Materials and methods for modulating immune responses

Abstract

Anti-TRGV9 molecules, such as anti-TRGV9 antibodies or antigen-binding fragments thereof, are described. Nucleic acids encoding the antibodies, compositions comprising the antibodies, methods of producing the antibodies, and methods of using the antibodies to treat or prevent disease are also described.

Description

[Technical Field]

[0001] (Cross-reference of related applications) This application is a compilation of U.S. Patent Applications No. 62 / 982,492, No. 62 / 982,505, No. 62 / 982,374, No. 62 / 982,462, No. 62 / 982,478, No. 62 / 982,469, No. 62 / 982,525, and No. 62 / 982,535, filed on February 27, 2020. , Filing No. 62 / 982,574, Filing No. 62 / 982,591, Filing No. 62 / 982,664, Filing No. 62 / 982,669, Filing No. 62 / 982,602, Filing No. 62 / 982,548, Filing No. 62 / 988,996, Filing No. 62 / 989,002 Filings No. 62 / 989,006 filed on March 13, 2020, No. 62 / 989,010 filed on March 13, 2020, No. 62 / 989,018 filed on March 13, 2020, No. 62 / 989,024 filed on March 13, 2020, No. 62 / 989,027 filed on March 13, 2020, No. 62 / 989,036 filed on March 13, 2020, No. 62 / 989,042 filed on March 13, 2020, No. 62 / 989,045 filed on March 13, 2020 Patent No. 62 / 989,052, Patent No. 62 / 989,057 filed on March 13, 2020, Patent No. 62 / 989,068 filed on March 13, 2020, Patent No. 62 / 989,075 filed on March 13, 2020, International Application US20 / 31749 filed on May 7, 2020, US Patent Application No. 63 / 074,655 filed on September 4, 2020, US Patent Application No. 63 / 074,676 filed on September 4, 2020, US Patent Application No. 63 / 074,854 filed on September 4, 2020,No. 700, No. 63 / 074,749 filed on September 4, 2020, No. 63 / 074,735 filed on September 4, 2020, No. 63 / 074,839 filed on September 4, 2020, No. 63 / 074,759 filed on September 4, 2020, No. 63 / 074,903 filed on September 4, 2020, No. 63 / 074,893 filed on September 4, 2020 Claiming the benefits of patent applications No. 63 / 074,925 filed on September 4, 2020, No. 63 / 074,937 filed on September 4, 2020, No. 63 / 074,962 filed on September 4, 2020, No. 63 / 074,946 filed on September 4, 2020, No. 63 / 112,462 filed on November 11, 2020, and No. 63 / 112,475 filed on November 11, 2020.

[0002] (Field of invention) The present invention relates, in particular, to T cell receptor (TCR) redirection technologies, such as those targeting T cell receptor gamma variable 9 (TRGV9) antibodies, TRGV9 molecules including bispecific antibodies, nucleic acids and expression vectors encoding antibodies, recombinant cells containing vectors, and compositions containing antibodies. Methods for producing antibodies and methods for using antibodies to modulate immune responses against cancer cells are also provided.

[0003] (Reference to electronically submitted sequence listings) This application includes a sequence listing, file “14620-381-228_SEQLISTING”, filed electronically via EFS-Web as an ASCII sequence listing having a size of 440,714 bytes, with a creation date of 22 February 2021. The sequence listing filed via EFS-Web is part of this specification and is incorporated herein by reference in its entirety. [Overview of the project] [Means for solving the problem]

[0004] For example, a T cell receptor redirection technology is provided that includes TRGV9 molecules such as TRGV9 antibodies and multispecific antibodies, as well as nucleic acids encoding the antibodies and expression vectors, recombinant cells containing the vectors, and compositions containing the antibodies.

[0005] In one embodiment, an antibody that binds to TRGV9 is provided herein. In some embodiments, the antibody includes a heavy chain variable region (VH) and a light chain variable region (VL).

[0006] In one embodiment, the TRGV9 antibody has the VH and VL amino acid sequences of L7A5_2(TRGV9_2). In one embodiment, the TRGV9 antibody includes (i) VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively having the amino acid sequence of SEQ ID NO: 34, and (ii) VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively having the amino acid sequence of SEQ ID NO: 8.

[0007] In one embodiment, the TRGV9 antibody has the VH and VL amino acid sequences of L7A5_3(TRGV9_3). In one embodiment, the TRGV9 antibody includes (i) VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively having the amino acid sequence of SEQ ID NO: 35, and (ii) VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively having the amino acid sequence of SEQ ID NO: 8.

[0008] In one embodiment, the TRGV9 antibody has the VH and VL amino acid sequences of L7A5_4(TRGV9_4). In one embodiment, the TRGV9 antibody includes (i) VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively having the amino acid sequence of SEQ ID NO: 36, and (ii) VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively having the amino acid sequence of SEQ ID NO: 8.

[0009] In one embodiment, the TRGV9 antibody has the VH and VL amino acid sequences of TRGV9Ab_var17. In one embodiment, the TRGV9 antibody includes (i) VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively having the amino acid sequence of SEQ ID NO: 65, and (ii) VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively having the amino acid sequence of VL CDR3, respectively having the amino acid sequence of SEQ ID NO: 66.

[0010] In one embodiment, the TRGV9 antibody has the VH and VL amino acid sequences of TRGV9Ab_var29. In one embodiment, the TRGV9 antibody includes (i) VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively having the amino acid sequence of SEQ ID NO: 67, and (ii) VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively having the amino acid sequence of VL CDR3, respectively having the amino acid sequence of SEQ ID NO: 68.

[0011] In one embodiment, the TRGV9 antibody has the VH and VL amino acid sequences of VG9B420. In one embodiment, the TRGV9 antibody includes (i) VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively having the amino acid sequence of SEQ ID NO: 104, and (ii) VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively having the amino acid sequence of SEQ ID NO: 105.

[0012] In one embodiment, the TRGV9 antibody has the VH and VL amino acid sequences of VG9SB10SC1087_P18_D08. In one embodiment, the TRGV9 antibody includes (i) VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively having the amino acid sequence of SEQ ID NO: 113, and (ii) VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively having the amino acid sequence of SEQ ID NO: 114.

[0013] In one embodiment, the TRGV9 antibody has the VH and VL amino acid sequences VG9SB10SC1087_P18_C12. In one embodiment, the TRGV9 antibody includes (i) VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively having the amino acid sequence of SEQ ID NO: 123, and (ii) VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively having the amino acid sequence of SEQ ID NO: 124.

[0014] In one embodiment, the TRGV9 antibody has the VH and VL amino acid sequences of VG9SB10SC1087_P19_C03. In one embodiment, the TRGV9 antibody includes (i) VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively having the amino acid sequence of SEQ ID NO: 133, and (ii) VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively having the amino acid sequence of SEQ ID NO: 134.

[0015] In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the TRGV9 antibody follow the Kabat numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the TRGV9 antibody follow the Chothia numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the TRGV9 antibody follow the AbM numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the TRGV9 antibody follow the Contact numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the TRGV9 antibody follow the IMGT numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the TRGV9 antibody follow an exemplary numbering system.

[0016] In some embodiments, the antibody binds to the TRGV9 antigen. In some embodiments, the antibody binds to the TRGV9 epitope. In some embodiments, the antibody specifically binds to TRGV9. In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 form binding sites for the TRGV9 antigen. In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 form binding sites for the TRGV9 epitope. In some embodiments, TRGV9 is present on the surface of T cells. In some embodiments, the T cells are γδ T cells.

[0017] In some embodiments, the TRGV9 antibody is a chimeric antibody. In some embodiments, the TRGV9 antibody is human. In some embodiments, the TRGV9 antibody is humanized. In some embodiments, the TRGV9 antibody is an isolated TRGV9 antibody. In some embodiments, the TRGV9 antibody is a TRGV9 antigen-binding fragment. In some embodiments, the TRGV9 antigen-binding fragment is a chimeric antibody. In some embodiments, the TRGV9 antigen-binding fragment is human. In some embodiments, the TRGV9 antigen-binding fragment is humanized. In some embodiments, the TRGV9 antigen-binding fragment is an isolated TRGV9 antigen-binding fragment. In some embodiments, the TRGV9 antibody is an IgG antibody. In some embodiments, the TRGV9 antibody is an IgG1 antibody. In some embodiments, the TRGV9 antibody is an IgG2 antibody. In some embodiments, the TRGV9 antibody is an IgG3 antibody. In some embodiments, the TRGV9 antibody is an IgG4 antibody. In some embodiments, the TRGV9 antibody contains a κ light chain. In some embodiments, the TRGV9 antibody contains a λ light chain. In some embodiments, the TRGV9 antibody is a monoclonal antibody. In some embodiments, the TRGV9 antibody is polyvalent. In some embodiments, the TRGV9 antibody can bind to at least three antigens. In some embodiments, the TRGV9 antibody can bind to at least four antigens. In some embodiments, the TRGV9 antibody can bind to at least five antigens. In some embodiments, the TRGV9 antibody is a multispecific antibody. In some embodiments, the TRGV9 antibody is a bispecific antibody. In some embodiments, the TRGV9 antibody is a triplicate antibody. In some embodiments, the TRGV9 antibody is a quadruplicate antibody.

[0018] In a particular embodiment, the TRGV9 antibody is a multispecific TRGV9 antibody. In a particular embodiment, the multispecific TRGV9 antibody is a bispecific TRGV9 antibody.

[0019] Accordingly, in one embodiment, a multispecific TRGV9 antibody is provided, which includes the TRGV9 antibody provided herein. In one embodiment, the multispecific TRGV9 antibody includes (a) a first binding domain that binds to TRGV9 and (b) a second binding domain that binds to a second target other than TRGV9.

[0020] In one embodiment, the first binding domain that binds to TRGV9 includes the VH and VL amino acid sequences of L7A5_1(TRGV9_1). In one embodiment, the first binding domain that binds to TRGV9 includes (i) VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and

[0021] In one embodiment, the first binding domain that binds to TRGV9 includes the VH and VL amino acid sequences of L7A5_2(TRGV9_2). In one embodiment, the first binding domain that binds to TRGV9 includes (i) VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and

[0022] In one embodiment, the first binding domain that binds to TRGV9 includes the VH and VL amino acid sequences of L7A5_3(TRGV9_3). In one embodiment, the first binding domain that binds to TRGV9 includes (i) VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and

[0023] In one embodiment, the first binding domain that binds to TRGV9 includes the VH and VL amino acid sequences of L7A5_4(TRGV9_4). In one embodiment, the first binding domain that binds to TRGV9 includes (i) VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and

[0024] In one embodiment, the first binding domain that binds to TRGV9 includes the VH and VL amino acid sequences of TRGV9Ab_var17. In one embodiment, the first binding domain that binds to TRGV9 includes (i) VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and

[0025] In one embodiment, the first binding domain that binds to TRGV9 includes the VH and VL amino acid sequences of TRGV9Ab_var29. In one embodiment, the first binding domain that binds to TRGV9 includes (i) VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and

[0026] In one embodiment, the first binding domain that binds to TRGV9 includes the VH and VL amino acid sequences of VG9_B3_RN. In one embodiment, the first binding domain that binds to TRGV9 includes (i) VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and

[0027] In one embodiment, the first binding domain that binds to TRGV9 includes the VH and VL amino acid sequences of VG9B420. In one embodiment, the first binding domain that binds to TRGV9 includes (i) VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and

[0028] In one embodiment, the first binding domain that binds to TRGV9 includes the VH and VL amino acid sequences of VG9SB10SC1087_P18_D08. In one embodiment, the first binding domain that binds to TRGV9 includes (i) VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and

[0029] In one embodiment, the first binding domain that binds to TRGV9 includes the VH and VL amino acid sequences of VG9SB10SC1087_P18_C12. In one embodiment, the first binding domain that binds to TRGV9 includes (i) VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and

[0030] In one embodiment, the first binding domain that binds to TRGV9 includes the VH and VL amino acid sequences of VG9SB10SC1087_P19_C03. In one embodiment, the first binding domain that binds to TRGV9 includes (i) VH, which has the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, which has the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and

[0031] In some embodiments, the amino acid sequences of the first binding domains that bind to TRGV9, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, follow the Kabat numbering system. In some embodiments, the amino acid sequences of the first binding domains that bind to TRGV9, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, follow the Chothia numbering system. In some embodiments, the amino acid sequences of the first binding domains that bind to TRGV9, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, follow the AbM numbering system. In some embodiments, the amino acid sequences of the first binding domains that bind to TRGV9, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, follow the Contact numbering system. In some embodiments, the amino acid sequences of the first binding domains that bind to TRGV9, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, follow the IMGT numbering system. In some embodiments, the amino acid sequences of the first binding domains that bind to TRGV9, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, follow an exemplary numbering system.

[0032] In some embodiments, the first binding domain binds to the TRGV9 antigen. In some embodiments, the first binding domain binds to the TRGV9 epitope. In some embodiments, the first binding domain specifically binds to TRGV9. In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of the first binding domain form a binding site for the TRGV9 antigen. In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of the first binding domain form a binding site for the TRGV9 epitope. In some embodiments, TRGV9 is present on the surface of T cells.

[0033] In some embodiments of the multispecific TRGV9 antibodies provided herein, the second target is not the TRGV9 antigen. In some embodiments of the multispecific TRGV9 antibodies provided herein, the second target is not the TRGV9 epitope.

[0034] In some embodiments of the multispecific TRGV9 antibodies provided herein, the second target is CD123. In one embodiment, the second binding domain that binds to CD123 comprises (i) VH, comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequence of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 15, and (ii) VL, comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequence of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of VL VL CDR3 having the amino acid sequence of SEQ ID NO: 16.

[0035] In some embodiments of the multispecific TRGV9 antibodies provided herein, the second target is CD33. In one embodiment, the second target is the C2 domain of CD33. In another embodiment, the second target is the V domain of CD33. In one embodiment, the second binding domain that binds to CD33 includes (i) VH, comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequence of VH VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequence of VL VL CDR1, VL CDR2, and VL CDR3, respectively.

[0036] In some embodiments of the multispecific TRGV9 antibodies provided herein, the second target is TRBC1. In one embodiment, the second binding domain that binds to TRBC1 comprises (i) VH, comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequence of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 55, and (ii) VL, comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequence of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of VL VL CDR3 having the amino acid sequence of SEQ ID NO: 56.

[0037] In some embodiments of the multispecific TRGV9 antibodies provided herein, the second target is B cell maturation antigen (BCMA). In one embodiment, the second binding domain binds to BCMA. In one embodiment, the second binding domain that binds to BCMA includes (i) VH, comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequence of VH VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL, comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequence of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL VL CDR1, VL CDR2, and VL CDR3, respectively.

[0038] In some embodiments of the multispecific TRGV9 antibodies provided herein, the second target is prostate-specific membrane antigen (PSMA). In one embodiment, the second binding domain binds to PSMA. In one embodiment, the second binding domain that binds to PSMA comprises (i) VH, comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequence of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 775, and (ii) VL, comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequence of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of VL VL CDR3 having the amino acid sequence of SEQ ID NO: 776.

[0039] In some embodiments of the multispecific TRGV9 antibodies provided herein, the second target is expressed by target cells. In some embodiments of the multispecific TRGV9 antibodies provided herein, the second target is on the surface of the target cells. In certain embodiments, the target cells are undesirable cells.

[0040] In one embodiment, the target cell is a cancer cell. In one embodiment, the target cell is a T cell. In one embodiment, the target cell is a B cell. In one embodiment, the target cell is a dendritic cell. In one embodiment, the target cell is an NK cell. In one embodiment, the target cell is a stem cell. In one embodiment, the target cell is a stem cell precursor. In one embodiment, the target cell is a monocyte. In one embodiment, the target cell is a macrophage. In one embodiment, the target cell is a granulocyte. In one embodiment, the target cell is a platelet. In one embodiment, the target cell is a red blood cell. In one embodiment, the target cell is an endothelial cell. In one embodiment, the target cell is an epithelial cell. In one embodiment, the second target is a pathogen. In one embodiment, the target cell is a cell containing a pathogen. In one embodiment, the target cell is a blood cell. In one embodiment, the target cell is a bone marrow cell.

[0041] In some embodiments, the amino acid sequences of the second binding domains VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 that bind to the second target follow the Kabat numbering system. In some embodiments, the amino acid sequences of the second binding domains VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 that bind to the second target follow the Chothia numbering system. In some embodiments, the amino acid sequences of the second binding domains VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 that bind to the second target follow the AbM numbering system. In some embodiments, the amino acid sequences of the second binding domains VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 that bind to a second target follow the Contact numbering system. In some embodiments, the amino acid sequences of the second binding domains VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 that bind to a second target follow the IMGT numbering system. In some embodiments, the amino acid sequences of the second binding domains VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 that bind to a second target follow an exemplary numbering system.

[0042] In some embodiments, the second binding domain binds to the antigen of the second target. In some embodiments, the second binding domain binds to the epitope of the second target. In some embodiments, the second binding domain specifically binds to the second target. In some embodiments, the second binding domain specifically binds to the antigen of the second target. In some embodiments, the second binding domain specifically binds to the epitope of the second target. In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of the second binding domain form a binding site for the antigen of the second target. In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of the second binding domain form a binding site for the epitope of the second target. In some embodiments, the second target is located on the surface of the target cell. In some embodiments, target cells expressing a second target are killed when the multispecific TRGV9 antibody binds to the T cells and TRGV9 on the surface of the second target. In certain embodiments, the T cells are γδ T cells.

[0043] In some embodiments, the first binding domain of the multispecific TRGV9 antibody is polyvalent. In some embodiments, the first binding domain of the multispecific TRGV9 antibody can bind to at least three antigens. In some embodiments, the first binding domain of the multispecific TRGV9 antibody can bind to at least four antigens. In some embodiments, the first binding domain of the multispecific TRGV9 antibody can bind to at least five antigens. In some embodiments, the second binding domain of the multispecific TRGV9 antibody is polyvalent. In some embodiments, the second binding domain of the multispecific TRGV9 antibody can bind to at least three antigens. In some embodiments, the second binding domain of the multispecific TRGV9 antibody can bind to at least four antigens. In some embodiments, the second binding domain of the multispecific TRGV9 antibody can bind to at least five antigens.

[0044] In some embodiments, the first binding domain is humanized. In some embodiments, the second binding domain is humanized. In some embodiments, both the first and second binding domains are humanized. In some embodiments, the multispecific TRGV9 antibody contains a κ light chain. In some embodiments, the multispecific TRGV9 antibody contains a λ light chain. In some embodiments, the multispecific TRGV9 antibody is an IgG antibody. In some embodiments, the IgG antibody is an IgG1 antibody. In some embodiments, the IgG antibody is an IgG2 antibody. In some embodiments, the IgG antibody is an IgG3 antibody. In some embodiments, the IgG antibody is an IgG4 antibody.

[0045] In some embodiments, the multispecific TRGV9 antibody has an EC of less than approximately 500 pM. 50 This induces T cell-dependent cytotoxicity in target cells expressing a second target in vitro. In some embodiments, the multispecific TRGV9 antibody has an EC of less than approximately 300 pM. 50This induces T cell-dependent cytotoxicity in target cells expressing a second target in vitro. In some embodiments, the multispecific TRGV9 antibody has an EC of less than approximately 160 pM. 50 This induces T cell-dependent cytotoxicity in target cells expressing a second target in vitro. In some embodiments, EC 50 This is evaluated using a mixture of T cell effector cells and target cells expressing a second target. In some embodiments, the effector cell to target cell ratio is about 0.01:1 to about 5:1. In some embodiments, the effector cell to target cell ratio is about 0.1:1 to about 2:1. In some embodiments, the effector cell to target cell ratio is about 1:1. In certain embodiments, the T cells are γδ T cells. In one embodiment, the target cells are Kasumi-3 AML target cells.

[0046] In another embodiment, a nucleic acid encoding the TRGV9 antibody provided herein is provided. A vector comprising the nucleic acid encoding the TRGV9 antibody provided herein is also provided. A host cell comprising a vector comprising the nucleic acid encoding the TRGV9 antibody provided herein is also provided. A kit comprising a vector comprising the nucleic acid encoding the TRGV9 antibody provided herein and a package therefor is also provided. A method for producing the TRGV9 antibody provided herein is also provided, comprising culturing cells comprising the nucleic acid encoding the TRGV9 antibody under conditions for producing the TRGV9 antibody. In another embodiment, a kit comprising the TRGV9 antibody provided herein and a package therefor is provided. In another embodiment, a pharmaceutical composition comprising the TRGV9 antibody provided herein and a pharmaceutically acceptable carrier is provided. In another embodiment, a method for producing a pharmaceutical composition comprising the TRGV9 antibody provided herein is provided, the method comprising combining the TRGV9 antibody with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition. In certain embodiments, the TRGV9 antibody is the multispecific TRGV9 antibody provided herein.

[0047] In another embodiment, a multispecific TRGV9 antibody is provided comprising a first means capable of binding to TRGV9 and a second means capable of binding to a second target. In one embodiment, the second target is not TRGV9. In another embodiment, a multispecific TRGV9 antibody is provided comprising a first means for binding to TRGV9 and a second means for binding to a second target. In one embodiment, the second target is not TRGV9. In some embodiments, TRGV9 is on the surface of a T cell. In some embodiments, the T cell is a γδ T cell. In some embodiments, the first means can specifically bind to TRGV9. In some embodiments, the first means specifically binds to TRGV9. In one embodiment, TRGV9 is a TRGV9 antigen. In another embodiment, TRGV9 is a TRGV9 epitope. In one embodiment, the first means is a paratope. In some embodiments, the paratope is a paratope of the TRGV9 antibody provided herein. In one embodiment, the first means is an antibody. In some embodiments, the antibody is the TRGV9 antibody provided herein. In some embodiments, the TRGV9 antibody is an antigen-binding fragment. In some embodiments, the second means can specifically bind to a second target. In some embodiments, the second means specifically binds to a second target. In some embodiments, the second target is the antigen of the second target. In some embodiments, the second target is the epitope of the second target. In some embodiments, the second target is on the surface of a target cell. In some embodiments, the second target is CD123. In some embodiments, the second target is CD33. In some embodiments, the second target is TRBC1. In some embodiments, the second target is BCMA. In some embodiments, the second target is PSMA. In one embodiment, the second means is a paratope. In some embodiments, the paratope is the paratope of the second binding arm provided herein. In some embodiments, the paratope is a paratope of the CD123 antibody provided herein.In some embodiments, the paratope is a paratope of the CD33 antibody provided herein. In some embodiments, the paratope is a paratope of the TRBC1 antibody provided herein. In some embodiments, the paratope is a paratope of the BCMA antibody provided herein. In some embodiments, the paratope is a paratope of the PSMA antibody provided herein. In one embodiment, the second means is an antibody that binds to a second target provided herein. In some embodiments, the second means is a CD123 antibody provided herein. In one embodiment, the CD123 antibody is its antigen-binding fragment. In some embodiments, the second means is a CD33 antibody provided herein. In one embodiment, the CD33 antibody is its antigen-binding fragment. In some embodiments, the second means is a TRBC1 antibody provided herein. In one embodiment, the TRBC1 antibody is its antigen-binding fragment. In some embodiments, the second means is a BCMA antibody provided herein. In one embodiment, the BCMA antibody is its antigen-binding fragment. In some embodiments, the second means is a PSMA antibody provided herein. In one embodiment, the PSMA antibody is its antigen-binding fragment.

[0048] In another embodiment, a process is provided for producing an antibody that binds to two or more targets, comprising: a step for performing the function of obtaining a first binding domain capable of binding to TRGV9; a step for performing the function of obtaining a second binding domain capable of binding to a second target; and a step for performing the function of providing an antibody capable of binding to TRGV9 and the second target. In some embodiments, the step for performing the function of obtaining a second binding domain capable of binding to the second target is repeated n times and further comprises n steps for performing the function of providing a first binding domain capable of binding to TRGV9 and n targets, where n is at least 2. In some embodiments, the second target is not TRGV9. In some embodiments, the first binding domain can specifically bind to TRGV9. In one embodiment, TRGV9 is the TRGV9 antigen. In another embodiment, TRGV9 is the TRGV9 epitope. In one embodiment, the first binding domain binds to the TRGV9 antigen. In one embodiment, the first binding domain binds to the TRGV9 epitope. In some embodiments, TRGV9 is located on the surface of a T cell. In some embodiments, the T cell is a γδ T cell. In some embodiments, the second binding domain can specifically bind to a second target. In one embodiment, the second binding domain binds to the antigen of the second target. In one embodiment, the second binding domain binds to the epitope of the second target. In some embodiments, the second target is located on the surface of a target cell. In some embodiments, the second target is CD123. In some embodiments, the second target is CD33. In some embodiments, the second target is TRBC1. In some embodiments, the second target is BCMA. In some embodiments, the second target is PSMA. In one embodiment, the target cell is a cancer cell.

[0049] In another embodiment, a method is provided for activating T cells expressing TRGV9, the method comprising contacting the T cells with a TRGV9 antibody provided herein. In one embodiment, the contact results in increased expression of CD69, CD25, and / or granzyme B compared to control T cells expressing TRGV9. In another embodiment, a method is provided for inactivating T cells expressing TRGV9, the method comprising contacting the T cells with an antibody that binds to TRGV9 provided herein. Also provided is a method for blocking the activation of T cells expressing TRGV9, the method comprising contacting the T cells with an antibody that binds to TRGV9 provided herein. Also provided is a method for modulating the activity of T cells expressing TRGV9, the method comprising contacting the T cells with an antibody that binds to TRGV9 provided herein. In certain embodiments, the T cells are γδ T cells. In some embodiments, the TRGV9 antibody is a multispecific TRGV9 antibody provided herein.

[0050] In another embodiment, a method is provided for directing T cells expressing TRGV9 to target cells, the method comprising contacting the T cells with a multispecific TRGV9 antibody provided herein, the contact directing the T cells to target cells. In another embodiment, a method is provided for inhibiting the growth or proliferation of target cells, the method comprising contacting the target cells with a multispecific TRGV9 antibody provided herein, the contact inhibiting the growth or proliferation of target cells. In some embodiments, the target cells are in the presence of T cells expressing TRGV9 while in contact with the multispecific TRGV9 antibody. In some embodiments, the target cells express a second target other than TRGV9. In some embodiments, the T cells are γδ T cells. In some embodiments, the second target is the antigen of the second target. In some embodiments, the second target is the epitope of the second target. In some embodiments, the second target is on the surface of the target cell. In some embodiments, the second target is CD123. In some embodiments, the second target is CD33. In some embodiments, the second target is TRBC1. In some embodiments, the second target is BCMA. In some embodiments, the second target is PSMA. In one embodiment, the target cell is a cancer cell.

