acid sequence having any percent identity described above to any one of SEQ ID NOs: 296-369, 570-583, and 652-671. To illustrate, a non-limiting example pairing of variable heavy and light chains includes a variable heavy chain comprising an amino acid sequence having at least 88% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, and 632-650, and a variable light chain comprising an amino acid sequence having at least 93% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 652, 662, and 669-671. In other aspects decribed herein, pairing of variable heavy and light chains includes a variable heavy chain comprising an amino acid sequence having any percent identity described above to any one of SEQ ID NOs: 228-295, 559-569, and 632-650, and a variable light chain comprising an amino acid sequence according to any one of SEQ ID NOs: 296-369, 570-583, and 652-671. In other aspects described herein, pairing of variable heavy and light chains includes a variable heavy chain comprising an amino acid sequence according to any one of SEQ ID NOs: 228-295, 559-569, and 632-650, and a variable light chain comprising an amino acid sequence having any percent identity described above to any one of SEQ ID NOs: 296-369, 570-583, and 652- 671. To illustrate, a non-limiting example pairing of variable heavy and light chains includes a variable heavy chain comprising an amino acid sequence having at least 92% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, 632, 633, 638-642, and 648-650, and a variable light chain comprising an amino acid sequence according to any one of SEQ ID NOs: 296-369, 570-583, 652-671. In yet other aspects described herein, the variable heavy chain comprises an amino acid sequence according to any one of SEQ ID NOs: 228-295, 559-569, and 632-650, and the variable light chain comprises an amino acid sequence according to any one of SEQ ID NOs: 296-369, 570-583, and 652-671.

