Materials and methods for modulating t cell mediated immunity

Abstract

To provide anti-T cell receptor gamma 9 (TRGV9) antibodies or antigen binding fragments thereof.SOLUTION: The present invention provides nucleic acids encoding anti-TRGV9 antibodies, compositions comprising the antibodies, methods of producing the antibodies, and methods of using the antibodies for treating or preventing diseases, such as cancer. In some embodiments, the antibodies comprise a heavy chain variable region (VH) and a light chain variable region (VL).SELECTED DRAWING: None

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application is a continuation of U.S. patent application Ser. No. 62 / 844,959, filed May 8, 2019. U.S. Patent Application No. 62 / 844,966, filed May 8, 2019; U.S. Patent Application No. 62 / 844,970, filed May 8, 2019 No. 62 / 844,976 filed on May 8, 2019, and U.S. Patent Application No. This application claims the benefit of U.S. Patent Application No. 62 / 844,995, each of which is hereby incorporated by reference. , which is incorporated herein by reference in its entirety.

[0002] FIELD OF THE INVENTION The present invention relates to, inter alia, anti-TRGV9 molecules, including anti-TRGV9 antibodies, anti-TRGV9 / anti-cancer Antigen-related bispecific antibodies, as well as nucleic acids and expression vectors encoding the antibodies, The present invention also relates to recombinant cells containing the antibody, and compositions containing the antibody. Methods of using antibodies to kill cells are provided.

[0003] (Reference to electronically submitted sequence listing) This application is filed under the file name "14620-021-228_SEQLIST" and 2020 Sequence listing in ASCII format with a creation date of May 4, 2015, and a size of 349,509 bytes via EFS-Web as a sequence listing. The sequence listing submitted herewith is a part of the present specification and is incorporated herein by reference in its entirety. Be absorbed. Summary of the Invention [Means for solving the problem]

[0004] In one embodiment, T Cell Receptor Gamma Variable 9 (TRG Provided herein are antibodies that bind to IL-14 (V9). In some embodiments, the antibody comprises a heavy chain The heavy chain variable region (VH) and the light chain variable region (LCH) are ble region, VL).

[0005] In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) a sequence The VH complementarity determining region having the amino acid sequence of No. 1 on, CDR)1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and SEQ ID NO: 31 and (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 4. a VL CDR1 having the amino acid sequence of SEQ ID NO: 5, a VL CDR2 having the amino acid sequence of SEQ ID NO: 6, and and a VL comprising a VL CDR3 having the amino acid sequence of SEQ ID NO: 6. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 34. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO: 8. In the example, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 34 and a VH having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody specifically binds to TRGV9. In other embodiments, TRGV9 is present on the surface of γδ T cells. In certain embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is an IgG1, IgG2, IgG3, or IgG4 isotype. In some embodiments, the antibody is a bispecific antibody. In other embodiments, the antibody is multivalent. In other embodiments, the antibody binds to at least three antigens. In some embodiments, the antibody is capable of binding to at least five antigens. This can be done.

[0006] In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) a sequence VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH having the amino acid sequence of SEQ ID NO: 2 a VH comprising a VH CDR2 and a VH CDR3 having the amino acid sequence of SEQ ID NO: 32; (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 4, the amino acid sequence of SEQ ID NO: 5 and a VL CDR3 having the amino acid sequence of SEQ ID NO: 6. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO: 35. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 35. and a VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody In other embodiments, TRGV9 specifically binds to a γδ T cell surface. In some embodiments, the antibody is a humanized antibody. In some embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is an IgG1, IgG2, or IgG3 antibody. In some embodiments, the antibody is a bispecific antibody. In certain embodiments, the antibody is multivalent. In other embodiments, the antibody is In some embodiments, the antibody is capable of binding to at least three antigens. It can bind to at least five antigens.

[0007] In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) a sequence VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH having the amino acid sequence of SEQ ID NO: 2 a VH comprising a VH CDR2 and a VH CDR3 having the amino acid sequence of SEQ ID NO: 33; (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 4, the amino acid sequence of SEQ ID NO: 5 and a VL CDR3 having the amino acid sequence of SEQ ID NO: 6. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO: 36. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 36. and a VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody In another embodiment, TRGV9 specifically binds to a γδ T cell surface. In some embodiments, the antibody is a humanized antibody. In some embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is an IgG1, IgG2, or IgG3 antibody. In some embodiments, the antibody is a bispecific antibody. In certain embodiments, the antibody is multivalent. In other embodiments, the antibody is In some embodiments, the antibody is capable of binding to at least three antigens. It can bind to at least five antigens.

[0008] In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) a sequence VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 76 a VH comprising a VH CDR2 and a VH CDR3 having the amino acid sequence of SEQ ID NO: 3; (ii) 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 a VL CDR2 having the amino acid sequence of SEQ ID NO: 6. In another aspect, provided herein is an antibody that binds to TRGV9, comprising an anti- The antibody comprises (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 60, an amino acid sequence of SEQ ID NO: 61, and a VH CDR2 having the amino acid sequence of SEQ ID NO: 62. VH CDR2 having the amino acid sequence of SEQ ID NO: 62, and VH CDR3 having the amino acid sequence of SEQ ID NO: 63. and (ii) a VH CDR1 having the amino acid sequence of SEQ ID NO: 63, comprising R3; 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 some embodiments, the antibody comprises a VL comprising a VL CDR3 comprising SEQ ID NO: In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 6. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO: 65. and a VL having the amino acid sequence of SEQ ID NO: 66. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 67. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO: 68. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 67 and a VH having the amino acid sequence of SEQ ID NO: 68 and a VL having the amino acid sequence of: In another embodiment, TRGV9 is present on the surface of γδ T cells. In some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is In other embodiments, the antibody is an IgG1, IgG2, IgG3, or IgG1 antibody. In some embodiments, the antibody is a bispecific antibody. In certain embodiments, the antibody is multivalent. In other embodiments, the antibody has at least three In some embodiments, the antibody is capable of binding to at least five antigens. It can be bonded to the original.