[0051] In another embodiment, a method is provided for eliminating target cells in a subject, the method comprising administering an effective amount of the multispecific TRGV9 antibody provided herein to the subject. In another embodiment, a method is provided for treating a disease, disorder, or condition (hereinafter "disease") caused in whole or in part by target cells in a subject, the method comprising administering an effective amount of the multispecific TRGV9 antibody provided herein to the subject. In another embodiment, a method is provided for preventing a disease caused in whole or in part by target cells in a subject, the method comprising administering an effective amount of the multispecific TRGV9 antibody provided herein to the subject. In another embodiment, a method is provided for modulating a disease caused in whole or in part by target cells in a subject, the method comprising administering an effective amount of the multispecific TRGV9 antibody provided herein to the subject. In some embodiments, the target cells express a second target other than TRGV9. In some embodiments, the second target is on the surface of the target cells. In some embodiments, the second target is CD123. In some embodiments, the second target is CD33. In some embodiments, the second target is TRBC1. In some embodiments, the second target is BCMA. In some embodiments, the second target is PSMA. In one embodiment, the target cell is a cancer cell. In one embodiment, the target cell is a T cell. In one embodiment, the target cell is a B cell. In one embodiment, the target cell is a dendritic cell. In one embodiment, the target cell is an NK cell. In one embodiment, the target cell is a stem cell. In one embodiment, the target cell is a stem cell precursor. In one embodiment, the target cell is a monocyte. In one embodiment, the target cell is a macrophage. In one embodiment, the target cell is a granulocyte. In one embodiment, the target cell is a platelet. In one embodiment, the target cell is a red blood cell. In one embodiment, the target cell is an endothelial cell. In one embodiment, the target cell is an epithelial cell. In one embodiment, the second target is a pathogen. In one embodiment, the target cell is a cell containing a pathogen. In one embodiment, the target cell is a blood cell. In one embodiment, the target cell is a bone marrow cell.In some embodiments, the second target is on cancer cells. In some embodiments, the target cells are cancer cells. In certain embodiments, the second target is on the surface of cancer cells. In some embodiments, the second target is an antigen on the surface of cancer cells. In some embodiments, the antigen on the surface of cancer cells is a tumor-specific antigen, a tumor-associated antigen, or a novel antigen. In certain embodiments, the disease is cancer. In some embodiments, the subject is a subject that requires the method. In some embodiments, the subject is human. In some embodiments, the method further includes identifying a subject that requires the method. [Brief explanation of the drawing]