[0215] In some aspects described herein, the immunoconjugate comprises an antibody or antigen-binding fragment thereof capable of specifically binding to TCR VB2 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 228, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 296; SEQ ID NO: 297; SEQ ID NO: 298; SEQ ID NO: 299; SEQ ID NO: 300; SEQ ID NO: 301; SEQ ID NO: 302; or SEQ ID NO: 303. In some aspects, the VB2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 229, and / or (ii) a variable light chain (VL) according toSEQ ID NO: 296; SEQ ID NO: 297; SEQ ID NO: 298; SEQ ID NO: 299; SEQ ID NO: 300; SEQ ID NO: 301; SEQ ID NO: 302; or SEQ ID NO: 303. In some aspects, the VB2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 230, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 296; SEQ ID NO: 297; SEQ ID NO: 298; SEQ ID NO: 299; SEQ ID NO: 300; SEQ ID NO: 301; SEQ ID NO: 302; or SEQ ID NO: 303. In some aspects, the VB2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 231, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 296; SEQ ID NO: 297; SEQ ID NO: 298; SEQ ID NO: 299; SEQ ID NO: 300; SEQ ID NO: 301; SEQ ID NO: 302; or SEQ ID NO: 303. In some aspects, the VB2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 232, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 296; SEQ ID NO: 297; SEQ ID NO: 298; SEQ ID NO: 299; SEQ ID NO: 300; SEQ ID NO: 301; SEQ ID NO: 302; or SEQ ID NO: 303. In some aspects, the VB2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 233, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 296; SEQ ID NO: 297; SEQ ID NO: 298; SEQ ID NO: 299; SEQ ID NO: 300; SEQ ID NO: 301; SEQ ID NO: 302; or SEQ ID NO: 303. In some aspects, the VB2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 234, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 296; SEQ ID NO: 297; SEQ ID NO: 298; SEQ ID NO: 299; SEQ ID NO: 300; SEQ ID NO: 301; SEQ ID NO: 302; or SEQ ID NO: 303. In some aspects, the VB2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 235, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 296; SEQ ID NO: 297; SEQ ID NO: 298; SEQ ID NO: 299; SEQ ID NO: 300; SEQ ID NO: 301; SEQ ID NO: 302; or SEQ ID NO: 303. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0216] In some aspects described herein, the immunoconjugate comprises an antibody or antigen binding fragment thereof capable of specifically binding to VB7.2 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In someaspects, the VB7.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 236, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 304; SEQ ID NO: 305; SEQ ID NO: 306; or SEQ ID NO: 307. In some aspects, the VB7.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 237, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 304; SEQ ID NO: 305; SEQ ID NO: 306; or SEQ ID NO: 307. In some aspects, the VB7.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 238, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 304; SEQ ID NO: 305; SEQ ID NO: 306; or SEQ ID NO: 307. In some aspects, the VB7.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 638, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 656; SEQ ID NO: 657; SEQ ID NO: 658; SEQ ID NO: 659; or SEQ ID NO: 660. In some aspects, the VB7.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 639, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 656; SEQ ID NO: 657; SEQ ID NO: 658; SEQ ID NO: 659; or SEQ ID NO: 660. In some aspects, the VB7.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 640, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 656; SEQ ID NO: 657; SEQ ID NO: 658; SEQ ID NO: 659; or SEQ ID NO: 660. In some aspects, the VB7.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 641, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 656; SEQ ID NO: 657; SEQ ID NO: 658; SEQ ID NO: 659; or SEQ ID NO: 660. In some aspects, the VB7.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 642, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 656;SEQ ID NO: 657; SEQ ID NO: 658; SEQ ID NO: 659; or SEQ ID NO: 660. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0217] In some aspects described herein, the immunoconjugate comprises an antibody or antigen binding fragment thereof capable of specifically binding to VB4, and, for examplecomprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB4 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 239, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 308; or SEQ ID NO: 309. In some aspects, the VB4 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 240, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 308; or SEQ ID NO: 309. In some aspects, the VB4 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 241, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 308; or SEQ ID NO: 309. In some aspects, the VB4 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 242, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 308; or SEQ ID NO: 309. In some aspects, the VB4 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 243, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 308; or SEQ ID NO: 309. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0218] In some aspects described herein, the immunoconjugate comprises an antibody or antigen binding fragment thereof capable of specifically binding to VB13.2 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL), In some aspects described herein, the antibody or antigen binding fragment thereof is capable of specifically binding to VB13.2 and, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 244, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 310; SEQ ID NO: 311; SEQ ID NO: 312; SEQ ID NO: 313; SEQ ID NO: 314; SEQ ID NO: 315; SEQ ID NO: 316; or SEQ ID NO: 317. In some aspects, the VB13.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 245, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 310; SEQ ID NO: 311; SEQ ID NO: 312; SEQ ID NO: 313; SEQ ID NO: 314; SEQ ID NO: 315; SEQ ID NO: 316; or SEQ ID NO: 317. In some aspects, the VB13.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 246, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 310; SEQ IDNO: 311; SEQ ID NO: 312; SEQ ID NO: 313; SEQ ID NO: 314; SEQ ID NO: 315; SEQ ID NO: 316; or SEQ ID NO: 317. In some aspects, the VB13.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 247, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 310; SEQ ID NO: 311; SEQ ID NO: 312; SEQ ID NO: 313; SEQ ID NO: 314; SEQ ID NO: 315; SEQ ID NO: 316; or SEQ ID NO: 317. In some aspects, the VB13.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 248, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 310; SEQ ID NO: 311; SEQ ID NO: 312; SEQ ID NO: 313; SEQ ID NO: 314; SEQ ID NO: 315; SEQ ID NO: 316; or SEQ ID NO: 317. In some aspects, the VB13.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 249, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 310; SEQ ID NO: 311; SEQ ID NO: 312; SEQ ID NO: 313; SEQ ID NO: 314; SEQ ID NO: 315; SEQ ID NO: 316; or SEQ ID NO: 317. In some aspects, the VB13.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 250, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 310; SEQ ID NO: 311; SEQ ID NO: 312; SEQ ID NO: 313; SEQ ID NO: 314; SEQ ID NO: 315; SEQ ID NO: 316; or SEQ ID NO: 317. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0219] In some aspects described herein, the immunoconjugate comprises an antibody or antigen binding fragment thereof capable of specifically binding to VB14 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB14 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 251, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 318; or SEQ ID NO: 319. SEQ ID NO: 320; SEQ ID NO: 321; SEQ ID NO: 322; or SEQ ID NO: 323. In some aspects, the VB14 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 252, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 318; or SEQ ID NO: 319. SEQ ID NO: 320; SEQ ID NO: 321; SEQ ID NO: 322; or SEQ ID NO: 323. In some aspects, the VB14 antibody or antigen binding fragment, for example, comprises (i) avariable heavy chain (VH) according to SEQ ID NO: 253, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 318; or SEQ ID NO: 319. SEQ ID NO: 320; SEQ ID NO: 321; SEQ ID NO: 322; or SEQ ID NO: 323. In some aspects, the VB14 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 254, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 318; or SEQ ID NO: 319. SEQ ID NO: 320; SEQ ID NO: 321; SEQ ID NO: 322; or SEQ ID NO: 323. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0220] In some aspects described herein, the immunoconjugate comprises an antibody or antigen binding fragment thereof capable of specifically binding to VB22 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB22 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 255, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 324; SEQ ID NO: 325; SEQ ID NO: 326; or SEQ ID NO: 327. In some aspects, the VB22 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 256, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 324; SEQ ID NO: 325; SEQ ID NO: 326; or SEQ ID NO: 327. In some aspects, the VB22 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 257, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 324; SEQ ID NO: 325; SEQ ID NO: 326; or SEQ ID NO: 327. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0221] In some aspects described herein, the immunoconjugate comprises an antibody or antigen binding fragment thereof capable of specifically binding to VB11 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB11 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 258, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 328; SEQ ID NO: 329; SEQ ID NO: 330; or SEQ ID NO: 331. Insome aspects, the VB11 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 259, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 328; SEQ ID NO: 329; SEQ ID NO: 330; or SEQ ID NO: 331, In some aspects, the VB11 antibody or antigen binding fragment, for example, comprises(i) a variable heavy chain (VH) according to SEQ ID NO: 260, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 328; SEQ ID NO: 329; SEQ ID NO: 330; or SEQ ID NO: 331. In some aspects, the VB11 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 261, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 332; SEQ ID NO: 333; SEQ ID NO: 334; SEQ ID NO: 335; or SEQ ID NO: 336. In some aspects, the VB11 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 262, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 332; SEQ ID NO: 333; SEQ ID NO: 334; SEQ ID NO: 335; or SEQ ID NO: 336. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0222] In some aspects described herein, the immunoconjugate comprises an antibody or antigen binding fragment thereof capable of specifically binding to VB12 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB12 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 263, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 337; SEQ ID NO: 338; SEQ ID NO: 339; SEQ ID NO: 340; or SEQ ID NO: 341. In some aspects, the VB12 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 264, and / or(ii) a variable light chain (VL) according to SEQ ID NO: 337; SEQ ID NO: 338; SEQ ID NO: 339; SEQ ID NO: 340; or SEQ ID NO: 341. In some aspects, the VB12 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 265, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 337; SEQ ID NO: 338; SEQ ID NO: 339; SEQ ID NO: 340; or SEQ ID NO: 341. In some aspects, the VB12 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 266, and / or (ii) a variable light chain (VL) according toSEQ ID NO: 337; SEQ ID NO: 338; SEQ ID NO: 339; SEQ ID NO: 340; or SEQ ID NO: 341. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0223] In some aspects described herein, the immunoconjugate comprises an antibody or antigen binding fragment thereof capable of specifically binding to VB8 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB8 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 267, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 342; SEQ ID NO: 343; or SEQ ID NO: 344. In some aspects, the VB8 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 268, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 342; SEQ ID NO: 343; or SEQ ID NO: 344. In some aspects, the VB8 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 269, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 342; SEQ ID NO: 343; or SEQ ID NO: 344. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0224] In some aspects described herein, the immunoconjugate comprises an antibody or antigen binding fragment thereof capable of specifically binding to VB13.1 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB13.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 270, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 345; SEQ ID NO: 346; or SEQ ID NO: 347. In some aspects, the VB13.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 271, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 345; SEQ ID NO: 346; or SEQ ID NO: 347. In some aspects, the VB13.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 272, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 345; SEQ ID NO: 346; or SEQ ID NO: 347. In some aspects, the VB13.1 antibody orantigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 273, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 345; SEQ ID NO: 346; or SEQ ID NO: 347. In some aspects, the VB13.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 643, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 661; SEQ ID NO: 662; or SEQ ID NO: 663; or SEQ ID NO: 664. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0225] In some aspects described herein, the immunoconjugate comprises an antibody or antigen binding fragment thereof capable of specifically binding to VB13.1 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB13.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 270, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 345; SEQ ID NO: 346; SEQ ID NO: 347; SEQ ID NO: 709; SEQ ID NO: 710; SEQ ID NO: 711; or SEQ ID NO: 712. In some aspects, the VB 13.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 271, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 345; SEQ ID NO: 346; SEQ ID NO: 347; SEQ ID NO: 709; SEQ ID NO: 710; SEQ ID NO: 711; or SEQ ID NO: 712. In some aspects, the VB13.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 272, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 345; SEQ ID NO: 346; SEQ ID NO: 347; SEQ ID NO: 709; SEQ ID NO: 710; SEQ ID NO: 711; or SEQ ID NO: 712. In some aspects, the VB13.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 273, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 345; SEQ ID NO: 346; SEQ ID NO: 347; SEQ ID NO: 709; SEQ ID NO: 710; SEQ ID NO: 711; or SEQ ID NO: 712. In some aspects, the VB13.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 643, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 661; SEQ ID NO: 662; or SEQ ID NO: 663; SEQ ID NO: 664; SEQ ID NO:709; SEQ ID NO: 710; SEQ ID NO: 711; or SEQ ID NO: 712. In some aspects, the VB13.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH)according to SEQ ID NO: 693, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 345; SEQ ID NO: 346; SEQ ID NO: 347; SEQ ID NO: 709; SEQ ID NO: 710; SEQ ID NO: 711; or SEQ ID NO: 712. In some aspects, the VB13.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 694, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 345; SEQ ID NO: 346; SEQ ID NO: 347; SEQ ID NO: 709; SEQ ID NO: 710; SEQ ID NO: 711; or SEQ ID NO: 712. In some aspects, the VB13.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 695, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 345; SEQ ID NO: 346; SEQ ID NO: 347; SEQ ID NO: 709; SEQ ID NO: 710; SEQ ID NO: 711; or SEQ ID NO: 712. In some aspects, the VB13.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 696, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 345; SEQ ID NO: 346; SEQ ID NO: 347; SEQ ID NO: 709; SEQ ID NO: 710; SEQ ID NO: 711; or SEQ ID NO: 712. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0226] In some aspects described herein, the immunconjugate comprises an antibody or antigen binding fragment thereof capable of specifically binding to VB5.1 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB5.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 274, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 348; SEQ ID NO: 349; or SEQ ID NO: 350. In some aspects, the VB5.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 275, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 348; SEQ ID NO: 349; or SEQ ID NO: 350. In some aspects, the VB5.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 276, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 348; SEQ ID NO: 349; or SEQ ID NO: 350. In some aspects, the VB5.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 277, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 348; SEQ ID NO: 349; or SEQ ID NO: 350. In some aspects, the VB5.1 antibody or antigenbinding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 278, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 348; SEQ ID NO: 349; or SEQ ID NO: 350. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0227] In some aspects described herein, the immunconjugate comprises an antibody or antigen binding fragment thereof capable of specifically binding to VB9 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB9 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 279, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 351; SEQ ID NO: 352; SEQ ID NO: 353; SEQ ID NO: 354. In some aspects, the VB9 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 280, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 351; SEQ ID NO: 352; SEQ ID NO: 353; or SEQ ID NO: 354, In some aspects, the VB9 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 281, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 351; SEQ ID NO: 352; SEQ ID NO: 353; or SEQ ID NO: 354. In some aspects, the VB9 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 282, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 351; SEQ ID NO: 352; SEQ ID NO: 353; or SEQ ID NO: 354. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0228] In some aspects described herein, the immunoconjugate comprises an antibody or antigen binding fragment thereof capable of specifically binding to VB17 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB17 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 283, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 355; SEQ ID NO: 356; or SEQ ID NO: 357. In some aspects, the VB17 antibody or antigen binding fragment, for example, comprises (i) a variable heavychain (VH) according to SEQ ID NO: 284, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 355; SEQ ID NO: 356; or SEQ ID NO: 357. In some aspects, the VB17 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 285, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 355; SEQ ID NO: 356; or SEQ ID NO: 357. In some aspects, the VB17 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 644, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 665; SEQ ID NO: 666; or SEQ ID NO: 667; or SEQ ID NO: 668. In some aspects, the VB17 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 645, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 665; SEQ ID NO: 666; or SEQ ID NO: 667; or SEQ ID NO: 668. In some aspects, the VB17 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 646, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 665; SEQ ID NO: 666; or SEQ ID NO: 667; or SEQ ID NO: 668. In some aspects, the VB17 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 647, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 665; SEQ ID NO: 666; or SEQ ID NO: 667; or SEQ ID NO: 668. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0229] In some aspects described herein, the immunoconjugate comprises an antibody or antigen binding fragment thereof capable of specifically binding to VB3 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 286, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 358; SEQ ID NO: 359; or SEQ ID NO: 360. In some aspects, the VB3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 287, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 358; SEQ ID NO: 359; or SEQ ID NO: 360. In some aspects, the VB3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 289, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 358;SEQ ID NO: 359; or SEQ ID NO: 360. In some aspects, the VB3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO:634, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 652; SEQ ID NO: 653; SEQ ID NO: 654; or SEQ ID NO: 655. In some aspects, the VB3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO:635, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 652; SEQ ID NO: 653; SEQ ID NO: 654; or SEQ ID NO: 655. In some aspects, the VB3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO:636, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 652; SEQ ID NO: 653; SEQ ID NO: 654; or SEQ ID NO: 655. In some aspects, the VB3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO:637, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 652; SEQ ID NO: 653; SEQ ID NO: 654; or SEQ ID NO: 655. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0230] In some aspects described herein, the immunoconjugate comprises an antibody or antigen binding fragment thereof capable of specifically binding to VB7.1 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB7.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 290, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 361; SEQ ID NO: 362; SEQ ID NO: 363; SEQ ID NO: 364; SEQ ID NO: 365; SEQ ID NO: 366; or SEQ ID NO: 367. In some aspects, the VB7.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 291, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 361; SEQ ID NO: 362; SEQ ID NO: 363; SEQ ID NO: 364; SEQ ID NO: 365; SEQ ID NO: 366; or SEQ ID NO: 367. In some aspects, the VB7.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 292, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 361; SEQ ID NO: 362; SEQ ID NO: 363; SEQ ID NO: 364; SEQ ID NO: 365; SEQ ID NO: 366; or SEQ ID NO: 367. In some aspects, the VB7.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 293, and / or (ii) avariable light chain (VL) according to SEQ ID NO: 361; SEQ ID NO: 362; SEQ ID NO: 363; SEQ ID NO: 364; SEQ ID NO: 365; SEQ ID NO: 366; or SEQ ID NO: 367. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0231] In some aspects described herein, the immunoconjugate comprises an antibody or antigen binding fragment thereof capable of specifically binding to VB7.1 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB7.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 290, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 361; SEQ ID NO: 362; SEQ ID NO: 363; SEQ ID NO: 364; SEQ ID NO: 365; SEQ ID NO: 366; SEQ ID NO: 367; SEQ ID NO: 705; SEQ ID NO: 706; SEQ ID NO: 707; or SEQ ID NO: 708. In some aspects, the VB7.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 291, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 361; SEQ ID NO: 362; SEQ ID NO: 363; SEQ ID NO: 364; SEQ ID NO: 365; SEQ ID NO: 366; SEQ ID NO: 367; SEQ ID NO: 705; SEQ ID NO: 706; SEQ ID NO: 707; or SEQ ID NO: 708. In some aspects, the VB7.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 292, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 361; SEQ ID NO: 362; SEQ ID NO: 363; SEQ ID NO: 364; SEQ ID NO: 365; SEQ ID NO: 366; SEQ ID NO: 367; SEQ ID NO: 705; SEQ ID NO: 706; SEQ ID NO: 707; or SEQ ID NO: 708. In some aspects, the VB7.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 293, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 361; SEQ ID NO: 362; SEQ ID NO: 363; SEQ ID NO: 364; SEQ ID NO: 365; SEQ ID NO: 366; SEQ ID NO: 367; SEQ ID NO: 705; SEQ ID NO: 706; SEQ ID NO: 707; or SEQ ID NO: 708. In some aspects, the VB7.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 689, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 361; SEQ ID NO: 362; SEQ ID NO: 363; SEQ ID NO: 364; SEQ ID NO: 365; SEQ ID NO: 366; SEQ ID NO: 367; SEQ ID NO: 705; SEQ ID NO: 706; SEQ ID NO: 707; or SEQ ID NO: 708. In some aspects, the VB7.1 antibody or antigenbinding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 690, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 361; SEQ ID NO: 362; SEQ ID NO: 363; SEQ ID NO: 364; SEQ ID NO: 365; SEQ ID NO: 366; SEQ ID NO: 367; SEQ ID NO: 705; SEQ ID NO: 706; SEQ ID NO: 707; or SEQ ID NO: 708. In some aspects, the VB7.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 691, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 361; SEQ ID NO: 362; SEQ ID NO: 363; SEQ ID NO: 364; SEQ ID NO: 365; SEQ ID NO: 366; SEQ ID NO: 367; SEQ ID NO: 705; SEQ ID NO: 706; SEQ ID NO: 707; or SEQ ID NO: 708. In some aspects, the VB7.1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 692, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 361; SEQ ID NO: 362; SEQ ID NO: 363; SEQ ID NO: 364; SEQ ID NO: 365; SEQ ID NO: 366; SEQ ID NO: 367; SEQ ID NO: 705; SEQ ID NO: 706; SEQ ID NO: 707; or SEQ ID NO: 708. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0232] In some aspects described herein, the immunoconjugate comprises an antibody or antigen binding fragment thereof capable of specifically binding to VB5.3 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB5.3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 294, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 368 or SEQ ID NO: 369. In some aspects, the VB5.3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 295, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 368 or SEQ ID NO: 369. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0233] In some aspects described herein, the immunoconjugate comprises an antibody or antigen binding fragment thereof capable of specifically binding to VB20 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In someaspects, the VB20 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 559, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 570; SEQ ID NO: 571; or SEQ ID NO: 572. In some aspects, the VB20 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 560, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 570; SEQ ID NO: 571; or SEQ ID NO: 572. In some aspects, the VB20 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 561, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 570; SEQ ID NO: 571; or SEQ ID NO: 572. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0234] In some aspects described herein, the immunoconjugate comprises an antibody or antigen binding fragment thereof capable of specifically binding to VB18 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB18 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 562, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 573; SEQ ID NO: 574; SEQ ID NO: 575. In some aspects, the VB18 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 563, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 573; SEQ ID NO: 574; SEQ ID NO: 575. In some aspects, the VB18 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 564, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 573; SEQ ID NO: 574; SEQ ID NO: 575. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0235] In some aspects described herein, the immunoconjugate comprises an antibody or antigen binding fragment thereof capable of specifically binding to VB13.6 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB13.6 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 565, and / or (ii) a variable light chain(VL) according to SEQ ID NO: 576; SEQ ID NO: 577. In some aspects, the VB13.6 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 566, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 576; SEQ ID NO: 577. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0236] In some aspects described herein, the immunoconjugate comprises an antibody or antigen binding fragment thereof capable of specifically binding to VB16 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB16 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 567, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 578; SEQ ID NO: 579; SEQ ID NO: 580; SEQ ID NO: 581; SEQ ID NO: 582; or SEQ ID NO: 583. In some aspects, the VB16 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 568, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 578; SEQ ID NO: 579; SEQ ID NO: 580; SEQ ID NO: 581; SEQ ID NO: 582; or SEQ ID NO: 583. In some aspects, the VB16 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 569, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 578; SEQ ID NO: 579; SEQ ID NO: 580; SEQ ID NO: 581; SEQ ID NO: 582; or SEQ ID NO: 583. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0237] In some aspects described herein, the immunoconjugate comprises an antibody or antigen binding fragment thereof capable of specifically binding to VB21.3 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB21.3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 648, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 669; SEQ ID NO: 670; or SEQ ID NO: 671. In some aspects, the VB21.3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 649, and / or (ii) a variable light chain (VL) according toSEQ ID NO: 669; SEQ ID NO: 670; or SEQ ID NO: 671. In some aspects, the VB21.3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 650, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 669; SEQ ID NO: 670; or SEQ ID NO: 671. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0238] In some aspects described herein, the immunoconjugate comprises an antibody or antigen binding fragment thereof capable of specifically binding to VB21.3 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB21.3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 648, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 669; SEQ ID NO: 670; SEQ ID NO: 671; SEQ ID NO: 713; SEQ ID NO: 714; SEQ ID NO: 715; or SEQ ID NO: 716. In some aspects, the VB21.3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 649, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 669; SEQ ID NO: 670; SEQ ID NO: 671; SEQ ID NO: 713; SEQ ID NO: 714; SEQ ID NO: 715; or SEQ ID NO: 716. In some aspects, the VB21.3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 650, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 669; SEQ ID NO: 670; SEQ ID NO: 671; SEQ ID NO: 713; SEQ ID NO: 714; SEQ ID NO: 715; or SEQ ID NO: 716. In some aspects, the VB21.3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 697, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 669; SEQ ID NO: 670; SEQ ID NO: 671; SEQ ID NO: 713; SEQ ID NO: 714; SEQ ID NO: 715; or SEQ ID NO: 716. In some aspects, the VB21.3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 698, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 669; SEQ ID NO: 670; SEQ ID NO: 671; SEQ ID NO: 713; SEQ ID NO: 714; SEQ ID NO: 715; or SEQ ID NO: 716. In some aspects, the VB21.3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 699, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 669; SEQ ID NO: 670; SEQ ID NO: 671; SEQ ID NO: 713; SEQ ID NO: 714; SEQ ID NO: 715; or SEQID NO: 716. In some aspects, the VB21.3 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 700, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 669; SEQ ID NO: 670; SEQ ID NO: 671; SEQ ID NO: 713; SEQ ID NO: 714; SEQ ID NO: 715; or SEQ ID NO: 716. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0239] In some aspects described herein, the immunoconjugate comprises an antibody or antigen binding fragment thereof capable of specifically binding to VB1 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 632, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 333; SEQ ID NO: 334; SEQ ID NO: 335; or SEQ ID NO: 336. In some aspects, the VB1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 633, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 333; SEQ ID NO: 334; SEQ ID NO: 335; or SEQ ID NO: 336. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0240] In some aspects described herein, the immunoconjugate comprises an antibody or antigen binding fragment thereof capable of specifically binding to VB1 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 632, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 333; SEQ ID NO: 334; SEQ ID NO: 335; SEQ ID NO: 336; SEQ ID NO: 701; SEQ ID NO: 702; SEQ ID NO: 703; or SEQ ID NO: 704. In some aspects, the VB1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 633, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 333; SEQ ID NO: 334; SEQ ID NO: 335; SEQ ID NO: 336; SEQ ID NO: 701; SEQ ID NO: 702; SEQ ID NO: 703; or SEQ ID NO: 704. In some aspects, the VB1 antibody orantigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 685, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 333; SEQ ID NO: 334; SEQ ID NO: 335; SEQ ID NO: 336; SEQ ID NO: 701; SEQ ID NO: 702; SEQ ID NO: 703; or SEQ ID NO: 704. In some aspects, the VB1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 686, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 333; SEQ ID NO: 334; SEQ ID NO: 335; SEQ ID NO: 336; SEQ ID NO: 701; SEQ ID NO: 702; SEQ ID NO: 703; or SEQ ID NO: 704. In some aspects, the VB1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 687, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 333; SEQ ID NO: 334; SEQ ID NO: 335; SEQ ID NO: 336; SEQ ID NO: 701; SEQ ID NO: 702; SEQ ID NO: 703; or SEQ ID NO: 704. In some aspects, the VB1 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 688, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 333; SEQ ID NO: 334; SEQ ID NO: 335; SEQ ID NO: 336; SEQ ID NO: 701; SEQ ID NO: 702; SEQ ID NO: 703; or SEQ ID NO: 704. In some aspects, the VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0241] In some aspects, the immunoconjugates of the present disclosure can be prepared by using a linking group in order to link a drug, chemotherapeutic drug, or cytotoxic agent to the antibody or functional equivalent. Suitable linking groups are well known in the art and include, for example, disulfide groups, thioether groups, acid labile groups, photolabile groups, peptidase labile groups and esterase labile groups. In some aspects, the linking group is cleavable. In some aspects, the linking group is noncleavable. In some aspects, the linking group may be an antibody or antigen binding fragment disclosed herein that specifically binds to the anti-TCRVB antibody or antigen binding fragment in the immunoconjugates of the present disclosure. In some aspects, the linking group binds to the Fc region of the anti- TCRVB antibody. In some aspects, the linking group may be a Fab fragment.