[0009] In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) a sequence VH CDR1 having the amino acid sequence of SEQ ID NO: 98, VH CDR2 having the amino acid sequence of SEQ ID NO: 99 VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 100. H, and (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO: 101, SEQ ID NO: 102 and VL CDR2 having the amino acid sequence of SEQ ID NO: 103. In some embodiments, the antibody comprises a VL comprising a L CDR3. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 105. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO: 104. and a VL having the amino acid sequence of SEQ ID NO: 105. In some embodiments, the antibody specifically binds to TRGV9. TRGV9 is present on the surface of γδ T cells. In some embodiments, the antibody In certain embodiments, the antibody is an IgG antibody. In other embodiments, The antibody may be of the IgG1, IgG2, IgG3, or IgG4 isotype. In embodiments, the antibody is a bispecific antibody. In certain embodiments, the antibody is multivalent. In other embodiments, the antibody is capable of binding to at least three antigens. In some embodiments, the antibody is capable of binding to at least five antigens.

[0010] In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) a sequence 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 a VH CDR3 having the amino acid sequence of SEQ ID NO: 109. , VH, and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 110, SEQ ID NO: 1 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 some embodiments, the antibody comprises a VL comprising a VL CDR3 comprising SEQ ID NO: 1. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 1. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO: 1. VH having the amino acid sequence of SEQ ID NO: 13 and VL having the amino acid sequence of SEQ ID NO: 114. In some embodiments, the antibody specifically binds to TRGV9. In some embodiments, the antibody is In certain embodiments, the antibody is an IgG antibody. In some cases, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype. In some embodiments, the antibody is a bispecific antibody. In other embodiments, the antibody is capable of binding to at least three antigens. In some embodiments, the antibody is capable of binding to at least five antigens.

[0011] In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) a sequence 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 a VH CDR3 having the amino acid sequence of SEQ ID NO: 119. , VH, and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 120, SEQ ID NO: 1 VL CDR2 having the amino acid sequence of SEQ ID NO: 122, and In some embodiments, the antibody comprises a VL comprising a VL CDR3 comprising SEQ ID NO: 1. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 1. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO: 1. VH having the amino acid sequence of SEQ ID NO: 23 and VL having the amino acid sequence of SEQ ID NO: 124. In some embodiments, the antibody specifically binds to TRGV9. In some embodiments, the antibody is In certain embodiments, the antibody is an IgG antibody. In some cases, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype. In some embodiments, the antibody is a bispecific antibody. In other embodiments, the antibody is capable of binding to at least three antigens. In some embodiments, the antibody is capable of binding to at least five antigens.

[0012] In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) a sequence 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 a VH CDR3 having the amino acid sequence of SEQ ID NO: 129. , VH, and (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO: 130, SEQ ID NO: 1 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 some embodiments, the antibody comprises a VL comprising a VL CDR3 comprising SEQ ID NO: 1. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 1. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO: 1. VH having the amino acid sequence of SEQ ID NO: 33 and VL having the amino acid sequence of SEQ ID NO: 134. In some embodiments, the antibody specifically binds to TRGV9. In some embodiments, the antibody is In certain embodiments, the antibody is an IgG antibody. In some cases, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype. In some embodiments, the antibody is a bispecific antibody. In other embodiments, the antibody is capable of binding to at least three antigens. In some embodiments, the antibody is capable of binding to at least five antigens.

[0013] Also provided are nucleic acids encoding antibodies that bind to TRGV9 provided herein. Also provided herein are vectors containing nucleic acids encoding antibodies that bind to TRGV9. Also provided herein are vectors encoding antibodies that bind to TRGV9. Also provided are host cells containing vectors containing nucleic acids comprising the TRs provided herein. A vector containing a nucleic acid encoding an antibody that binds to GV9 and a package therefor. Yes, kits are provided.

[0014] Also provided herein are antibodies that bind to TRGV9 and a pharmaceutically acceptable carrier. Also provided is a method for producing the pharmaceutical composition, the method comprising: , comprising combining the antibody with a pharmaceutically acceptable carrier to obtain a pharmaceutical composition.

[0015] Also provided is a method of activating γδ T cells expressing TRGV9, the method comprising: The method includes contacting a T cell with an antibody that binds to TRGV9 provided herein. In some embodiments, the contacting comprises contacting a control γδ T cell that expresses TRGV9 with a control γδ T cell that expresses TRGV9. In comparison, this results in increased expression of CD69, CD25, and / or granzyme B. In one embodiment, a method for inactivating γδ T cells expressing TRGV9 is provided, the method comprising: contacting the cell with an antibody that binds to TRGV9 provided herein; In one embodiment, a method of blocking activation of γδ T cells expressing TRGV9 is provided, the method comprising: The method includes contacting a T cell with an antibody that binds to TRGV9 provided herein. Also provided is a method of modulating the activity of γδ T cells expressing TRGV9, the method comprising: δ T cells with an antibody that binds to TRGV9 provided herein. .

[0016] In another embodiment, (a) a first binding domain that binds to TRGV9; and (b) a TRGV9 and a second binding domain that binds to a second target that is not a In certain embodiments, the first binding domain of the bispecific antibody is In some embodiments, TRGV9 specifically binds to γδ T cells. In some embodiments, the antibody is a humanized antibody. In certain embodiments, In other embodiments, the antibody is an IgG antibody. 3, or IgG4 isotype.

[0017] In another aspect, provided herein is a bispecific antibody, the antibody (a) binding to TRGV9. (b) a first binding domain that binds to a second target that is not TRGV9; a first binding domain, the first binding domain having (i) the amino acid sequence of SEQ ID NO: 1; VH CDR1 having the amino acid sequence of SEQ ID NO: 2, and VH CDR2 having the amino acid sequence of SEQ ID NO: 3 (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 4; VL CDR1 having the amino acid sequence of SEQ ID NO: 5, VL CDR2 having the amino acid sequence of SEQ ID NO: 6, and VL CDR3 having the amino acid sequence of SEQ ID NO: 7. and a VL comprising a VL CDR3 having the amino acid sequence of SEQ ID NO: 6. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 7. In some embodiments, the first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:8. In some embodiments, the first binding domain has the amino acid sequence of SEQ ID NO:7. and a VL having the amino acid sequence of SEQ ID NO: 8. The first binding domain of the bispecific antibody specifically binds to TRGV9. In some embodiments, TRGV9 is present on the surface of γδ T cells. The antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In some embodiments, the antibody is an IgG1, IgG2, IgG3, or IgG4 isotype.