[0052] The above summary, as well as the following detailed description of specific embodiments of this application, will be better understood when read in conjunction with the accompanying drawings. However, it should be understood that this application is not limited to the embodiments shown in the drawings themselves. [Figure 1] A schematic diagram shows the binding of an exemplary multispecific TRGV9 antibody containing a first binding domain that binds to TRGV9, and a second binding domain that binds to a second target antigen on target cells, recruiting γδ T cells to the target cells and inducing target cell death. The second target antigen may be a tumor-associated antigen (TAA), and the target cells may be tumor cells. The anti-TRGV9 / anti-TAA bispecific antibody can recruit γδ T cells to cancer cells and induce cancer cell death. [Figure 2] This graph shows that zoledronic acid selectively increases Vγ9Vδ2 cells from all peripheral blood mononuclear cells (PBMCs). [Figure 3A]This section describes the phenotypic characterization of Vγ9+γδ T cells. Figure 3A shows a schematic diagram of the gate used to illustrate γδ T cell differentiation (left). Representative FACS dot plots show the differentiation profiles of Vγ9+γδ T cells from fresh PBMCs (left) and PBMCs cultured ex vivo for 14 days with zoledronic acid + IL-2 + IL-15 (right). The numbers in the quadrants reflect the frequency (mean ± SEM) of each population of fresh and activated Vγ9+γδ T cells. The data shown are the mean (± SEM) of 5 donors (n=5) from a single experiment. Figure 3B shows the number of representative dot plots reflecting the frequency (mean ± SEM) of Vγ9+γδ T cells positive for each activation marker from either fresh PBMCs (top) or PBMCs cultured for 14 days with zoledronic acid + IL-2 + IL-15 (bottom). The data presented are the mean (±SEM) values ​​from seven donors (n=7) for CD62L, CD69, and CD44 expression data from two independent experiments. n represents five donors for NKG2D expression data and two donors each for CD45RO and CD71 expression data from a single experiment. Figure 3C shows the number of gated dots in a dot plot indicating the frequency (mean ±SEM) of Vγ9+γδ T cells positive for each inhibitory receptor surface expression from either fresh PBMCs (top panel) or PBMCs cultured for 14 days with zoledronic acid + IL-2 + IL-15 (bottom panel). The data presented herein are the mean (±SEM) values ​​from five donors (n=5) for PD1, CTLA4, TIGIT, and LAG3 surface expression data, and from seven donors (n=7) for 2B4 and TIM3 surface expression data, from two independent experiments. Figure 3D shows representative FACS dot plots demonstrating the frequency (mean ± SEM) of Vγ9+γδ T cells expressing intracellular granzyme B (left column) and perforin (right column) from fresh PBMCs (top panel) and PBMCs cultured ex vivo for 14 days with zoledronic acid + IL-2 + IL-15 (bottom panel). The data shown are the mean (± SEM) values ​​for granzyme B and perforin data from 4 (n=4) and 7 (n=7) donors, respectively, from two independent experiments.Figure 3E shows a bar graph representing the mean (±SEM) concentrations (pg / mL) of cytokines in the cell culture supernatant at days 0 and 14 of PBMC culture with zoledronic acid + IL-2 + IL-15. The data shown are the mean (±SEM) of four wells (n=4) from a single donor. [Figure 3B]This section describes the phenotypic characterization of Vγ9+γδ T cells. Figure 3A shows a schematic diagram of the gate used to illustrate γδ T cell differentiation (left). Representative FACS dot plots show the differentiation profiles of Vγ9+γδ T cells from fresh PBMCs (left) and PBMCs cultured ex vivo for 14 days with zoledronic acid + IL-2 + IL-15 (right). The numbers in the quadrants reflect the frequency (mean ± SEM) of each population of fresh and activated Vγ9+γδ T cells. The data shown are the mean (± SEM) of 5 donors (n=5) from a single experiment. Figure 3B shows the number of representative dot plots reflecting the frequency (mean ± SEM) of Vγ9+γδ T cells positive for each activation marker from either fresh PBMCs (top) or PBMCs cultured for 14 days with zoledronic acid + IL-2 + IL-15 (bottom). The data presented are the mean (±SEM) values ​​from seven donors (n=7) for CD62L, CD69, and CD44 expression data from two independent experiments. n represents five donors for NKG2D expression data and two donors each for CD45RO and CD71 expression data from a single experiment. Figure 3C shows the number of gated dots in a dot plot indicating the frequency (mean ±SEM) of Vγ9+γδ T cells positive for each inhibitory receptor surface expression from either fresh PBMCs (top panel) or PBMCs cultured for 14 days with zoledronic acid + IL-2 + IL-15 (bottom panel). The data presented herein are the mean (±SEM) values ​​from five donors (n=5) for PD1, CTLA4, TIGIT, and LAG3 surface expression data, and from seven donors (n=7) for 2B4 and TIM3 surface expression data, from two independent experiments. Figure 3D shows representative FACS dot plots demonstrating the frequency (mean ± SEM) of Vγ9+γδ T cells expressing intracellular granzyme B (left column) and perforin (right column) from fresh PBMCs (top panel) and PBMCs cultured ex vivo for 14 days with zoledronic acid + IL-2 + IL-15 (bottom panel). The data shown are the mean (± SEM) values ​​for granzyme B and perforin data from 4 (n=4) and 7 (n=7) donors, respectively, from two independent experiments.Figure 3E shows a bar graph representing the mean (±SEM) concentrations (pg / mL) of cytokines in the cell culture supernatant at days 0 and 14 of PBMC culture with zoledronic acid + IL-2 + IL-15. The data shown are the mean (±SEM) of four wells (n=4) from a single donor. [Figure 3C]This section describes the phenotypic characterization of Vγ9+γδ T cells. Figure 3A shows a schematic diagram of the gate used to illustrate γδ T cell differentiation (left). Representative FACS dot plots show the differentiation profiles of Vγ9+γδ T cells from fresh PBMCs (left) and PBMCs cultured ex vivo for 14 days with zoledronic acid + IL-2 + IL-15 (right). The numbers in the quadrants reflect the frequency (mean ± SEM) of each population of fresh and activated Vγ9+γδ T cells. The data shown are the mean (± SEM) of 5 donors (n=5) from a single experiment. Figure 3B shows the number of representative dot plots reflecting the frequency (mean ± SEM) of Vγ9+γδ T cells positive for each activation marker from either fresh PBMCs (top) or PBMCs cultured for 14 days with zoledronic acid + IL-2 + IL-15 (bottom). The data presented are the mean (±SEM) values ​​from seven donors (n=7) for CD62L, CD69, and CD44 expression data from two independent experiments. n represents five donors for NKG2D expression data and two donors each for CD45RO and CD71 expression data from a single experiment. Figure 3C shows the number of gated dots in a dot plot indicating the frequency (mean ±SEM) of Vγ9+γδ T cells positive for each inhibitory receptor surface expression from either fresh PBMCs (top panel) or PBMCs cultured for 14 days with zoledronic acid + IL-2 + IL-15 (bottom panel). The data presented herein are the mean (±SEM) values ​​from five donors (n=5) for PD1, CTLA4, TIGIT, and LAG3 surface expression data, and from seven donors (n=7) for 2B4 and TIM3 surface expression data, from two independent experiments. Figure 3D shows representative FACS dot plots demonstrating the frequency (mean ± SEM) of Vγ9+γδ T cells expressing intracellular granzyme B (left column) and perforin (right column) from fresh PBMCs (top panel) and PBMCs cultured ex vivo for 14 days with zoledronic acid + IL-2 + IL-15 (bottom panel). The data shown are the mean (± SEM) values ​​for granzyme B and perforin data from 4 (n=4) and 7 (n=7) donors, respectively, from two independent experiments.Figure 3E shows a bar graph representing the mean (±SEM) concentrations (pg / mL) of cytokines in the cell culture supernatant at days 0 and 14 of PBMC culture with zoledronic acid + IL-2 + IL-15. The data shown are the mean (±SEM) of four wells (n=4) from a single donor. [Figure 3D]This section describes the phenotypic characterization of Vγ9+γδ T cells. Figure 3A shows a schematic diagram of the gate used to illustrate γδ T cell differentiation (left). Representative FACS dot plots show the differentiation profiles of Vγ9+γδ T cells from fresh PBMCs (left) and PBMCs cultured ex vivo for 14 days with zoledronic acid + IL-2 + IL-15 (right). The numbers in the quadrants reflect the frequency (mean ± SEM) of each population of fresh and activated Vγ9+γδ T cells. The data shown are the mean (± SEM) of 5 donors (n=5) from a single experiment. Figure 3B shows the number of representative dot plots reflecting the frequency (mean ± SEM) of Vγ9+γδ T cells positive for each activation marker from either fresh PBMCs (top) or PBMCs cultured for 14 days with zoledronic acid + IL-2 + IL-15 (bottom). The data presented are the mean (±SEM) values ​​from seven donors (n=7) for CD62L, CD69, and CD44 expression data from two independent experiments. n represents five donors for NKG2D expression data and two donors each for CD45RO and CD71 expression data from a single experiment. Figure 3C shows the number of gated dots in a dot plot indicating the frequency (mean ±SEM) of Vγ9+γδ T cells positive for each inhibitory receptor surface expression from either fresh PBMCs (top panel) or PBMCs cultured for 14 days with zoledronic acid + IL-2 + IL-15 (bottom panel). The data presented herein are the mean (±SEM) values ​​from five donors (n=5) for PD1, CTLA4, TIGIT, and LAG3 surface expression data, and from seven donors (n=7) for 2B4 and TIM3 surface expression data, from two independent experiments. Figure 3D shows representative FACS dot plots demonstrating the frequency (mean ± SEM) of Vγ9+γδ T cells expressing intracellular granzyme B (left column) and perforin (right column) from fresh PBMCs (top panel) and PBMCs cultured ex vivo for 14 days with zoledronic acid + IL-2 + IL-15 (bottom panel). The data shown are the mean (± SEM) values ​​for granzyme B and perforin data from 4 (n=4) and 7 (n=7) donors, respectively, from two independent experiments.Figure 3E shows a bar graph representing the mean (±SEM) concentrations (pg / mL) of cytokines in the cell culture supernatant at days 0 and 14 of PBMC culture with zoledronic acid + IL-2 + IL-15. The data shown are the mean (±SEM) of four wells (n=4) from a single donor. [Figure 3E]This section describes the phenotypic characterization of Vγ9+γδ T cells. Figure 3A shows a schematic diagram of the gate used to illustrate γδ T cell differentiation (left). Representative FACS dot plots show the differentiation profiles of Vγ9+γδ T cells from fresh PBMCs (left) and PBMCs cultured ex vivo for 14 days with zoledronic acid + IL-2 + IL-15 (right). The numbers in the quadrants reflect the frequency (mean ± SEM) of each population of fresh and activated Vγ9+γδ T cells. The data shown are the mean (± SEM) of 5 donors (n=5) from a single experiment. Figure 3B shows the number of representative dot plots reflecting the frequency (mean ± SEM) of Vγ9+γδ T cells positive for each activation marker from either fresh PBMCs (top) or PBMCs cultured for 14 days with zoledronic acid + IL-2 + IL-15 (bottom). The data presented are the mean (±SEM) values ​​from seven donors (n=7) for CD62L, CD69, and CD44 expression data from two independent experiments. n represents five donors for NKG2D expression data and two donors each for CD45RO and CD71 expression data from a single experiment. Figure 3C shows the number of gated dots in a dot plot indicating the frequency (mean ±SEM) of Vγ9+γδ T cells positive for each inhibitory receptor surface expression from either fresh PBMCs (top panel) or PBMCs cultured for 14 days with zoledronic acid + IL-2 + IL-15 (bottom panel). The data presented herein are the mean (±SEM) values ​​from five donors (n=5) for PD1, CTLA4, TIGIT, and LAG3 surface expression data, and from seven donors (n=7) for 2B4 and TIM3 surface expression data, from two independent experiments. Figure 3D shows representative FACS dot plots demonstrating the frequency (mean ± SEM) of Vγ9+γδ T cells expressing intracellular granzyme B (left column) and perforin (right column) from fresh PBMCs (top panel) and PBMCs cultured ex vivo for 14 days with zoledronic acid + IL-2 + IL-15 (bottom panel). The data shown are the mean (± SEM) values ​​for granzyme B and perforin data from 4 (n=4) and 7 (n=7) donors, respectively, from two independent experiments.Figure 3E shows a bar graph representing the mean (±SEM) concentrations (pg / mL) of cytokines in the cell culture supernatant at days 0 and 14 of PBMC culture with zoledronic acid + IL-2 + IL-15. The data shown are the mean (±SEM) of four wells (n=4) from a single donor. [Figure 4] This histogram demonstrates that VG1 (an anti-TRGV9 / anti-CD123 bispecific antibody) recruits Vγ9+ T cells, as demonstrated by conjugate formation between γδ T cells and Kasumi-3 cells. [Figure 5A] Graphs demonstrating VG1 (anti-TRGV9 / anti-CD123 bispecific antibody) bispecificity-mediated γδ T cell cytotoxicity against Kasumi-3 cells are shown for different effector-to-target cell ratios (1:1 for Figure 5A, 5:1 for Figure 5B, and 10:1 for Figure 5C). [Figure 5B] Graphs demonstrating VG1 (anti-TRGV9 / anti-CD123 bispecific antibody) bispecificity-mediated γδ T cell cytotoxicity against Kasumi-3 cells are shown for different effector-to-target cell ratios (1:1 for Figure 5A, 5:1 for Figure 5B, and 10:1 for Figure 5C). [Figure 5C] Graphs demonstrating VG1 (anti-TRGV9 / anti-CD123 bispecific antibody) bispecificity-mediated γδ T cell cytotoxicity against Kasumi-3 cells are shown for different effector-to-target cell ratios (1:1 for Figure 5A, 5:1 for Figure 5B, and 10:1 for Figure 5C). [Figure 6A] The graphs shown demonstrate the expression of CD69 (Figure 6A), CD25 (Figure 6B), or granzyme B (Figure 6C) on Vγ9+γδ T cells, non-Vγ9+γδ T cells, and Pan-T cells (non-γδ T cells) co-cultured with Kasumi-3 cells and VG1, VG3, or without bispecific antibodies. [Figure 6B]The graphs shown demonstrate the expression of CD69 (Figure 6A), CD25 (Figure 6B), or granzyme B (Figure 6C) on Vγ9+γδ T cells, non-Vγ9+γδ T cells, and Pan-T cells (non-γδ T cells) co-cultured with Kasumi-3 cells and VG1, VG3, or without bispecific antibodies. [Figure 6C] The graphs shown demonstrate the expression of CD69 (Figure 6A), CD25 (Figure 6B), or granzyme B (Figure 6C) on Vγ9+γδ T cells, non-Vγ9+γδ T cells, and Pan-T cells (non-γδ T cells) co-cultured with Kasumi-3 cells and VG1, VG3, or without bispecific antibodies. [Figure 7] A schematic diagram is shown demonstrating the binding of an anti-TRGV9 / anti-CD33 bispecific antibody to γδ T cells, which are recruited to CD33+ cancer cells, and induce cancer cell death. [Figure 8] This shows an SDS-PAGE (non-reducing) gel demonstrating the integrity of the VG4 bispecific antibody. [Figure 9] The graph shows the binding of the anti-CD33 antibody (clone C33B904) to the MOLM-13 tumor cell line, as measured by FACS. [Figure 10] The graph shows the binding of the anti-CD33 antibody (clone C33B904) to the Kasumi-1 tumor cell line, as measured by FACS. [Figure 11] The graph shows the binding of the anti-CD33 antibody (clone C33B904) to the OCI-AML-3 tumor cell line, as measured by FACS. [Figure 12] The graph demonstrates that the anti-TRGV9 / anti-CD33 bispecific antibody mediated γδ T cell cytotoxicity against CD33-expressing Kasumi-3 cells in a 1:1 effector-to-target cell ratio. Effector cells were enriched γδ T cells isolated from PBMCs. [Figure 13]The graph demonstrates that the anti-TRGV9 / anti-CD33 bispecific antibody mediated γδ T cell cytotoxicity against CD33-expressing Kasumi-3 cells in a 5:1 effector-to-target cell ratio. Effector cells were enriched γδ T cells isolated from PBMCs. [Figure 14] The graph demonstrates that the anti-TRGV9 / anti-CD33 bispecific antibody mediated γδ T cell cytotoxicity against CD33-expressing Kasumi-3 cells in a 1:1 effector-to-target cell ratio. The effector cells were PBMCs derived from healthy donors. [Figure 15] This diagram illustrates the binding of an anti-TRGV9 / anti-TRBC1 bispecific antibody to γδ T cells, which are recruited to TRBC1+ cancer cells, thereby inducing cancer cell death. [Figure 16] This study demonstrates the selective cell binding of anti-TRBC1 (JOVI-1 mIgG2a, TRB1B1) to transfected Jurkat cells. The EC50 of binding was ~1~2 nM. TRB1B1 did not show significant binding to HPB-ALL cell lines endogenously expressing the TRBC2 TCR. [Figure 17] The study showed selective protein binding of anti-TRBC1 (JOVI-1 mIgG2a, TRB1B1) to recombinant TCRs containing the TRBC1 constant domain (TRB1W16). TRB1B1 did not show significant binding to recombinant TCRs using the TRBC2 constant domain (TRB2W16). [Figure 18] This shows the phenotype of Vγ9+ cells used in the JOVI-1×Vg9 bispecific (TRB1B50) cytotoxicity test from healthy donors. [Figure 19] This report demonstrates that the anti-TRGV9 / anti-TRBC1 bispecific antibody mediates γδ T cell cytotoxicity against TRBC1-expressing Jurkat cells in vitro. The cytotoxicity values ​​expressed here are calculated by subtracting the basal cytotoxicity values ​​observed in the absence of the bispecific antibody. EC50 values ​​were calculated as described in the method. Representative data presented herein are from a single experiment. [Figure 20]This study demonstrates bispecific antibody-mediated cytotoxicity. Using enlarged and enriched Vγ9Vδ2 T cells from various donors, cytotoxicity was induced in Jurkat cell lines in the presence of Vγ9xJovi at the indicated concentrations (E:T ratio 1:1). The assay was performed for 16 hours. The percentage of target cells killed under various conditions is shown in the figure. [Figure 21] The anti-TRGV9 / anti-BCMA bispecific antibody (BCV9B106(B3)) binds to γδ T cells (left panel) and mediates γδ T cell cytotoxicity against BCMA-expressing H929 cells in vitro (right panel). EC50 values ​​were calculated as described in the methods. Representative data presented herein are from a single experiment. [Figure 22] The anti-TRGV9 / anti-BCMA bispecific antibody (HC1:VG9B420-LH-scFv;HC2:BCMA-Fab(BCMB519-Fab)(BCV9B71.001)) binds to γδ T cells (left panel) and mediates γδ T cell cytotoxicity against BCMA-expressing H929 cells in vitro (right panel). EC50 values ​​were calculated as described in the methods. Representative data presented herein are from a single experiment. [Figure 23] The anti-TRGV9 / anti-BCMA bispecific antibody (VG9SB10SC1087_P18_D08-Fab RF, BCMA-scFv(BCMB519-scFv)(BCV9B100.001)) binds to γδ T cells (left panel) and mediates γδ T cell cytotoxicity against BCMA-expressing H929 cells in vitro (right panel). EC50 values ​​were calculated as described in the methods. Representative data presented herein are from a single experiment. [Figure 24]The anti-TRGV9 / anti-BCMA bispecific antibody (VG9SB10SC1087_P18_C12-Fab RF, BCMA-scFv(BCMB519-scFv)(BCV9B101.001)) binds to γδ T cells (left panel) and mediates γδ T cell cytotoxicity against BCMA-expressing H929 cells in vitro (right panel). EC50 values ​​were calculated as described in the methods. Representative data presented herein are from a single experiment. [Figure 25] The anti-TRGV9 / anti-BCMA bispecific antibody (VG9SB10SC1087_P19_C03-Fab RF, BCMA-scFv(BCMB519-scFv)(BCV9B103.001)) binds to γδ T cells (left panel) and mediates γδ T cell cytotoxicity against BCMA-expressing H929 cells in vitro (right panel). EC50 values ​​were calculated as described in the methods. Representative data presented herein are from a single experiment. [Figure 26] This document describes the humanization of a mouse anti-Vγ9 antibody. Humanization of mouse clone 7A5 was performed according to the process outlined by Singh et al., Mabs. 2015.7:778-791. Based on sequence homology, germline IGHV1-8*01 and IGKV4-1*01 were selected for framework adaptation. Potential iso-Asp isomerization sites (DG motifs) were also included in the design. [Figure 27A]Epitope and paratope mappings are shown. Figure 27A shows the HX-MS epitope mappings of mouse anti-human TCRVγ9 [clone 7A5] mAb and Vγ9 / Vδ2 fused to human Fc. The sequences of VG9 (sequence number 789 (amino acids 20-261 of sequence number 156)) and VD2 (sequence number 790 (amino acids 20-248 of sequence number 157)) are shown below. The peptide region containing amino acids 49-68 of sequence number 789 (L49VSISYDGTVRKESGIPSGK68 (sequence number 774) (italicized)) was protected with mAb 7A5. The molecular model of TCR Vγ9-Vδ2 (using crystal structure PBD:1HXM, see Allison et al., Nature. 2001. 411:820-824) and residues in the epitopes are highlighted in spherical representation. Figure 27B shows the HDX paratope mapping in mouse clone 7A5 (Vg9_7A5_VH SEQ ID NO: 7, Vg9_7A5_VL SEQ ID NO: 8). Molecular models of Fab containing residues in the paratope are highlighted. [Figure 27B] Epitope and paratope mappings are shown. Figure 27A shows the HX-MS epitope mappings of mouse anti-human TCRVγ9 [clone 7A5] mAb and Vγ9 / Vδ2 fused to human Fc. The sequences of VG9 (sequence number 789 (amino acids 20-261 of sequence number 156)) and VD2 (sequence number 790 (amino acids 20-248 of sequence number 157)) are shown below. The peptide region containing amino acids 49-68 of sequence number 789 (L49VSISYDGTVRKESGIPSGK68 (sequence number 774) (italicized)) was protected with mAb 7A5. The molecular model of TCR Vγ9-Vδ2 (using crystal structure PBD:1HXM, see Allison et al., Nature. 2001. 411:820-824) and residues in the epitopes are highlighted in spherical representation. Figure 27B shows the HDX paratope mapping in mouse clone 7A5 (Vg9_7A5_VH SEQ ID NO: 7, Vg9_7A5_VL SEQ ID NO: 8). Molecular models of Fab containing residues in the paratope are highlighted. [Figure 28A]This shows that healthy individuals contain a wide range of Vγ9+γδ T cells in all PBMCs. Figure 28A shows the frequency of Vγ9+γδ T cells (TCRVγ9+CD3+) in all PBMCs. The numbers in the quadrants represent the frequency of each population. Figure 28B shows a scatter dot plot graph summarizing the frequency (mean ± SEM) of Vγ9+γδ T cells in all PBMCs of healthy individuals. Each dot represents data from a healthy individual. [Figure 28B] This shows that healthy individuals contain a wide range of Vγ9+γδ T cells in all PBMCs. Figure 28A shows the frequency of Vγ9+γδ T cells (TCRVγ9+CD3+) in all PBMCs. The numbers in the quadrants represent the frequency of each population. Figure 28B shows a scatter dot plot graph summarizing the frequency (mean ± SEM) of Vγ9+γδ T cells in all PBMCs of healthy individuals. Each dot represents data from a healthy individual. [Figure 29A]This shows the characterization of Vγ9+γδ T cells. The left and center panels of Figure 29A show graphs summarizing the frequency of Vγ9+γδ T cells in total PBMCs at day 0 and day 14 in cultures containing zoledronic acid, which selectively activates and increases Vγ9+γδ T cells. The right panel of Figure 29A shows representative data from n=15 donors from six independent experiments. The graphs represent the percentage of Vγ9+γδ T cells among total CD3+ T cells at day 0 and day 14 of activation, with each dot representing data from a donor. The two left panels of Figure 29B show that the numbers in the representative FACS plots represent the differentiation profile of Vγ9+γδ T cells at day 0 and day 14 in cultures containing zoledronic acid. The two right-hand panels of Figure 29B show scatter plots summarizing the frequencies of positive Vγ9+γδ T cells for naive (CD27+CD45RA+), central memory (CD27+CD45RA-), effector memory (CD27-CD45RA-), and effector memory cells re-expressing the CD45RA (EMRA, CD27-CD45RA+) phenotype at day 0 and day 14 of cultures containing zoledronic acid. Each dot represents data from a healthy donor. Representative data from n=13 donors from four independent experiments are plotted. Figure 29C shows a number of representative FACS plots showing the frequency (mean ± SEM) of Vγ9+γδ T cells positive for intracellular expression of granzyme B and perforin at day 0 (top row) and day 14 (bottom row). The figures show data on the intracellular expression of granzyme B and perforin from fresh Vγ9+γδ T cells (day 0) from n=12 and n=7 donors, as well as data from activated Vγ9+γδ T cells (day 14) from n=14 and n=9 donors. [Figure 29B]This shows the characterization of Vγ9+γδ T cells. The left and center panels of Figure 29A show graphs summarizing the frequency of Vγ9+γδ T cells in total PBMCs at day 0 and day 14 in cultures containing zoledronic acid, which selectively activates and increases Vγ9+γδ T cells. The right panel of Figure 29A shows representative data from n=15 donors from six independent experiments. The graphs represent the percentage of Vγ9+γδ T cells among total CD3+ T cells at day 0 and day 14 of activation, with each dot representing data from a donor. The two left panels of Figure 29B show that the numbers in the representative FACS plots represent the differentiation profile of Vγ9+γδ T cells at day 0 and day 14 in cultures containing zoledronic acid. The two right-hand panels of Figure 29B show scatter plots summarizing the frequencies of positive Vγ9+γδ T cells for naive (CD27+CD45RA+), central memory (CD27+CD45RA-), effector memory (CD27-CD45RA-), and effector memory cells re-expressing the CD45RA (EMRA, CD27-CD45RA+) phenotype at day 0 and day 14 of cultures containing zoledronic acid. Each dot represents data from a healthy donor. Representative data from n=13 donors from four independent experiments are plotted. Figure 29C shows a number of representative FACS plots showing the frequency (mean ± SEM) of Vγ9+γδ T cells positive for intracellular expression of granzyme B and perforin at day 0 (top row) and day 14 (bottom row). The figures show data on the intracellular expression of granzyme B and perforin from fresh Vγ9+γδ T cells (day 0) from n=12 and n=7 donors, as well as data from activated Vγ9+γδ T cells (day 14) from n=14 and n=9 donors. [Figure 29C]This shows the characterization of Vγ9+γδ T cells. The left and center panels of Figure 29A show graphs summarizing the frequency of Vγ9+γδ T cells in total PBMCs at day 0 and day 14 in cultures containing zoledronic acid, which selectively activates and increases Vγ9+γδ T cells. The right panel of Figure 29A shows representative data from n=15 donors from six independent experiments. The graphs represent the percentage of Vγ9+γδ T cells among total CD3+ T cells at day 0 and day 14 of activation, with each dot representing data from a donor. The two left panels of Figure 29B show that the numbers in the representative FACS plots represent the differentiation profile of Vγ9+γδ T cells at day 0 and day 14 in cultures containing zoledronic acid. The two right-hand panels of Figure 29B show scatter plots summarizing the frequencies of positive Vγ9+γδ T cells for naive (CD27+CD45RA+), central memory (CD27+CD45RA-), effector memory (CD27-CD45RA-), and effector memory cells re-expressing the CD45RA (EMRA, CD27-CD45RA+) phenotype at day 0 and day 14 of cultures containing zoledronic acid. Each dot represents data from a healthy donor. Representative data from n=13 donors from four independent experiments are plotted. Figure 29C shows a number of representative FACS plots showing the frequency (mean ± SEM) of Vγ9+γδ T cells positive for intracellular expression of granzyme B and perforin at day 0 (top row) and day 14 (bottom row). The figures show data on the intracellular expression of granzyme B and perforin from fresh Vγ9+γδ T cells (day 0) from n=12 and n=7 donors, as well as data from activated Vγ9+γδ T cells (day 14) from n=14 and n=9 donors. [Figure 30A]This study demonstrates that the anti-TRGV9 / anti-CD123 bispecific antibody binds to Vγ9+γδ T cells and CD123-expressing tumor cells. CD123-expressing target cells and PBMCs activated and enlarged with zoledronic acid on day 14 were incubated in the presence or absence of the indicated Vγ9 bispecific and NULL-arm bispecific control antibodies. Bound bispecific antibody staining was evaluated by flow cytometry. Figure 30A shows the frequency of Vγ9 bispecifically bound Kasumi-3 cells in three independent experiments for the Kasumi-3 cell line. The EC50 values ​​shown in the graph refer to the mean of the three independent experiments. Figure 30B shows Vγ9+γδ T cells at various concentrations in two independent experiments using eight healthy donors. The EC50 values ​​shown in the graph refer to two healthy donors. The lines on the right and left reflect the indicated Vγ9 bispecific antibody and its corresponding Vγ9 NULL-arm bispecific control antibody, respectively. The EC50 values ​​shown in the graph were derived using a four-parameter dose-response curve with the concentration of the bispecific antibody shown on the x-axis (logarithmic scale) and specific binding on the y-axis (linear scale). Figure 30C shows that Vγ9+γδ T cells were removed from Pan-T cells in the total PBMCs by FACS sorting. Pan-T cells from which total Pan-T cells and Vγ9+γδ T cells were removed were incubated in the presence and absence of the bispecific antibodies shown at various concentrations. Representative FACS plots show the effect of removing Vγ9+γδ T cells from Pan-T cells. The numbers in the quadrants represent the frequency of each population. The binding of Vγ9 / CD123 and Vγ9 / NULL bispecific antibodies to Pan-T cells (Vγ9-unremoved Pan-T cells) and pan-T cells from which Vγ9+γδ T cells were removed (Vγ9-removed Pan-T cells) at the indicated concentrations is shown. Figure 30D shows that CD123-expressing Kasumi-3 and non-expressing 22Rv1 cell lines were stained with an anti-CD123 monoclonal antibody. The overlaid representative histograms show the staining of CD123, isotype control, and FMO control for Kasumi-3 (left) and 22Rv1 (right) cell lines (top panel).At the bottom, representative graphs show the binding of Vγ9 / CD123 and Vγ9 / NULL bispecific antibodies to the Kasumi-3 (left) cell line at the indicated concentrations. The EC50 values ​​shown in the graphs were derived using a four-parameter dose-response curve with the concentration of the indicated bispecific antibody on the x-axis (logarithmic scale) and specific binding on the y-axis (linear scale). [Figure 30B]This study demonstrates that the anti-TRGV9 / anti-CD123 bispecific antibody binds to Vγ9+γδ T cells and CD123-expressing tumor cells. CD123-expressing target cells and PBMCs activated and enlarged with zoledronic acid on day 14 were incubated in the presence or absence of the indicated Vγ9 bispecific and NULL-arm bispecific control antibodies. Bound bispecific antibody staining was evaluated by flow cytometry. Figure 30A shows the frequency of Vγ9 bispecifically bound Kasumi-3 cells in three independent experiments for the Kasumi-3 cell line. The EC50 values ​​shown in the graph refer to the mean of the three independent experiments. Figure 30B shows Vγ9+γδ T cells at various concentrations in two independent experiments using eight healthy donors. The EC50 values ​​shown in the graph refer to two healthy donors. The lines on the right and left reflect the indicated Vγ9 bispecific antibody and its corresponding Vγ9 NULL-arm bispecific control antibody, respectively. The EC50 values ​​shown in the graph were derived using a four-parameter dose-response curve with the concentration of the bispecific antibody shown on the x-axis (logarithmic scale) and specific binding on the y-axis (linear scale). Figure 30C shows that Vγ9+γδ T cells were removed from Pan-T cells in the total PBMCs by FACS sorting. Pan-T cells from which total Pan-T cells and Vγ9+γδ T cells were removed were incubated in the presence and absence of the bispecific antibodies shown at various concentrations. Representative FACS plots show the effect of removing Vγ9+γδ T cells from Pan-T cells. The numbers in the quadrants represent the frequency of each population. The binding of Vγ9 / CD123 and Vγ9 / NULL bispecific antibodies to Pan-T cells (Vγ9-unremoved Pan-T cells) and pan-T cells from which Vγ9+γδ T cells were removed (Vγ9-removed Pan-T cells) at the indicated concentrations is shown. Figure 30D shows that CD123-expressing Kasumi-3 and non-expressing 22Rv1 cell lines were stained with an anti-CD123 monoclonal antibody. The overlaid representative histograms show the staining of CD123, isotype control, and FMO control for Kasumi-3 (left) and 22Rv1 (right) cell lines (top panel).At the bottom, representative graphs show the binding of Vγ9 / CD123 and Vγ9 / NULL bispecific antibodies to the Kasumi-3 (left) cell line at the indicated concentrations. The EC50 values ​​shown in the graphs were derived using a four-parameter dose-response curve with the concentration of the indicated bispecific antibody on the x-axis (logarithmic scale) and specific binding on the y-axis (linear scale). [Figure 30C]This study demonstrates that the anti-TRGV9 / anti-CD123 bispecific antibody binds to Vγ9+γδ T cells and CD123-expressing tumor cells. CD123-expressing target cells and PBMCs activated and enlarged with zoledronic acid on day 14 were incubated in the presence or absence of the indicated Vγ9 bispecific and NULL-arm bispecific control antibodies. Bound bispecific antibody staining was evaluated by flow cytometry. Figure 30A shows the frequency of Vγ9 bispecifically bound Kasumi-3 cells in three independent experiments for the Kasumi-3 cell line. The EC50 values ​​shown in the graph refer to the mean of the three independent experiments. Figure 30B shows Vγ9+γδ T cells at various concentrations in two independent experiments using eight healthy donors. The EC50 values ​​shown in the graph refer to two healthy donors. The lines on the right and left reflect the indicated Vγ9 bispecific antibody and its corresponding Vγ9 NULL-arm bispecific control antibody, respectively. The EC50 values ​​shown in the graph were derived using a four-parameter dose-response curve with the concentration of the bispecific antibody shown on the x-axis (logarithmic scale) and specific binding on the y-axis (linear scale). Figure 30C shows that Vγ9+γδ T cells were removed from Pan-T cells in the total PBMCs by FACS sorting. Pan-T cells from which total Pan-T cells and Vγ9+γδ T cells were removed were incubated in the presence and absence of the bispecific antibodies shown at various concentrations. Representative FACS plots show the effect of removing Vγ9+γδ T cells from Pan-T cells. The numbers in the quadrants represent the frequency of each population. The binding of Vγ9 / CD123 and Vγ9 / NULL bispecific antibodies to Pan-T cells (Vγ9-unremoved Pan-T cells) and pan-T cells from which Vγ9+γδ T cells were removed (Vγ9-removed Pan-T cells) at the indicated concentrations is shown. Figure 30D shows that CD123-expressing Kasumi-3 and non-expressing 22Rv1 cell lines were stained with an anti-CD123 monoclonal antibody. The overlaid representative histograms show the staining of CD123, isotype control, and FMO control for Kasumi-3 (left) and 22Rv1 (right) cell lines (top panel).At the bottom, representative graphs show the binding of Vγ9 / CD123 and Vγ9 / NULL bispecific antibodies to the Kasumi-3 (left) cell line at the indicated concentrations. The EC50 values ​​shown in the graphs were derived using a four-parameter dose-response curve with the concentration of the indicated bispecific antibody on the x-axis (logarithmic scale) and specific binding on the y-axis (linear scale). [Figure 30D]This study demonstrates that the anti-TRGV9 / anti-CD123 bispecific antibody binds to Vγ9+γδ T cells and CD123-expressing tumor cells. CD123-expressing target cells and PBMCs activated and enlarged with zoledronic acid on day 14 were incubated in the presence or absence of the indicated Vγ9 bispecific and NULL-arm bispecific control antibodies. Bound bispecific antibody staining was evaluated by flow cytometry. Figure 30A shows the frequency of Vγ9 bispecifically bound Kasumi-3 cells in three independent experiments for the Kasumi-3 cell line. The EC50 values ​​shown in the graph refer to the mean of the three independent experiments. Figure 30B shows Vγ9+γδ T cells at various concentrations in two independent experiments using eight healthy donors. The EC50 values ​​shown in the graph refer to two healthy donors. The lines on the right and left reflect the indicated Vγ9 bispecific antibody and its corresponding Vγ9 NULL-arm bispecific control antibody, respectively. The EC50 values ​​shown in the graph were derived using a four-parameter dose-response curve with the concentration of the bispecific antibody shown on the x-axis (logarithmic scale) and specific binding on the y-axis (linear scale). Figure 30C shows that Vγ9+γδ T cells were removed from Pan-T cells in the total PBMCs by FACS sorting. Pan-T cells from which total Pan-T cells and Vγ9+γδ T cells were removed were incubated in the presence and absence of the bispecific antibodies shown at various concentrations. Representative FACS plots show the effect of removing Vγ9+γδ T cells from Pan-T cells. The numbers in the quadrants represent the frequency of each population. The binding of Vγ9 / CD123 and Vγ9 / NULL bispecific antibodies to Pan-T cells (Vγ9-unremoved Pan-T cells) and pan-T cells from which Vγ9+γδ T cells were removed (Vγ9-removed Pan-T cells) at the indicated concentrations is shown. Figure 30D shows that CD123-expressing Kasumi-3 and non-expressing 22Rv1 cell lines were stained with an anti-CD123 monoclonal antibody. The overlaid representative histograms show the staining of CD123, isotype control, and FMO control for Kasumi-3 (left) and 22Rv1 (right) cell lines (top panel).At the bottom, representative graphs show the binding of Vγ9 / CD123 and Vγ9 / NULL bispecific antibodies to the Kasumi-3 (left) cell line at the indicated concentrations. The EC50 values ​​shown in the graphs were derived using a four-parameter dose-response curve with the concentration of the indicated bispecific antibody on the x-axis (logarithmic scale) and specific binding on the y-axis (linear scale). [Figure 31A]This shows that the Vγ9 / CD123 bispecific antibody selectively recruits and activates, inducing cytotoxicity mediated by Vγ9+γδ T cells. Figure 31A shows labeled enriched γδ T cells in cell traces co-cultured with yellow-labeled kasumi-3 cells in cell traces at a 1:1 ET ratio for 1 hour at 37°C in the presence of 1 μg / mL of the indicated bispecific antibody. Cell-to-cell binding was determined using flow cytometry, and cells in the upper right quadrant of the FACS plot were quantified as bi-positive. The numbers in the quadrants indicate the frequency of each population. Figures 31B and 31C show PanT cells (effectors) from fresh PBMCs co-cultured with Kasumi-3 cells (target) at a 1:1 ET ratio for 72 hours at 37°C in or without the indicated bispecific antibody. Figure 31D shows Vγ9+γδ T cells, Vγ9-γδ T cells, and non-γδ T cells that were positive for CD69 (left), CD25 (right) surface expression, and intracellular granzyme B expression. Figure 31D shows Vγ9 / CD123 bispecificity-mediated γδ T cell cytotoxicity against CD123 cells. PBMCs cultured with 14 zoledronic acids (effector) were co-cultured with CFSE-labeled target (Kasumi-3) cells at an ET ratio of 1:1 (by normalizing the ET ratio against the increased frequency of Vγ9+γδ T cells in the PBMCs) for 16 hours in the presence of indicated concentrations of Vγ9 bispecificity and Vγ9 NULL arm control antibodies. Target cell lysis was determined by 7-AAD staining and flow cytometry. The graphs show the frequency of specific target cell lysis at indicated concentrations of Vγ9 bispecificity antibody and their respective Vγ9 / NULL arm controls. The EC50 values ​​shown in the representative graph are the average values ​​for Vγ9 / CD123 from eight healthy donors from three independent experiments. Figure 31E shows that the bispecificity of Vγ9 / CD123 effectively mediates AMLγδ T cell cytotoxicity against Kasumi-3 cells. The upper and lower lines in the representative graph show the frequency of target (kasumi-3) cell lysis (%7-AAD+ cells) mediated by Vγ9 / CD123 and Vγ9 / Null bispecific antibodies, respectively, during 16-hour co-culture of ZolAML patient PBMCs and target cells on day 14.Figure 31F shows the effect of removing Vγ9+γδ T cells from pan-T cells. The numbers in the quadrants represent the frequency of each population. The graph shows the frequency of target cell lysis (%7-AAD+ cells) mediated by Vγ9 / CD123 and Vγ9 / NULL bispecific antibodies at the indicated concentrations when co-culturing pan-T cells (without Vγ9 removal) and pan-T cells (with Vγ9 removal) with target (Kasumi-3) cells (center graph). The lower graphs show target cell lysis mediated by CD3 / CD123 and CD3 / NULL bispecific antibodies at the indicated concentrations. [Figure 31B]This shows that the Vγ9 / CD123 bispecific antibody selectively recruits and activates, inducing cytotoxicity mediated by Vγ9+γδ T cells. Figure 31A shows labeled enriched γδ T cells in cell traces co-cultured with yellow-labeled kasumi-3 cells in cell traces at a 1:1 ET ratio for 1 hour at 37°C in the presence of 1 μg / mL of the indicated bispecific antibody. Cell-to-cell binding was determined using flow cytometry, and cells in the upper right quadrant of the FACS plot were quantified as bi-positive. The numbers in the quadrants indicate the frequency of each population. Figures 31B and 31C show PanT cells (effectors) from fresh PBMCs co-cultured with Kasumi-3 cells (target) at a 1:1 ET ratio for 72 hours at 37°C in or without the indicated bispecific antibody. Figure 31D shows Vγ9+γδ T cells, Vγ9-γδ T cells, and non-γδ T cells that were positive for CD69 (left), CD25 (right) surface expression, and intracellular granzyme B expression. Figure 31D shows Vγ9 / CD123 bispecificity-mediated γδ T cell cytotoxicity against CD123 cells. PBMCs cultured with 14 zoledronic acids (effector) were co-cultured with CFSE-labeled target (Kasumi-3) cells at an ET ratio of 1:1 (by normalizing the ET ratio against the increased frequency of Vγ9+γδ T cells in the PBMCs) for 16 hours in the presence of indicated concentrations of Vγ9 bispecificity and Vγ9 NULL arm control antibodies. Target cell lysis was determined by 7-AAD staining and flow cytometry. The graphs show the frequency of specific target cell lysis at indicated concentrations of Vγ9 bispecificity antibody and their respective Vγ9 / NULL arm controls. The EC50 values ​​shown in the representative graph are the average values ​​for Vγ9 / CD123 from eight healthy donors from three independent experiments. Figure 31E shows that the bispecificity of Vγ9 / CD123 effectively mediates AMLγδ T cell cytotoxicity against Kasumi-3 cells. The upper and lower lines in the representative graph show the frequency of target (kasumi-3) cell lysis (%7-AAD+ cells) mediated by Vγ9 / CD123 and Vγ9 / Null bispecific antibodies, respectively, during 16-hour co-culture of ZolAML patient PBMCs and target cells on day 14.Figure 31F shows the effect of removing Vγ9+γδ T cells from pan-T cells. The numbers in the quadrants represent the frequency of each population. The graph shows the frequency of target cell lysis (%7-AAD+ cells) mediated by Vγ9 / CD123 and Vγ9 / NULL bispecific antibodies at the indicated concentrations when co-culturing pan-T cells (without Vγ9 removal) and pan-T cells (with Vγ9 removal) with target (Kasumi-3) cells (center graph). The lower graphs show target cell lysis mediated by CD3 / CD123 and CD3 / NULL bispecific antibodies at the indicated concentrations. [Figure 31C]This shows that the Vγ9 / CD123 bispecific antibody selectively recruits and activates, inducing cytotoxicity mediated by Vγ9+γδ T cells. Figure 31A shows labeled enriched γδ T cells in cell traces co-cultured with yellow-labeled kasumi-3 cells in cell traces at a 1:1 ET ratio for 1 hour at 37°C in the presence of 1 μg / mL of the indicated bispecific antibody. Cell-to-cell binding was determined using flow cytometry, and cells in the upper right quadrant of the FACS plot were quantified as bi-positive. The numbers in the quadrants indicate the frequency of each population. Figures 31B and 31C show PanT cells (effectors) from fresh PBMCs co-cultured with Kasumi-3 cells (target) at a 1:1 ET ratio for 72 hours at 37°C in or without the indicated bispecific antibody. Figure 31D shows Vγ9+γδ T cells, Vγ9-γδ T cells, and non-γδ T cells that were positive for CD69 (left), CD25 (right) surface expression, and intracellular granzyme B expression. Figure 31D shows Vγ9 / CD123 bispecificity-mediated γδ T cell cytotoxicity against CD123 cells. PBMCs cultured with 14 zoledronic acids (effector) were co-cultured with CFSE-labeled target (Kasumi-3) cells at an ET ratio of 1:1 (by normalizing the ET ratio against the increased frequency of Vγ9+γδ T cells in the PBMCs) for 16 hours in the presence of indicated concentrations of Vγ9 bispecificity and Vγ9 NULL arm control antibodies. Target cell lysis was determined by 7-AAD staining and flow cytometry. The graphs show the frequency of specific target cell lysis at indicated concentrations of Vγ9 bispecificity antibody and their respective Vγ9 / NULL arm controls. The EC50 values ​​shown in the representative graph are the average values ​​for Vγ9 / CD123 from eight healthy donors from three independent experiments. Figure 31E shows that the bispecificity of Vγ9 / CD123 effectively mediates AMLγδ T cell cytotoxicity against Kasumi-3 cells. The upper and lower lines in the representative graph show the frequency of target (kasumi-3) cell lysis (%7-AAD+ cells) mediated by Vγ9 / CD123 and Vγ9 / Null bispecific antibodies, respectively, during 16-hour co-culture of ZolAML patient PBMCs and target cells on day 14.Figure 31F shows the effect of removing Vγ9+γδ T cells from pan-T cells. The numbers in the quadrants represent the frequency of each population. The graph shows the frequency of target cell lysis (%7-AAD+ cells) mediated by Vγ9 / CD123 and Vγ9 / NULL bispecific antibodies at the indicated concentrations when co-culturing pan-T cells (without Vγ9 removal) and pan-T cells (with Vγ9 removal) with target (Kasumi-3) cells (center graph). The lower graphs show target cell lysis mediated by CD3 / CD123 and CD3 / NULL bispecific antibodies at the indicated concentrations. [Figure 31D]This shows that the Vγ9 / CD123 bispecific antibody selectively recruits and activates, inducing cytotoxicity mediated by Vγ9+γδ T cells. Figure 31A shows labeled enriched γδ T cells in cell traces co-cultured with yellow-labeled kasumi-3 cells in cell traces at a 1:1 ET ratio for 1 hour at 37°C in the presence of 1 μg / mL of the indicated bispecific antibody. Cell-to-cell binding was determined using flow cytometry, and cells in the upper right quadrant of the FACS plot were quantified as bi-positive. The numbers in the quadrants indicate the frequency of each population. Figures 31B and 31C show PanT cells (effectors) from fresh PBMCs co-cultured with Kasumi-3 cells (target) at a 1:1 ET ratio for 72 hours at 37°C in or without the indicated bispecific antibody. Figure 31D shows Vγ9+γδ T cells, Vγ9-γδ T cells, and non-γδ T cells that were positive for CD69 (left), CD25 (right) surface expression, and intracellular granzyme B expression. Figure 31D shows Vγ9 / CD123 bispecificity-mediated γδ T cell cytotoxicity against CD123 cells. PBMCs cultured with 14 zoledronic acids (effector) were co-cultured with CFSE-labeled target (Kasumi-3) cells at an ET ratio of 1:1 (by normalizing the ET ratio against the increased frequency of Vγ9+γδ T cells in the PBMCs) for 16 hours in the presence of indicated concentrations of Vγ9 bispecificity and Vγ9 NULL arm control antibodies. Target cell lysis was determined by 7-AAD staining and flow cytometry. The graphs show the frequency of specific target cell lysis at indicated concentrations of Vγ9 bispecificity antibody and their respective Vγ9 / NULL arm controls. The EC50 values ​​shown in the representative graph are the average values ​​for Vγ9 / CD123 from eight healthy donors from three independent experiments. Figure 31E shows that the bispecificity of Vγ9 / CD123 effectively mediates AMLγδ T cell cytotoxicity against Kasumi-3 cells. The upper and lower lines in the representative graph show the frequency of target (kasumi-3) cell lysis (%7-AAD+ cells) mediated by Vγ9 / CD123 and Vγ9 / Null bispecific antibodies, respectively, during 16-hour co-culture of ZolAML patient PBMCs and target cells on day 14.Figure 31F shows the effect of removing Vγ9+γδ T cells from pan-T cells. The numbers in the quadrants represent the frequency of each population. The graph shows the frequency of target cell lysis (%7-AAD+ cells) mediated by Vγ9 / CD123 and Vγ9 / NULL bispecific antibodies at the indicated concentrations when co-culturing pan-T cells (without Vγ9 removal) and pan-T cells (with Vγ9 removal) with target (Kasumi-3) cells (center graph). The lower graphs show target cell lysis mediated by CD3 / CD123 and CD3 / NULL bispecific antibodies at the indicated concentrations. [Figure 31E]This shows that the Vγ9 / CD123 bispecific antibody selectively recruits and activates, inducing cytotoxicity mediated by Vγ9+γδ T cells. Figure 31A shows labeled enriched γδ T cells in cell traces co-cultured with yellow-labeled kasumi-3 cells in cell traces at a 1:1 ET ratio for 1 hour at 37°C in the presence of 1 μg / mL of the indicated bispecific antibody. Cell-to-cell binding was determined using flow cytometry, and cells in the upper right quadrant of the FACS plot were quantified as bi-positive. The numbers in the quadrants indicate the frequency of each population. Figures 31B and 31C show PanT cells (effectors) from fresh PBMCs co-cultured with Kasumi-3 cells (target) at a 1:1 ET ratio for 72 hours at 37°C in or without the indicated bispecific antibody. Figure 31D shows Vγ9+γδ T cells, Vγ9-γδ T cells, and non-γδ T cells that were positive for CD69 (left), CD25 (right) surface expression, and intracellular granzyme B expression. Figure 31D shows Vγ9 / CD123 bispecificity-mediated γδ T cell cytotoxicity against CD123 cells. PBMCs cultured with 14 zoledronic acids (effector) were co-cultured with CFSE-labeled target (Kasumi-3) cells at an ET ratio of 1:1 (by normalizing the ET ratio against the increased frequency of Vγ9+γδ T cells in the PBMCs) for 16 hours in the presence of indicated concentrations of Vγ9 bispecificity and Vγ9 NULL arm control antibodies. Target cell lysis was determined by 7-AAD staining and flow cytometry. The graphs show the frequency of specific target cell lysis at indicated concentrations of Vγ9 bispecificity antibody and their respective Vγ9 / NULL arm controls. The EC50 values ​​shown in the representative graph are the average values ​​for Vγ9 / CD123 from eight healthy donors from three independent experiments. Figure 31E shows that the bispecificity of Vγ9 / CD123 effectively mediates AMLγδ T cell cytotoxicity against Kasumi-3 cells. The upper and lower lines in the representative graph show the frequency of target (kasumi-3) cell lysis (%7-AAD+ cells) mediated by Vγ9 / CD123 and Vγ9 / Null bispecific antibodies, respectively, during 16-hour co-culture of ZolAML patient PBMCs and target cells on day 14.Figure 31F shows the effect of removing Vγ9+γδ T cells from pan-T cells. The numbers in the quadrants represent the frequency of each population. The graph shows the frequency of target cell lysis (%7-AAD+ cells) mediated by Vγ9 / CD123 and Vγ9 / NULL bispecific antibodies at the indicated concentrations when co-culturing pan-T cells (without Vγ9 removal) and pan-T cells (with Vγ9 removal) with target (Kasumi-3) cells (center graph). The lower graphs show target cell lysis mediated by CD3 / CD123 and CD3 / NULL bispecific antibodies at the indicated concentrations. [Figure 31F]This shows that the Vγ9 / CD123 bispecific antibody selectively recruits and activates, inducing cytotoxicity mediated by Vγ9+γδ T cells. Figure 31A shows labeled enriched γδ T cells in cell traces co-cultured with yellow-labeled kasumi-3 cells in cell traces at a 1:1 ET ratio for 1 hour at 37°C in the presence of 1 μg / mL of the indicated bispecific antibody. Cell-to-cell binding was determined using flow cytometry, and cells in the upper right quadrant of the FACS plot were quantified as bi-positive. The numbers in the quadrants indicate the frequency of each population. Figures 31B and 31C show PanT cells (effectors) from fresh PBMCs co-cultured with Kasumi-3 cells (target) at a 1:1 ET ratio for 72 hours at 37°C in or without the indicated bispecific antibody. Figure 31D shows Vγ9+γδ T cells, Vγ9-γδ T cells, and non-γδ T cells that were positive for CD69 (left), CD25 (right) surface expression, and intracellular granzyme B expression. Figure 31D shows Vγ9 / CD123 bispecificity-mediated γδ T cell cytotoxicity against CD123 cells. PBMCs cultured with 14 zoledronic acids (effector) were co-cultured with CFSE-labeled target (Kasumi-3) cells at an ET ratio of 1:1 (by normalizing the ET ratio against the increased frequency of Vγ9+γδ T cells in the PBMCs) for 16 hours in the presence of indicated concentrations of Vγ9 bispecificity and Vγ9 NULL arm control antibodies. Target cell lysis was determined by 7-AAD staining and flow cytometry. The graphs show the frequency of specific target cell lysis at indicated concentrations of Vγ9 bispecificity antibody and their respective Vγ9 / NULL arm controls. The EC50 values ​​shown in the representative graph are the average values ​​for Vγ9 / CD123 from eight healthy donors from three independent experiments. Figure 31E shows that the bispecificity of Vγ9 / CD123 effectively mediates AMLγδ T cell cytotoxicity against Kasumi-3 cells. The upper and lower lines in the representative graph show the frequency of target (kasumi-3) cell lysis (%7-AAD+ cells) mediated by Vγ9 / CD123 and Vγ9 / Null bispecific antibodies, respectively, during 16-hour co-culture of ZolAML patient PBMCs and target cells on day 14.Figure 31F shows the effect of removing Vγ9+γδ T cells from pan-T cells. The numbers in the quadrants represent the frequency of each population. The graph shows the frequency of target cell lysis (%7-AAD+ cells) mediated by Vγ9 / CD123 and Vγ9 / NULL bispecific antibodies at the indicated concentrations when co-culturing pan-T cells (without Vγ9 removal) and pan-T cells (with Vγ9 removal) with target (Kasumi-3) cells (center graph). The lower graphs show target cell lysis mediated by CD3 / CD123 and CD3 / NULL bispecific antibodies at the indicated concentrations. [Figure 32A] This study demonstrates that the Vγ9 / CD123 bispecific antibody potently mediates the activation, proliferation, and effector function of Vγ9+γδ T cells in all PBMCs. CFSE-labeled PBMCs were cultured at a concentration of 3 ng / mL in the presence or absence of kasumi-3 cells, and further in the presence of the bispecific antibody. Figure 32A shows the frequency of Vγ9+ cells positive for CD69 and CD25 surface expression. Figure 32B shows the CFSE dilution (proliferation profile). Figure 32C shows the ability to eliminate exogenously added Kasumi-3 cells. Each dot represents data from an individual donor. Representative data from n=5 donors from two independent experiments are shown here. [Figure 32B] This study demonstrates that the Vγ9 / CD123 bispecific antibody potently mediates the activation, proliferation, and effector function of Vγ9+γδ T cells in all PBMCs. CFSE-labeled PBMCs were cultured at a concentration of 3 ng / mL in the presence or absence of kasumi-3 cells, and further in the presence of the bispecific antibody. Figure 32A shows the frequency of Vγ9+ cells positive for CD69 and CD25 surface expression. Figure 32B shows the CFSE dilution (proliferation profile). Figure 32C shows the ability to eliminate exogenously added Kasumi-3 cells. Each dot represents data from an individual donor. Representative data from n=5 donors from two independent experiments are shown here. [Figure 32C]This study demonstrates that the Vγ9 / CD123 bispecific antibody potently mediates the activation, proliferation, and effector function of Vγ9+γδ T cells in all PBMCs. CFSE-labeled PBMCs were cultured at a concentration of 3 ng / mL in the presence or absence of kasumi-3 cells, and further in the presence of the bispecific antibody. Figure 32A shows the frequency of Vγ9+ cells positive for CD69 and CD25 surface expression. Figure 32B shows the CFSE dilution (proliferation profile). Figure 32C shows the ability to eliminate exogenously added Kasumi-3 cells. Each dot represents data from an individual donor. Representative data from n=5 donors from two independent experiments are shown here. [Figure 33] This study demonstrates that selective redirection of Vγ9+γδ T cells does not induce a cytokine storm compared to Pan-T cell redirection. As shown in Figure 30, all PBMCs were cultured in or without spiked kasumi-3 cells, and in or without the indicated bispecific antibody (3 ng / mL). From day 3 of culture, 100 μL of culture medium was removed daily from the wells without disturbing the cells, and fresh medium was replenished until day 8 of the culture. Cytokines were evaluated from the cell culture supernatant from days 3 to 8. Figure 33 shows the concentrations of various cytokines or effector molecules in the culture supernatant of all PBMCs stimulated with the indicated bispecific antibody. Circles and squares represent PBMCs from four individual donors stimulated with the indicated bispecific antibody or the NULL-arm control bispecific antibody, respectively. Representative data from n=4 donors from one independent experiment are shown here. [Figure 34]This shows the mean tumor growth dynamics of NOD SCID mice with subcutaneous KG-1 tumor xenografts. Female NOD SCID mice subcutaneously inoculated with 1.5 × 10⁶ KG-1 cells were subcutaneously treated weekly with PBS or Vγ9Vδ2 γδ T cells. All mice received 15 μg / kg of IL-2 and 1.5 mg / kg of (Vβ17xDLL3) as shown. Tumor volume (left) of each mouse was measured every 3 days during the experimental period. Values ​​are expressed as the mean ± SEM of 6 animals in each group. Statistical analysis was performed by two-way ANOVA followed by a Bonferroni post-test using Graph Pad Prism (version 8.3.0). *p<0.05 & ****p<0.0001 (when each test group was compared to group 1 - tumor + PBS (control) group). [Figure 35] This shows the binding kinetics of mouse anti-human TCR Vγ9 [clone 7A5] and recombinant Vγ9-Vδ2-Fc antigen by SPR at 25°C. Different concentrations of the antigen (100 nM from top to bottom in the plot) were passed through surface-trapped anti-Vγ9 mAb. Experimental data (black dotted line) and 1:1 Langmuir binding fitting (smooth line) are shown. The dissociation phase follows the association phase (initial ~250 seconds). Global fitting to a simple 1:1 Langmuir binding model yields kon = 1.3 ± 0.2 × 10⁵ M⁻¹ S⁻¹ and koff = 2.43 ± 0.3 × 10⁻⁴ S⁻¹, resulting in a KD = 1.9 nM. [Figure 36A] This shows that the Vγ9+ subset of γδ T cells is suitable for retargeting for tumor elimination. Figure 36A shows positive results for the activation marker on day 0 (top row) and day 14 (bottom row).