[0242] The drug, chemotherapeutic drug, or cytotoxic agent can, for example, be linked to the anti-TCRVB antibody or fragment thereof through a disulfide bond. The linker molecule or crosslinking agent comprises a reactive chemical group that can react with theanti- TCRVB antibody or fragment thereof. In certain aspects, reactive chemical groups for reaction with the cell-binding agent are A-succinimidyl esters and A-sulfosuccinimidyl esters. Additionally the linker molecule comprises a reactive chemical group, in certain embodiments a dithiopyridyl group that can react with the drug to form a disulfide bond. In certain embodiments, linker molecules include, for example, A-succinimidyl 3-(2- pyridyldithio) propionate (SPDP) (see, e.g., Carlsson et al., Biochem. J., 173: 723-737 (1978)), A-succinimidyl 4-(2-pyridyldithio)butanoate (SPDB) (see, e.g., U.S. Patent No. 4,563,304), A-succinimidyl 4-(2-pyridyldithio)2-sulfobutanoate (sulfo-SPDB) (see US Publication No. 20090274713) , A-succinimidyl 4-(2-pyridyldithio) pentanoate (SPP) (see, e.g., CAS Registry number 341498-08-6), 2-iminothiolane, or acetylsuccinic anhydride. For example, the antibody or cell binding agent can be modified with crosslinking reagents and the antibody or cell binding agent containing free or protected thiol groups thus derived is then reacted with a disulfide- or thiol-containing maytansinoid to produce conjugates. The conjugates can be purified by chromatography, including but not limited to HPLC, sizeexclusion, adsorption, ion exchange and affinity capture, dialysis or tangential flow filtration. In certain aspects, the anti-TCRVB antibody is linked to the cytotoxic agent via a SPDB or sulfo-SPDB linker. In certain aspects, the anti-TCRVB antibody is linked to the cytotoxic agent via a SMCC linker.

[0243] In some respects, the drug, chemotherapeutic drug, or cytotoxic agent can, for example, be linked to the anti-TCRVB antibody or fragment thereof. In certain aspects, the anti-TCRVB antibody is linked to the cytotoxic agent via an azido-PEG-NHS ester linker.

[0244] Immunoconjugates of the present disclosure with non-cleavable linkers can also be prepared. Such crosslinkers are described in the art (see ThermoScientific Pierce Crosslinking Technical Handbook and US Patent Application Publication No. 2005 / 0169933) and include but are not limited to, A-succinimidyl 4-(maleimidomethyl) cyclohexanecarboxylate (SMCC), A-succinimidyl-4-(A-maleimidomethyl)-cyclohexane-l- carboxy-(6-amidocaproate), which is a “long chain” analog of SMCC (LC-SMCC), K- maleimidoundecanoic acid A-succinimidyl ester (KMUA), P-maleimidopropanoic acid A- succinimidyl ester (BMPS), y-maleimidobutyric acid A-succinimidyl ester (GMBS), £- maleimidocaproic acid A-hydroxysuccinimide ester (EMCS), m-maleimidobenzoyl-A- hydroxy succinimide ester (MBS), A-(a-maleimidoacetoxy)-succinimide ester (AMAS), succinimidyl-6-(P-maleimidopropionamido)hexanoate (SMPH), A-succinimidyl 4-(p-maleimidophenyl)-butyrate (SMPB), and A-(p-maleimidophenyl)isocyanate (PMPI), N- succinimidyl-4-(iodoacetyl)-aminobenzoate (SIAB), A-succinimidyl iodoacetate (SIA), N- succinimidyl bromoacetate (SBA), and A-succinimidyl 3-(bromoacetamido)propionate (SBAP). In certain embodiments, the antibody is modified with crosslinking reagents such as succinimidyl 4-(N-maleimidomethyl)-cyclohexane-l -carboxylate (SMCC), sulfo-SMCC, maleimidobenzoyl-N-hydroxy succinimide ester (MBS), sulfo-MBS or succinimidyl- iodoacetate, as described in the literature, to introduce 1-10 reactive groups (Yoshitake et al, Eur. J. Biochem., 101 :395-399 (1979); Hashida et al, J. Applied Biochem., 56-63 (1984); and Liu et al, Biochem., 18:690-697 (1979)). The modified antibody is then reacted with the thiol-containing chemotherapeutic drug or cytotoxic agent to produce a conjugate. The conjugate can be purified by gel filtration through a Sephadex G25 column or by dialysis or tangential flow filtartion. The modified antibodies are treated with the thiol-containing chemotherapeutic drug or cytotoxic agent (1 to 2 molar equivalent / maleimido group) and immunoconjugates are purified by gel filtration through a Sephadex G-25 column, chromatography on a ceramic hydroxyapatite column, dialysis or tangential flow filtration or a combination of methods thereof.III. Cytotoxic Agents / Chemotherapeutic drugs

[0245] Cancer therapy may involve surgery, chemotherapy, hormonal therapy and / or radiation treatment to eradicate neoplastic cells in a subject (See, for example, Stockdale, 1998, "Principles of Cancer Patient Management", in Scientific American: Medicine, vol. 3, Rubenstein and Federman, eds., Chapter 12, Section IV). Cancer therapy can also involve biologies or immunotherapy. All of these approaches pose potential drawbacks for the subject. Surgery, for example, may be contraindicated due to the health of the subject or may be unacceptable to the subject. Additionally, surgery may not completely remove the neoplastic tissue. Radiation therapy is only effective when the neoplastic tissue exhibits a higher sensitivity to radiation than normal tissue, and radiation therapy can also often elicit serious side effects. Hormonal therapy is rarely given as a single drug and although can be effective, is often used to prevent or delay recurrence of cancer after other treatments have removed the majority of the cancer cells. Biological therapies / immunotherapies are limited in number and may produce side effects such as rashes or swellings, flu-like symptoms, including fever, chills and fatigue, digestive tract problems or allergic reactions.