[0018] In another aspect, provided herein is a bispecific antibody, the antibody (a) binding to TRGV9. (b) a first binding domain that binds to a second target that is not TRGV9; a first binding domain, the first binding domain having (i) the amino acid sequence of SEQ ID NO: 1; VH CDR1, 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) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 4. a VL CDR1 having the amino acid sequence of SEQ ID NO: 5, a VL CDR2 having the amino acid sequence of SEQ ID NO: 6, and and a VL comprising a VL CDR3 having the amino acid sequence of SEQ ID NO: 6. In an embodiment, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:34. In some embodiments, the first binding domain comprises a V having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises the amino acid sequence of SEQ ID NO: 34. and a VL having the amino acid sequence of SEQ ID NO: 8. The first binding domain of the bispecific antibody specifically binds to TRGV9. In some embodiments, TRGV9 is present on the surface of γδ T cells. In certain embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In this embodiment, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype. be.

[0019] In another aspect, provided herein is a bispecific antibody, the antibody (a) binding to TRGV9. (b) a first binding domain that binds to a second target that is not TRGV9; a first binding domain, the first binding domain having (i) the amino acid sequence of SEQ ID NO: 1; VH CDR1, 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) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 4. a VL CDR1 having the amino acid sequence of SEQ ID NO: 5, a VL CDR2 having the amino acid sequence of SEQ ID NO: 6, and and a VL comprising a VL CDR3 having the amino acid sequence of SEQ ID NO: 6. In an embodiment, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:35. In some embodiments, the first binding domain comprises a V having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises the amino acid sequence of SEQ ID NO: 35. and a VL having the amino acid sequence of SEQ ID NO: 8. The first binding domain of the bispecific antibody specifically binds to TRGV9. In some embodiments, TRGV9 is present on the surface of γδ T cells. In certain embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In this embodiment, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype. be.

[0020] In another aspect, provided herein is a bispecific antibody, the antibody (a) binding to TRGV9. (b) a first binding domain that binds to a second target that is not TRGV9; a first binding domain, the first binding domain having (i) the amino acid sequence of SEQ ID NO: 1; VH CDR1, 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) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 4. a VL CDR1 having the amino acid sequence of SEQ ID NO: 5, a VL CDR2 having the amino acid sequence of SEQ ID NO: 6, and and a VL comprising a VL CDR3 having the amino acid sequence of SEQ ID NO: 6. In an embodiment, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:36. In some embodiments, the first binding domain comprises a V having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises the amino acid sequence of SEQ ID NO: 36. and a VL having the amino acid sequence of SEQ ID NO: 8. The first binding domain of the bispecific antibody specifically binds to TRGV9. In some embodiments, TRGV9 is present on the surface of γδ T cells. In certain embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In this embodiment, the antibody is of the IgG1, IgG2, IgG3, or IgG4 isotype. be.

[0021] In another aspect, provided herein is a bispecific antibody, the antibody (a) binding to TRGV9. (b) a first binding domain that binds to a second target that is not TRGV9; a first binding domain, the first binding domain having (i) the amino acid sequence of SEQ ID NO: 1; VH CDR1, 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) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 77. VL CDR1 having the amino acid sequence of SEQ ID NO: 5, VL CDR2 having the amino acid sequence of SEQ ID NO: 6, and and a VL comprising a VL CDR3 having the amino acid sequence of SEQ ID NO:6. Provided herein are bispecific antibodies, the antibodies comprising: (a) a first antibody that binds to TRGV9; (b) a second binding domain that binds to a second target that is not TRGV9; and the first binding domain comprises (i) a VH CD having the amino acid sequence of SEQ ID NO: 60. R1, a VH CDR2 having the amino acid sequence of SEQ ID NO: 61, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 62 and (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 63. a VL CDR1 having the amino acid sequence of SEQ ID NO: 64, a VL CDR2 having the sequence and a VL comprising a VL CDR3 having the amino acid sequence of No. 6. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 65. In some embodiments, the first binding domain comprises a VL having the amino acid sequence of SEQ ID NO: 66. In some embodiments, the first binding domain comprises the amino acid sequence of SEQ ID NO: 65. and a VL having the amino acid sequence of SEQ ID NO: 66. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 67. In some embodiments, the first binding domain comprises a VL having the amino acid sequence of SEQ ID NO: 68. In some embodiments, the first binding domain comprises the amino acid sequence of SEQ ID NO: 67. and a VL having the amino acid sequence of SEQ ID NO: 68. The first binding domain of the specific antibody specifically binds to TRGV9. In some embodiments, TRGV9 is present on the surface of γδ T cells. The antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In some embodiments, the antibody is an IgG1, IgG2, IgG3, or IgG4 isotype.

[0022] In another aspect, provided herein is a bispecific antibody, the antibody (a) binding to TRGV9. (b) a first binding domain that binds to a second target that is not TRGV9; and a binding domain, wherein the first binding domain (i) has the amino acid sequence of SEQ ID NO: 89. VH CDR1 having the amino acid sequence of SEQ ID NO: 90, VH CDR2 having the amino acid sequence of SEQ ID NO: (ii) a VH comprising a VH CDR3 having an amino acid sequence of SEQ ID NO: 92; VL CDR1 having the amino acid sequence of SEQ ID NO: 93 2, and a VL comprising a VL CDR3 having the amino acid sequence of SEQ ID NO: 94. In some embodiments, the first binding domain comprises a V having the amino acid sequence of SEQ ID NO: 95. In some embodiments, the first binding domain comprises the amino acid sequence of SEQ ID NO: 96. In some embodiments, the first binding domain comprises a VL having the sequence SEQ ID NO: 95. and a VL having the amino acid sequence of SEQ ID NO: 96. In certain embodiments, the first binding domain of the bispecific antibody specifically binds to TRGV9. In some embodiments, TRGV9 is present on the surface of γδ T cells. In some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG In other embodiments, the antibody is an IgG1, IgG2, IgG3, or IgG4 antibody. It is an isotype.