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[0057] In the background art and throughout this specification, various publications, articles, and patents are cited or referenced, and each of these references is incorporated herein by reference in its entirety. The considerations of documents, operations, materials, devices, articles, etc., included herein are for the purpose of providing context for the present invention. Such considerations do not constitute an endorsement that any or all of these things constitute part of the prior art to any of the disclosed or claimed inventions.

[0058] Unless otherwise specified, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art in which the present invention pertains. Otherwise, certain terms used herein have the meanings set forth herein.

[0059] When used in this specification and the appended claims, it should be noted that the singular forms "a," "an," and "the" refer to multiple objects unless otherwise clearly indicated by the context.

[0060] Unless otherwise specified, all numerical values, such as concentrations or concentration ranges, described herein should be understood in all cases as being modified by the term “approximately.” Therefore, numerical values ​​typically include ±10% of the stated value. For example, a concentration of 1 mg / mL includes 0.9 mg / mL to 1.1 mg / mL. Similarly, a concentration range of 1% to 10% (w / v) includes 0.9% (w / v) to 11% (w / v). When used herein, the use of numerical ranges explicitly includes all possible subranges, including integers and fractions of values ​​within that range, and all individual numerical values ​​within that range, unless the context explicitly indicates otherwise.

[0061] Unless otherwise stated, the term “at least” preceding a set of elements should be understood to refer to all of those elements. Those skilled in the art will recognize or confirm many equivalents to the specific embodiments of the invention described herein by simply using ordinary experimental procedures. Such equivalents are intended to be encompassed by the invention.

[0062] When used herein, the terms “comprises,” “comprising,” “includes,” “including,” “has,” “having,” “contains,” or “containing,” or any other variation thereof, are intended to include the integer or set of integers mentioned, but not to exclude other integers or sets of integers, and are intended to be non-exclusive or non-restrictive. For example, a composition, mixture, process, method, article, or apparatus comprising a set of elements is not necessarily limited to those elements alone, and may include other elements not expressly enumerated or not inherently present in such composition, mixture, process, method, article, or apparatus. Furthermore, unless expressly otherwise indicated, “or” refers to an inclusive “or” and not an exclusive “or.” For example, condition A or B is satisfied by one of the following: A is true (or exists) and B is false (or does not exist); A is false (or does not exist) and B is true (or exists); or both A and B are true (or exist).

[0063] When used herein, the connecting term "and / or" between multiple enumerated elements is understood to encompass both individual and combined options. For example, when two elements are connected by "and / or," the first option refers to the applicability of the first element without the second element. The second option refers to the applicability of the second element without the first element. The third option refers to the applicability of the first and second elements together. Any one of these options is included in the meaning and therefore satisfies the requirements of the term "and / or" when used herein. The simultaneous applicability of two or more of the options is also included in the meaning and therefore satisfies the requirements of the term "and / or."

[0064] When used herein, variations of the term "consists of," "consist of," or "consisting of" include, when used throughout the specification and claims, any enumerated integer or set of integers, but no additional integers or sets of integers are added to the specified method, structure, or composition.

[0065] When used herein, variations of the term "consists essentially of," "consist essentially of," or "consisting essentially of" include, when used throughout the specification and claims, any enumerated integer or set of integers, and optionally any enumerated integer or set of integers that does not substantially alter the basic or novel properties of the specified method, structure, or composition. See MPEP §2111.03.

[0066] As used herein, “subject” means any animal, preferably a mammal, most preferably a human. As used herein, the term “mammal” encompasses all mammals. Examples of mammals, but not limited to, include cattle, horses, sheep, pigs, cats, dogs, mice, rats, rabbits, guinea pigs, monkeys, and humans, more preferably humans.

[0067] The terms “about,” “approximately,” “generally,” and “substantially,” as used herein when referring to the dimensions or features of preferred components of an invention, should also be understood, as those skilled in the art will understand, to indicate that the described dimensions / features are not strict boundaries or parameters and do not exclude slight differences from them that are functionally the same or similar. At a minimum, such references involving numerical parameters will include variations in which the minimum significant figures do not change when using mathematical and industrial principles accepted in the art (e.g., rounding, measurement, or other systematic errors, manufacturing tolerances, etc.).

[0068] The term “identical” or “identity” percentage refers to two or more sequences or subsequences that are identical or have a specific percentage of identical amino acid residues or nucleotides when compared and aligned to maximize the match, when measured using one of the following sequence comparison algorithms or by visual inspection, in relation to two or more nucleic acid or polypeptide sequences (e.g., anti-TRGV9 / anti-cancer-associated antigen bispecific antibody and the polynucleotide encoding it, anti-TRGV9 / anti-CD123 bispecific antibody and the polynucleotide encoding it, TRGV9 polypeptide and the TRGV9 / polynucleotide encoding it, CD123 polypeptide and the CD123 polynucleotide encoding it).

[0069] For sequence comparison, typically one sequence acts as the reference sequence against which the test sequence is compared. When using a sequence comparison algorithm, the test and reference sequences are input into a computer, and sub-sequence coordinates and sequence algorithm program parameters are specified, if necessary. The sequence comparison algorithm then calculates the sequence identity percentage of the test sequence to the reference sequence based on the specified program parameters.

[0070] The optimal alignment of sequences for comparison can be achieved, for example, by the local homology algorithm in Smith & Waterman, Adv. Appl. Math. 2:482 (1981), the homology alignment algorithm in Needleman & Wunsch, J. Mol. Biol. 48:443 (1970), the similarity search method in Pearson & Lipman, Proc. Nat'l. Acad. Sci. USA 85:2444 (1988), computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, WI), or by visual inspection (generally, Current Protocols in Molecular Biology, FMAusubel et al., eds., Current Protocols, a joint venture between Greene Publishing Associates, Inc. and John Wiley & Sons, Inc., (1995) This can be done by (see Supplement)(Ausubel).

[0071] Examples of suitable algorithms for determining sequence identity percentage and sequence similarity are the BLAST and BLAST2.0 algorithms described in Altschul et al., (1990) J.Mol.Biol.215:403-410 and Altschul et al., (1997) Nucleic Acids Res.25:3389-3402, respectively. Software for performing BLAST analysis is publicly available through the National Center for Biotechnology Information. This algorithm first involves identifying high-scoring sequence pairs (HSPs) by identifying short words of length W in the query sequence that either match when aligned with words of the same length in the database sequence, or satisfy a threshold score T of some positive value. T is referred to as the adjacent word score threshold (Altschul et al., above). These initial adjacent word hits serve as seeds to initiate a search to find longer HSPs that contain them. Next, extend the word hits along each sequence in both directions, as long as the cumulative alignment score can be increased.

[0072] For nucleotide sequences, the cumulative score is calculated using parameter M (reward score for matching residue pairs, always greater than 0) and parameter N (penalty score for mismatched residues, always less than 0). For amino acid sequences, the cumulative score is calculated using a scoring matrix. Word hit extension in each direction is stopped when the cumulative alignment score falls by amount X from its maximum value, when the cumulative score becomes zero or less due to the accumulation of one or more negative scoring residues, or when the end of either sequence is reached. The parameters W, T, and X of the BLAST algorithm determine the sensitivity and speed of the alignment. The BLASTN program (for nucleotide sequences) uses, by default, a word length (W) of 11, an expected value of 10, M=5, N=-4, and comparison of both strands. For amino acid sequences, the BLASTP program uses a word length (W) of 3, an expected value (E) of 10, and a BLOSUM62 scoring matrix by default (see Henikoff & Henikoff, Proc. Natl. Acad. Sci. USA 89:10915 (1989)).

[0073] In addition to calculating the sequence identity percentage, the BLAST algorithm also performs a statistical analysis of the similarity between two sequences (see, e.g., Karlin & Altschul, Proc. Nat'l. Acad. Sci. USA 90:5873-5787 (1993)). One measure of similarity provided by the BLAST algorithm is the minimum sum probability (P(N)), which provides an indicator of the probability that a match between two nucleotide sequences or two amino acid sequences occurs by chance. For example, a nucleic acid is considered similar to a reference sequence if the minimum sum probability in the comparison between the test nucleic acid and the reference nucleic acid is less than about 0.1, more preferably less than about 0.01, and most preferably less than about 0.001.

[0074] A further indicator that two nucleic acid sequences or polypeptides are substantially identical is that the polypeptide encoded by the first nucleic acid is immunologically cross-reactive with the polypeptide encoded by the second nucleic acid, as described below. Thus, the polypeptide is typically substantially identical to the second polypeptide, for example, the two peptides differ only by conserved substitutions. Another indicator that two nucleic acid sequences are substantially identical is that the two molecules hybridize with each other under stringent conditions.

[0075] As used herein, the term “polynucleotide” is synonymous with “nucleic acid molecule,” “nucleotide,” or “nucleic acid,” and refers to any polyribonucleotide or polydeoxyribonucleotide that may be unmodified RNA or DNA, or modified RNA or DNA. “Polynucleotides” include, but are not limited to, single-stranded and double-stranded DNA, DNA as a mixture of single-stranded and double-stranded regions, single-stranded and double-stranded RNA, RNA as a mixture of single-stranded and double-stranded regions, and hybrid molecules containing DNA and RNA that may be single-stranded or, more typically, double-stranded or a mixture of single-stranded and double-stranded regions. In addition, “polynucleotide” refers to a triple-stranded region containing RNA or DNA, or both RNA and DNA. The term polynucleotide also includes DNA or RNA containing one or more modified bases, and DNA or RNA having a backbone modified for stability or other reasons. “Modified” bases include, for example, tritylated bases and unusual bases, such as inosine. Various modifications can be made to DNA and RNA. Therefore, "polynucleotides" encompass chemically, enzymatically, or metabolically modified forms of polynucleotides typically found in nature, as well as chemical forms that possess the characteristics of viral and cellular DNA and RNA. "Polynucleotides" also include relatively short nucleic acid chains (often called oligonucleotides).

[0076] As used herein, the term "vector" refers to a replicon that can replicate or express another nucleic acid segment by functionally inserting that segment.

[0077] As used herein, the term “host cell” refers to a cell containing the nucleic acid molecule of the present invention. A “host cell” may be any type of cell, for example, a primary cell, a cell in culture, or a cell line derived from a cell line. In one embodiment, a “host cell” is a cell transfected with the nucleic acid molecule of the present invention. In another embodiment, a “host cell” is a descendant or potential descendant of such a transfected cell. A descendant of a cell may or may not be identical to the parent cell, for example, due to mutations that may occur in subsequent generations, environmental influences, or the incorporation of the nucleic acid molecule into the host cell genome.

[0078] As used herein, the term “expression” refers to the biosynthesis of a gene product. Such expression includes the transcription of a gene into RNA, the translation of RNA into one or more polypeptides, and further includes all naturally occurring post-transcriptional and post-translational modifications. The bispecific antibodies expressed may be present in the cytoplasm of a host cell, in an extracellular environment such as a cell culture growth medium, or immobilized on the cell membrane.

[0079] As used herein, the terms “peptide,” “polypeptide,” or “protein” may refer to a molecule composed of amino acids that can be recognized as a protein by those skilled in the art. Conventional one- or three-letter codes for amino acid residues are used herein. The terms “peptide,” “polypeptide,” and “protein” may be used interchangeably herein to refer to a polymer of amino acids of any length. The polymer may be linear or branched, may contain modified amino acids, and may be interrupted by non-amino acids. The terms also encompass amino acid polymers that are naturally modified or modified by intervention. Examples of interventions include, for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other operation or modification, such as conjugate with a labeling component. The definition also includes, for example, polypeptides containing one or more analogues of amino acids (including, for example, non-natural amino acids), and other modifications known in the art.

[0080] The peptide sequences described herein are written according to common convention, with the N-terminal region of the peptide on the left and the C-terminal region on the right. Although the isomer forms of amino acids are known, unless otherwise explicitly indicated, only the L-form of the amino acids is shown.

[0081] antibody TRGV9 antibodies, nucleic acids encoding the antibody and expression vectors, recombinant cells containing the vector, and compositions comprising the antibody are provided herein. In some embodiments, isolated TRGV9 antibodies, nucleic acids encoding the antibody and expression vectors, recombinant cells containing the vector, and compositions comprising the antibody are provided. Methods for producing antibodies and methods for using antibodies to treat diseases are also provided. The antibodies disclosed herein have one or more desirable functional properties, including but not limited to high affinity binding to TRGV9 or high specificity for TRGV9. In some embodiments, the antibodies disclosed herein have the ability to treat or prevent a disease or disorder when administered to a subject alone or in combination with other therapies. In some embodiments, the TRGV9 antibody comprises a TRGV9 antigen-binding fragment. In some embodiments, the TRGV9 antibody consists of a TRGV9 antigen-binding fragment. In other embodiments, the TRGV9 antibody is a multispecific TRGV9 antibody. In yet another embodiment, the multispecific TRGV9 antibody is a bispecific TRGV9 antibody. While TRGV9 antibodies are exemplified herein, it is understood that other molecules that bind to TRGV9 are also intended. Such molecules include other alternative conjugates, including equivalents of the antibodies and other antibody-binding fragments provided herein.

[0082] Furthermore, TRGV9 multispecific antibodies, nucleic acids encoding multispecific antibodies and expression vectors, recombinant cells containing vectors, and compositions comprising multispecific antibodies are also provided herein. Methods for producing antibodies and methods for using multispecific antibodies to treat diseases, including cancer, are also provided. The antibodies disclosed herein have one or more desirable functional properties. In some embodiments, the multispecific antibodies provided herein have high affinity binding to TRGV9. In some embodiments, the multispecific antibodies provided herein have high affinity binding to a second target antigen. In some embodiments, the multispecific antibodies provided herein have high specificity to TRGV9. In some embodiments, the multispecific antibodies provided herein have high specificity to a second target antigen. In some embodiments, the multispecific antibodies provided herein, when administered alone, have the ability to treat or prevent a disease or disorder. In some embodiments, the multispecific antibodies provided herein, when administered in combination with other therapies, have the ability to treat or prevent a disease or disorder. In certain embodiments, the multispecific antibody is a bispecific antibody. In some embodiments, the TRGV9 antibody includes its antigen-binding fragment.

[0083] As used herein, the term “antibody” is used broadly and includes antibody molecules, including immunoglobulins, or human, humanized, complex, and chimeric antibodies, as well as antibody fragments, which are monoclonal or polyclonal. In general, an antibody is a protein or peptide chain that exhibits binding specificity to a particular antigen. The structure of antibodies is known. Immunoglobulins can be assigned to five main classes (i.e., IgA, IgD, IgE, IgG, and IgM) depending on the amino acid sequence of the heavy chain constant domain. IgA and IgG are further subdivided as isotypes IgA1, IgA2, IgG1, IgG2, IgG3, and IgG4. Thus, the antibodies of the present invention can be any of the five main classes or the corresponding subclasses. In certain embodiments, the antibodies provided herein are IgG1, IgG2, IgG3, or IgG4. The antibody light chains of vertebrate species can be assigned to one of two distinct types, namely κ and λ, based on the amino acid sequence of their constant domain. Therefore, the antibodies provided herein may contain kappa or lambda light chain constant domains. According to certain embodiments, the antibodies of the present invention include heavy chain and / or light chain constant regions derived from rat or human antibodies.

[0084] In addition to the heavy and light chain constant domains, the antibody includes an antigen-binding region consisting of a light chain variable region (VL) and a heavy chain variable region (VH), each of which contains three domains (i.e., complementarity-determining region 1 (CDR1), CDR2, and CDR3). "CDR" refers to one of the three hypervariable regions (HCDR1, HCDR2, or HCDR3) within the non-framework region of the immunoglobulin (Ig or antibody) VH β-sheet framework, or one of the three hypervariable regions (LCDR1, LCDR2, or LCDR3) within the non-framework region of the antibody VL β-sheet framework. Therefore, CDRs are variable region sequences scattered within the framework region sequence. CDR regions are well known to those skilled in the art and are defined, for example, by Kabat as the region of most hypervariability within the antibody variable (V) domain (Kabat et al., J. Biol. Chem. 252:6609-6616). (1977); Kabat, Adv. Prot. Chem. 32:1-75 (1978)). The CDR region sequence has also been structurally defined by Chothia as residues that are not part of the conserved β-sheet framework and are therefore adaptable to different conformations (Chothia and Lesk, J. Mol. Biol. 196:901-917 (1987)). Both terms are well recognized in the art. The CDR region sequence has also been defined by AbM, Contact, and IMGT. Exemplary CDR region sequences are illustrated herein, for example, in the sequence listing and the tables provided in the following examples. The location of CDRs within a standard antibody variable region has been determined by comparison of numerous structures (Al-Lazikani et al., J. Mol. Biol. 273:927-948 (1997); Morea et al., Methods 20:267-279). (2000)). Since the number of residues in the hypervariable region varies between antibodies, additional residues at standard positions are conventionally numbered by adding a, b, c, etc., after the residue number in the standard variable region numbering scheme (Al-Lazikani et al., supra (1997)). Such nomenclature is well known to those skilled in the art.

[0085] The light chain variable region CDR1 domain is referred to herein interchangeably as LCDR1 or VL CDR1. The light chain variable region CDR2 domain is referred herein interchangeably as LCDR2 or VL CDR2. The light chain variable region CDR3 domain is referred herein interchangeably as LCDR3 or VL CDR3. The heavy chain variable region CDR1 domain is referred herein interchangeably as HCDR1 or VH CDR1. The heavy chain variable region CDR2 domain is referred herein interchangeably as HCDR2 or VH CDR2. The heavy chain variable region CDR1 domain is referred herein interchangeably as HCDR3 or VH CDR3.

[0086] As used herein, the terms VH or VL, “hypervariable region,” refer to regions of antibody variable regions that are hypervariable in sequence and / or form structurally defined loops. Generally, antibodies contain six hypervariable regions: three VH (HCDR1, HCDR2, HCDR3) and three VL (LCDR1, LCDR2, LCDR3). Numerous descriptions of hypervariable regions are used and are incorporated herein. “Kabat” CDR is based on sequence variability and is the most commonly used (see, e.g., Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD. (1991)). “Chothia” instead refers to the location of structural loops (see, e.g., Chothia and Lesk, J. Mol. Biol. 196:901-917 (1987)). The end of the Chothia CDR-HCDR1 loop, when numbered using the Kabat numbering rules, varies from H32 to H34 depending on the loop length (this is because the Kabat numbering scheme places insertions at H35A and H35B; if neither 35A nor 35B is present, the loop ends at 32; if only 35A is present, the loop ends at 33; and if both 35A and 35B are present, the loop ends at 34). The "AbM" hypervariable region represents a compromise between Kabat CDR and Chothia structural loops and is used by Oxford Molecular's AbM antibody modeling software (see, for example, Martin, in Antibody Engineering, Vol. 2, Chapter 3, Springer Verlag). The "Contact" hypervariable region is based on the analysis of available composite crystal structures.