[0246] With respect to chemotherapy, there are a variety of chemotherapeutic drugs available for treatment of cancer. A significant majority of cancer chemotherapeutics act by inhibiting DNA synthesis, either directly, or indirectly by inhibiting the biosynthesis of the deoxyribonucleotide triphosphate precursors, to prevent DNA replication and concomitant cell division (See, for example, Gilman et al., Goodman and Gilman's: The Pharmacological Basis of Therapeutics, Eighth Ed. (Pergamom Press, New York, 1990)).

[0247] Despite the availability of a variety of chemotherapeutic drugs, chemotherapy has many drawbacks (See, for example, Stockdale, 1998, "Principles of Cancer Patient Management" in Scientific American Medicine, vol. 3, Rubenstein and Federman, eds., ch. 12, sect. 10). Almost all chemotherapeutic drugs are toxic, and chemotherapy causes significant, and often dangerous, side effects, including severe nausea, bone marrow depression, and immunosuppression. Cytotoxic agent and / or chemotherapeutic drugs can also be used in autoimmune or inflammatory disorders. However, methods for reducing the systemic toxicity and off-target effects of chemotherapeutic drugs are needed.

[0248] In the present disclosure, the systemic toxicity and off-target effects of chemotherapeutic drugs can be mitigated by coupling chemotherapeutic drugs to an antibody or antigen binding fragment that specifically binds to TCRVB in the form of an immunoconjugate. The use of anti-TCRVB antibodies or antigen binding fragments disclosed herein in an immunoconjugate provides targeted delivery of chemotherapeutic or cytotoxic drugs improved treatment of cancer, autoimmune, or inflammatory disorders.

[0249] In some aspects, the chemotherapeutic drug or cytotoxic agent refers to a non- nucleic acid molecule that is used to treat cancer, autoimmune, or inflammatory disorders and / or that has cytotoxic ability. Such more traditional or conventional chemotherapeutic drugs can be described by mechanism of action or by chemical compound class. In some aspects, the chemotherapeutic is selected from the group of alkylating drugs (e.g., melphalan, mitobronitol, cyclophosphamide, streptozotocin, triaziquone), anthracy clines (e.g., doxorubicin, epirubicin, idarubicin, mitoxantrone, valrubicin), cytoskeletal disruptors (e.g., abaxrane, cabazitaxel, paclitaxel, taxotere, tesetaxel, Monomethyl auristatin F (MMAF), Monomethyl auristatin E (MMAE)), epothilones (e.g, ixabepilone), histone deacetylase inhibitors (e.g., entinostat, romidepsin, vorinostat, zabadinostat), inhibitors of topoisomerase I (e.g., exatecan, deruxtecan, belotecan, camptothecin, irinotecan, topotecan) or topoisomerase II (e.g., etoposide, teniposide, tafluposide), kinase inhibitors (e.g., bortezomib, erlotinib,gefitinib, imatinib), nucleotide analogs or precursors thereof (e.g., azacitidine, capecitabine, fluorouracil, methotrexate), peptide antibiotics (e.g., actinomycin, bleomycin), platinum based drugs (e.g., cisplatin, nedaplatin, oxaliplatin, satraplatin), retinoids (e.g., alitretinoin, bexarotene, tretinoin), and vinka alkaloids and derivatives (e.g., vinblastine, vincristine, vindesine).

[0250] In some aspects, the chemotherapeutic drug is a topoisomerase I inhibitor. In some aspects, the topoisomerase I inhibitor is exatecan, belotecan, camptothecin, irinotecan, or topotecan. In some aspects, the topoisomerase I inhibitor is exatecan.

[0251] In some aspects, the chemotherapeutic drug is a topoisomerase I inhibitor. In some aspects, the topoisomerase I inhibitor is deruxtecan.

[0252] In some aspects, the chemotherapeutic drug is a JAK inhibitor. In some aspects, the JAK inhibitor is ruxolitinib, tofacitinib, oclacitinib, baricitinib, peficitinib, upadacitinib, fedratinib, delgocitinib, filgotinib, abrocitinib, pacritinib, deucravacitinib, ritlecitinib, or momelotinib.

[0253] In some aspects, the chemotherapeutic drug is a BET inhibitor. In some aspects, the BET inhibitor is I-BET 151 (GSK1210151A), I-BET 762 (GSK525762), OTX-015, TEN- 010, CPI-203, pelabresib (CPI-0610), olinone, RVX-208, ABBV-744, LY294002, AZD5153, MT-1, MS645, ZEN-3694, BMS-986158, NUV-868, or PLX51107.

[0254] In some aspects, the chemotherapeutic drug is a BCL-2 inhibitor. In some aspects, the BCL-2 inhibitor is venetoclax (ABT-199), Oblimersen sodium (G3139), Obatoclax mesylate (GX15-070), Navitoclax (ABT-263), Palcitoclax (APG-1252), or AT-101 (R-(-)- gossypol acetic acid).

[0255] In some aspects, the chemotherapeutic drug is a cytoskeletal disruptor. In some aspects, the cytoskeletal disruptor is abaxrane, cabazitaxel, paclitaxel, taxotere, tesetaxel, Monomethyl auristatin F (MMAF), Monomethyl auristatin E (MMAE). In some aspects, the cytoskeletal disruptor is Monomethyl auristatin F (MMAF). In some aspects, the cytoskeletal disruptor is Monomethyl auristatin E (MMAE).

[0256] In some aspects, the chemotherapeutic drug is an AKT inhibitor. In some aspects, the AKT inhibitor is a ATP-competitive inhibitors selected from the group consisting of isoquinoline-5-sulfonamides (e.g., H-8. H-89), azepane derivatives (e.g., derived from (-)- balanol), aminofurazans (e.g., GSK690693), heterocyclic rings (e.g., CCT128930, AZD5363, ipatasertib), phenylpyrazole derivatives (e.g., AT7867, AT13148), andthiophenecarboxamide derivatives (e.g., GSK2110183, DC120, GSK2141795). In some aspects, the AKT inhibitor is an allosteric inhibitor selected from the group consisting of 2,3- diphenylquinoxaline analogues (e.g., MK-2206), alkylphospholipids (e.g., edelfosine, miltefosine, erufosine), indole-3 -carbinol analogues (e.g., OSU-A9), sulfonamide derivatives (e.g., PH-316, PHT-427), and thiourea derivatives (e.g., PIT-1, PIT-2, DM-PIT-1), purine derivatives (e.g., triciribine, ARQ 092). In some aspects, the AKT inhibitor is an irreversible inhibitor selected from the group consisting of antibiotics, lactoquinomycin, Frenolicin B, kalafungin, medermycin, Boc-Phe-vinyl ketone, 4-hydroxynonenal (4-HNE), 1,6- naphthyridinone derivatives, and imidazo-l,2-pyridine derivatives. See, Nitulescu, et al. Int J Oncol. 48(3) 869-995, which has been incorporated by reference herein.

[0257] In some aspects, the chemotherapeutic drug is an Aurora kinase A, B, or C inhibitor. In some aspects, the Aurora B kinase inhibitor is selected from the group consisting of Hesperadin, Barasertib, AZDI 152, AT9283, Danusertib (PHA-739358), AMG900, CYC116, BI 811283, AZD2811, SP-96, GSK1070916, reversine, CCT129202, CCT137690, SNS-314, quercetin, and VX-680. See, Borah, et al. Molecules. 26(7): 1981, which has been incorporated by reference herein.

[0258] In some aspects, the chemotherapeutic drug is an ERK inhibitor. In some aspects, the ERK inhibitor is selected from the group consisting of AZD0364, GDC-0994, MK-8353, BVD-523, HH2710, KO-947, LTT462, LY3214996, and ONC201. See, Pan, et al. Acta Pharm Sin B. 12(5):2171 -2192, which has been incorporated by reference herein.

[0259] In some aspects, the chemotherapeutic drug is a PI3K inhibitor. In some aspects, the PI3K inhibitor is selected from the group consisting of PI103; PI828; LY294002; wortmannin; demethoxyviridin; IC486068; IC87114; GDC-0941; GDC-0980; perifosine; CAL101; PX-866; IPI-145; BAY 80-6946; BEZ235; P6503; TGR1202; SF1126; INK1117; BKM120; IL147; XL765; Palomid 529; GSK1059615; ZSTK474; PWT33597; TG100-115; CAL263; GNE-447; CUDC-907; and AEZS-136.

[0260] In some aspects, the chemotherapeutic drug is a MEK inhibitor. In some aspects, the MEK inhibitor is selected from the group consisting of binimetinib, CC-90003, DEL- 22379, GDC-0973 (cobimetinib), selumetinib, and trametinib. See, Han, et al. Journal of Hematology & Oncology. 14(1): 1, which has been incorporated by reference herein.

[0261] In some aspects, the chemotherapeutic drug is a MAPK inhibitor. In some aspects, the MAPK inhibitor is selected from the group consisting of Famesyltransf erase inhibitors(FTIs), Sorafenib, Vemurafenib, PLX8394, Dabrafenib, Ulixertinib, Simvastatin, Alisertib, and Teriflunomide.

[0262] In some aspects, the chemotherapeutic drug is a B-RAF inhibitor. In some aspects, the B-RAF inhibitor is selected from the group consisting of Vemurafenib, Dabrafenib, Encorafenib, and Sorafenib. See, Sanchez, et al. Drugs. 78(5): 549-566, which has been incorporated by reference herein.

[0263] In some aspects, the chemotherapeutic drug is a RAS inhibitor. In some aspects, the RAS inhibitor is selected from the group consisting of Ganetespib, Apatinib, Oncrasin-1, GDC-0449, ARS-1620, ARS-853, AMG 510, MRTX849, BGB324, ABT-737, AZD6244, NVP-BEZ235, R115777, PPIN-1, PPIN-2, pan-RAS Inhibitor 3144, Deltarasin, and Sotorasib. See, Shetu, et al. Int J Mol Sci. 23(7)3706, which has been incorporated by reference herein.