[0023] In another aspect, provided herein is a bispecific antibody, the antibody (a) binding to TRGV9. (b) a first binding domain that binds to a second target that is not TRGV9; and a binding domain, wherein the first binding domain has (i) the amino acid sequence of SEQ ID NO: 98. VH CDR1 having the amino acid sequence of SEQ ID NO: 99, VH CDR2 having the amino acid sequence of SEQ ID NO: (ii) a VH comprising a VH CDR3 having an amino acid sequence of SEQ ID NO: 101; VL CDR1 having the amino acid sequence of SEQ ID NO: 102 and a VL comprising a VL CDR2 and a VL CDR3 having the amino acid sequence of SEQ ID NO: 103. In some embodiments, the first binding domain comprises the amino acid sequence of SEQ ID NO: 104. In some embodiments, the first binding domain comprises a VH having SEQ ID NO: 105. In some embodiments, the first binding domain comprises a VL having the amino acid sequence: VH having the amino acid sequence of SEQ ID NO: 104 and VH having the amino acid sequence of SEQ ID NO: 105 In certain embodiments, the first binding domain of the bispecific antibody comprises a TRGV VL. In some embodiments, TRGV9 specifically binds to γδ T cells. In some embodiments, the antibody is a humanized antibody. In certain embodiments, In other embodiments, the antibody is an IgG antibody. 3, or IgG4 isotype.

[0024] In another aspect, provided herein is a bispecific antibody, the antibody (a) binding to TRGV9. (b) a first binding domain that binds to a second target that is not TRGV9; and a binding domain, wherein the first binding domain (i) has the amino acid sequence of SEQ ID NO: 107. a VH CDR1 having the amino acid sequence of SEQ ID NO: 108, a VH CDR2 having the sequence (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 1; VL CDR1 having the amino acid sequence of SEQ ID NO: 10, VL CDR2 having the amino acid sequence of SEQ ID NO: 111 a VL CDR2, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 112; In some embodiments, the first binding domain comprises the amino acid sequence of SEQ ID NO: 113. In some embodiments, the first binding domain comprises a VH having the sequence SEQ ID NO: 1. In some embodiments, the first binding domain comprises a VL having a sequence of 14 amino acids. VH having the amino acid sequence of SEQ ID NO: 113 and VH having the amino acid sequence of SEQ ID NO: 114. In certain embodiments, the first binding domain of the bispecific antibody comprises a VL comprising a TR In some embodiments, TRGV9 specifically binds to the γδ T cell surface. In some embodiments, the antibody is a humanized antibody. In some embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is an IgG1, IgG2, or IgG3 antibody. It is of the IgG3 or IgG4 isotype.

[0025] In another aspect, provided herein is a bispecific antibody, the antibody (a) binding to TRGV9. (b) a first binding domain that binds to a second target that is not TRGV9; a first binding domain having (i) the amino acid sequence of SEQ ID NO: 117; a VH CDR1 having the amino acid sequence of SEQ ID NO: 118, a VH CDR2 having the sequence (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 1; VL CDR1 having the amino acid sequence of SEQ ID NO: 20, VL CDR2 having the amino acid sequence of SEQ ID NO: 121 a VL CDR2, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 122; In some embodiments, the first binding domain comprises the amino acid sequence of SEQ ID NO: 123. In some embodiments, the first binding domain comprises a VH having the sequence SEQ ID NO: 1. In some embodiments, the first binding domain comprises a VL having a 24 amino acid sequence. VH having the amino acid sequence of SEQ ID NO: 123 and VH having the amino acid sequence of SEQ ID NO: 124. In certain embodiments, the first binding domain of the bispecific antibody comprises a VL comprising a TR In some embodiments, TRGV9 specifically binds to the γδ T cell surface. In some embodiments, the antibody is a humanized antibody. In some embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is an IgG1, IgG2, or IgG3 antibody. It is of the IgG3 or IgG4 isotype.

[0026] In another aspect, provided herein is a bispecific antibody, the antibody (a) binding to TRGV9. (b) a first binding domain that binds to a second target that is not TRGV9; a first binding domain having (i) the amino acid sequence of SEQ ID NO: 127; a VH CDR1 having the amino acid sequence of SEQ ID NO: 128, a VH CDR2 having the sequence (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 129; VL CDR1 having the amino acid sequence of SEQ ID NO: 30, VL CDR2 having the amino acid sequence of SEQ ID NO: 131 a VL CDR2, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 132; In some embodiments, the first binding domain comprises the amino acid sequence of SEQ ID NO: 133. In some embodiments, the first binding domain comprises a VH having the sequence SEQ ID NO: 1. In some embodiments, the first binding domain comprises a VL having a sequence of 34 amino acids. VH having the amino acid sequence of SEQ ID NO: 133 and VH having the amino acid sequence of SEQ ID NO: 134. In certain embodiments, the first binding domain of the bispecific antibody comprises a VL comprising a TR In some embodiments, TRGV9 specifically binds to the γδ T cell surface. In some embodiments, the antibody is a humanized antibody. In some embodiments, the antibody is an IgG antibody. In other embodiments, the antibody is an IgG1, IgG2, or IgG3 antibody. It is of the IgG3 or IgG4 isotype.

[0027] In another embodiment, the antibody comprises (a) a first binding domain that binds to TRGV9; and (b) a first binding domain that binds to a surface of a cancer cell. and a second binding domain that binds to a cancer antigen present on the surface of the antibody. In some embodiments, the antigen on the surface of the cancer cell is a tumor-specific antigen, In certain embodiments, the first binding domain of the bispecific antibody is a tumor-associated antigen or a neoantigen. In some embodiments, the domain specifically binds to TRGV9. In some embodiments, the bispecific antibody is present on the surface of γδ T cells. Upon binding to TRGV9 on the surface of the cell and to antigens on the surface of the cancer cell, the cancer cell is killed. In some embodiments, the first binding domain is humanized or the second binding domain is humanized. The antibody may be humanized or both the first and second binding domains may be humanized. , and humanized. In some embodiments, the bispecific antibody is an IgG antibody. In some embodiments, the antibody is an IgG1, IgG2, IgG3, or IgG4 isoform. It is a type.