[0087] Recently, a universal numbering system has been developed and widely adopted: the ImMunoGeneTics (IMGT) Information System (registered trademark) (Lafranc et al., Dev.Comp.Immunol.27(1):55-77 (2003)). IMGT is an integrated information system specializing in immunoglobulins (IG), T cell receptors (TR), and major histocompatibility complexes (MHC) of humans and other vertebrates. In this specification, CDRs are referred to in terms of both their amino acid sequence and their position in the light or heavy chain. Because the "position" of CDRs within the structure of immunoglobulin variable domains is conserved across species and exists in structures referred to as loops, CDRs and framework residues can be easily identified by using a numbering system that aligns variable domain sequences according to their structural features. This information can be used to transplant and replace CDR residues from immunoglobulins of one species into acceptor frameworks, typically from human antibodies. Further numbering systems (AHon) have been developed by Honegger and Pluckthun, J.Mol.Biol.309:657-670 (2001). For example, correspondences between numbering systems, including Kabat numbering and IMGT-specific numbering systems, are well known to those skilled in the art (e.g., Kabat, see above; Chothia and Lesk, see above; Martin, see above; Lefranc et al., see above). The exemplary systems shown herein combine Kabat and Chothia.

[0088] [Table 1]

[0089] The hypervariable region may include the following "extended hypervariable regions": 24-36 or 24-34 (LCDR1), 46-56 or 50-56 (LCDR2), and 89-97 or 89-96 (LCDR3) within the VL, and 26-35 or 26-35A (HCDR1), 50-65 or 49-65 (HCDR2), and 93-102, 94-102, or 95-102 (HCDR3) within the VH. CDR sequences reflecting each of the above numbering schemes, as included in the sequence listing, are provided herein.

[0090] The term "constant region" or "constant domain" refers to the carboxyl-terminal portions of the light and heavy chains that do not directly participate in antibody binding to an antigen but exhibit various effector functions, such as interaction with the Fc receptor. This term refers to a portion of the immunoglobulin molecule that has a more conserved amino acid sequence compared to other parts of the immunoglobulin, which are variable regions containing the antigen-binding site. The constant region may include the CH1, CH2, and CH3 regions of the heavy chain, as well as the CL region of the light chain.

[0091] The term "framework" or "FR" residue refers to a variable region residue adjacent to a CDR. FR residues are found, for example, in chimeric antibodies, human antibodies, human domain antibodies, diabodies, linear antibodies, and bispecific antibodies. FR residues are variable domain residues other than hypervariable region residues or CDR residues.

[0092] As used herein, the term “isolated antibody” means an antibody that is substantially free from other antibodies having different antigen specificities (for example, an isolated antibody that specifically binds to TRGV9 is substantially free from antibodies that do not bind to Vγ9, and an isolated antibody that specifically binds to a second target (e.g., CD123) is substantially free from antibodies that do not bind to a second target (e.g., CD123). Furthermore, an isolated antibody is substantially free from other cellular material and / or chemical substances).

[0093] As used herein, the term “monoclonal antibody” refers to an antibody obtained from a substantially homogeneous population of antibodies, that is, the individual antibodies constituting the population are identical except for trace amounts of spontaneously occurring mutations. The monoclonal antibodies of the present invention can be produced by hybridoma, phage display technology, single lymphocyte gene cloning technology, or recombinant DNA method. For example, a monoclonal antibody may be produced by a hybridoma containing B cells obtained from a transgenic non-human animal, such as a transgenic mouse or rat, and having a genome containing human heavy chain and light chain transgenes.

[0094] As used herein, the term “antigen-binding fragment” refers to antibody fragments such as, for example, diabodies, Fab, Fab', F(ab')2, Fv fragments, disulfide-stabilized Fv fragments (dsFv), (dsFv)2, bispecific dsFv (dsFv-dsFv'), disulfide-stabilized diabodies (dsdiabodies), single-chain antibody molecules (scFv), single-domain antibodies (sdAb), scFv dimers (bivalent diabodies), multispecific antibodies formed from a portion of an antibody containing one or more CDRs, camelized single-domain antibodies, nanobodies, domain antibodies, bivalent domain antibodies, or any other antibody fragments that bind to an antigen but do not contain a complete antibody structure. Antigen-binding fragments can bind to the same antigen to which a parent antibody or parent antibody fragment binds. According to certain embodiments, an antigen-binding fragment comprises a light chain variable region, a light chain constant region, and a heavy chain Fd fragment. According to other certain embodiments, an antigen-binding fragment comprises Fab and F(ab').

[0095] As used herein, the term "single-chain antibody" refers to a single-chain antibody conventionally known in the art, comprising a heavy-chain variable region and a light-chain variable region linked by a short peptide of about 15 to about 20 amino acids. As used herein, the term "single-domain antibody" refers to a single-domain antibody conventionally known in the art, comprising a heavy-chain variable region and a heavy-chain constant region, or comprising only the heavy-chain variable region.

[0096] As used herein, the term “human antibody” means an antibody produced by a human, or an antibody prepared using any technique known in the art that has an amino acid sequence corresponding to a human-produced antibody. This definition of a human antibody includes intact or full-length antibodies, fragments thereof, and / or antibodies comprising at least one human heavy chain and / or light chain polypeptide.

[0097] As used herein, the term "humanized antibody" refers to a non-human antibody that has been modified to increase sequence homology to a human antibody, while retaining the antigen-binding properties of the antibody, thereby reducing the antigenicity of the antigen in the human body.

[0098] As used herein, the term “chimeric antibody” refers to an antibody whose immunoglobulin molecule’s amino acid sequence originates from two or more species. The variable regions of both the light and heavy chains often correspond to the variable regions of an antibody derived from one species of mammal (e.g., mouse, rat, rabbit) that possesses the desired specificity, affinity, and capability, while the constant region corresponds to the sequence of an antibody derived from another species of mammal (e.g., human) to avoid inducing an immune response in that species.

[0099] As used herein, the term “multispecific antibody” refers to an antibody comprising multiple immunoglobulin variable domain sequences, wherein a first immunoglobulin variable domain sequence has binding specificity to a first epitope, and a second immunoglobulin variable domain sequence has binding specificity to a second epitope. In some embodiments, the first and second epitopes do not overlap or substantially overlap. In one embodiment, the first and second epitopes are on different antigens, for example, on different proteins (or different subunits of a polymer protein). In one embodiment, the multispecific antibody comprises a third, fourth, or fifth immunoglobulin variable domain. In one embodiment, the multispecific antibody is a bispecific antibody molecule, a triplicate antibody molecule, or a quadruplicate antibody molecule.

[0100] As used herein, the term “bispecific antibody” refers to a multispecific antibody that binds to two or fewer epitopes or two or fewer antigens. A bispecific antibody is characterized by a first immunoglobulin variable domain sequence having binding specificity to a first epitope (e.g., an epitope on the TRGV9 antigen) and a second immunoglobulin variable domain sequence having binding specificity to a second epitope. In one embodiment, the first and second epitopes are on different antigens, for example, on different proteins (or different subunits of a multimeric protein). In one embodiment, the bispecific antibody comprises a heavy chain variable domain sequence and a light chain variable domain sequence having binding specificity to a first epitope, and a heavy chain variable domain sequence and a light chain variable domain sequence having binding specificity to a second epitope. In one embodiment, the bispecific antibody comprises a semi-antibody or fragment thereof having binding specificity to a first epitope and a semi-antibody or fragment thereof having binding specificity to a second epitope. In some embodiments, the bispecific antibody comprises an scFv or fragment thereof having binding specificity to a first epitope and an scFv or fragment thereof having binding specificity to a second epitope. In some embodiments, the first epitope is located at TRGV9 and the second epitope is located at CD123. In some embodiments, the first epitope is located at TRGV9 and the second epitope is located at CD33. In some embodiments, the first epitope is located at TRGV9 and the second epitope is located at TRBC1. In some embodiments, the first epitope is located at TRGV9 and the second epitope is located at BCMA. In some embodiments, the first epitope is located at TRGV9 and the second epitope is located at PSMA. In one embodiment, the first epitope is located at TRGV9, and the second epitope is located at PD-1, PD-L1, CTLA-4, EGFR, HER-2, CD19, CD20, CD3, and / or other cancer-related immunosuppressive factors or surface antigens.

[0101] As used herein, the term “half-antibody” refers to one immunoglobulin heavy chain associated with one immunoglobulin light chain. An exemplary half-antibody is shown in SEQ ID NO: 17. Those skilled in the art will readily understand that a half-antibody may contain its fragments and may have, for example, an antigen-binding domain consisting of a single variable domain derived from a camelid.

[0102] As used herein, the term “TRGV9” refers to a polypeptide capable of forming a T cell receptor when expressed on the surface of γδ T cells. TRGV9-expressing γδ T cells are the first T cells to develop in human fetuses and constitute the major γδ T cell subset in healthy adult peripheral blood cells. The term “TRGV9” includes any TRGV9 variants, isoforms, and species homologs that are naturally expressed by cells (including T cells) or that can be expressed on cells transfected with a gene or cDNA encoding its polypeptide. In certain embodiments, TRGV9 is human TRGV9. An exemplary human TRGV9 amino acid sequence is provided by GenBank accession number NG_001336.2. Exemplary human TRGV9 is also provided in Figure 27A and Sequence ID No. 789.

[0103] The term "CD123" refers to a cell-borne molecule that helps transmit the signal for interleukin-3, a soluble cytokine important in the immune system. CD123 may also be referred to as the "interleukin-3 receptor." The receptor belongs to the type I cytokine receptor family and is a heterodimer with a unique alpha chain paired with a common beta subunit (beta-c or CD131). CD123 receptors can be found on pluripotent progenitor cells and can induce tyrosine phosphorylation in cells, promoting proliferation and differentiation within hematopoietic cell lines. CD123 can also be expressed in the acute myeloid leukemia (AML) subtype. Unless otherwise specified, the term "CD123" includes any CD123 variants, isoforms, and species homologs that are naturally expressed by cells (including T cells) or that can be expressed on cells transfected with the gene or cDNA encoding its polypeptide, and in certain embodiments, "CD123" refers to human CD123. The human CD123 amino acid sequence is provided by GenBank accession number AY789109.1.

[0104] The term "CD33" refers to a 67kD single-pass transmembrane glycoprotein and is a member of the sialic acid-binding immunoglobulin-like lectin (Sigrec) family. Its precise biological function is unknown, but in normal individuals, it is thought to be primarily a myeloid differentiation antigen, being low in myeloid progenitor cells, neutrophils, and macrophages, but highly expressed in circulating monocytes and dendritic cells. CD33 has been detected in 85–90% of blast cells and leukemia stem cells from patients with acute myeloid leukemia (AML). Unless otherwise specified, the term "CD33" includes any CD33 variant, isoform, and species homolog, which may be expressed spontaneously by cells or on cells transfected with the gene or cDNA encoding its polypeptide; "CD33" refers to human CD33. The human CD33 amino acid sequence is provided by GenBank accession number BC028152.1.

[0105] As used herein, an antibody that "specifically binds" to a target refers to an antibody that binds to the target with a K -7 D of 1×10 -8 M or less, for example, 1×10 -9 M or less, 5×10 -9 M or less, 1×10 -10 M or less, 5×10 -10 M or less, or 1×10 M or less. In certain embodiments, the target is a human target. The target can be, for example, TRGV9, CD123, CD33, TRBC1, BCMA, or PSMA.

[0106] The term "KD" refers to the dissociation constant obtained from the ratio of Kd to Ka (i.e., Kd / Ka), expressed in molar concentration (M). The KD value of an antibody can be determined using methods in the art in view of the present disclosure. For example, the KD of an antibody can be determined by using surface plasmon resonance, for example by using a biosensor system such as a Biacore® system, or by using biolayer interferometry technology such as the Octet RED96 system. The smaller the KD value of an antibody, the higher the affinity with which the antibody binds to the target antigen.

[0107] In one aspect, provided herein is an antibody that binds TRGV9. In some embodiments, the antibody comprises a heavy chain variable (VH) region and a light chain variable (VL) region. In some embodiments, the TRGV9 antibody is not a single domain antibody or a nanobody. In some embodiments, the TRGV9 antibody is a humanized antibody.

[0108] In some embodiments, a TRGV9 antibody comprising any one of the VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 of the antibodies described herein is provided herein. In some embodiments, a TRGV9 antibody comprising any one of the VH region of the antibodies described herein is provided herein. In some embodiments, a TRGV9 antibody comprising any one of the VL region of the antibodies described herein is provided herein. In some embodiments, a TRGV9 antibody comprising any one of the VH region of the antibodies described herein and any one of the VL region of the antibodies described herein is provided herein. In some embodiments, a TRGV9 antibody comprising any one of the VH CDR1, VH CDR2, and VH CDR3 of the antibodies described herein is provided herein. In some embodiments, a TRGV9 antibody comprising any one of the VL CDR1, VL CDR2, and VL CDR3 of the antibodies described herein is provided herein. In some embodiments, TRGV9 antibodies are provided herein that include one of the antibodies described herein, VH CDR1, VH CDR2, and VH CDR3, and one of the antibodies described herein, VL CDR1, VL CDR2, and VL CDR3. Representative VH and VL amino acid sequences, including the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the TRGV9 antibodies provided herein, are provided in the sequence listing and in Tables 1 to 39.

[0109] In some embodiments, the TRGV9 antibody is a multispecific TRGV9 antibody provided herein. In some embodiments, the multispecific TRGV9 antibody is a bispecific TRGV9 antibody. In one embodiment, the multispecific TRGV9 antibody comprises (a) a first binding domain that binds to TRGV9, and (b) a second binding domain that binds to a second target other than TRGV9.

[0110] In some embodiments, the first binding domain that binds to TRGV9 includes a VH region, a VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 of any one of the TRGV9 antibodies described herein. In some embodiments, the first binding domain that binds to TRGV9 includes a VH region of any one of the TRGV9 antibodies described herein. In some embodiments, the first binding domain that binds to TRGV9 includes a VL region of any one of the TRGV9 antibodies described herein. In some embodiments, the first binding domain that binds to TRGV9 includes a VH region and a VL region of any one of the TRGV9 antibodies described herein. In some embodiments, the first binding domain that binds to TRGV9 includes a VH CDR1, VH CDR2, and VH CDR3 of any one of the TRGV9 antibodies described herein. In some embodiments, the first binding domain that binds to TRGV9 includes VL CDR1, VL CDR2, and VL CDR3 of any one of the TRGV9 antibodies described herein. In some embodiments, the first binding domain that binds to TRGV9 includes VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of any one of the TRGV9 antibodies described herein. Representative VH and VL amino acid sequences, including the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the TRGV9 antibodies provided herein, are provided in the sequence listing and in Tables 1 to 39.

[0111] In some embodiments, the second target is CD123. In some embodiments, the second binding domain that binds to CD123 has the VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 of the CD123 antibody provided herein. In some embodiments, the second binding domain that binds to CD123 has the VH region of the CD123 antibody provided herein. In some embodiments, the second binding domain that binds to CD123 has the VL region of the CD123 antibody provided herein. In some embodiments, the second binding domain that binds to CD123 has the VH region and VL region of the CD123 antibody provided herein. In some embodiments, the second binding domain that binds to CD123 has VH CDR1, VH CDR2, and VH CDR3 of the CD123 antibody provided herein. In some embodiments, the second binding domain that binds to CD123 has VL CDR1, VL CDR2, and VL CDR3 of the CD123 antibody provided herein. In some embodiments, the second binding domain that binds to CD123 has VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of the CD123 antibody provided herein.

[0112] In some embodiments, the second target is CD33. In some embodiments, the second binding domain that binds to CD33 has the VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 of the CD33 antibody provided herein. In some embodiments, the second binding domain that binds to CD33 has the VH region of the CD33 antibody provided herein. In some embodiments, the second binding domain that binds to CD33 has the VL region of the CD33 antibody provided herein. In some embodiments, the second binding domain that binds to CD33 has the VH region and VL region of the CD33 antibody provided herein. In some embodiments, the second binding domain that binds to CD33 has VH CDR1, VH CDR2, and VH CDR3 of the CD33 antibody provided herein. In some embodiments, the second binding domain that binds to CD33 is VL CDR1, VL CDR2, and VL CDR3 of the CD33 antibody provided herein. In some embodiments, the second binding domain that binds to CD33 is VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of the CD33 antibody provided herein.

[0113] In some embodiments, the second target is TRBC1. In some embodiments, the second binding domain that binds to TRBC1 has the VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 of the TRBC1 antibody provided herein. In some embodiments, the second binding domain that binds to TRBC1 has the VH region of the TRBC1 antibody provided herein. In some embodiments, the second binding domain that binds to TRBC1 has the VL region of the TRBC1 antibody provided herein. In some embodiments, the second binding domain that binds to TRBC1 has the VH region and VL region of the TRBC1 antibody provided herein. In some embodiments, the second binding domain that binds to TRBC1 has VH CDR1, VH CDR2, and VH CDR3 of the TRBC1 antibody provided herein. In some embodiments, the second binding domain that binds to TRBC1 has VL CDR1, VL CDR2, and VL CDR3 of the TRBC1 antibody provided herein. In some embodiments, the second binding domain that binds to TRBC1 has VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of the TRBC1 antibody provided herein.

[0114] In some embodiments, the second target is BCMA. In some embodiments, the second binding domain that binds to BCMA has the VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, V CDR2, and / or VL CDR3 of the BCMA antibody provided herein. In some embodiments, the second binding domain that binds to BCMA has the VH region of the BCMA antibody provided herein. In some embodiments, the second binding domain that binds to BCMA has the VL region of the BCMA antibody provided herein. In some embodiments, the second binding domain that binds to BCMA has the VH region and VL region of the BCMA antibody provided herein. In some embodiments, the second binding domain that binds to BCMA has VH CDR1, VH CDR2, and VH CDR3 of the BCMA antibody provided herein. In some embodiments, the second binding domain that binds to BCMA has VL CDR1, VL CDR2, and VL CDR3 of the BCMA antibody provided herein. In some embodiments, the second binding domain that binds to BCMA is VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of the BCMA antibodies provided herein.

[0115] In some embodiments, the second target is PSMA. In some embodiments, the second binding domain that binds to PSMA has the VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, V CDR2, and / or VL CDR3 of the PSMA antibody provided herein. In some embodiments, the second binding domain that binds to PSMA has the VH region of the PSMA antibody provided herein. In some embodiments, the second binding domain that binds to PSMA has the VL region of the PSMA antibody provided herein. In some embodiments, the second binding domain that binds to PSMA has the VH region and VL region of the PSMA antibody provided herein. In some embodiments, the second binding domain that binds to PSMA has VH CDR1, VH CDR2, and VH CDR3 of the PSMA antibody provided herein. In some embodiments, the second binding domain that binds to PSMA has VL CDR1, VL CDR2, and VL CDR3 of the PSMA antibody provided herein. In some embodiments, the second binding domain that binds to PSMA is VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of the PSMA antibody provided herein.

[0116] In some embodiments, the antibody specifically binds to TRGV9. In other embodiments, TRGV9 is located on the surface of T cells.

[0117] In some embodiments, the TRGV9 antibody is a chimeric antibody. In some embodiments, the TRGV9 antibody is human. In some embodiments, the TRGV9 antibody is humanized. In some embodiments, the TRGV9 antibody is an isolated TRGV9 antibody. In certain embodiments, an intact TRGV9 antibody is provided.

[0118] In some embodiments, the TRGV9 antibody is an IgG antibody. In some embodiments, the TRGV9 antibody is an IgG1 antibody. In some embodiments, the TRGV9 antibody is an IgG2 antibody. In some embodiments, the TRGV9 antibody is an IgG3 antibody. In some embodiments, the TRGV9 antibody is an IgG4 antibody. In some embodiments, the TRGV9 antibody contains a κ light chain. In some embodiments, the TRGV9 antibody contains a λ light chain. In some embodiments, the TRGV9 antibody is a monoclonal antibody. In some embodiments, the TRGV9 antibody is polyvalent. In some embodiments, the TRGV9 antibody can bind to at least three antigens. In some embodiments, the TRGV9 antibody can bind to at least four antigens. In some embodiments, the TRGV9 antibody can bind to at least five antigens. In some embodiments, the TRGV9 antibody is a multispecific antibody. In some embodiments, the TRGV9 antibody is a bispecific antibody. In some embodiments, the TRGV9 antibody is a tripspecific antibody. In some embodiments, the TRGV9 antibody is a quadruple-specific antibody.

[0119] In other embodiments, a TRGV9 antibody is provided, and an antigen-binding fragment of the TRGV9 antibody is provided. In some embodiments, the antigen-binding fragment of the TRGV9 antibody is a functional fragment. In some embodiments, the TRGV9 antigen-binding fragment is a chimeric fragment. In some embodiments, the TRGV9 antigen-binding fragment is human. In some embodiments, the TRGV9 antigen-binding fragment is humanized. In one embodiment, the TRGV9 antigen-binding fragment is an isolated TRGV9 antigen-binding fragment.

[0120] In some embodiments, the antigen-binding fragment is a diabody. In some embodiments, the antigen-binding fragment is Fab. In some embodiments, the antigen-binding fragment is Fab'. In some embodiments, the antigen-binding fragment is F(ab')2. In some embodiments, the antigen-binding fragment is an Fv fragment. In some embodiments, the antigen-binding fragment is a disulfide-stabilized Fv fragment (dsFv). In some embodiments, the antigen-binding fragment is (dsFv)2. In some embodiments, the antigen-binding fragment is a bispecific dsFv (dsFv-dsFv'). In some embodiments, the antigen-binding fragment is a disulfide-stabilized diabody (ds diabody). In some embodiments, the antigen-binding fragment is a single-chain antibody molecule (scFv). In some embodiments, the antigen-binding fragment is a single-domain antibody (sdAb). In some embodiments, the antigen-binding fragment is an scFv dimer (bivalent diabody). In some embodiments, the antigen-binding fragment is a multispecific antibody formed from a portion of an antibody containing one or more CDRs. In some embodiments, the antigen-binding fragment is a camelized single-domain antibody. In some embodiments, the antigen-binding fragment is a nanobody. In some embodiments, the antigen-binding fragment is a domain antibody. In some embodiments, the antigen-binding fragment is a bivalent domain antibody. In some embodiments, the antigen-binding fragment is an antibody fragment that binds to an antigen but does not contain a complete antibody structure.

[0121] In some embodiments, the TRGV9 antibody is a multispecific antibody. In other embodiments, the TRGV9 antibody is a bispecific antibody. In some embodiments, the multispecific antibody comprises an antigen-binding fragment of the TRGV9 antibody provided herein. In other embodiments, the bispecific antibody comprises an antigen-binding fragment of the TRGV9 antibody provided herein. In some embodiments, the TRGV9 antibody is an agonist antibody. In some embodiments, the TRGV9 antibody activates T cells. In other embodiments, the TRGV9 antibody is an antagonist antibody. In some embodiments, the TRGV9 antibody inactivates T cells. In some embodiments, the TRGV9 antibody blocks T cell activation. In some embodiments, the TRGV9 antibody modulates T cell activity. In some embodiments, the TRGV9 antibody neither activates nor inactivates γδ T cells. In certain embodiments, the T cells are γδ T cells.

[0122] In certain embodiments, the γδ T cells are human γδ T cells. In certain embodiments, a bispecific antibody is provided, comprising the TRGV9 antibody provided herein in knob-in-hole form. In some embodiments, the TRGV9 antibody provided herein may be included in a bispecific antibody. In some embodiments, the TRGV9 bispecific antibody provided herein may be included in a multispecific antibody. In some embodiments, the bispecific antibody provided herein comprises a first binding domain containing the TRGV9 antibody provided herein that binds to a first TRGV9 epitope, and a second binding domain containing the TRGV9 antibody provided herein that binds to a second TRGV9 epitope, wherein the first and second TRGV9 epitopes are not the same. In certain embodiments, the TRGV9 antibody or its antigen-binding fragment provided herein binds specifically to TRGV9. In certain embodiments, the TRGV9 antibody or its antigen-binding fragment provided herein does not bind to the Vδ2 epitope.

[0123] In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences follow the Kabat numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences follow the Chothia numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences follow an exemplary numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences follow the Contact numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences follow the IMGT numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences follow the AbM numbering system. An exemplary set of six CDRs (VH CDR1-3 and VL CDR1-3) for a particular antibody embodiment is provided herein. Other sets of CDRs are also conceived and are within the scope of the antibody embodiments provided herein.

[0124] In one embodiment, the TRGV9 antibody provided herein has the VH and VL amino acid sequences of L7A5_1(TRGV9_1). In one embodiment, the TRGV9 antibody provided herein comprises VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3, respectively, having the amino acid sequence of SEQ ID NO: 7. In one embodiment, the TRGV9 antibody provided herein comprises VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3, respectively, having the amino acid sequence of VL SEQ ID NO: 8. In one embodiment, a TRGV9 antibody is provided herein, comprising (i) VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 7, respectively, and (ii) VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of VL VL CDR3 having the amino acid sequence of SEQ ID NO: 8, respectively. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 3, and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 4, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VL CDR3 having the amino acid sequence of SEQ ID NO: 6. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 160, VH CDR2 having the amino acid sequence of SEQ ID NO: 161, and VH CDR3 having the amino acid sequence of SEQ ID NO: 162, and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 163, VL CDR2 having the amino acid sequence of SEQ ID NO: 164, and VL CDR3 having the amino acid sequence of SEQ ID NO: 165.In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 166, VH CDR2 having the amino acid sequence of SEQ ID NO: 167, and VH CDR3 having the amino acid sequence of SEQ ID NO: 168; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 169, VL CDR2 having the amino acid sequence of SEQ ID NO: 170, and VL CDR3 having the amino acid sequence of SEQ ID NO: 171. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 172, VH CDR2 having the amino acid sequence of SEQ ID NO: 173, and VH CDR3 having the amino acid sequence of SEQ ID NO: 174; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 175, VL CDR2 having the amino acid sequence of SEQ ID NO: 176, and VL CDR3 having the amino acid sequence of SEQ ID NO: 177. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 178, VH CDR2 having the amino acid sequence of SEQ ID NO: 179, and VH CDR3 having the amino acid sequence of SEQ ID NO: 180; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 181, VL CDR2 having the amino acid sequence of SEQ ID NO: 182, and VL CDR3 having the amino acid sequence of SEQ ID NO: 183. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 178, VH CDR2 having the amino acid sequence of SEQ ID NO: 700, and VH CDR3 having the amino acid sequence of SEQ ID NO: 701; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 181, VL CDR2 having the amino acid sequence of SEQ ID NO: 182, and VL CDR3 having the amino acid sequence of SEQ ID NO: 183.In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 184, VH CDR2 having the amino acid sequence of SEQ ID NO: 185, and VH CDR3 having the amino acid sequence of SEQ ID NO: 186; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 187, VL CDR2 having the amino acid sequence of SEQ ID NO: 188, and VL CDR3 having the amino acid sequence of SEQ ID NO: 189. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 190, VH CDR2 having the amino acid sequence of SEQ ID NO: 191, and VH CDR3 having the amino acid sequence of SEQ ID NO: 192; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 193, VL CDR2 having the amino acid sequence of SEQ ID NO: 194, and VL CDR3 having the amino acid sequence of SEQ ID NO: 195. In some embodiments, the antibody includes a VH having the amino acid sequence of SEQ ID NO: 7. In some embodiments, the antibody includes a VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody includes a VH having the amino acid sequence of SEQ ID NO: 7 and a VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody includes a heavy chain having the amino acid sequence of SEQ ID NO: 23. In some embodiments, the antibody includes a light chain having the amino acid sequence of SEQ ID NO: 24. In some embodiments, the antibody includes a heavy chain having the amino acid sequence of SEQ ID NO: 23 and a light chain having the amino acid sequence of SEQ ID NO: 24. In some embodiments, the antibody includes the amino acid sequence of SEQ ID NO: 17. In some embodiments, the antibody includes a heavy chain having the amino acid sequence of SEQ ID NO: 69. In some embodiments, the antibody includes a light chain having the amino acid sequence of SEQ ID NO: 24. In some embodiments, the antibody includes a heavy chain having the amino acid sequence of SEQ ID NO: 69 and a light chain having the amino acid sequence of SEQ ID NO: 24. In some embodiments, the antibody includes a VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 7. In some embodiments, the antibody includes a VL containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 8.In some embodiments, the antibody includes a VH containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 7, and a VL containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody includes a heavy chain containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 23. In some embodiments, the antibody includes a light chain containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the antibody includes a heavy chain containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 23, and a light chain containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the antibody includes the amino acid sequence of SEQ ID NO: 17. In some embodiments, the antibody includes a heavy chain containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 69. In some embodiments, the antibody includes a light chain containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the antibody comprises a heavy chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 69, and a light chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 24.