[0264] In some aspects, the chemotherapeutic drug is a degrader. In some aspects, the degrader is selected from the group of AKT and Myc degraders. In some aspects, the degrader is a protein degrader. In some aspects, the protein degrader is selected from the group consisting of immunomodulatory drugs (iMiDs), molecular glue (MG), selective estrogen receptor degraders (SERDs), and proteolysis-targeting chimeras (PROTACs). See, Fang, et al. Trends Pharamcol Sci. 44(5):303-317; Xue, et al. Expert Opin Drug Discov. 18(4):467-483, which have been incorporated by reference herein.

[0265] In some aspects, the chemotherapeutic drug is a cytotoxic agent. In some aspects, the cytotoxic agent is selected from alkylating drugs, anthracyclines, cytoskeletal disruptors, epothilones, kinase inhibitors, histone deacetylase inhibitors, inhibitors of topoisomerase I or II, nucleotide analogs or precursors thereof, peptide antibiotics, platinum based drugs, retinoids, and vinka alkaloids and derivatives as previously defined.

[0266] In some aspects, the chemotherapeutic drug is a Wern syndrome helicase.

[0267] In some aspects, the chemotherapeutic drug is a cell cycle inhibitor. In some aspects, the cell cycle inhibitor is selected from the group consisting of polo-like kinases inhibitors and cyclin-dependent kinase inhibitors.

[0268] In some aspects, the cell cycle inhibitor is an aurora kinase inhibitor. In some aspects, the aurora kinase inhibitor is Barasertib, Alisertib (MLN8237), Danusertib (PHA- 739358), AT9283, PF-03814735, or AMG 900. In some aspects, the cell cycle inhibitor is a Chk inhibitor. In some aspects, the Chk inhibitor is Prexasertib (LY2606368) or AZD7762.In some aspects, the cell cycle inhibitor is a Chkl inhibitor. In some aspects, the Chkl inhibitor is GDC-0575, Rabusertib (LY2603618), VX-803 (M4344), CHIR-124, PF-477736, PDO 166285, or SAR-020106. In some aspects, the cell cycle inhibitor is a Chk2 inhibitor. In some aspects, the Chk2 inhibitor is BML-277. In some aspects, the polo-like kinase (PLK) inhibitor is BI 6727, BI 2536, GSK461364A, Rigosertib or Volasertib. In some aspects, the cell cycle inhibitor is a cyclin-dependent kinase (CDK) inhibitor such as Palbociclib, Abemaciclib, Dinaciclib, Ribociclib, TP-1287, Alvocidib, NUV-422. In some aspects, the cyclin-dependent kinase inhibitor is a CDK1, CDK2, CDK4, CDK6, CDK7 or some combination of CDK inhibitors. In some aspects, the cytoskeletal disruptor is a taxane (e.g., paclitaxel, docetaxel, or cabazitaxel) colchicine, vinblastine, evodaimine, 6a- acetoxyanopterine, cytochalasin, latrunculin, staurosporine, sinularin, phalloidin,or eribulin.

[0269] In some aspects, the chemotherapeutic drug is a protein degrader. In some aspects, the protein degrader is a proteolysis-targeting chimera (PROTAC) molecule.IV. Methods of Treatment

[0270] In some aspects described herein are methods for treating cancer in a subject in need thereof, the method comprising: administering to the subject a therapeutically effective amount of a composition comprising an immunoconjugate comprising a chemotherapeutic drug or cytotoxic agent disclosed herein comprising an antibody or antigen-binding fragment thereof capable of specifically binding to a TCR VB region, comprising a (i) heavy chain variable region (VH) having an amino acid sequence according to any of SEQ ID NOs: 228- 295, 559-569, and 632-650, or (ii) a light chain variable region (VL) having an amino acid sequence according to any of SEQ ID NOs: 296-369, 570-583, 652-671. In some aspects described herein are methods for treating cancer in a subject in need thereof, the method comprising: administering to the subject a therapeutically effective amount of a composition comprising an immunoconjugate comprising a chemotherapeutic drug or cytotoxic agent disclosed herein comprising an antibody or antigen-binding fragment thereof capable of specifically binding to a TCR VB region, comprising a (i) heavy chain variable region (VH) having an amino acid sequence according to any of SEQ ID NOs: 228-295, 559-569, and 632-650, and (ii) a light chain variable region (VL) having an amino acid sequence according to any of SEQ ID NOs: 296-369, 570-583, and 652-671.

[0271] In some aspects described herein are methods for treating T-cell mediated diseases in a subject in need thereof, the method comprising for example; administering to the subjecta therapeutically effective amount of a composition comprising an immunoconjugate comprising a chemotherapeutic drug or cytotoxic agent disclosed herein comprising an antibody or antigen-binding fragment thereof capable of specifically binding to a TCR VB region, comprising a (i) heavy chain variable region (VH) having an amino acid sequence according to any of SEQ ID NOs: 228-295, 559-569, and 632-650, or (ii) a light chain variable region (VL) having an amino acid sequence according to any of SEQ ID NOs: 228- 295, 559-569, and 652-671. In some aspects described herein are methods for treating T-cell mediated diseases in a subject in need thereof, the method comprising for example; administering to the subject a therapeutically effective amount of a composition comprising an immunoconjugate comprising a chemotherapeutic drug or cytotoxic agent disclosed herein comprising an antibody or antigen-binding fragment thereof capable of specifically binding to a TCR VB region, comprising a (i) heavy chain variable region (VH) having an amino acid sequence according to any of SEQ ID NOs: 228-295, 559-569, and 632-650, and (ii) a light chain variable region (VL) having an amino acid sequence according to any of SEQ ID NOs: 296-369, 570-583, and 652-671.

[0272] In some aspects of the methods described herein, the immunoconjugate disclosed herein comprises an antibody or antigen-binding fragment for example, comprises (i) a variable heavy chain (VH) which comprises: (a) CDR1, CDR2 and CDR3 according to SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12, respectively; or (b) CDR1, CDR2 and CDR3 according to SEQ ID NO:370, SEQ ID NO:371, and SEQ ID NO:372, respectively; or (c) CDR1, CDR2 and CDR3 according to SEQ ID NO:373, SEQ ID NO:374, and SEQ ID NO:375 respectively; or (d) CDR1, CDR2 and CDR3 according to SEQ ID NO:376, SEQ ID NO:377, and SEQ ID NO:378, respectively; or (e) CDR1, CDR2 and CDR3 according to SEQ ID NO:379, SEQ ID NO:380, and SEQ ID NO:381 respectively; or (f) CDR1, CDR2 and CDR3 according to SEQ ID NO:382, SEQ ID NO:383, and SEQ ID NO:384, respectively; or (g) CDR1, CDR2 and CDR3 according to SEQ ID NO:385, SEQ ID NO:386, and SEQ ID NO:387, respectively; or (h) CDR1, CDR2 and CDR3 according to SEQ ID NO:388, SEQ ID NO:389, and SEQ ID NO:390, respectively; or (i) CDR1, CDR2 and CDR3 according to SEQ ID NO:391, SEQ ID NO:392, and SEQ ID NO:393, respectively; or (j) CDR1, CDR2 and CDR3 according to SEQ ID NO:394, SEQ ID NO:395, and SEQ ID NO: 396, respectively; or (k) CDR1, CDR2 and CDR3 according to SEQ ID NO: 397, SEQ ID NO: 398, and SEQ ID NO: 399, respectively; or (1) CDR1, CDR2 and CDR3 according toSEQ ID N0:400, SEQ ID NO:401, and SEQ ID NO:402, respectively; or (m) CDR1, CDR2 and CDR3 according to SEQ ID NO:403, SEQ ID NO:404, and SEQ ID NO:405, respectively; or (n) CDR1, CDR2 and CDR3 according to SEQ ID NO:406, SEQ ID NO:407, and SEQ ID NO:408, respectively; or (o) CDR1, CDR2 and CDR3 according to SEQ ID NO:409, SEQ ID NO:410, and SEQ ID NO:411, respectively; or (p) CDR1, CDR2 and CDR3 according to SEQ ID NO:412, SEQ ID NO:413, and SEQ ID NO:414, respectively; or (q) CDR1, CDR2 and CDR3 according to SEQ ID NO:415, SEQ ID NO:416, and SEQ ID NO:417, respectively; or (r) CDR1, CDR2 and CDR3 according to SEQ ID NO:584, SEQ ID NO:585, and SEQ ID NO:586, respectively; or (s) CDR1, CDR2 and CDR3 according to SEQ ID NO:587, SEQ ID NO:588, and SEQ ID NO:589, respectively; or (t) CDR1, CDR2 and CDR3 according to SEQ ID NO:590, SEQ ID NO:591, and SEQ ID NO:592, respectively; or (u) CDR1, CDR2 and CDR3 according to SEQ ID NO:593, SEQ ID NO:594, and SEQ ID NO:595, respectively, or (v) CDR1, CDR2, and CDR3 according to SEQ ID NO:370, SEQ ID NO:681, and SEQ ID NO:372, respectively, or (w) CDR1, CDR2, and CDR3 according to SEQ ID NO:675, SEQ ID NO:676, and SEQ ID NO:677, respectively; and / or (ii) a variable light chain (VL) which comprises: (a) CDR1, CDR2 and CDR3 according to SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, respectively; or (b) CDR1, CDR2 and CDR3 according to SEQ ID NO:418, SEQ ID NO:419, SEQ ID NO:420, respectively; or (c) CDR1, CDR2 and CDR3 according to SEQ ID NO:421, SEQ ID NO:422, SEQ ID NO:423, respectively; or (d) CDR1, CDR2 and CDR3 according to SEQ ID NO:424, SEQ ID NO:425, SEQ ID NO:426, respectively; or (e) CDR1, CDR2 and CDR3 according to SEQ ID NO:427, SEQ ID NO:428, SEQ ID NO:429, respectively; or (f) CDR1, CDR2 and CDR3 according to SEQ ID NO:430, SEQ ID NO:431, SEQ ID NO:432, respectively; or (g) CDR1, CDR2 and CDR3 according to SEQ ID NO:433, SEQ ID NO:434, SEQ ID NO:435, respectively; or (h) CDR1, CDR2 and CDR3 according to SEQ ID NO:436, SEQ ID NO:437, SEQ ID NO:438, respectively; or (i) CDR1, CDR2 and CDR3 according to SEQ ID NO:439, SEQ ID NO:440, SEQ ID NO:441, respectively; or (j) CDR1, CDR2 and CDR3 according to SEQ ID NO:442, SEQ ID NO:443, SEQ ID NO:444, respectively; or (k) CDR1, CDR2 and CDR3 according to SEQ ID NO:445, SEQ ID NO:446, SEQ ID NO:447, respectively; or (1) CDR1, CDR2 and CDR3 according to SEQ ID NO:448, SEQ ID NO:449, SEQ ID NO:450, respectively; or (m) CDR1, CDR2 and CDR3 according to SEQ ID NO:451, SEQ ID NO:452, SEQ ID NO:453, respectively; or (n) CDR1, CDR2 and CDR3 according to SEQ IDNO:454, SEQ ID NO:455, SEQ ID NO:456, respectively; or (o) CDR1, CDR2 and CDR3 according to SEQ ID NO:457, SEQ ID NO:458, SEQ ID NO:459, respectively; or (p) CDR1, CDR2 and CDR3 according to SEQ ID NO:460, SEQ ID NO:461, SEQ ID NO:462, respectively; or (q) CDR1, CDR2 and CDR3 according to SEQ ID NO:463, SEQ ID NO:464, SEQ ID NO:465, respectively; or (r) CDR1, CDR2 and CDR3 according to SEQ ID NO:596, SEQ ID NO:597, SEQ ID NO:598, respectively; or (s) CDR1, CDR2 and CDR3 according to SEQ ID NO:599, SEQ ID NO:600, SEQ ID NO:601, respectively; or (t) CDR1, CDR2 and CDR3 according to SEQ ID NO: 602, SEQ ID NO: 603, SEQ ID NO: 604, respectively; or (u) CDR1, CDR2 and CDR3 according to SEQ ID NO:605, SEQ ID NO:606, SEQ ID NO:607, respectively, or SEQ ID NO: 608, SEQ ID NO: 609, SEQ ID NO: 610, respectively; or (v) CDR1, CDR2, and CDR3 according to SEQ ID NO:682, SEQ ID NO:419, and SEQ ID NO:420, respectively, SEQ ID NO:682, SEQ ID NO:683, SEQ ID NO:420, respectively, or SEQ ID NO:419, SEQ ID NO:684, SEQ ID NO:420, respectively (w) CDR1, CDR2, and CDR3 according to SEQ ID NO:678, SEQ ID NO:679, and SEQ ID NO:680, respectively.