[0028] In another embodiment, the antibody comprises: (a) a first binding domain that binds to TRGV9; and (b) a first binding domain that binds to CD123. and a second binding domain that binds to a specific In this embodiment, the first binding domain of the bispecific antibody specifically binds to TRGV9. In some embodiments, TRGV9 is present on the surface of γδ T cells. In some embodiments, CD123 is on the surface of the cell. CD9 is present on the surface of γδ T cells, and CD123 is present on the surface of the cells. In embodiments, the bispecific antibody binds to TRGV9 on the surface of γδ T cells and When CD123 binds to the surface of cells, the cells bearing CD123 on their surface are killed. In embodiments, CD123 is on the surface of cancer cells. In certain embodiments, TRGV9 is present on the surface of γδ T cells, and CD123 is present on the surface of cancer cells. In embodiments, the bispecific antibody binds to TRGV9 on the surface of γδ T cells and In some embodiments, the first binding domain is a cytotoxic domain that binds to CD123 and kills the cancer cell. The main binding domain may be humanized, the second binding domain may be humanized, or the first binding domain may be humanized. Both the first binding domain and the second binding domain are humanized. In some embodiments, the bispecific antibody is an IgG antibody. G1, IgG2, IgG3, or IgG4 isotype.

[0029] In another aspect, provided herein is a bispecific antibody, the antibody (a) binding to TRGV9. and (b) a second binding domain that binds to CD123. The second binding domain comprises (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 9; VH CDR2 having the amino acid sequence of SEQ ID NO: 10, and the amino acid sequence of SEQ ID NO: 11 and (ii) a VH having the amino acid sequence of SEQ ID NO: 12. L CDR1, VL CDR2 having the amino acid sequence of SEQ ID NO: 13, and SEQ ID NO: 14 In some embodiments, the VL comprises a VL CDR3 having the amino acid sequence: The second binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 15. In embodiments, the second binding domain comprises a VL having the amino acid sequence of SEQ ID NO: 16. In some embodiments, the second binding domain has the amino acid sequence of SEQ ID NO: 15. and a VL having the amino acid sequence of SEQ ID NO: 16. In certain embodiments, TRGV9 is expressed on γδ T cells. CD123 is present on the surface of cells. The bispecific antibody binds to TRGV9 on the surface of γδ T cells and CD123 on the surface of the cells. Upon binding, cells bearing CD123 on their surface are killed. D123 is on the surface of cancer cells. In certain embodiments, TRGV9 is expressed by γδ T cells and CD123 is on the surface of cancer cells. The bispecific antibody binds to TRGV9 on the surface of γδ T cells and CD123 on the surface of the cells. In some embodiments, the first binding domain is a humanized The second binding domain may be humanized or the first binding domain and In some embodiments, both the first and second binding domains are humanized. In some embodiments, the antibody is an IgG antibody. It is an IgG3 or IgG4 isotype.

[0030] In some embodiments of the various bispecific antibodies provided herein, the antibody is directed against TRGV9. The first binding domain that binds is V having the amino acid sequence as provided herein. H CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and In some embodiments, the first binding domain that binds to TRGV9 comprises a VL CDR3 and a VL CDR4. The main VH domain has the amino acid sequence as provided herein. In some embodiments, the TRG The first binding domain that binds to V9 has an amino acid sequence as provided herein. The VL domain includes VL CDR1, VL CDR2, and VL CDR3. In some embodiments, the first binding domain that binds to TRGV9 is a polypeptide of any of the polypeptides provided herein. VH CDR1, VH CDR2, and VH CDR3 and VL CDR of a VL domain having the amino acid sequence provided herein In some embodiments, the VL CDR1, VL CDR2, and VL CDR3 are included. The first binding domain that binds to GV9 has the amino acid sequence as provided herein. In some embodiments, the first binding domain that binds to TRGV9 comprises a VH domain having the following structure: The domains include VL domains having amino acid sequences as provided herein. In some embodiments, the first binding domain that binds to TRGV9 is a polypeptide as provided herein. and a VH domain having an amino acid sequence as provided herein. and a VL domain having a sequence.

[0031] Also provided herein is (a) a first binding domain that binds to TRGV9. and (b) a second binding domain that binds to a second target that is not TRGV9. Nucleic acids encoding the alloantibodies are provided. Also provided herein are vectors containing nucleic acids encoding the bispecific antibodies. The present invention also includes a vector comprising nucleic acid encoding a bispecific antibody that binds to TRGV9, as provided by Also provided herein are host cells, including those capable of expressing TRGV9. The kit includes a vector containing nucleic acid encoding a human antibody and a package therefor. It is served.

[0032] In another aspect, (a) a first binding domain that binds to TRGV9, and (b) a TRGV and a second binding domain that binds to a second target other than 9, and a pharmaceutically acceptable carrier. Provided herein are pharmaceutical compositions comprising any of the bispecific antibodies provided herein. Both are contemplated in the pharmaceutical composition. In certain embodiments, the second binding domain is Binds to CD123.

[0033] In another aspect, a method for directing TRGV9-expressing γδ T cells to cancer cells is described herein. and a method for contacting γδ T cells with a bispecific antibody provided herein. In some embodiments, the contacting comprises contacting γδ T cells with cancer cells. Give direction.

[0034] In another aspect, a method for inhibiting the growth or proliferation of cancer cells that express a cancer antigen on the cell surface is provided. Provided herein are methods comprising contacting cancer cells with a bispecific antibody provided herein. In some embodiments, contacting the cancer cells with the pharmaceutical composition comprises: In some embodiments, the cancer cells are contacted with the bispecific antibody. During contact, the cells are in the presence of γδ T cells expressing TRGV9.

[0035] In another aspect, provided herein is a method for eliminating cancer cells in a subject, the method comprising: comprises administering to a subject an effective amount of a bispecific antibody as provided herein. In some embodiments, the subject is a subject in need of the method. In this embodiment, the subject is a human.