[0125] In one embodiment, the TRGV9 antibody provided herein has the VH and VL amino acid sequences of TRGV9Ab_2(L7A5_2). In one embodiment, the TRGV9 antibody provided herein contains VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 34. In one embodiment, the TRGV9 antibody provided herein contains VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 8. In one embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of SEQ ID NO: 34, and (ii) VL, comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of SEQ ID NO: 8, and (ii) VL, comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of SEQ ID NO: 8. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 31, and (ii) VL, comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 4, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VL CDR3 having the amino acid sequence of SEQ ID NO: 6. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 196, VH CDR2 having the amino acid sequence of SEQ ID NO: 197, and VH CDR3 having the amino acid sequence of SEQ ID NO: 198; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 199, VL CDR2 having the amino acid sequence of SEQ ID NO: 200, and VL CDR3 having the amino acid sequence of SEQ ID NO: 201.In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 202, VH CDR2 having the amino acid sequence of SEQ ID NO: 203, and VH CDR3 having the amino acid sequence of SEQ ID NO: 204; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 205, VL CDR2 having the amino acid sequence of SEQ ID NO: 206, and VL CDR3 having the amino acid sequence of SEQ ID NO: 207. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 208, VH CDR2 having the amino acid sequence of SEQ ID NO: 209, and VH CDR3 having the amino acid sequence of SEQ ID NO: 210; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 211, VL CDR2 having the amino acid sequence of SEQ ID NO: 212, and VL CDR3 having the amino acid sequence of SEQ ID NO: 213. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 214, VH CDR2 having the amino acid sequence of SEQ ID NO: 215, and VH CDR3 having the amino acid sequence of SEQ ID NO: 216; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 217, VL CDR2 having the amino acid sequence of SEQ ID NO: 218, and VL CDR3 having the amino acid sequence of SEQ ID NO: 219. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 214, VH CDR2 having the amino acid sequence of SEQ ID NO: 702, and VH CDR3 having the amino acid sequence of SEQ ID NO: 703; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 217, VL CDR2 having the amino acid sequence of SEQ ID NO: 218, and VL CDR3 having the amino acid sequence of SEQ ID NO: 219.In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 220, VH CDR2 having the amino acid sequence of SEQ ID NO: 221, and VH CDR3 having the amino acid sequence of SEQ ID NO: 222; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 223, VL CDR2 having the amino acid sequence of SEQ ID NO: 224, and VL CDR3 having the amino acid sequence of SEQ ID NO: 225. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 226, VH CDR2 having the amino acid sequence of SEQ ID NO: 227, and VH CDR3 having the amino acid sequence of SEQ ID NO: 228; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 229, VL CDR2 having the amino acid sequence of SEQ ID NO: 230, and VL CDR3 having the amino acid sequence of SEQ ID NO: 231. In some embodiments, the antibody comprises VH having the amino acid sequence of SEQ ID NO: 34. In some embodiments, the antibody comprises VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody comprises VH having the amino acid sequence of SEQ ID NO: 34 and VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody comprises VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 34. In some embodiments, the antibody comprises VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody comprises VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 34 and VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 8.

[0126] In one embodiment, the TRGV9 antibody provided herein has the VH and VL amino acid sequences of TRGV9Ab_3(L7A5_3). In one embodiment, the TRGV9 antibody provided herein contains VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 35. In one embodiment, the TRGV9 antibody provided herein contains VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 8. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of SEQ ID NO: 35, and (ii) VL, comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of SEQ ID NO: 8. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 32, and (ii) VL, comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 4, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VL CDR3 having the amino acid sequence of SEQ ID NO: 6. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 232, VH CDR2 having the amino acid sequence of SEQ ID NO: 233, and VH CDR3 having the amino acid sequence of SEQ ID NO: 234; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 235, VL CDR2 having the amino acid sequence of SEQ ID NO: 236, and VL CDR3 having the amino acid sequence of SEQ ID NO: 237.In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 238, VH CDR2 having the amino acid sequence of SEQ ID NO: 239, and VH CDR3 having the amino acid sequence of SEQ ID NO: 240; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 241, VL CDR2 having the amino acid sequence of SEQ ID NO: 242, and VL CDR3 having the amino acid sequence of SEQ ID NO: 243. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 244, VH CDR2 having the amino acid sequence of SEQ ID NO: 245, and VH CDR3 having the amino acid sequence of SEQ ID NO: 246; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 247, VL CDR2 having the amino acid sequence of SEQ ID NO: 248, and VL CDR3 having the amino acid sequence of SEQ ID NO: 249. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 250, VH CDR2 having the amino acid sequence of SEQ ID NO: 251, and VH CDR3 having the amino acid sequence of SEQ ID NO: 252; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 253, VL CDR2 having the amino acid sequence of SEQ ID NO: 254, and VL CDR3 having the amino acid sequence of SEQ ID NO: 255. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 250, VH CDR2 having the amino acid sequence of SEQ ID NO: 704, and VH CDR3 having the amino acid sequence of SEQ ID NO: 705; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 253, VL CDR2 having the amino acid sequence of SEQ ID NO: 254, and VL CDR3 having the amino acid sequence of SEQ ID NO: 255.In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 256, VH CDR2 having the amino acid sequence of SEQ ID NO: 257, and VH CDR3 having the amino acid sequence of SEQ ID NO: 258; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 259, VL CDR2 having the amino acid sequence of SEQ ID NO: 260, and VL CDR3 having the amino acid sequence of SEQ ID NO: 261. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 262, VH CDR2 having the amino acid sequence of SEQ ID NO: 263, and VH CDR3 having the amino acid sequence of SEQ ID NO: 264; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 265, VL CDR2 having the amino acid sequence of SEQ ID NO: 266, and VL CDR3 having the amino acid sequence of SEQ ID NO: 267. In some embodiments, the antibody comprises VH having the amino acid sequence of SEQ ID NO: 35. In some embodiments, the antibody comprises VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody comprises VH having the amino acid sequence of SEQ ID NO: 35 and VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody comprises VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 35. In some embodiments, the antibody comprises VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody comprises VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 35 and VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 8.

[0127] In one embodiment, the TRGV9 antibody provided herein has the VH and VL amino acid sequences of TRGV9Ab_4(L7A5_4). In one embodiment, the TRGV9 antibody provided herein contains VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 36. In one embodiment, the TRGV9 antibody provided herein contains VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 8. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of SEQ ID NO: 36, and (ii) VL, comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of SEQ ID NO: 8. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 33, and (ii) VL, comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 4, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VL CDR3 having the amino acid sequence of SEQ ID NO: 6. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 268, VH CDR2 having the amino acid sequence of SEQ ID NO: 269, and VH CDR3 having the amino acid sequence of SEQ ID NO: 270; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 271, VL CDR2 having the amino acid sequence of SEQ ID NO: 272, and VL CDR3 having the amino acid sequence of SEQ ID NO: 273.In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 274, VH CDR2 having the amino acid sequence of SEQ ID NO: 275, and VH CDR3 having the amino acid sequence of SEQ ID NO: 276; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 277, VL CDR2 having the amino acid sequence of SEQ ID NO: 278, and VL CDR3 having the amino acid sequence of SEQ ID NO: 279. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 280, VH CDR2 having the amino acid sequence of SEQ ID NO: 281, and VH CDR3 having the amino acid sequence of SEQ ID NO: 282; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 283, VL CDR2 having the amino acid sequence of SEQ ID NO: 284, and VL CDR3 having the amino acid sequence of SEQ ID NO: 285. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 286, VH CDR2 having the amino acid sequence of SEQ ID NO: 287, and VH CDR3 having the amino acid sequence of SEQ ID NO: 288; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 289, VL CDR2 having the amino acid sequence of SEQ ID NO: 290, and VL CDR3 having the amino acid sequence of SEQ ID NO: 291. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 286, VH CDR2 having the amino acid sequence of SEQ ID NO: 706, and VH CDR3 having the amino acid sequence of SEQ ID NO: 707; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 289, VL CDR2 having the amino acid sequence of SEQ ID NO: 290, and VL CDR3 having the amino acid sequence of SEQ ID NO: 291.In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 292, VH CDR2 having the amino acid sequence of SEQ ID NO: 293, and VH CDR3 having the amino acid sequence of SEQ ID NO: 294; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 295, VL CDR2 having the amino acid sequence of SEQ ID NO: 296, and VL CDR3 having the amino acid sequence of SEQ ID NO: 297. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 298, VH CDR2 having the amino acid sequence of SEQ ID NO: 299, and VH CDR3 having the amino acid sequence of SEQ ID NO: 300; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 301, VL CDR2 having the amino acid sequence of SEQ ID NO: 302, and VL CDR3 having the amino acid sequence of SEQ ID NO: 303. In some embodiments, the antibody comprises VH having the amino acid sequence of SEQ ID NO: 36. In some embodiments, the antibody comprises VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody comprises VH having the amino acid sequence of SEQ ID NO: 36 and VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody comprises VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 36. In some embodiments, the antibody comprises VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody comprises VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 36 and VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 8.

[0128] In one embodiment, the TRGV9 antibody provided herein has the VH and VL amino acid sequences of TRGV9Ab_var17. In one embodiment, the TRGV9 antibody provided herein has the VH and VL amino acid sequences of TRGV9Ab_var29. In one embodiment, the TRGV9 antibody provided herein contains VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 65. In one embodiment, the TRGV9 antibody provided herein contains VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 66. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 65, and (ii) VL, comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 66. In another embodiment, a TRGV9 antibody is provided herein, comprising VH, comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 67. In another embodiment, a TRGV9 antibody is provided herein, comprising VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 68. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 67, and (ii) VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 68.In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 76, and VH CDR3 having the amino acid sequence of SEQ ID NO: 3, and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 77, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VL CDR3 having the amino acid sequence of SEQ ID NO: 6. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 60, VH CDR2 having the amino acid sequence of SEQ ID NO: 61, and VH CDR3 having the amino acid sequence of SEQ ID NO: 62, and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 63, VL CDR2 having the amino acid sequence of SEQ ID NO: 64, and VL CDR3 having the amino acid sequence of SEQ ID NO: 6. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 304, VH CDR2 having the amino acid sequence of SEQ ID NO: 305, and VH CDR3 having the amino acid sequence of SEQ ID NO: 306; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 307, VL CDR2 having the amino acid sequence of SEQ ID NO: 308, and VL CDR3 having the amino acid sequence of SEQ ID NO: 309. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 310, VH CDR2 having the amino acid sequence of SEQ ID NO: 311, and VH CDR3 having the amino acid sequence of SEQ ID NO: 312; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 313, VL CDR2 having the amino acid sequence of SEQ ID NO: 314, and VL CDR3 having the amino acid sequence of SEQ ID NO: 315.In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 316, VH CDR2 having the amino acid sequence of SEQ ID NO: 317, and VH CDR3 having the amino acid sequence of SEQ ID NO: 318; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 319, VL CDR2 having the amino acid sequence of SEQ ID NO: 320, and VL CDR3 having the amino acid sequence of SEQ ID NO: 321. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 322, VH CDR2 having the amino acid sequence of SEQ ID NO: 323, and VH CDR3 having the amino acid sequence of SEQ ID NO: 324; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 325, VL CDR2 having the amino acid sequence of SEQ ID NO: 326, and VL CDR3 having the amino acid sequence of SEQ ID NO: 327. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 322, VH CDR2 having the amino acid sequence of SEQ ID NO: 708, and VH CDR3 having the amino acid sequence of SEQ ID NO: 709; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 325, VL CDR2 having the amino acid sequence of SEQ ID NO: 326, and VL CDR3 having the amino acid sequence of SEQ ID NO: 327. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 328, VH CDR2 having the amino acid sequence of SEQ ID NO: 329, and VH CDR3 having the amino acid sequence of SEQ ID NO: 330; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 331, VL CDR2 having the amino acid sequence of SEQ ID NO: 332, and VL CDR3 having the amino acid sequence of SEQ ID NO: 333.In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 334, VH CDR2 having the amino acid sequence of SEQ ID NO: 335, and VH CDR3 having the amino acid sequence of SEQ ID NO: 336; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 337, VL CDR2 having the amino acid sequence of SEQ ID NO: 338, and VL CDR3 having the amino acid sequence of SEQ ID NO: 339. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 340, VH CDR2 having the amino acid sequence of SEQ ID NO: 341, and VH CDR3 having the amino acid sequence of SEQ ID NO: 342; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 343, VL CDR2 having the amino acid sequence of SEQ ID NO: 344, and VL CDR3 having the amino acid sequence of SEQ ID NO: 345. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 346, VH CDR2 having the amino acid sequence of SEQ ID NO: 347, and VH CDR3 having the amino acid sequence of SEQ ID NO: 348; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 349, VL CDR2 having the amino acid sequence of SEQ ID NO: 350, and VL CDR3 having the amino acid sequence of SEQ ID NO: 351. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 352, VH CDR2 having the amino acid sequence of SEQ ID NO: 353, and VH CDR3 having the amino acid sequence of SEQ ID NO: 354; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 355, VL CDR2 having the amino acid sequence of SEQ ID NO: 356, and VL CDR3 having the amino acid sequence of SEQ ID NO: 357.In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 358, VH CDR2 having the amino acid sequence of SEQ ID NO: 359, and VH CDR3 having the amino acid sequence of SEQ ID NO: 360; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 361, VL CDR2 having the amino acid sequence of SEQ ID NO: 362, and VL CDR3 having the amino acid sequence of SEQ ID NO: 363. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 358, VH CDR2 having the amino acid sequence of SEQ ID NO: 710, and VH CDR3 having the amino acid sequence of SEQ ID NO: 711; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 361, VL CDR2 having the amino acid sequence of SEQ ID NO: 362, and VL CDR3 having the amino acid sequence of SEQ ID NO: 363. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 364, VH CDR2 having the amino acid sequence of SEQ ID NO: 365, and VH CDR3 having the amino acid sequence of SEQ ID NO: 366; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 367, VL CDR2 having the amino acid sequence of SEQ ID NO: 368, and VL CDR3 having the amino acid sequence of SEQ ID NO: 369. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 370, VH CDR2 having the amino acid sequence of SEQ ID NO: 371, and VH CDR3 having the amino acid sequence of SEQ ID NO: 372; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 373, VL CDR2 having the amino acid sequence of SEQ ID NO: 374, and VL CDR3 having the amino acid sequence of SEQ ID NO: 375. In some embodiments, the antibody comprises VH having the amino acid sequence of SEQ ID NO: 65. In some embodiments, the antibody comprises VL having the amino acid sequence of SEQ ID NO: 66. In some embodiments, the antibody comprises VH having the amino acid sequence of SEQ ID NO: 65 and VL having the amino acid sequence of SEQ ID NO: 66.In some embodiments, the antibody includes a VH having the amino acid sequence of SEQ ID NO: 67. In some embodiments, the antibody includes a VL having the amino acid sequence of SEQ ID NO: 68. In some embodiments, the antibody includes a VH having the amino acid sequence of SEQ ID NO: 67 and a VL having the amino acid sequence of SEQ ID NO: 68. In some embodiments, the antibody includes a heavy chain having the amino acid sequence of SEQ ID NO: 71. In some embodiments, the antibody includes a light chain having the amino acid sequence of SEQ ID NO: 72. In some embodiments, the antibody includes a heavy chain having the amino acid sequence of SEQ ID NO: 71 and a light chain having the amino acid sequence of SEQ ID NO: 72. In some embodiments, the antibody includes the amino acid sequence of SEQ ID NO: 70. In some embodiments, the antibody includes a heavy chain having the amino acid sequence of SEQ ID NO: 74. In some embodiments, the antibody includes a light chain having the amino acid sequence of SEQ ID NO: 75. In some embodiments, the antibody includes a heavy chain having the amino acid sequence of SEQ ID NO: 74 and a light chain having the amino acid sequence of SEQ ID NO: 75. In some embodiments, the antibody includes the amino acid sequence of SEQ ID NO: 73. In some embodiments, the antibody includes a VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 65. In some embodiments, the antibody comprises a VL containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 66. In some embodiments, the antibody is... The antibody comprises a VH containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 65, and a VL containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 66. In some embodiments, the antibody comprises a VH containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 67. In some embodiments, the antibody comprises a VL containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 68. In some embodiments, the antibody comprises a VH containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 67, and a VL containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 68. In some embodiments, the antibody comprises a heavy chain containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 71. In some embodiments, the antibody comprises a light chain containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 72. In some embodiments, the antibody comprises a heavy chain containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 71, and a light chain containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 72. In some embodiments, the antibody contains the amino acid sequence of SEQ ID NO: 70. In some embodiments, the antibody comprises a heavy chain containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 74. In some embodiments, the antibody comprises a light chain containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 75. In some embodiments, the antibody comprises a heavy chain containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 74, and a light chain containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 75. In some embodiments, the antibody contains the amino acid sequence of SEQ ID NO: 73.

[0129] In one embodiment, the TRGV9 antibody provided herein has the VH and VL amino acid sequences of VG3_B3_RN. In one embodiment, the TRGV9 antibody provided herein contains VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 95. In one embodiment, the TRGV9 antibody provided herein contains VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 96. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of SEQ ID NO: 95, and (ii) VL, comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of SEQ ID NO: 96. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of SEQ ID NO: 91, and (ii) VL, comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of SEQ ID NO: 94. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 376, VH CDR2 having the amino acid sequence of SEQ ID NO: 377, and VH CDR3 having the amino acid sequence of SEQ ID NO: 378; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 379, VL CDR2 having the amino acid sequence of SEQ ID NO: 380, and VL CDR3 having the amino acid sequence of SEQ ID NO: 381.In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 382, ​​VH CDR2 having the amino acid sequence of SEQ ID NO: 383, and VH CDR3 having the amino acid sequence of SEQ ID NO: 384; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 385, VL CDR2 having the amino acid sequence of SEQ ID NO: 386, and VL CDR3 having the amino acid sequence of SEQ ID NO: 387. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 388, VH CDR2 having the amino acid sequence of SEQ ID NO: 389, and VH CDR3 having the amino acid sequence of SEQ ID NO: 390; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 391, VL CDR2 having the amino acid sequence of SEQ ID NO: 392, and VL CDR3 having the amino acid sequence of SEQ ID NO: 393. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 394, VH CDR2 having the amino acid sequence of SEQ ID NO: 395, and VH CDR3 having the amino acid sequence of SEQ ID NO: 396; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 397, VL CDR2 having the amino acid sequence of SEQ ID NO: 398, and VL CDR3 having the amino acid sequence of SEQ ID NO: 399. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 394, VH CDR2 having the amino acid sequence of SEQ ID NO: 712, and VH CDR3 having the amino acid sequence of SEQ ID NO: 713; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 397, VL CDR2 having the amino acid sequence of SEQ ID NO: 398, and VL CDR3 having the amino acid sequence of SEQ ID NO: 399.In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 400, VH CDR2 having the amino acid sequence of SEQ ID NO: 401, and VH CDR3 having the amino acid sequence of SEQ ID NO: 402; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 403, VL CDR2 having the amino acid sequence of SEQ ID NO: 404, and VL CDR3 having the amino acid sequence of SEQ ID NO: 405. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 406, VH CDR2 having the amino acid sequence of SEQ ID NO: 407, and VH CDR3 having the amino acid sequence of SEQ ID NO: 408; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 409, VL CDR2 having the amino acid sequence of SEQ ID NO: 410, and VL CDR3 having the amino acid sequence of SEQ ID NO: 411. In some embodiments, the antibody includes VH having the amino acid sequence of SEQ ID NO: 95. In some embodiments, the antibody includes VL having the amino acid sequence of SEQ ID NO: 96. In some embodiments, the antibody includes VH having the amino acid sequence of SEQ ID NO: 95 and VL having the amino acid sequence of SEQ ID NO: 96. In some embodiments, the antibody includes the amino acid sequence of SEQ ID NO: 97. In some embodiments, the antibody includes VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 95. In some embodiments, the antibody includes VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 96. In some embodiments, the antibody includes VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 95 and VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 96. In some embodiments, the antibody includes an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 97.

[0130] In one embodiment, the TRGV9 antibody provided herein has the VH and VL amino acid sequences of VG9B420. In one embodiment, the TRGV9 antibody provided herein contains VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 104. In one embodiment, the TRGV9 antibody provided herein contains VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 105. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 104, and (ii) VL, comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 105. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 98, VH CDR2 having the amino acid sequence of SEQ ID NO: 99, and VH CDR3 having the amino acid sequence of SEQ ID NO: 100; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 101, VL CDR2 having the amino acid sequence of SEQ ID NO: 102, and VL CDR3 having the amino acid sequence of SEQ ID NO: 103. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 412, VH CDR2 having the amino acid sequence of SEQ ID NO: 413, and VH CDR3 having the amino acid sequence of SEQ ID NO: 414; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 415, VL CDR2 having the amino acid sequence of SEQ ID NO: 416, and VL CDR3 having the amino acid sequence of SEQ ID NO: 417.In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 418, VH CDR2 having the amino acid sequence of SEQ ID NO: 419, and VH CDR3 having the amino acid sequence of SEQ ID NO: 420; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 421, VL CDR2 having the amino acid sequence of SEQ ID NO: 422, and VL CDR3 having the amino acid sequence of SEQ ID NO: 423. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 424, VH CDR2 having the amino acid sequence of SEQ ID NO: 425, and VH CDR3 having the amino acid sequence of SEQ ID NO: 426; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 427, VL CDR2 having the amino acid sequence of SEQ ID NO: 428, and VL CDR3 having the amino acid sequence of SEQ ID NO: 429. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 430, VH CDR2 having the amino acid sequence of SEQ ID NO: 431, and VH CDR3 having the amino acid sequence of SEQ ID NO: 432; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 433, VL CDR2 having the amino acid sequence of SEQ ID NO: 434, and VL CDR3 having the amino acid sequence of SEQ ID NO: 435. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 430, VH CDR2 having the amino acid sequence of SEQ ID NO: 714, and VH CDR3 having the amino acid sequence of SEQ ID NO: 715; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 433, VL CDR2 having the amino acid sequence of SEQ ID NO: 434, and VL CDR3 having the amino acid sequence of SEQ ID NO: 435.In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 436, VH CDR2 having the amino acid sequence of SEQ ID NO: 437, and VH CDR3 having the amino acid sequence of SEQ ID NO: 438; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 439, VL CDR2 having the amino acid sequence of SEQ ID NO: 440, and VL CDR3 having the amino acid sequence of SEQ ID NO: 441. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 442, VH CDR2 having the amino acid sequence of SEQ ID NO: 443, and VH CDR3 having the amino acid sequence of SEQ ID NO: 444; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 445, VL CDR2 having the amino acid sequence of SEQ ID NO: 446, and VL CDR3 having the amino acid sequence of SEQ ID NO: 447. In some embodiments, the antibody comprises VH having the amino acid sequence of SEQ ID NO: 104. In some embodiments, the antibody comprises VL having the amino acid sequence of SEQ ID NO: 105. In some embodiments, the antibody comprises VH having the amino acid sequence of SEQ ID NO: 104 and VL having the amino acid sequence of SEQ ID NO: 105. In some embodiments, the antibody comprises the amino acid sequence of SEQ ID NO: 106. In some embodiments, the antibody comprises VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 104. In some embodiments, the antibody comprises VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 105. In some embodiments, the antibody comprises VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 104 and VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 105. In some embodiments, the antibody comprises the amino acid sequence of SEQ ID NO: 106.

[0131] In one embodiment, the TRGV9 antibody provided herein has the VH and VL amino acid sequences of VG9SB10SC1087_P18_D08. In one embodiment, the TRGV9 antibody provided herein contains VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 113. In one embodiment, the TRGV9 antibody provided herein contains VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 114. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of SEQ ID NO: 113, and (ii) VL, comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of SEQ ID NO: 114. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 107, VH CDR2 having the amino acid sequence of SEQ ID NO: 108, and VH CDR3 having the amino acid sequence of SEQ ID NO: 109; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 110, VL CDR2 having the amino acid sequence of SEQ ID NO: 111, and VL CDR3 having the amino acid sequence of SEQ ID NO: 112. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 448, VH CDR2 having the amino acid sequence of SEQ ID NO: 449, and VH CDR3 having the amino acid sequence of SEQ ID NO: 450; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 451, VL CDR2 having the amino acid sequence of SEQ ID NO: 452, and VL CDR3 having the amino acid sequence of SEQ ID NO: 453.In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 454, VH CDR2 having the amino acid sequence of SEQ ID NO: 455, and VH CDR3 having the amino acid sequence of SEQ ID NO: 456; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 457, VL CDR2 having the amino acid sequence of SEQ ID NO: 458, and VL CDR3 having the amino acid sequence of SEQ ID NO: 459. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 460, VH CDR2 having the amino acid sequence of SEQ ID NO: 461, and VH CDR3 having the amino acid sequence of SEQ ID NO: 462; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 463, VL CDR2 having the amino acid sequence of SEQ ID NO: 464, and VL CDR3 having the amino acid sequence of SEQ ID NO: 465. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 466, VH CDR2 having the amino acid sequence of SEQ ID NO: 467, and VH CDR3 having the amino acid sequence of SEQ ID NO: 468; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 469, VL CDR2 having the amino acid sequence of SEQ ID NO: 470, and VL CDR3 having the amino acid sequence of SEQ ID NO: 471. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 466, VH CDR2 having the amino acid sequence of SEQ ID NO: 716, and VH CDR3 having the amino acid sequence of SEQ ID NO: 717; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 469, VL CDR2 having the amino acid sequence of SEQ ID NO: 470, and VL CDR3 having the amino acid sequence of SEQ ID NO: 471.In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 472, VH CDR2 having the amino acid sequence of SEQ ID NO: 473, and VH CDR3 having the amino acid sequence of SEQ ID NO: 474; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 475, VL CDR2 having the amino acid sequence of SEQ ID NO: 476, and VL CDR3 having the amino acid sequence of SEQ ID NO: 477. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 478, VH CDR2 having the amino acid sequence of SEQ ID NO: 479, and VH CDR3 having the amino acid sequence of SEQ ID NO: 480; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 481, VL CDR2 having the amino acid sequence of SEQ ID NO: 482, and VL CDR3 having the amino acid sequence of SEQ ID NO: 483. In some embodiments, the antibody includes a VH having the amino acid sequence of SEQ ID NO: 113. In some embodiments, the antibody includes a VL having the amino acid sequence of SEQ ID NO: 114. In some embodiments, the antibody includes a VH having the amino acid sequence of SEQ ID NO: 113 and a VL having the amino acid sequence of SEQ ID NO: 114. In some embodiments, the antibody includes a heavy chain having the amino acid sequence of SEQ ID NO: 115. In some embodiments, the antibody includes a light chain having the amino acid sequence of SEQ ID NO: 116. In some embodiments, the antibody includes a heavy chain having the amino acid sequence of SEQ ID NO: 115 and a light chain having the amino acid sequence of SEQ ID NO: 116. In some embodiments, the antibody includes a VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 113. In some embodiments, the antibody includes a VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 114. In some embodiments, the antibody comprises VH, which includes an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 113, and VL, which includes an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 114.In some embodiments, the antibody comprises a heavy chain containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 115. In some embodiments, the antibody comprises a light chain containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 116. In some embodiments, the antibody comprises a heavy chain containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 115, and a light chain containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 116.