[0273] In some aspects of the methods described herein, the immunoconjugate disclosed herein comprises a variable heavy chain comprises an amino acid sequence having at least 85% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, and 650. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable heavy chain comprises an amino acid sequence having at least 86% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, and 650. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable heavy chain comprises an amino acid sequence having at least 87% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, and 650. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable heavy chain comprises an amino acid sequence having at least 88% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, and 650. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable heavy chain comprises an amino acid sequence having at least 89% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, 639, 641, 642, and 650. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable heavy chain comprises an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, 632, 638, 639, 641, 642, and 650. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable heavy chain comprises an aminoacid sequence having at least 91% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, 632, 633, 638-642, 648, and 650. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable heavy chain comprises an amino acid sequence having at least 92% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, 632, 633, 638-642, and 648-650. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable heavy chain comprises an amino acid sequence having at least 93% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, 632, 633, 638-642, and 648-650. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable heavy chain comprises an amino acid sequence having at least 94% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, 632, 633, 638-642, and 648-650. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable heavy chain comprises an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 228-295, and 559-569, 632, 633, 638-643, and 648-650. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable heavy chain comprises an amino acid sequence having at least 96% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, 632, 633, 635, 637-643, and 647-650. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable heavy chain comprises an amino acid sequence having at least 97% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, 632-643, and 646-650. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable heavy chain comprises an amino acid sequence having at least 98% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, and 632-650.In some aspects described herein, the immunoconjugate disclosed herein comprises a variable heavy chain comprises an amino acid sequence having at least 99% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, and 632-650. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable heavy chain comprises an amino acid sequence according to any one of SEQ ID NOs: 228-295, 559-569, and 632-650.

[0274] In some aspects of the methods described herein, the immunoconjugate disclosed herein comprises an antibody or antigen-binding fragment comprising a heavy chain variable region (VH) as described above, further comprises a light chain variable region (VL) having an amino acid sequence according to any of SEQ ID NOs: 296-369, 570-583, and 652-671.- I l l -

[0275] In some aspects of the methods described herein, the immunoconjugate disclosed herein comprises a variable light chain comprises an amino acid sequence having at least 85% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, and 671. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable light chain comprises an amino acid sequence having at least 86% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 662 and 671. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable light chain comprises an amino acid sequence having at least 87% sequence identity to any one of SEQ ID NOs: 296-369, 570- 583, 662, and 671. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable light chain comprises an amino acid sequence having at least 88% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 662, 670, and 671. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable light chain comprises an amino acid sequence having at least 89% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 662, 670, and 671. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable light chain comprises an amino acid sequence having at least 90% sequence identity to any one of SEQ ID NOs: 296-369, 570- 583, 662, 670, and 671. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable light chain comprises an amino acid sequence having at least 91% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 662, 670, and 671. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable light chain comprises an amino acid sequence having at least 92% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 662, and 669-671. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable light chain comprises an amino acid sequence having at least 93% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 652, 662, and 669-671. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable light chain comprises an amino acid sequence having at least 94% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 652, 661, 662, and 669-671. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable light chain comprises an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 652-654, 657, 659, 661, 662, and 669-671. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable light chain comprises an amino acid sequence having at least 96%sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 661, 662, 664, 667, and 669-671. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable light chain comprises an amino acid sequence having at least 97% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 652-662, 664, 665, 667, and 669-671. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable light chain comprises an amino acid sequence having at least 98% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 652-665, 667, and 669-671. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable light chain comprises an amino acid sequence having at least 99% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 652-665, and 667-671. In some aspects described herein, the immunoconjugate disclosed herein comprises a variable light chain comprises an amino acid sequence according to any one of SEQ ID NOs: 296-369, 570-583, and 652-671.

[0276] In some aspects of the methods described herein the immunoconjugate disclosed herein comprises an antibody or antigen-binding fragment comprising a light chain variable region (VL) as described above, further comprises a heavy chain variable region (VH) having an amino acid sequence according to any of SEQ ID NOs: 228-295, 559-569, 632-650.

[0277] In some aspects of the methods described herein, the immunoconjugate disclosed herein comprises a variable heavy chain comprises an amino acid sequence having any percent identity described above to any one of SEQ ID NOs: 228-295, 559-569, and 632-650, and the variable light chain comprises an amino acid sequence having any percent identity described above to any one of SEQ ID NOs: 296-369, 570-583, and 652-671. To illustrate, a non-limiting example pairing of variable heavy and light chains includes a variable heavy chain comprising an amino acid sequence having at least 88% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, and 650 and a variable light chain comprising an amino acid sequence having at least 93% sequence identity to any one of SEQ ID NOs: 296-369, 570-583, 652, 662, and 669-671. In other aspects of the methods decribed herein, pairing of variable heavy and light chains includes a variable heavy chain comprising an amino acid sequence having any percent identity described above to any one of SEQ ID NOs: 228-295, 559-569, and 632-650, and a variable light chain comprising an amino acid sequence according to any one of SEQ ID NOs: 296-369, 570-583, and 652-671. In other aspects described herein, pairing of variable heavy and light chains includes a variable heavy chain comprising an amino acid sequence according to any one of SEQ ID NOs: 228-295, 559-569,and 632-650, and a variable light chain comprising an amino acid sequence having any percent identity described above to any one of SEQ ID NOs: 296-369, 570-583, and 652-671. To illustrate, a non-limiting example pairing of variable heavy and light chains includes a variable heavy chain comprising an amino acid sequence having at least 92% sequence identity to any one of SEQ ID NOs: 228-295, 559-569, , 632, 633, 638-642, and 648-650, and a variable light chain comprising an amino acid sequence according to any one of SEQ ID NOs: 296-369, 570-583, and 652-671. In yet other aspects described herein, the variable heavy chain comprises an amino acid sequence according to any one of SEQ ID NOs: 228- 295, 559-569, and 632-650, and the variable light chain comprises an amino acid sequence according to any one of SEQ ID NOs: 296-369, 570-583, and 652-671.