[0036] In another aspect, a method for activating γδ T cells expressing TRGV9 is provided herein. and the method comprises contacting γδ T cells with a bispecific antibody as provided herein. This includes:

[0037] Provided herein is an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof is a. a first heavy chain (HC1); and b. a second heavy chain (HC2); and c. the first light chain (LC1); d. a second light chain (LC2), HC1 is associated with LC1, HC2 is associated with LC2, and HC1 is i. SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3, respectively; ii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31, respectively; iii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32, respectively; or iv. comprising the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33, respectively. Heavy chain complementarity determining region 1 (HCDR) 1), HCDR2, and HCDR3, LC1 comprises the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. Light chain complementarity determining region 1 (LCDR) 1), LCDR2, and LCDR2, forming a binding site for a first antigen; HC2 and LC2 form a binding site for a second antigen. The TRGV9 bispecific antibody or antigen-binding fragment thereof is represented by SEQ ID NO: 7, SEQ ID NO: 34, SEQ ID NO: 35, or SEQ ID NO: 36 HC1 contains an amino acid sequence with 95% identity to the amino acid sequence of SEQ ID NO: 8. The amino acid sequence of the present invention comprises an amino acid sequence having at least 95% identity to the amino acid sequence of the present invention. In the present invention, an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof is 7, SEQ ID NO: 34, SEQ ID NO: 35, or SEQ ID NO: 36. HC1 comprises the amino acid sequence of SEQ ID NO:8, and LC1 comprises the amino acid sequence of SEQ ID NO:8.

[0038] Also, an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof is described herein. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof is provided in a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is L C1 is related to HC2, HC1 is related to LC1, and HC2 is related to LC 2, and HC1 is the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively. HCDR1, HCDR2, and HCDR3 each contain the sequence LCDR1 and LCDR2 containing the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6; and LCDR3, which form a binding site for a first antigen, and HC2 and LC2 , which forms a binding site for a second antigen. In one embodiment, an isolated TRGV9 bilayer The specific antibody or antigen-binding fragment thereof has at least one sequence that is specific to the amino acid sequence of SEQ ID NO:7. HC1 contains an amino acid sequence having 95% identity with SEQ ID NO: 8, and LC1 contains an amino acid sequence having 95% identity with SEQ ID NO: 8. The amino acid sequence may be at least 95% identical to the amino acid sequence. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof has the sequence HC1 comprises the amino acid sequence of SEQ ID NO: 7, and LC1 comprises the amino acid sequence of SEQ ID NO: 8. .

[0039] Also, an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof is described herein. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof is provided in a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is L C1 is related to HC2, HC1 is related to LC1, and HC2 is related to LC 2, and HC1 corresponds to the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31, respectively. HCDR1, HCDR2, and HCDR3 each contain the following amino acid sequences: LCDR1 and LCDR2 containing the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6 and LCDR3 to form a binding site for a first antigen, and In one embodiment, the isolated TRGV9 antibody forms a binding site for a second antigen. The bispecific antibody or antigen-binding fragment thereof may have a sequence similar to that of SEQ ID NO:34. HC1 comprises an amino acid sequence having at least 95% identity with SEQ ID NO: 8. The amino acid sequence of the present invention has at least 95% identity to the amino acid sequence of the present invention. In embodiments, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises: HC1 comprises the amino acid sequence of SEQ ID NO: 34, and LC1 comprises the amino acid sequence of SEQ ID NO: 8. Includes.

[0040] Also, an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof is described herein. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof is provided in a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is L C1 is related to HC2, HC1 is related to LC1, and HC2 is related to LC 2, and HC1 corresponds to the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32, respectively. HCDR1, HCDR2, and HCDR3 each contain the following amino acid sequences: LCDR1 and LCDR2 containing the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6 and LCDR3 to form a binding site for a first antigen, and In one embodiment, the isolated TRGV9 antibody forms a binding site for a second antigen. The bispecific antibody or antigen-binding fragment thereof may have a sequence similar to that of SEQ ID NO:35. HC1 comprises an amino acid sequence having at least 95% identity with SEQ ID NO: 8. The amino acid sequence of the present invention has at least 95% identity to the amino acid sequence of the present invention. In embodiments, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises: HC1 comprises the amino acid sequence of SEQ ID NO: 35, and LC1 comprises the amino acid sequence of SEQ ID NO: 8. Includes.

[0041] Also, an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof is described herein. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof is provided in a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is L C1 is related to HC2, HC1 is related to LC1, and HC2 is related to LC 2, and HC1 corresponds to the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33, respectively. HCDR1, HCDR2, and HCDR3 each contain the following amino acid sequences: LCDR1 and LCDR2 containing the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6 and LCDR3 to form a binding site for a first antigen, and In one embodiment, the isolated TRGV9 antibody forms a binding site for a second antigen. The bispecific antibody or antigen-binding fragment thereof may have a sequence similar to that of SEQ ID NO:36. HC1 comprises an amino acid sequence having at least 95% identity with SEQ ID NO: 8. The amino acid sequence of the present invention has at least 95% identity to the amino acid sequence of the present invention. In embodiments, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises: HC1 comprises the amino acid sequence of SEQ ID NO: 36, and LC1 comprises the amino acid sequence of SEQ ID NO: 8. Includes.

[0042] Also, an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof is described herein. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof is provided in a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is L C1 is related to HC2, HC1 is related to LC1, and HC2 is related to LC 2, and HC1 corresponds to the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 76, and SEQ ID NO: 3, respectively. HCDR1, HCDR2, and HCDR3 each contain the following amino acid sequences: LCDR1, LCDR2, LCDR3, LCDR4, LCDR5, LCDR6, LCDR7, LCDR8, LCDR9, LCDR10, LCDR11, LCDR12, LCDR13, LCDR14, LCDR15, LCDR16, LCDR17, LCDR18, LCDR19 ...11, LCDR19, LCDR112, LCDR13, LCDR14, LCDR15 HC2 and LCDR2, and LCDR3 form a binding site for a first antigen, 2 forms a binding site for a second antigen. In one embodiment, isolated TRGV9 The bispecific antibody or antigen-binding fragment thereof may be HC1 comprises an amino acid sequence having at least 95% identity with SEQ ID NO: LC1 No. 66. In another embodiment, an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises an HC1 comprising the amino acid sequence of SEQ ID NO: 65, and an LC1 comprising the amino acid sequence of SEQ ID NO: 66. In one embodiment, the isolated TRGV9 bispecific antibody or its antigen-binding The fragment has at least 95% identity to the amino acid sequence of SEQ ID NO:67. HC1 contains an amino acid sequence similar to that of SEQ ID NO: 68, and LC1 contains an amino acid sequence similar to that of SEQ ID NO: 69. In another embodiment, the isolated T The RGV9 bispecific antibody or antigen-binding fragment thereof has the amino acid sequence of SEQ ID NO: 67 and LC1 comprises the amino acid sequence of SEQ ID NO:68.