[0132] In one embodiment, the TRGV9 antibody provided herein has the VH and VL amino acid sequences of VG9SB10SC1087_P18_C12. In one embodiment, the TRGV9 antibody provided herein contains VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 123. In one embodiment, the TRGV9 antibody provided herein contains VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 124. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 123, and (ii) VL, comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 124. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 117, VH CDR2 having the amino acid sequence of SEQ ID NO: 118, and VH CDR3 having the amino acid sequence of SEQ ID NO: 119; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 120, VL CDR2 having the amino acid sequence of SEQ ID NO: 121, and VL CDR3 having the amino acid sequence of SEQ ID NO: 122. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 484, VH CDR2 having the amino acid sequence of SEQ ID NO: 485, and VH CDR3 having the amino acid sequence of SEQ ID NO: 486; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 487, VL CDR2 having the amino acid sequence of SEQ ID NO: 488, and VL CDR3 having the amino acid sequence of SEQ ID NO: 489.In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 490, VH CDR2 having the amino acid sequence of SEQ ID NO: 491, and VH CDR3 having the amino acid sequence of SEQ ID NO: 492; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 493, VL CDR2 having the amino acid sequence of SEQ ID NO: 494, and VL CDR3 having the amino acid sequence of SEQ ID NO: 495. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 496, VH CDR2 having the amino acid sequence of SEQ ID NO: 497, and VH CDR3 having the amino acid sequence of SEQ ID NO: 498; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 499, VL CDR2 having the amino acid sequence of SEQ ID NO: 500, and VL CDR3 having the amino acid sequence of SEQ ID NO: 501. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 502, VH CDR2 having the amino acid sequence of SEQ ID NO: 503, and VH CDR3 having the amino acid sequence of SEQ ID NO: 504; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 505, VL CDR2 having the amino acid sequence of SEQ ID NO: 506, and VL CDR3 having the amino acid sequence of SEQ ID NO: 507. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 502, VH CDR2 having the amino acid sequence of SEQ ID NO: 718, and VH CDR3 having the amino acid sequence of SEQ ID NO: 719; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 505, VL CDR2 having the amino acid sequence of SEQ ID NO: 506, and VL CDR3 having the amino acid sequence of SEQ ID NO: 507.In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 508, VH CDR2 having the amino acid sequence of SEQ ID NO: 509, and VH CDR3 having the amino acid sequence of SEQ ID NO: 510; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 511, VL CDR2 having the amino acid sequence of SEQ ID NO: 512, and VL CDR3 having the amino acid sequence of SEQ ID NO: 513. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 514, VH CDR2 having the amino acid sequence of SEQ ID NO: 515, and VH CDR3 having the amino acid sequence of SEQ ID NO: 516; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 517, VL CDR2 having the amino acid sequence of SEQ ID NO: 518, and VL CDR3 having the amino acid sequence of SEQ ID NO: 519. In some embodiments, the antibody includes a VH having the amino acid sequence of SEQ ID NO: 123. In some embodiments, the antibody includes a VL having the amino acid sequence of SEQ ID NO: 124. In some embodiments, the antibody includes a VH having the amino acid sequence of SEQ ID NO: 123 and a VL having the amino acid sequence of SEQ ID NO: 124. In some embodiments, the antibody includes a heavy chain having the amino acid sequence of SEQ ID NO: 125. In some embodiments, the antibody includes a light chain having the amino acid sequence of SEQ ID NO: 126. In some embodiments, the antibody includes a heavy chain having the amino acid sequence of SEQ ID NO: 125 and a light chain having the amino acid sequence of SEQ ID NO: 126. In some embodiments, the antibody includes a VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 123. In some embodiments, the antibody includes a VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 124. In some embodiments, the antibody comprises VH, which includes an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 123, and VL, which includes an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 124.In some embodiments, the antibody comprises a heavy chain containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 125. In some embodiments, the antibody comprises a light chain containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 126. In some embodiments, the antibody comprises a heavy chain containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 125, and a light chain containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 126.

[0133] In one embodiment, the TRGV9 antibody provided herein has the VH and VL amino acid sequences of VG9SB10SC1087_P19_C03. In one embodiment, the TRGV9 antibody provided herein contains VH, which includes VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 133. In one embodiment, the TRGV9 antibody provided herein contains VL, which includes VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 134. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 133, and (ii) VL, comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 134. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 127, VH CDR2 having the amino acid sequence of SEQ ID NO: 128, and VH CDR3 having the amino acid sequence of SEQ ID NO: 129; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 130, VL CDR2 having the amino acid sequence of SEQ ID NO: 131, and VL CDR3 having the amino acid sequence of SEQ ID NO: 132. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 520, VH CDR2 having the amino acid sequence of SEQ ID NO: 521, and VH CDR3 having the amino acid sequence of SEQ ID NO: 522; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 523, VL CDR2 having the amino acid sequence of SEQ ID NO: 524, and VL CDR3 having the amino acid sequence of SEQ ID NO: 525.In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 526, VH CDR2 having the amino acid sequence of SEQ ID NO: 527, and VH CDR3 having the amino acid sequence of SEQ ID NO: 528; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 529, VL CDR2 having the amino acid sequence of SEQ ID NO: 530, and VL CDR3 having the amino acid sequence of SEQ ID NO: 531. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 532, VH CDR2 having the amino acid sequence of SEQ ID NO: 533, and VH CDR3 having the amino acid sequence of SEQ ID NO: 534; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 535, VL CDR2 having the amino acid sequence of SEQ ID NO: 536, and VL CDR3 having the amino acid sequence of SEQ ID NO: 537. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 538, VH CDR2 having the amino acid sequence of SEQ ID NO: 539, and VH CDR3 having the amino acid sequence of SEQ ID NO: 540; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 541, VL CDR2 having the amino acid sequence of SEQ ID NO: 542, and VL CDR3 having the amino acid sequence of SEQ ID NO: 543. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 538, VH CDR2 having the amino acid sequence of SEQ ID NO: 720, and VH CDR3 having the amino acid sequence of SEQ ID NO: 721; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 541, VL CDR2 having the amino acid sequence of SEQ ID NO: 542, and VL CDR3 having the amino acid sequence of SEQ ID NO: 543.In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 544, VH CDR2 having the amino acid sequence of SEQ ID NO: 545, and VH CDR3 having the amino acid sequence of SEQ ID NO: 546; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 547, VL CDR2 having the amino acid sequence of SEQ ID NO: 548, and VL CDR3 having the amino acid sequence of SEQ ID NO: 549. In another embodiment, a TRGV9 antibody is provided herein, comprising (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 550, VH CDR2 having the amino acid sequence of SEQ ID NO: 551, and VH CDR3 having the amino acid sequence of SEQ ID NO: 552; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 553, VL CDR2 having the amino acid sequence of SEQ ID NO: 554, and VL CDR3 having the amino acid sequence of SEQ ID NO: 555. In some embodiments, the antibody includes a VH having the amino acid sequence of SEQ ID NO: 133. In some embodiments, the antibody includes a VL having the amino acid sequence of SEQ ID NO: 134. In some embodiments, the antibody includes a VH having the amino acid sequence of SEQ ID NO: 133 and a VL having the amino acid sequence of SEQ ID NO: 134. In some embodiments, the antibody includes a heavy chain having the amino acid sequence of SEQ ID NO: 135. In some embodiments, the antibody includes a light chain having the amino acid sequence of SEQ ID NO: 136. In some embodiments, the antibody includes a heavy chain having the amino acid sequence of SEQ ID NO: 135 and a light chain having the amino acid sequence of SEQ ID NO: 136. In some embodiments, the antibody includes a VH having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 133. In some embodiments, the antibody includes a VL having an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 134. In some embodiments, the antibody comprises VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 133, and VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 134.In some embodiments, the antibody comprises a heavy chain containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 135. In some embodiments, the antibody comprises a light chain containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 136. In some embodiments, the antibody comprises a heavy chain containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 135, and a light chain containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 136.

[0134] In some embodiments, the VH CDR1, VH CDR2, and VH CDR3 amino acid sequences of the TRGV9 antibody follow the Kabat numbering system. In some embodiments, the VH CDR1, VH CDR2, and VH CDR3 amino acid sequences of the TRGV9 antibody follow the Chothia numbering system. In some embodiments, the VH CDR1, VH CDR2, and VH CDR3 amino acid sequences of the TRGV9 antibody follow the AbM numbering system. In some embodiments, the VH CDR1, VH CDR2, and VH CDR3 amino acid sequences of the TRGV9 antibody follow the Contact numbering system. In some embodiments, the VH CDR1, VH CDR2, and VH CDR3 amino acid sequences of the TRGV9 antibody follow the IMGT numbering system. In some embodiments, the VH CDR1, VH CDR2, and VH CDR3 amino acid sequences of the TRGV9 antibody follow an exemplary numbering system. In some embodiments, the VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the TRGV9 antibody follow the Kabat numbering system. In some embodiments, the VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the TRGV9 antibody follow the Chothia numbering system. In some embodiments, the VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the TRGV9 antibody follow the AbM numbering system. In some embodiments, the VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the TRGV9 antibody follow the Contact numbering system. In some embodiments, the VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the TRGV9 antibody follow the IMGT numbering system. In some embodiments, the VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the TRGV9 antibody follow an exemplary numbering system.

[0135] In some embodiments, the TRGV9 antibody is a multispecific antibody. In other embodiments, the TRGV9 antibody is a bispecific antibody. In some embodiments, the multispecific antibody comprises an antigen-binding fragment of the TRGV9 antibody provided herein. In some embodiments, the multispecific antibody comprises a first binding domain that binds to a first TRGV9 epitope and a second domain that binds to a second TRGV9 epitope, wherein the first and second TRGV9 epitopes are different. In certain embodiments, the multispecific antibody further comprises a third binding domain that binds to a target other than TRGV9. In some embodiments, the multispecific antibody comprises a heavy chain variable region and a light chain variable region. In some embodiments, the first binding domain comprises a heavy chain variable region and a light chain variable region. In some embodiments, the second binding domain comprises a heavy chain variable region and a light chain variable region. In some embodiments, the first binding domain includes a heavy chain variable region and a light chain variable region, and the second binding domain includes a heavy chain variable region and a light chain variable region. In some embodiments, the first binding domain of the TRGV9 antibody is not a single-domain antibody or nanobody. In some embodiments, the second binding domain of the TRGV9 antibody is not a single-domain antibody or nanobody.

[0136] In certain embodiments, the TRGV9 antibody includes a VH region and a VL region. In some embodiments, the TRGV9 antibody is not a single-chain antibody. In some embodiments, the TRGV9 antibody is not a single-domain antibody. In some embodiments, the TRGV9 antibody is not a nanobody. In some embodiments, the TRGV9 antibody is not a VHH antibody. In some embodiments, the TRGV9 antibody is not a llama antibody. In some embodiments, the TRGV9 bispecific antibody does not contain a single-chain antibody. In some embodiments, the TRGV9 bispecific antibody does not contain a single-domain antibody. In some embodiments, the TRGV9 bispecific antibody does not contain a nanobody. In some embodiments, the TRGV9 bispecific antibody does not contain a VHH antibody. In some embodiments, the TRGV9 bispecific antibody does not contain a llama antibody.

[0137] In some embodiments, the TRGV9 antibodies provided herein do not include VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 730, 731, and 732, respectively. In some embodiments, the TRGV9 antibodies provided herein do not include VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 733, 734, and 735, respectively. In some embodiments, the TRGV9 antibodies provided herein do not include VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 736, 737, and 738, respectively. In some embodiments, the TRGV9 antibodies provided herein do not include VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 739, 740, and 741, respectively. In some embodiments, the TRGV9 antibodies provided herein do not include VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 742, 743, and 744, respectively. In some embodiments, the TRGV9 antibodies provided herein do not include VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 745, 746, and 747, respectively. In some embodiments, the TRGV9 antibodies provided herein do not include VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs. 748, 749, and 750, respectively. In some embodiments, the TRGV9 antibodies provided herein do not include a VH domain having the amino acid sequence of SEQ ID NOs. 751. In some embodiments, the TRGV9 antibodies provided herein do not include a VH domain having the amino acid sequence of SEQ ID NOs. 752. In some embodiments, the TRGV9 antibodies provided herein do not include a VH domain having the amino acid sequence of SEQ ID NOs. 753. In some embodiments, the TRGV9 antibody provided herein does not contain a VH domain having the amino acid sequence of SEQ ID NO: 754. In some embodiments, the TRGV9 antibody provided herein does not contain a VH domain having the amino acid sequence of SEQ ID NO: 755.In some embodiments, the TRGV9 antibody provided herein does not contain a VH domain having the amino acid sequence of SEQ ID NO: 756. In some embodiments, the TRGV9 antibody provided herein does not contain a VH domain having the amino acid sequence of SEQ ID NO: 757.

[0138] In another embodiment, a TRGV9 antibody is provided herein, comprising a VH domain containing a VH CDR3 having the amino acid sequence APNxGzYTbDF (SEQ ID NO: 758), where x is Y or M, z is M or D, and b is I or L. In another embodiment, a TRGV9 antibody is provided herein, comprising a VH domain containing the amino acid sequence of SEQ ID NO: 758. In another embodiment, a TRGV9 antibody is provided herein, comprising a VH domain containing a VH CDR1 having the amino acid sequence GxTFzz (SEQ ID NO: 761), where x is F, D, or G, and z is S or N. In another embodiment, a TRGV9 antibody is provided herein, comprising a VH domain containing the amino acid sequence of SEQ ID NO: 761. In another embodiment, a TRGV9 antibody is provided herein, comprising a VL domain containing a VL CDR1 having the amino acid sequence RxSQSz (SEQ ID NO: 762), where x is A or S, and Z is V or L. In another embodiment, a TRGV9 antibody comprising a VL domain containing the amino acid sequence of SEQ ID NO: 761 is provided herein.

[0139] In another embodiment, an antibody that binds to TRGV9 is provided herein, the antibody comprising (i) VH, comprising VH CDR1, VH CDR2, and VH CDR3, and (ii) VL, comprising VL CDR1, VL CDR2, and VL CDR3. In some embodiments, VH CDR1 comprises a first polar amino acid. In some embodiments, VH CDR1 comprises a last polar uncharged amino acid. In some embodiments, VH CDR1 comprises at least one tyrosine. In some embodiments, VH CDR1 comprises at least 20% hydrophobic amino acids. In some embodiments, VH CDR1 comprises at least two hydrophobic amino acids. In some embodiments, VH CDR1 comprises at least about 40% hydrophobic amino acids. In some embodiments, VH CDR1 contains a first polar amino acid, a last polar uncharged amino acid, at least one tyrosine, at least 20% hydrophobic amino acids, at least two hydrophobic amino acids, and at least about 40% hydrophobic amino acids. Any combination of two or more of the above structural features of VH CDR1 is also intended. In some embodiments, VH CDR2 contains a polar amino acid at residue 13. In some embodiments, VH CDR2 contains hydrophobicity at amino acid position 15. In some embodiments, VH CDR2 contains phenylalanine (F) or leucine (L) at position 15. In some embodiments, VH CDR2 contains a polar amino acid at position 14. In some embodiments, VH CDR2 contains lysine (K) or serine (S) at position 14. In some embodiments, VH CDR2 contains a hydrophobic amino acid at position 2. In some embodiments, VH CDR2 includes a hydrophobic amino acid at position 3. In some embodiments, VH CDR2 includes the second-to-last polar amino acid. In some embodiments, VH CDR2 includes a polar amino acid at residue 13, a hydrophobic amino acid at position 15, phenylalanine (F) or leucine (L) at position 15, a polar amino acid at position 14, lysine (K) or serine (S) at position 14, a hydrophobic amino acid at position 2 or 3, and the second-to-last polar amino acid.Any combination of two or more of the above structural features of VH CDR2 is also intended. In some embodiments, VH CDR3 does not contain a polar charged amino acid at position 3. In some embodiments, VH CDR3 contains a hydrophobic or polar charged amino acid at position 7. In some embodiments, VH CDR3 contains a polar uncharged or hydrophobic amino acid at position 6. In some embodiments, VH CDR3 does not contain a polar charged amino acid at position 3, but contains a hydrophobic or polar charged amino acid at position 7 and a polar uncharged or hydrophobic amino acid at position 6. Any combination of two or more of the above structural features of VH CDR3 is also intended. In some embodiments, VL CDR1 contains a polar amino acid at position 4. In some embodiments, VL CDR1 contains a first amino acid that is polar charged. In some embodiments, VL CDR1 contains a polar uncharged or hydrophobic amino acid at position 2. In some embodiments, VL CDR1 contains serine at position 3. In some embodiments, VL CDR1 contains a polar amino acid at position 5. In some embodiments, VL CDR1 contains a hydrophobic amino acid at position 6. In some embodiments, VL CDR1 contains a polar amino acid at position 4, a first polarly charged amino acid, a polar uncharged or hydrophobic amino acid at position 2, serine at position 3, a polar amino acid at position 5, and a hydrophobic amino acid at position 6. Any combination of two or more of the above structural features of VL CDR1 is also intended. In some embodiments, VL CDR2 contains a polar amino acid at position 7. In some embodiments, VL CDR2 contains a polarly charged or hydrophobic amino acid at position 6. In some embodiments, VL CDR2 contains a polarly charged amino acid at position 3. In some embodiments, VL CDR2 contains a polar uncharged amino acid at position 4. In some embodiments, VL CDR2 contains a hydrophobic amino acid at position 2. In some embodiments, VL CDR2 includes a polar amino acid at position 7, a polar charged or hydrophobic amino acid at position 6, a polar charged amino acid at position 3, a polar uncharged amino acid at position 4, and a hydrophobic amino acid at position 2. Any combination of two or more of the above structural features of VL CDR2 is also intended. In some embodiments, VL CDR3 includes a hydrophobic terminal amino acid.In some embodiments, VL CDR3 contains a terminal tyrosine. In some embodiments, VL CDR3 contains a polar uncharged amino acid at position 5. In some embodiments, VL CDR3 contains a polar amino acid at position 2. In some embodiments, VL CDR3 contains a polar uncharged or hydrophobic amino acid at position 1. In some embodiments, VL CDR3 contains a hydrophobic amino acid at position 3. In some embodiments, VL CDR3 contains a hydrophilic or polar uncharged amino acid at position 6. In some embodiments, VL CDR3 does not contain a polar or hydrophobic amino acid at position 7. In some embodiments, VL CDR3 contains a hydrophobic terminal amino acid, a terminal tyrosine, a polar uncharged amino acid at position 5, a polar amino acid at position 2, a polar uncharged or hydrophobic amino acid at position 1, a hydrophobic amino acid at position 3, a hydrophilic or polar uncharged amino acid at position 6, and does not contain a polar or hydrophobic amino acid at position 7. Any combination of two or more of the above structural features of VL CDR3 is also intended. In certain embodiments, residue numbering follows exemplary numbering.

[0140] In another embodiment, an antibody that binds to TRGV9 is provided herein, comprising (i) VH, including VH CDR1, VH CDR2, and VH CDR3, and (ii) VL, including VL CDR1, VL CDR2, and VL CDR3.

[0141] In some embodiments of the TRGV9 antibodies provided herein, VH CDR1 contains at least three polar amino acids. In some embodiments, VH CDR1 contains at least 40% polar amino acids. In some embodiments, VH CDR1 contains glycine (G) at position 1. In some embodiments, VH CDR1 does not contain a polar uncharged amino acid at position 2. In some embodiments, VH CDR1 contains a polar uncharged amino acid at position 3. In some embodiments, VH CDR1 contains threonine (T) or serine (S) at position 3. In some embodiments, VH CDR1 contains a hydrophobic amino acid at position 4. In some embodiments, VH CDR1 contains phenylalanine (F) or isoleucine (I) at position 4. In some embodiments, VH CDR1 contains a polar uncharged amino acid at position 5. In some embodiments, VH CDR1 contains threonine (T), serine (S), or asparagine (N) at position 5. In some embodiments, VH CDR1 contains a polar amino acid at position 6. In some embodiments, VH CDR1 contains an acidic amino acid or a polar uncharged amino acid at position 6. In some embodiments, VH CDR1 does not contain a polar uncharged amino acid at position 7. Any combination of two or more of the above structural features of VH CDR1 is also intended. In some embodiments, amino acid residue numbering follows Chothia.

[0142] In some embodiments of the TRGV9 antibodies provided herein, VH CDR2 does not contain a charged amino acid at position 1. In some embodiments, VH CDR2 does not contain a charged amino acid at position 2. In some embodiments, VH CDR2 contains glycine (G), a hydrophobic, or polar charged amino acid at position 2. In some embodiments, VH CDR2 does not contain a hydrophobic or polar charged amino acid at position 4. In some embodiments, VH CDR2 does not contain a hydrophobic or polar uncharged amino acid at the last position. In some embodiments, VH CDR2 contains glycine (G) or a polar uncharged amino acid at the last position. Any combination of two or more of the above structural features of VH CDR2 is also contemplated. In some embodiments, the amino acid residue numbering follows Chothia.

[0143] In some embodiments of the TRGV9 antibodies provided herein, VH CDR3 does not contain a polar charged amino acid at position 1. In some embodiments, VH CDR3 does not contain a polar charged amino acid at position 2. In some embodiments, VH CDR3 contains glycine (G), tyrosine (Y), or a polar uncharged amino acid at position 2. In some embodiments, VH CDR3 does not contain a polar uncharged amino acid at position 3. In some embodiments, VH CDR3 contains glycine (G), aspartic acid (D), or a hydrophobic amino acid at position 3. In some embodiments, VH CDR3 does not contain a polar charged amino acid at position 5. In some embodiments, VH CDR3 does not contain a polar uncharged amino acid at position 6. In some embodiments, VH CDR3 contains aspartic acid (D) or a hydrophobic amino acid at position 6. In some embodiments, VH CDR3 contains the second-to-last hydrophobic amino acid. In some embodiments, VH CDR3 does not contain a polar uncharged amino acid at position 7. In some embodiments, VH CDR3 contains terminal aspartic acid (D) or terminal alanine (A). Any combination of two or more of the above structural features of VH CDR3 is also contemplated. In some embodiments, the amino acid residue numbering follows Chothia.

[0144] In some embodiments of the TRGV9 antibodies provided herein, VL CDR1 contains serine (S) at position 1. In some embodiments, VL CDR1 contains glutamine (G) or glutamic acid (E) at position 2. In some embodiments, VL CDR1 contains a polar uncharged amino acid at position 3. In some embodiments, VL CDR1 contains serine (S) or asparagine (N) at position 3. In some embodiments, VL CDR1 contains a hydrophobic amino acid at position 4. In some embodiments, VL CDR1 contains leucine (L), valine (V), or isoleucine (I) at position 4. In some embodiments, VL CDR1 contains serine (S) or tyrosine (Y) at position 7. In some embodiments, VL CDR1 contains the second to last polar uncharged amino acid. In some embodiments, VL CDR1 contains terminal tyrosine (Y) or terminal lysine (K). Any combination of two or more of the above-described structural features of VL CDR1 is also considered. In one embodiment, the amino acid residue numbering follows Chothia.

[0145] In some embodiments of the TRGV9 antibodies provided herein, VL CDR2 contains a hydrophobic amino acid at position 2. In some embodiments, VL CDR2 contains alanine (A) or isoleucine (I) at position 2. In some embodiments, VL CDR2 contains a polar terminal amino acid. In some embodiments, VL CDR2 contains terminal serine (S) or terminal lysine (K). Any combination of two or more of the above structural features of VL CDR2 is also intended. In some embodiments, the amino acid residue numbering follows Chothia.

[0146] In some embodiments of the TRGV9 antibodies provided herein, VL CDR3 does not contain a polar uncharged amino acid at position 1. In some embodiments, VL CDR3 contains arginine (R) or a hydrophobic amino acid at position 1. In some embodiments, VL CDR3 does not contain a hydrophobic amino acid at position 3. In some embodiments, VL CDR3 contains arginine (R) or a polar uncharged amino acid at position 3. In some embodiments, VL CDR3 does not contain a polar charged amino acid at position 4. In some embodiments, VL CDR3 contains serine (S) or a hydrophobic amino acid at position 4. In some embodiments, VL CDR3 contains tyrosine (Y) or proline (P) as the second to last amino acid. In some embodiments, VL CDR3 contains histidine (H) or proline (P) at position 5. In some embodiments, VL CDR3 contains terminal histidine (H), terminal lysine (L), or terminal tyrosine (Y). Any combination of two or more of the structural features of VL CDR3 described above is also intended. In one embodiment, the amino acid residue numbering follows Chothia.