[0278] In some aspects of the methods described herein, the immunoconjugate disclosed herein comprises an antibody or antigen-binding fragment thereof is capable of specifically binding to TCR VB2 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 228, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 296; SEQ ID NO: 297; SEQ ID NO: 298; SEQ ID NO: 299; SEQ ID NO: 300; SEQ ID NO: 301; SEQ ID NO: 302; or SEQ ID NO: 303. In some aspects, the immunoconjugate disclosed herein comprises a VB2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 229, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 296; SEQ ID NO: 297; SEQ ID NO: 298; SEQ ID NO: 299; SEQ ID NO: 300; SEQ ID NO: 301; SEQ ID NO: 302; or SEQ ID NO: 303. In some aspects, the immunoconjugate disclosed herein comprises a VB2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 230, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 296; SEQ ID NO: 297; SEQ ID NO: 298; SEQ ID NO: 299; SEQ ID NO: 300; SEQ ID NO: 301; SEQ ID NO: 302; or SEQ ID NO: 303. In some aspects, the immunoconjugate disclosed herein comprises a VB2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 231, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 296; SEQ ID NO: 297; SEQ ID NO: 298; SEQ ID NO: 299; SEQ ID NO: 300; SEQ ID NO: 301; SEQ ID NO: 302; or SEQ ID NO: 303. In some aspects, the immunoconjugate disclosed herein comprises a VB2 antibody or antigen binding fragment, for example, comprises (i) avariable heavy chain (VH) according to SEQ ID NO: 232, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 296; SEQ ID NO: 297; SEQ ID NO: 298; SEQ ID NO: 299; SEQ ID NO: 300; SEQ ID NO: 301; SEQ ID NO: 302; or SEQ ID NO: 303. In some aspects, the immunoconjugate disclosed herein comprises a VB2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 233, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 296; SEQ ID NO: 297; SEQ ID NO: 298; SEQ ID NO: 299; SEQ ID NO: 300; SEQ ID NO: 301; SEQ ID NO: 302; or SEQ ID NO: 303. In some aspects, the immunoconjugate disclosed herein comprises a VB2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 234, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 296; SEQ ID NO: 297; SEQ ID NO: 298; SEQ ID NO: 299; SEQ ID NO: 300; SEQ ID NO: 301; SEQ ID NO: 302; or SEQ ID NO: 303. In some aspects, the immunoconjugate disclosed herein comprises a VB2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 235, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 296; SEQ ID NO: 297; SEQ ID NO: 298; SEQ ID NO: 299; SEQ ID NO: 300; SEQ ID NO: 301; SEQ ID NO: 302; or SEQ ID NO: 303. In some aspects, the immunoconjugate disclosed herein comprises a VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0279] In some aspects of the methods described herein, the immunoconjugate disclosed herein comprises an antibody or antigen binding fragment thereof is capable of specifically binding to VB7.2 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the VB7.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 236, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 304; SEQ ID NO: 305; SEQ ID NO: 306; or SEQ ID NO: 307. In some aspects, the immunoconjugate disclosed herein comprises a VB7.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 237, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 304; SEQ ID NO: 305; SEQ ID NO: 306; or SEQ ID NO: 307. In some aspects, the immunoconjugate disclosed herein comprises a VB7.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) accordingto SEQ ID NO: 238, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 304; SEQ ID NO: 305; SEQ ID NO: 306; or SEQ ID NO: 307. In some aspects, the immunoconjugate disclosed herein comprises a VB7.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 638, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 656; SEQ ID NO: 657; SEQ ID NO: 658; SEQ ID NO: 659; or SEQ ID NO: 660. In some aspects, the immunoconjugate disclosed herein comprises a VB7.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 639, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 656; SEQ ID NO: 657; SEQ ID NO: 658; SEQ ID NO: 659; or SEQ ID NO: 660. In some aspects, the immunoconjugate disclosed herein comprises a VB7.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 640, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 656; SEQ ID NO: 657; SEQ ID NO: 658; SEQ ID NO: 659; or SEQ ID NO: 660. In some aspects, the immunoconjugate disclosed herein comprises a VB7.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 641, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 656; SEQ ID NO: 657; SEQ ID NO: 658; SEQ ID NO: 659; or SEQ ID NO: 660. In some aspects, the immunoconjugate disclosed herein comprises a VB7.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 642, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 656;SEQ ID NO: 657; SEQ ID NO: 658; SEQ ID NO: 659; or SEQ ID NO: 660. In some aspects, the immunoconjugate disclosed herein comprises a VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0280] In some aspects of the methods described herein, the immunoconjugate disclosed herein comprises an antibody or antigen binding fragment thereof is capable of specifically binding to VB4, and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the immunoconjugate disclosed herein comprises a VB4 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 239, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 308; or SEQ ID NO: 309. In some aspects, the immunoconjugate disclosed hereincomprises a VB4 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 240, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 308; or SEQ ID NO: 309. In some aspects, the immunoconjugate disclosed herein comprises a VB4 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 241, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 308; or SEQ ID NO: 309. In some aspects, the immunoconjugate disclosed herein comprises a VB4 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 242, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 308; or SEQ ID NO: 309. In some aspects, the immunoconjugate disclosed herein comprises a VB4 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 243, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 308; or SEQ ID NO: 309. In some aspects, the immunoconjugate disclosed herein comprises a VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0281] In some aspects of the methods described herein, the immunoconjugate disclosed herein comprises an antibody or antigen binding fragment thereof is capable of specifically binding to VB13.2 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL), In some aspects described herein, the immunoconjugate disclosed herein comprises an antibody or antigen binding fragment thereof is capable of specifically binding to VB13.2 and, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 244, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 310; SEQ ID NO: 311; SEQ ID NO: 312; SEQ ID NO: 313; SEQ ID NO: 314; SEQ ID NO: 315; SEQ ID NO: 316; or SEQ ID NO: 317. In some aspects, the immunoconjugate disclosed herein comprises an VB13.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 245, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 310; SEQ ID NO: 311; SEQ ID NO: 312; SEQ ID NO: 313; SEQ ID NO: 314; SEQ ID NO: 315; SEQ ID NO: 316; or SEQ ID NO: 317. In some aspects, the immunoconjugate disclosed herein comprises an VB13.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO:246, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 310; SEQ ID NO: 311; SEQ ID NO: 312; SEQ ID NO: 313; SEQ ID NO: 314; SEQ ID NO: 315; SEQ ID NO: 316; or SEQ ID NO: 317. In some aspects, the immunoconjugate disclosed herein comprises an VB13.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 247, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 310; SEQ ID NO: 311; SEQ ID NO: 312; SEQ ID NO: 313; SEQ ID NO: 314; SEQ ID NO: 315; SEQ ID NO: 316; or SEQ ID NO: 317. In some aspects, the immunoconjugate disclosed herein comprises a VB13.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 248, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 310; SEQ ID NO: 311; SEQ ID NO: 312; SEQ ID NO: 313; SEQ ID NO: 314; SEQ ID NO: 315; SEQ ID NO: 316; or SEQ ID NO: 317. In some aspects, the immunoconjugate disclosed herein comprises a VB13.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 249, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 310; SEQ ID NO: 311; SEQ ID NO: 312; SEQ ID NO: 313; SEQ ID NO: 314; SEQ ID NO: 315; SEQ ID NO: 316; or SEQ ID NO: 317. In some aspects, the immunoconjugate disclosed herein comprises a VB13.2 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 250, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 310; SEQ ID NO: 311; SEQ ID NO: 312; SEQ ID NO: 313; SEQ ID NO: 314; SEQ ID NO: 315; SEQ ID NO: 316; or SEQ ID NO: 317. In some aspects, the immunoconjugate disclosed herein comprises a VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0282] In some aspects of the methods described herein, the immunoconjugate disclosed herein comprises an antibody or antigen binding fragment thereof is capable of specifically binding to VB14 and, for example comprises (i) a variable heavy chain (VH), and / or a variable light chain (VL). In some aspects, the immunoconjugate disclosed herein comprises a VB14 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 251, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 318; or SEQ ID NO: 319. SEQ ID NO: 320; SEQ ID NO: 321; SEQ ID NO: 322; or SEQ ID NO: 323. In some aspects, the immunoconjugate disclosed herein comprisesa VB14 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 252, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 318; or SEQ ID NO: 319. SEQ ID NO: 320; SEQ ID NO: 321; SEQ ID NO: 322; or SEQ ID NO: 323. In some aspects, the immunoconjugate disclosed herein comprises a VB14 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 253, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 318; or SEQ ID NO: 319. SEQ ID NO: 320; SEQ ID NO: 321; SEQ ID NO: 322; or SEQ ID NO: 323. In some aspects, the immunoconjugate disclosed herein comprises a VB14 antibody or antigen binding fragment, for example, comprises (i) a variable heavy chain (VH) according to SEQ ID NO: 254, and / or (ii) a variable light chain (VL) according to SEQ ID NO: 318; or SEQ ID NO: 319. SEQ ID NO: 320; SEQ ID NO: 321; SEQ ID NO: 322; or SEQ ID NO: 323. In some aspects, the immunoconjugate disclosed herein comprises a VH and VL described above comprises an amino acid sequence having at least 85%, at least 90%, at least 91% at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or about 100% percent identity to any one SEQ ID NO. described above.

[0283] In some aspects of the methods...

Claims

1. WHAT IS CLAIMED IS:

1. An immunoconjugate having the formula (A) - (L) - (C), wherein:(A) is an antibody or antigen binding fragment thereof that specifically binds to TCRVP, wherein the antibody comprises:(a) (i) a variable chain (VH) comprising CDR1, CDR2, and CDR3 according to SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, respectively;(b) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:370, SEQ ID NO:681, and SEQ ID NO:372, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:418, SEQ ID NO:419, SEQ ID NO:420, respectively, SEQ ID NO: 682, SEQ ID NO: 419, SEQ ID NO: 420, respectively, SEQ ID NO: 682, SEQ ID NO: 683, SEQ ID NO: 420, respectively, or SEQ ID NO: 418, SEQ ID NO: 684, SEQ ID NO: 420, respectively;(c) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:373, SEQ ID NO:374, and SEQ ID NO:375 respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:421, SEQ ID NO:422, SEQ ID NO:423, respectively;(d) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:376, SEQ ID NO:377, and SEQ ID NO:378, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:424, SEQ ID NO:425, SEQ ID NO:426, respectively;(e) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:379, SEQ ID NO:380, and SEQ ID NO:381 respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:427, SEQ ID NO:428, SEQ ID NO:429, respectively;(f) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:382, SEQ ID NO:383, and SEQ ID NO:384, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:430, SEQ ID NO:431, SEQ ID NO:432, respectively;(g) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:385, SEQ ID NO:386, and SEQ ID NO:387, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:433, SEQ ID NO:434, SEQ ID NO:435, respectively;(h) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:388, SEQ ID NO:389, and SEQ ID NO:390, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:436, SEQ ID NO:437, SEQ ID NO:438, respectively;(i) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:391, SEQ ID NO:392, and SEQ ID NO:393 respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:439, SEQ ID NO:440, SEQ ID NO:441, respectively;(j) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:394, SEQ ID NO:395, and SEQ ID NO:396, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:442, SEQ ID NO:443, SEQ ID NO:444, respectively;(k) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:397, SEQ ID NO:398, and SEQ ID NO:399, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:445, SEQ ID NO:446, SEQ ID NO:447, respectively;(l) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:400, SEQ ID NO:401, and SEQ ID NO:402, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:448, SEQ ID NO:449, SEQ ID NO:450, respectively;(m) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:403, SEQ ID NO:404, and SEQ ID NO:405 respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:451, SEQ ID NO:452, SEQ ID NO:453, respectively;(n) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:406, SEQ ID NO:407, and SEQ ID NO:408, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:454, SEQ ID NO:455, SEQ ID NO:456, respectively;(o) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:409, SEQ ID NO:410, and SEQ ID NO:411, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:457, SEQ ID NO:458, SEQ ID NO:459, respectively;(p) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:412, SEQ ID NO:413, and SEQ ID NO:414, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:460, SEQ ID NO:461, SEQ ID NO:462, respectively;(q) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:415, SEQ ID NO:416, and SEQ ID NO:417, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:463, SEQ ID NO:464, SEQ ID NO:465, respectively;(r) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:584, SEQ ID NO:585, and SEQ ID NO:586, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:596, SEQ ID NO:597, SEQ ID NO:598, respectively;(s) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:587, SEQ ID NO:588, and SEQ ID NO:589, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:599, SEQ ID NO:600, SEQ ID NO:601, respectively;(t) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:590, SEQ ID NO:591, and SEQ ID NO:592, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO: 602, SEQ ID NO: 603, SEQ ID NO: 604, respectively;(u) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:593, SEQ ID NO:594, and SEQ ID NO:595, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:605, SEQ ID NO:606, SEQ ID NO:607, respectively, or SEQ ID NO: 608, SEQ ID NO: 609, SEQ ID NO: 610, respectively; or(v) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:675, SEQ ID NO:676, and SEQ ID NO:677, respectively,and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO: 678, SEQ ID NO: 679, SEQ ID NO: 680, respectively;(L) is a linker; and(C) is a cytotoxic agent, wherein said linker (L) links (A) to (C).