[0043] Also, an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof is described herein. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof is provided in a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is L C1 is related to HC2, HC1 is related to LC1, and HC2 is related to LC 2, and HC1 corresponds to the sequences of SEQ ID NO: 60, SEQ ID NO: 61, and SEQ ID NO: 62, respectively. HCDR1, HCDR2, and HCDR3 each contain an amino acid sequence. LCDR1, L comprising the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 64, and SEQ ID NO: 6 The first antigen-binding site is formed by the CDR2 and LCDR3. and LC2 form a binding site for a second antigen. The GV9 bispecific antibody or antigen-binding fragment thereof has the amino acid sequence of SEQ ID NO: 65. HC1 comprises an amino acid sequence having at least 95% identity to An amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 66 In another embodiment, an isolated TRGV9 bispecific antibody or its antigen-binding fragment is The ment comprises HC1 comprising the amino acid sequence of SEQ ID NO: 65, and LC1 comprises the amino acid sequence of SEQ ID NO: 66. In one embodiment, the isolated TRGV9 bispecific antibody or its anti- The original binding fragment has at least 95% identity to the amino acid sequence of SEQ ID NO:67. and LC1 comprises an HC1 having an amino acid sequence having the amino acid sequence of SEQ ID NO: 68. In another embodiment, the isolated polypeptide comprises an amino acid sequence having at least 95% identity to the polypeptide. The TRGV9 bispecific antibody or antigen-binding fragment thereof has the amino acid sequence of SEQ ID NO: 67. HC1 comprises the amino acid sequence of SEQ ID NO:68, and LC1 comprises the amino acid sequence of SEQ ID NO:69.

[0044] Also, an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof is described herein. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof is provided in a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is L C1 is related to HC2, HC1 is related to LC1, and HC2 is related to LC 2, and HC1 corresponds to the sequences of SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, respectively. HCDR1, HCDR2, and HCDR3 each contain an amino acid sequence. LCDR1 comprising the amino acid sequences of SEQ ID NO: 92, SEQ ID NO: 93, and SEQ ID NO: 94; a first antigen-binding site comprising LCDR2 and LCDR3; and and LC2 form a binding site for a second antigen. The RGV9 bispecific antibody or antigen-binding fragment thereof has the amino acid sequence of SEQ ID NO: 95 and LC1 comprises an HC1 having an amino acid sequence having at least 95% identity to , an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 96 In another embodiment, an isolated TRGV9 bispecific antibody or its antigen-binding fragment is provided. The fragment comprises HC1 having the amino acid sequence of SEQ ID NO: 95, and LC1 having the amino acid sequence of SEQ ID NO: 96. It contains the amino acid sequence of

[0045] Also, an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof is described herein. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof is provided in a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is L C1 is related to HC2, HC1 is related to LC1, and HC2 is related to LC 2, and HC1 is SEQ ID NO: 98, SEQ ID NO: 99, and SEQ ID NO: 100, respectively. LC1 comprises HCDR1, HCDR2, and HCDR3, each of which contains an amino acid sequence. LCs containing the amino acid sequences of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 103, respectively. DR1, LCDR2, and LCDR3, forming a binding site for a first antigen. HC2 and LC2 form a binding site for a second antigen. The TRGV9 bispecific antibody or antigen-binding fragment thereof has the amino acid sequence of SEQ ID NO: 104. HC1 containing an amino acid sequence having at least 95% identity to the amino acid sequence , LC1 has at least 95% identity to the amino acid sequence of SEQ ID NO: 105 In another embodiment, the isolated TRGV9 bispecific antibody or its The antigen-binding fragment comprises an HC1 comprising the amino acid sequence of SEQ ID NO: 104, and an LC1 comprising , comprising the amino acid sequence of SEQ ID NO: 105.

[0046] Also, an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof is described herein. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof is provided in a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is L C1 is related to HC2, HC1 is related to LC1, and HC2 is related to LC 2, and HC1 is SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 10 9 amino acid sequences, and HCDR1, HCDR2, and HCDR3, Containing the amino acid sequences of SEQ ID NO: 110, SEQ ID NO: 111, and SEQ ID NO: 112, respectively comprising LCDR1, LCDR2, and LCDR3, forming a binding site for a first antigen; In one embodiment, HC2 and LC2 form a binding site for a second antigen. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof is selected from the group consisting of SEQ ID NO: 113 HC1 containing an amino acid sequence having at least 95% identity to the amino acid sequence of LC1 has at least 95% identity to the amino acid sequence of SEQ ID NO: 114. In another embodiment, the isolated TRGV9 bispecific antibody or The antigen-binding fragment comprises an HC1 comprising the amino acid sequence of SEQ ID NO: 113, and an LC 1 comprises the amino acid sequence of SEQ ID NO:114.

[0047] Also, an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof is described herein. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof is provided in a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is L C1 is related to HC2, HC1 is related to LC1, and HC2 is related to LC 2, and HC1 is SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 11, respectively. 9 amino acid sequences, and HCDR1, HCDR2, and HCDR3, Each of the amino acid sequences of SEQ ID NO: 120, SEQ ID NO: 121, and SEQ ID NO: 122 is included. comprising LCDR1, LCDR2, and LCDR3, forming a binding site for a first antigen; In one embodiment, HC2 and LC2 form a binding site for a second antigen. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof is selected from the group consisting of SEQ ID NO: 123 HC1 containing an amino acid sequence having at least 95% identity to the amino acid sequence of LC1 has at least 95% identity to the amino acid sequence of SEQ ID NO: 124. In another embodiment, the isolated TRGV9 bispecific antibody or The antigen-binding fragment comprises an HC1 comprising the amino acid sequence of SEQ ID NO: 123, and an LC 1 comprises the amino acid sequence of SEQ ID NO:124.