[0147] In another embodiment, a TRGV9 antibody is provided herein, comprising VH containing VH CDR1 having the amino acid sequence GX1TFX2X3X4 (SEQ ID NO: 777), where X1 is F, D, or G, X2 is T, S, or N, X3 is D, S, or N, and X4 is H, N, or Y. In another embodiment, a TRGV9 antibody is provided herein, comprising VH containing the amino acid sequence of SEQ ID NO: 777. In another embodiment, a TRGV9 antibody is provided herein, comprising VH containing VH CDR2 having the amino acid sequence PGX1G (SEQ ID NO: 778), where X1 is D or S. In another embodiment, a TRGV9 antibody is provided herein, comprising VH containing the amino acid sequence of SEQ ID NO: 778. In another embodiment, a TRGV9 antibody is provided herein, comprising VH containing VH CDR3 having the amino acid sequence X1GX2YTX3D (SEQ ID NO: 779), where X1 is Y or M, X2 is D or M, and X3 is I or L. In another embodiment, a TRGV9 antibody is provided herein, comprising VH containing the amino acid sequence of SEQ ID NO: 779. In another embodiment, a TRGV9 antibody is provided herein, comprising VL containing VL CDR1 having the amino acid sequence SQSX1LYSSNX2X3 (SEQ ID NO: 780), where X1 is L or V, X2 is Q or N, and X3 is K or KNY. In another embodiment, a TRGV9 antibody is provided herein, comprising VL containing the amino acid sequence of SEQ ID NO: 780.

[0148] In another embodiment, TRGV9 antibodies comprising VH including VH CDR1, VH CDR2, and VH CDR3 are provided herein. In some embodiments, VH CDR1 comprises the amino acid sequence GX1TFX2X3X4 (SEQ ID NO: 777), where X1 is F, D, or G, X2 is T, S, or N, X3 is D, S, or N, and X4 is H, N, or Y. In some embodiments, VH CDR1 comprises the amino acid sequence of SEQ ID NO: 178. In some embodiments, VH CDR1 comprises the amino acid sequence of SEQ ID NO: 394. In some embodiments, VH CDR1 comprises the amino acid sequence of SEQ ID NO: 430. In some embodiments, VH CDR1 comprises the amino acid sequence of SEQ ID NO: 466. In some embodiments, VH CDR1 comprises the amino acid sequence of SEQ ID NO: 502. In some embodiments, VH CDR1 comprises the amino acid sequence of SEQ ID NO: 538. In some embodiments, VH CDR2 comprises the amino acid sequence PGX1G (SEQ ID NO: 778), where X1 is D or S. In some embodiments, VH CDR3 comprises the amino acid sequence X1GX2YTX3D (SEQ ID NO: 779), where X1 is Y or M, X2 is D or M, and X3 is I or L. In another embodiment, a TRGV9 antibody comprising VL, including VL CDR1, VL CDR2, and VL CDR3, is provided herein. In one embodiment, VL CDR1 comprises the amino acid sequence SQSX1LYSSNX2X3 (SEQ ID NO: 780), where X1 is L or V, X2 is Q or N, and X3 is K or KNY. In some embodiments, VL CDR2 comprises the amino acid sequence SEQ ID NO: 182. In some embodiments, VL CDR2 comprises the amino acid sequence SEQ ID NO: 398. In some embodiments, VL CDR2 contains the amino acid sequence of SEQ ID NO: 434. In some embodiments, VL CDR2 contains the amino acid sequence of SEQ ID NO: 470. In some embodiments, VL CDR3 contains the amino acid sequence of SEQ ID NO: 542. In some embodiments, VL CDR3 contains the amino acid sequence of SEQ ID NO: 399. In some embodiments, VL CDR3 contains the amino acid sequence of SEQ ID NO: 435.In some embodiments, VL CDR3 includes the amino acid sequence of SEQ ID NO: 471. In some embodiments, VL CDR3 includes the amino acid sequence of SEQ ID NO: 507. In some embodiments, VL CDR3 includes the amino acid sequence of SEQ ID NO: 543.

[0149] In another embodiment, a multispecific TRGV9 antibody is provided, comprising the TRGV9 antibody provided herein. In some embodiments, the multispecific TRGV9 antibody is a bispecific antibody. In one embodiment, a multispecific TRGV9 antibody is provided herein, comprising VH CDR1, VH CDR2, and VH CDR3 of the TRGV9 antibody provided herein. In one embodiment, a multispecific TRGV9 antibody is provided herein, comprising VL CDR1, VL CDR2, and VL CDR3 of the TRGV9 antibody provided herein. In one embodiment, a multispecific TRGV9 antibody is provided herein, comprising VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of the TRGV9 antibody provided herein. In one embodiment, a multispecific TRGV9 antibody is provided herein, comprising VH of the TRGV9 antibody provided herein. In one embodiment, a multispecific TRGV9 antibody is provided herein, the antibody comprising VL of the TRGV9 antibody provided herein. In another embodiment, a multispecific TRGV9 antibody is provided herein, the antibody comprising VH and VL of the TRGV9 antibody provided herein.

[0150] In one embodiment, a multispecific TRGV9 antibody is provided herein, comprising (a) a first binding domain that binds to TRGV9 and (b) a second binding domain that binds to a second target other than TRGV9. In some embodiments of the multispecific TRGV9 antibody provided herein, the second target is not the TRGV9 antigen. In some embodiments of the multispecific TRGV9 antibody provided herein, the second target is not the TRGV9 epitope.

[0151] In one embodiment of the multispecific TRGV9 antibody provided herein, the first binding domain that binds to TRGV9 includes the VH and VL amino acid sequences of L7A5_1(TRGV9_1). In one embodiment, the first binding domain includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 7. In one embodiment, the first binding domain includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 8. In one embodiment, the first binding domain includes (i) VH comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequence of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 7, and (ii) VL comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequence of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of VL VL CDR3 having the amino acid sequence of SEQ ID NO: 8. In one embodiment, the first binding domain includes (i) VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 3, and (ii) VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 4, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VL CDR3 having the amino acid sequence of SEQ ID NO: 6. In one embodiment, the first binding domain comprises (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 160, VH CDR2 having the amino acid sequence of SEQ ID NO: 161, and VH CDR3 having the amino acid sequence of SEQ ID NO: 162; and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 163, VL CDR2 having the amino acid sequence of SEQ ID NO: 164, and VL CDR3 having the amino acid sequence of SEQ ID NO: 165.In one embodiment, the first binding domain includes VH, comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 166, VH CDR2 having the amino acid sequence of SEQ ID NO: 167, and VH CDR3 having the amino acid sequence of SEQ ID NO: 168, and (ii) VL, comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 169, VL CDR2 having the amino acid sequence of SEQ ID NO: 170, and VL CDR3 having the amino acid sequence of SEQ ID NO: 171. In one embodiment, the first binding domain includes VH, comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 172, VH CDR2 having the amino acid sequence of SEQ ID NO: 173, and VH CDR3 having the amino acid sequence of SEQ ID NO: 174, and (ii) VL, comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 175, VL CDR2 having the amino acid sequence of SEQ ID NO: 176, and VL CDR3 having the amino acid sequence of SEQ ID NO: 177. In one embodiment, the first binding domain includes VH, comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 178, VH CDR2 having the amino acid sequence of SEQ ID NO: 179, and VH CDR3 having the amino acid sequence of SEQ ID NO: 180, and (ii) VL, comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 181, VL CDR2 having the amino acid sequence of SEQ ID NO: 182, and VL CDR3 having the amino acid sequence of SEQ ID NO: 183. In one embodiment, the first binding domain includes VH, comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 178, VH CDR2 having the amino acid sequence of SEQ ID NO: 700, and VH CDR3 having the amino acid sequence of SEQ ID NO: 701, and (ii) VL, comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 181, VL CDR2 having the amino acid sequence of SEQ ID NO: 182, and VL CDR3 having the amino acid sequence of SEQ ID NO: 183.In one embodiment, the first binding domain includes VH, comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 184, VH CDR2 having the amino acid sequence of SEQ ID NO: 185, and VH CDR3 having the amino acid sequence of SEQ ID NO: 186, and (ii) VL, comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 187, VL CDR2 having the amino acid sequence of SEQ ID NO: 188, and VL CDR3 having the amino acid sequence of SEQ ID NO: 189. In one embodiment, the first binding domain includes VH, comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 190, VH CDR2 having the amino acid sequence of SEQ ID NO: 191, and VH CDR3 having the amino acid sequence of SEQ ID NO: 192, and (ii) VL, comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 193, VL CDR2 having the amino acid sequence of SEQ ID NO: 194, and VL CDR3 having the amino acid sequence of SEQ ID NO: 195. In some embodiments, the first binding domain includes VH having the amino acid sequence of SEQ ID NO: 7. In some embodiments, the first binding domain includes VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain includes VH having the amino acid sequence of SEQ ID NO: 7 and VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain includes a heavy chain having the amino acid sequence of SEQ ID NO: 23. In some embodiments, the first binding domain includes a light chain having the amino acid sequence of SEQ ID NO: 24. In some embodiments, the first binding domain includes a heavy chain having the amino acid sequence of SEQ ID NO: 23 and a light chain having the amino acid sequence of SEQ ID NO: 24. In some embodiments, the first binding domain includes the amino acid sequence of SEQ ID NO: 17. In some embodiments, the first binding domain includes a heavy chain having the amino acid sequence of SEQ ID NO: 69. In some embodiments, the first binding domain includes a light chain having the amino acid sequence of SEQ ID NO: 24. In some embodiments, the first binding domain includes a heavy chain having the amino acid sequence of SEQ ID NO: 69 and a light chain having the amino acid sequence of SEQ ID NO: 24. In some embodiments, the first binding domain includes a VH having an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 7.In some embodiments, the first binding domain includes VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain includes VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 7, and VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain includes a heavy chain, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 23. In some embodiments, the first binding domain includes a light chain, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 24. In some embodiments, the first binding domain includes a heavy chain, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 23, and a light chain, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 24. In some embodiments, the first binding domain includes the amino acid sequence of SEQ ID NO: 17. In some embodiments, the first binding domain includes a heavy chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 69. In some embodiments, the first binding domain includes a light chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 24. In some embodiments, the first binding domain includes a heavy chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 69, and a light chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 24.

[0152] In one embodiment of the multispecific TRGV9 antibody provided herein, the first binding domain that binds to TRGV9 includes the VH and VL amino acid sequences of L7A5_2(TRGV9_2). In one embodiment, the first binding domain includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 34. In one embodiment, the first binding domain includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 8. In one embodiment, the first binding domain includes (i) VH comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequence of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 34, and (ii) VL comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequence of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of VL VL CDR3 having the amino acid sequence of SEQ ID NO: 8. In one embodiment, the first binding domain includes (i) VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 31, and (ii) VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 4, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VL CDR3 having the amino acid sequence of SEQ ID NO: 6. In one embodiment, the first binding domain comprises (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 196, VH CDR2 having the amino acid sequence of SEQ ID NO: 197, and VH CDR3 having the amino acid sequence of SEQ ID NO: 198, and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 199, VL CDR2 having the amino acid sequence of SEQ ID NO: 200, and VL CDR3 having the amino acid sequence of SEQ ID NO: 201.In one embodiment, the first binding domain includes VH, comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 202, VH CDR2 having the amino acid sequence of SEQ ID NO: 203, and VH CDR3 having the amino acid sequence of SEQ ID NO: 204, and (ii) VL, comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 205, VL CDR2 having the amino acid sequence of SEQ ID NO: 206, and VL CDR3 having the amino acid sequence of SEQ ID NO: 207. In one embodiment, the first binding domain includes VH, comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 208, VH CDR2 having the amino acid sequence of SEQ ID NO: 209, and VH CDR3 having the amino acid sequence of SEQ ID NO: 210, and (ii) VL, comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 211, VL CDR2 having the amino acid sequence of SEQ ID NO: 212, and VL CDR3 having the amino acid sequence of SEQ ID NO: 213. In one embodiment, the first binding domain includes VH, comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 214, VH CDR2 having the amino acid sequence of SEQ ID NO: 215, and VH CDR3 having the amino acid sequence of SEQ ID NO: 216, and (ii) VL, comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 217, VL CDR2 having the amino acid sequence of SEQ ID NO: 218, and VL CDR3 having the amino acid sequence of SEQ ID NO: 219. In one embodiment, the first binding domain includes VH, comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 214, VH CDR2 having the amino acid sequence of SEQ ID NO: 702, and VH CDR3 having the amino acid sequence of SEQ ID NO: 703, and (ii) VL, comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 217, VL CDR2 having the amino acid sequence of SEQ ID NO: 218, and VL CDR3 having the amino acid sequence of SEQ ID NO: 219.In one embodiment, the first binding domain includes VH, comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 220, VH CDR2 having the amino acid sequence of SEQ ID NO: 221, and VH CDR3 having the amino acid sequence of SEQ ID NO: 222; and VL, comprising (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 223, VL CDR2 having the amino acid sequence of SEQ ID NO: 224, and VL CDR3 having the amino acid sequence of SEQ ID NO: 225. In one embodiment, the first binding domain includes VH, comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 226, VH CDR2 having the amino acid sequence of SEQ ID NO: 227, and VH CDR3 having the amino acid sequence of SEQ ID NO: 228; and VL, comprising (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 229, VL CDR2 having the amino acid sequence of SEQ ID NO: 230, and VL CDR3 having the amino acid sequence of SEQ ID NO: 231. In some embodiments, the first binding domain includes VH having the amino acid sequence of SEQ ID NO: 34. In some embodiments, the first binding domain includes VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain includes VH having the amino acid sequence of SEQ ID NO: 34 and VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain includes VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 34. In some embodiments, the first binding domain includes VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain includes VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 34 and VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 8.

[0153] In one embodiment of the multispecific TRGV9 antibody provided herein, the first binding domain that binds to TRGV9 includes the VH and VL amino acid sequences of L7A5_3(TRGV9_3). In one embodiment, the first binding domain includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 35. In one embodiment, the first binding domain includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 8. In one embodiment, the first binding domain includes (i) VH comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequence of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 35, and (ii) VL comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequence of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of VL VL CDR3 having the amino acid sequence of SEQ ID NO: 8. In one embodiment, the first binding domain includes (i) VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 32, and (ii) VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 4, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VL CDR3 having the amino acid sequence of SEQ ID NO: 6. In one embodiment, the first binding domain comprises (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 232, VH CDR2 having the amino acid sequence of SEQ ID NO: 233, and VH CDR3 having the amino acid sequence of SEQ ID NO: 234, and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 235, VL CDR2 having the amino acid sequence of SEQ ID NO: 236, and VL CDR3 having the amino acid sequence of SEQ ID NO: 237.In one embodiment, the first binding domain includes VH, comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 238, VH CDR2 having the amino acid sequence of SEQ ID NO: 239, and VH CDR3 having the amino acid sequence of SEQ ID NO: 240, and (ii) VL, comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 241, VL CDR2 having the amino acid sequence of SEQ ID NO: 242, and VL CDR3 having the amino acid sequence of SEQ ID NO: 243. In one embodiment, the first binding domain includes VH, comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 244, VH CDR2 having the amino acid sequence of SEQ ID NO: 245, and VH CDR3 having the amino acid sequence of SEQ ID NO: 246, and (ii) VL, comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 247, VL CDR2 having the amino acid sequence of SEQ ID NO: 248, and VL CDR3 having the amino acid sequence of SEQ ID NO: 249. In one embodiment, the first binding domain includes (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 250, VH CDR2 having the amino acid sequence of SEQ ID NO: 251, and VH CDR3 having the amino acid sequence of SEQ ID NO: 252, and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 253, VL CDR2 having the amino acid sequence of SEQ ID NO: 254, and VL CDR3 having the amino acid sequence of SEQ ID NO: 255. In one embodiment, the first binding domain includes (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 250, VH CDR2 having the amino acid sequence of SEQ ID NO: 704, and VH CDR3 having the amino acid sequence of SEQ ID NO: 705, and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 253, VL CDR2 having the amino acid sequence of SEQ ID NO: 254, and VL CDR3 having the amino acid sequence of SEQ ID NO: 255.In one embodiment, the first binding domain includes VH, comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 256, VH CDR2 having the amino acid sequence of SEQ ID NO: 257, and VH CDR3 having the amino acid sequence of SEQ ID NO: 258, and (ii) VL, comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 259, VL CDR2 having the amino acid sequence of SEQ ID NO: 260, and VL CDR3 having the amino acid sequence of SEQ ID NO: 261. In one embodiment, the first binding domain includes VH, comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 262, VH CDR2 having the amino acid sequence of SEQ ID NO: 263, and VH CDR3 having the amino acid sequence of SEQ ID NO: 264, and (ii) VL, comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 265, VL CDR2 having the amino acid sequence of SEQ ID NO: 266, and VL CDR3 having the amino acid sequence of SEQ ID NO: 267. In some embodiments, the first binding domain includes VH having the amino acid sequence of SEQ ID NO: 35. In some embodiments, the first binding domain includes VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain includes VH having the amino acid sequence of SEQ ID NO: 35 and VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain includes VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 35. In some embodiments, the first binding domain includes VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain includes VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 35 and VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 8.

[0154] In one embodiment of the multispecific TRGV9 antibody provided herein, the first binding domain that binds to TRGV9 includes the VH and VL amino acid sequences of L7A5_4(TRGV9_4). In one embodiment, the first binding domain includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 36. In one embodiment, the first binding domain includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 8. In one embodiment, the first binding domain includes (i) VH comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequence of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 36, and (ii) VL comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequence of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of VL VL CDR3 having the amino acid sequence of SEQ ID NO: 8. In one embodiment, the first binding domain includes (i) VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 33, and (ii) VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 4, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VL CDR3 having the amino acid sequence of SEQ ID NO: 6. In one embodiment, the first binding domain comprises (i) VH, which includes VH CDR1 having the amino acid sequence of SEQ ID NO: 268, VH CDR2 having the amino acid sequence of SEQ ID NO: 269, and VH CDR3 having the amino acid sequence of SEQ ID NO: 270, and (ii) VL, which includes VL CDR1 having the amino acid sequence of SEQ ID NO: 271, VL CDR2 having the amino acid sequence of SEQ ID NO: 272, and VL CDR3 having the amino acid sequence of SEQ ID NO: 273.In one embodiment, the first binding domain includes VH, comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 274, VH CDR2 having the amino acid sequence of SEQ ID NO: 275, and VH CDR3 having the amino acid sequence of SEQ ID NO: 276, and (ii) VL, comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 277, VL CDR2 having the amino acid sequence of SEQ ID NO: 278, and VL CDR3 having the amino acid sequence of SEQ ID NO: 279. In one embodiment, the first binding domain includes VH, comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 280, VH CDR2 having the amino acid sequence of SEQ ID NO: 281, and VH CDR3 having the amino acid sequence of SEQ ID NO: 282, and (ii) VL, comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 283, VL CDR2 having the amino acid sequence of SEQ ID NO: 284, and VL CDR3 having the amino acid sequence of SEQ ID NO: 285. In one embodiment, the first binding domain includes VH, comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 286, VH CDR2 having the amino acid sequence of SEQ ID NO: 287, and VH CDR3 having the amino acid sequence of SEQ ID NO: 288, and (ii) VL, comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 289, VL CDR2 having the amino acid sequence of SEQ ID NO: 290, and VL CDR3 having the amino acid sequence of SEQ ID NO: 291. In one embodiment, the first binding domain includes VH, comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 286, VH CDR2 having the amino acid sequence of SEQ ID NO: 706, and VH CDR3 having the amino acid sequence of SEQ ID NO: 707, and (ii) VL, comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 289, VL CDR2 having the amino acid sequence of SEQ ID NO: 290, and VL CDR3 having the amino acid sequence of SEQ ID NO: 291.In one embodiment, the first binding domain includes VH, comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 292, VH CDR2 having the amino acid sequence of SEQ ID NO: 293, and VH CDR3 having the amino acid sequence of SEQ ID NO: 294, and (ii) VL, comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 295, VL CDR2 having the amino acid sequence of SEQ ID NO: 296, and VL CDR3 having the amino acid sequence of SEQ ID NO: 297. In one embodiment, the first binding domain includes VH, comprising (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 298, VH CDR2 having the amino acid sequence of SEQ ID NO: 299, and VH CDR3 having the amino acid sequence of SEQ ID NO: 300, and (ii) VL, comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 301, VL CDR2 having the amino acid sequence of SEQ ID NO: 302, and VL CDR3 having the amino acid sequence of SEQ ID NO: 303. In some embodiments, the first binding domain includes VH having the amino acid sequence of SEQ ID NO: 36. In some embodiments, the first binding domain includes VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain includes VH having the amino acid sequence of SEQ ID NO: 36 and VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain includes VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 36. In some embodiments, the first binding domain includes VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain includes VH having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 36 and VL having an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 8.

[0155] In one embodiment of the multispecific TRGV9 antibody provided herein, the first binding domain that binds to TRGV9 includes the VH and VL amino acid sequences of TRGV9Ab_var17. In one embodiment, the first binding domain includes VH, which comprises VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH having the amino acid sequence of SEQ ID NO: 65. In one embodiment, the first binding domain includes VL, which comprises VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 66. In one embodiment, the first binding domain includes (i) VH comprising VH CDR1, VH CDR2, and VH CDR3, each having the amino acid sequences of VH VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 65, and (ii) VL comprising VL CDR1, VL CDR2, and VL CDR3, each having the amino acid sequences of VL VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of VL VL CDR3 having the amino acid sequence of SEQ ID NO: 66. In one embodiment of the multispecific TRGV9 antibody provided herein, the first binding domain includes the VH and VL amino...

Claims

1. A multispecific TRGV9 antibody comprising (a) a first binding domain that binds to T cell receptor γ-variable 9 (TRGV9), and (b) a second binding domain that binds to a second target which is CD33, TRBC1, BCMA, or PSMA, The first binding domain is, (1) (i) VH having the amino acid sequence of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively, (2) (i) VH having the amino acid sequence of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively, (3) (i) VH having the amino acid sequence of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively, or (4) (i) VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of VH having the amino acid sequence of SEQ ID NO: 133, and (ii) VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of VL having the amino acid sequence of VL having the amino acid sequence of VL having the amino acid sequence of SEQ ID NO: 134, A multispecific TRGV9 antibody wherein the second target is present on the surface of target cells, and the target cells are cancer cells selected from the group consisting of cells of adrenal cancer, anal cancer, appendiceal cancer, bile duct cancer, bladder cancer, bone cancer, brain cancer, breast cancer, cervical cancer, colorectal cancer, esophageal cancer, gallbladder cancer, gestational trophoblast cancer, head and neck cancer, Hodgkin lymphoma, intestinal cancer, kidney cancer, leukemia, liver cancer, lung cancer, melanoma, mesothelioma, multiple myeloma, neuroendocrine tumor, non-Hodgkin lymphoma, oral cancer, ovarian cancer, pancreatic cancer, prostate cancer, paranasal sinus cancer, skin cancer, soft tissue sarcoma, spinal cancer, gastric cancer, testicular cancer, pharyngeal cancer, thyroid cancer, uterine cancer, endometrial cancer, vaginal cancer, and vulvar cancer.

2. (a) The multispecific TRGV9 antibody is a bispecific antibody, (b) The multispecific TRGV9 antibody is a trispecific antibody, or (c) The multispecific TRGV9 antibody according to claim 1, wherein the multispecific TRGV9 antibody is a quadrispecific antibody.

3. A multispecific TRGV9 antibody, (a) A first binding domain that binds to TRGV9, wherein the first binding domain is (1) (i) VH having the amino acid sequence of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively, (2) (i) VH having the amino acid sequence of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively, (3) (i) VH having the amino acid sequence of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively, (4) (i) VH having the amino acid sequence of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively, (5) (i) VH having the amino acid sequence of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively, (6) (i) VH having the amino acid sequence of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively, and VL having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively, or (7) (i) VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of VH CDR1, VH CDR2, and VH CDR3, respectively, and (ii) VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of VL CDR1, VL CDR2, and VL CDR3, respectively, (b) comprising a second binding domain that binds to a second target which is CD33, TRBC1, BCMA, or PSMA, A multispecific TRGV9 antibody wherein the second target is present on the surface of target cells, and the target cells are cancer cells selected from the group consisting of cells of adrenal cancer, anal cancer, appendiceal cancer, bile duct cancer, bladder cancer, bone cancer, brain cancer, breast cancer, cervical cancer, colorectal cancer, esophageal cancer, gallbladder cancer, gestational trophoblast cancer, head and neck cancer, Hodgkin lymphoma, intestinal cancer, kidney cancer, leukemia, liver cancer, lung cancer, melanoma, mesothelioma, multiple myeloma, neuroendocrine tumor, non-Hodgkin lymphoma, oral cancer, ovarian cancer, pancreatic cancer, prostate cancer, paranasal sinus cancer, skin cancer, soft tissue sarcoma, spinal cancer, gastric cancer, testicular cancer, pharyngeal cancer, thyroid cancer, uterine cancer, endometrial cancer, vaginal cancer, and vulvar cancer.

4. A nucleic acid encoding a multispecific TRGV9 antibody according to any one of claims 1 to 3.

5. A vector comprising the nucleic acid described in claim 4.

6. A host cell comprising the vector described in claim 5.

7. A pharmaceutical composition comprising a multispecific TRGV9 antibody according to any one of claims 1 to 3 and a pharmaceutically acceptable carrier.

8. A method for producing the pharmaceutical composition described in claim 7, comprising combining a multispecific TRGV9 antibody described in any one of claims 1 to 3 with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition.

9. A composition for use in a method for activating T cells expressing TRGV9, wherein the composition comprises a multispecific TRGV9 antibody according to any one of claims 1 to 3, and the method comprises contacting the T cells with the multispecific TRGV9 antibody.

10. A process for producing a multispecific TRGV9 antibody according to any one of claims 1 to 3, the process comprising: obtaining a first binding domain that binds to TRGV9 present on a T cell; obtaining a second binding domain that binds to a second target on the surface of a target cell; and providing a multispecific TRGV9 antibody according to any one of claims 1 to 3 that binds to TRGV9 present on a T cell and the second target on the surface of a target cell.

11. A composition for use in a method for directing T cells expressing TRGV9 to target cells, wherein the composition comprises a multispecific TRGV9 antibody according to any one of claims 1 to 3, the method comprises contacting the multispecific TRGV9 antibody with the target cells, the second target is located on the surface of the target cells, and the contact directs the T cells to the target cells.

12. A composition for use in a method for inhibiting the growth or proliferation of target cells, wherein the composition comprises a multispecific TRGV9 antibody according to any one of claims 1 to 3, and the method comprises contacting the multispecific TRGV9 antibody with target cells on which a second target exists on the surface of the target cells, wherein the contact occurs in the presence of T cells expressing TRGV9, and the contact results in inhibition of the growth or proliferation of the target cells.

13. A composition for use in a method for eliminating target cells in a subject, wherein the composition comprises a multispecific TRGV9 antibody according to any one of claims 1 to 3, and the method comprises contacting the multispecific TRGV9 antibody with the target cells on which the second target is present on the surface of the target cells, wherein the contact occurs in the presence of T cells expressing TRGV9, and the contact results in the elimination of the target cells.

14. A composition for use in a method for treating a disease in a subject, wherein the composition comprises a multispecific TRGV9 antibody according to any one of claims 1 to 3, and the method comprises administering an effective amount of the multispecific TRGV9 antibody to the subject, wherein the disease is caused in whole or in part by target cells on which the second target is present on the surface of the target cells.

15. The composition according to claim 13 or 14, wherein the subject is a subject requiring the method described above.

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