2. An immunoconjugate having the formula (Al) - (A2) - (L) - (C), wherein:(Al) is an antibody or antigen binding fragment thereof that specifically binds to TCRVP wherein the antibody comprises:(a) (i) a variable chain (VH) comprising CDR1, CDR2, and CDR3 according to SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, respectively;(b) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:370, SEQ ID NO:681, and SEQ ID NO:372, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:418, SEQ ID NO:419, SEQ ID NO:420, respectively, SEQ ID NO: 682, SEQ ID NO: 419, SEQ ID NO: 420, respectively, SEQ ID NO: 682, SEQ ID NO: 683, SEQ ID NO: 420, respectively, or SEQ ID NO: 418, SEQ ID NO: 684, SEQ ID NO: 420, respectively;(c) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:373, SEQ ID NO:374, and SEQ ID NO:375 respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:421, SEQ ID NO:422, SEQ ID NO:423, respectively;(d) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:376, SEQ ID NO:377, and SEQ ID NO:378, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:424, SEQ ID NO:425, SEQ ID NO:426, respectively;(e) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:379, SEQ ID NO:380, and SEQ ID NO:381 respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:427, SEQ ID NO:428, SEQ ID NO:429, respectively;(f) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:382, SEQ ID NO:383, and SEQ ID NO:384, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:430, SEQ ID NO:431, SEQ ID NO:432, respectively;(g) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:385, SEQ ID NO:386, and SEQ ID NO:387, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:433, SEQ ID NO:434, SEQ ID NO:435, respectively;(h) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:388, SEQ ID NO:389, and SEQ ID NO:390, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:436, SEQ ID NO:437, SEQ ID NO:438, respectively;(i) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:391, SEQ ID NO:392, and SEQ ID NO:393 respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:439, SEQ ID NO:440, SEQ ID NO:441, respectively;(j) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:394, SEQ ID NO:395, and SEQ ID NO:396, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:442, SEQ ID NO:443, SEQ ID NO:444, respectively;(k) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:397, SEQ ID NO:398, and SEQ ID NO:399, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:445, SEQ ID NO:446, SEQ ID NO:447, respectively;(l) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:400, SEQ ID NO:401, and SEQ ID NO:402, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:448, SEQ ID NO:449, SEQ ID NO:450, respectively;(m) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:403, SEQ ID NO:404, and SEQ ID NO:405 respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:451, SEQ ID NO:452, SEQ ID NO:453, respectively;(n) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:406, SEQ ID NO:407, and SEQ ID NO:408, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:454, SEQ ID NO:455, SEQ ID NO:456, respectively;(o) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:409, SEQ ID NO:410, and SEQ ID NO:411, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:457, SEQ ID NO:458, SEQ ID NO:459, respectively;(p) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:412, SEQ ID NO:413, and SEQ ID NO:414, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:460, SEQ ID NO:461, SEQ ID NO:462, respectively;(q) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:415, SEQ ID NO:416, and SEQ ID NO:417, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:463, SEQ ID NO:464, SEQ ID NO:465, respectively;(r) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:584, SEQ ID NO:585, and SEQ ID NO:586, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:596, SEQ ID NO:597, SEQ ID NO:598, respectively;(s) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:587, SEQ ID NO:588, and SEQ ID NO:589, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:599, SEQ ID NO:600, SEQ ID NO:601, respectively;(t) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:590, SEQ ID NO:591, and SEQ ID NO:592, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO: 602, SEQ ID NO: 603, SEQ ID NO: 604, respectively;(u) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:593, SEQ ID NO:594, and SEQ ID NO:595, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according toSEQ ID NO:605, SEQ ID NO:606, SEQ ID NO:607, respectively, or SEQ ID NO: 608, SEQ ID NO: 609, SEQ ID NO: 610, respectively; or(v) (i) a variable heavy chain (VH) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO:675, SEQ ID NO:676, and SEQ ID NO:677, respectively, and / or (ii) a variable light chain (VL) comprising CDR1, CDR2 and CDR3 according to SEQ ID NO: 678, SEQ ID NO: 679, SEQ ID NO: 680, respectively;(A2) is an antibody or antigen binding fragment thereof that specifically binds to TCRVP;(L) is a linker; and(C) is a cytotoxic agent, wherein said linker (L) links (A2) to (C).

3. The immunoconjugate of claim 1 or 2, wherein,(a) the variable heavy chain (VH) comprises any one of SEQ ID NOs: 228-295, 559-569, 632-650, and 685-700; and / or(b) the variable heavy light chain (VL) comprises any one of SEQ ID NOs: 296- 369, 570-583, 652-671, and 701-716.

4. The immunoconjugate of any one of claims 1-3, wherein the antibody or antigen binding fragment thereof that specifically binds to TCRVP binds to TCRVP2, and comprises:(a) the variable heavy chain (VH) comprises CDR1, CDR2 and CDR3 according to SEQ ID NO: 10, SEQ ID NO: 11, and SEQ ID NO: 12; and / or(b) the variable light chain (VL) comprises CDR1, CDR2 and CDR3 according to SEQ ID NO: 13, SEQ ID NO: 14, and SEQ ID NO: 15.

5. The immunoconjugate of any one of claims 1-4, wherein the antibody or antigen binding fragment thereof that specifically binds to TCRVP binds to TCRVP2, and comprises:(a) the variable heavy chain (VH) comprises SEQ ID NO: 230; and(b) the variable light chain (VL) comprises SEQ ID NO: 299.

6. The immunoconjugate of any one of claims 1-5, wherein said linker is selected from the group consisting of a cleavable linker, a non-cleavable linker, a hydrophilic linker, and a dicarboxylic acid based linker.

7. The immunoconjugate of claim 6, wherein said linker is selected from the group consisting: A-succinimidyl 4-(2-pyridyldithio)pentanoate (SPP) or / f-succinimidyl 4-(2- pyridyldithio)-2-sulfopentanoate (sulfo-SPP); A-succinimidyl 4-(2- pyridyldithiojbutanoate (SPDB) or A-succinimidyl 4-(2-pyridyldithio)-2-sulfobutanoate (sulfo-SPDB); A-succinimidyl 4-(maleimidomethyl) cyclohexanecarboxylate (SMCC); A-sulfosuccinimidyl 4-(maleimidomethyl) cyclohexanecarboxylate (sulfoSMCC); N- succinimidyl-4-(iodoacetyl)-aminobenzoate (SIAB); A-succinimidyl-[(N- maleimidopropionamidoj-tetraethyleneglycol] ester (NHS-PEG4-maleimide); and Azido- dPEG24-TFP-ester .

8. The immunoconjugate of any one of claims 1-7, wherein the cytotoxic agent is is selected from the group consisting of: a JAK inhibitor, a BET inhibitor, a BCL2 inhibitor, a MEK inhibitor, a PI3K inhibitor, a MAPK inhibitor, am alkylating agent, a cytoskeletal disruptor, a histone deacetylase inhibitor, a topoisomerase I inhibitor, a topoisomerase II inhibitor, nucleotide analogs or precursors thereof, peptide antibiotics, a protein degrader, platinum-based agents, retinoids, vinka alkaloids and derivatives thereof, and combinations thereof.

9. The immunoconjugate of any one of claims 1-7, wherein the cytotoxic agent is selected from the group consisting of Exatecan, Deruxtecan, Monomethyl auristatin F (MMAF), and Monomethyl auristatin E (MMAE).

10. The immunoconjugate of any one of claims 1-8, wherein the PI3K inhibitor is selected from the group consisting of: PI103; PI828; LY294002; wortmannin; demethoxyviridin; IC486068; IC87114; GDC-0941; GDC-0980; perifosine; CAL101; PX-866; IPI-145; BAY 80-6946; BEZ235; P6503; TGR1202; SF1126; INK1117; BKM120; IL147; XL765; Palomid 529; GSK1059615; ZSTK474; PWT33597; TG100-115; CAL263; GNE-447; CUDC-907; and AEZS-136.

11. The immunoconjugate of any one of claims 1-10, wherein the antibody or antigen binding fragment that specifically binds to TCRVP is a full-length antibody.

12. The immunoconjugate of any one claims 1-10, wherein the antibody or antigen binding fragment that specifically binds to TCRVP is an antigen binding fragment thereof.

13. The immunoconjugate of any one of claims 1-12, wherein the antibody or antigen binding fragment thereof that specifically binds to TCRVP is a full-length antibody.

14. The immunoconjugate of any one claims 1-12, wherein the antibody or antigen binding fragment thereof that specifically binds to the antibody or antigen binding fragment that specifically binds to TCRVP is an antigen binding fragment thereof.

15. The immunoconjugate of claim 12 or 14, wherein said antigen binding fragment comprises a Fab, a Fab', a F(ab')2, a Fd, a single chain Fv or scFv, a disulfide linked Fv, a V NAR domain, a IgNar, an intrabody, an IgG-CH2, a minibody, a F(ab')3, a tetrabody, a triabody, a diabody, a single-domain antibody, DVD-Ig, Fcab, mAb2, a (scFv)2, DARPin, or a scFv-Fc.

16. The immunoconjugate of claim 15, wherein said antigen binding fragment comprises a Fab fragment.

17. An immunoconjugate comprising:(Al) an antibody that specifically binds to VP2 comprising the heavy chain variable domain of SEQ ID NO: 230, and the light chain variable domain of SEQ ID NO: 299;(A2) a Fab fragment comprising an anti-human IgG Fc Antibody;(L) with Non-Cleavable Linker; and(C) Exatecan, Deruxtecan, MMAF, or MMAE; wherein (L) links (A2) to (C), and (A2) binds to (Al).

18. The immunoconjugate of any one of claims 1-15 or 17, wherein said antibody or antigen binding fragment comprises a Fc domain.

19. The immunoconjugate of claim 18, wherein the Fc domain comprises a mutation.

20. The immunoconjugate of claim 19, wherein the mutation reduces effector function.

21. The immunoconjugate of claim 19, wherein the mutation is L234A / L235A.

22. A pharmaceutical composition comprising the immunoconjugate of any one of claims 1- 21 and a pharmaceutically acceptable carrier.

23. A kit comprising the immunoconjugate of any one of claims 1-21.

24. A method of treating cancer in a subject, comprising administering a therapeutically effective amount of the immunoconjugate of any one of claims 1-21 or the pharmaceutical composition of claim 22 to the subject.

25. A method of increasing cancer cell cytotoxicity comprising contacting a cancer cell with the immunoconjugatge of any one of claims 1-21 or the pharmaceutical composition of claim 22.

26. The method of claim 24 or 25, wherein the cancer is selected from the group consisting of T- cell Lymphoma, T-cell Leukemia, Cutaneous T-cell Lymphoma, Peripheral T-cell Lymphoma (PTCL), Not Otherwise Specified PTCL (PTCL-NOS), Angioimmunoblastic T-cell Lymphoma (AITL), Anaplastic Large-cell Lymphoma (ALCL), Enteropathy- Associated T-cell Lymphoma (EATL), Adult T-cell Leukemia / Lymphoma (ATLL), Hepatosplenic T- cell Lymphoma (HSTL), Subcutaneous Panniculitis-Like T-cell Lymphoma (SPTCL), T-cell Acute Lymphoblastic Leukemia (T-ALL), T-cell Chronic Lymphocytic Leukemia, Large Granular Lymphocyte Leukemia, T-cell Prolymphocytic Leukemia, Lympomatoid Papulosis, Small Medium Pleiomorphic T-cell Lymphoma, Mycosis Fungoides, Sezary Syndrome, and Cytotoxic T-cell Lymphoma.

27. A method of treating a T-cell mediated disease in a subject, comprising administering a therapeutically effective amount of the immunoconjugate of any one of claims 1-21 or the pharmaceutical composition of claim 22 to the subject.

28. The method of claim 27, wherein the T-cell mediated disease is selected from the group consisting of Atherosclerosis, Parkinson’s disease, Alzheimer’s disease, Type 1 Diabetes Mellitus, Grave’s Disease, Hashimoto’s Thyroiditis, Addison's Disease, Rheumatoid Arthritis (RA), Multiple Sclerosis (MS), Psoriasis, Psoriatic Arthritis, Lichen Planus, Lichen Planopilaris, Morphea, Scleroderma, Systemic Sclerosis, acute or chronic Graft- Versus-Host Disease (GVHD), Cardiac Organ Transplant Rejection, Pulmonary Organ Transplant Rejection, Renal Organ Transplant Rejection, Interstitial Lung Disease, Scleroderma, Alopecia Areata, Vitiligo, Celiac Disease (Sprue), Myasthenia Gravis, Pernicious Anemia, Sjogren’s Syndrome, Systemic Lupus Erythematosus, ChronicInflammatory Demyelinating Polyneuropathy, Guillain-Barre Syndrome, Inflammatory Bowel Disease, Crohn’s Disease, and Ulcerative Colitis.

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