[0048] Also, an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof is described herein. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof is provided in a) HC1, (b) HC2, (c) LC1, and (d) LC2, wherein HC1 is L C1 is related to HC2, HC1 is related to LC1, and HC2 is related to LC 2, and HC1 is SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 12 9 amino acid sequences, and HCDR1, HCDR2, and HCDR3, Containing the amino acid sequences of SEQ ID NO: 130, SEQ ID NO: 131, and SEQ ID NO: 132, respectively comprising LCDR1, LCDR2, and LCDR3, forming a binding site for a first antigen; In one embodiment, HC2 and LC2 form a binding site for a second antigen. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof is selected from the group consisting of SEQ ID NO: 133 HC1 containing an amino acid sequence having at least 95% identity to the amino acid sequence of LC1 has at least 95% identity to the amino acid sequence of SEQ ID NO: 134. In another embodiment, the isolated TRGV9 bispecific antibody or The antigen-binding fragment comprises an HC1 comprising the amino acid sequence of SEQ ID NO: 133, and an LC 1 comprises the amino acid sequence of SEQ ID NO:134.

[0049] In another embodiment, the binding site for the first antigen binds to TRGV9 on γδ T cells. Combine.

[0050] In another embodiment, the binding site for the second antigen is a cancer antigen present on the surface of a cancer cell. Combine with.

[0051] In another embodiment, the bispecific antibody binds to TRGV9 present on the surface of γδ T cells. The binding of cancer antigens that bind and are present on the surface of cancer cells results in the death of the cancer cells.

[0052] In another embodiment, the TRGV9 bispecific antibody comprises a humanized HC1 and a humanized LC1. nothing.

[0053] In another embodiment, HC2 and LC2 of the TRGV9 antibody bind to CD123.

[0054] In another embodiment, the bispecific antibody or antigen-binding fragment thereof is G2, IgG3, or IgG4 isotype.

[0055] In certain embodiments, the bispecific antibody or antigen-binding fragment thereof is an IgG4 antibody. It is a sotype.

[0056] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof has a saturation of about 5 EC<0.00pM50 Induces γδ T cell-dependent cytotoxicity of cancer cells in vitro Lead.

[0057] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof has a saturation of about 3 EC<0.00pM 50 Induces γδ T cell-dependent cytotoxicity of cancer cells in vitro Lead.

[0058] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof has a saturation of about 1 EC<60pM 50 Induces γδ T cell-dependent cytotoxicity of cancer cells in vitro Lead.

[0059] In one embodiment, EC 50 γδ T effector cells and Kasumi3 AML It is evaluated on a mixture of target cells.

[0060] In another embodiment, the effector cell to target cell ratio is from about 0.01:1 to about 5:1. be.

[0061] In yet another embodiment, the ratio of effector cells to target cells is about 0.1:1 to about 2:1 is.

[0062] In certain embodiments, the ratio of effector cells to target cells is about 1:1.

[0063] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof is a multivalent is.

[0064] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof comprises at least It can bind to at least three antigens.

[0065] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof comprises at least It can bind to at least five antigens.

[0066] Also provided is an isolated γδ T cell bispecific antibody or antigen-binding fragment thereof. The isolated γδ T cell bispecific antibody or antigen-binding fragment thereof is a. HC1 and b. HC2 and c. LC1; d. LC2, and HC1 is associated with LC1, HC2 is associated with LC2, HC1 and LC1 form the binding site for the first antigen on γδ T cells, HC2 and LC2 form the binding site for a second antigen.

[0067] Also, a first means capable of specifically binding to a T cell receptor gamma chain and a T cell receptor and a second means capable of specifically binding to a target molecule that is not a receptor gamma chain. Bispecific antibodies are provided herein.

[0068] Also disclosed are processes for generating molecules that can specifically bind to two or more target molecules. The molecule is an oligopeptide capable of binding to the T cell receptor gamma chain. or a process that serves to obtain a polypeptide and an oligopeptide capable of binding to a target. a step for obtaining a target molecule or polypeptide from the T cell receptor gamma chain and a target molecule; and (b) performing a step of providing a molecule capable of specifically binding to the molecule.

[0069] In one embodiment, an oligopeptide or polypeptide capable of binding to a target is obtained. The process for achieving the function is repeated n times, and the T cell receptor gamma chain and n target molecules are synthesized. and further comprising n steps for performing the function of providing a molecule capable of specifically binding to and n is at least 2.

[0070] Isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof is provided herein, a. HC1 and b. HC2 and c. LC1; d. LC2, and HC1 is associated with LC1, HC2 is associated with LC2, and HC1 is i. SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3, respectively; ii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31, respectively; iii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32, respectively; or iv. comprising the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33, respectively. comprising HCDR1, HCDR2, and HCDR3, LC1 comprises the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. A first molecule comprising LCDR1, LCDR2, and LCDR3 that specifically binds to Vγ9. HC2 forms a binding site for the antigen, and HC3 is SEQ ID NO: 9, SEQ ID NO: 10, and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 11; LC2 has the amino acid sequences of SEQ ID NO: 12, SEQ ID NO: 13, and SEQ ID NO: 14, respectively. and LCDR1, LCDR2, and LCDR3, which specifically bind to CD123. In one embodiment, the isolated anti-TRGV9 / Anti-CD123 bispecific antibodies or antigen-binding fragments include those represented by SEQ ID NO: 7, SEQ ID NO: 34, At least 95% of an amino acid sequence selected from SEQ ID NO: 35 or SEQ ID NO: 36 HC1 includes an amino acid sequence having identity to SEQ ID NO: 8, and LC1 includes an amino acid sequence having identity to SEQ ID NO: 8. In another embodiment, the amino acid sequence comprises an amino acid sequence having at least 95% identity to the sequence. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment is an amino acid sequence selected from sequence number 7, SEQ ID NO: 34, SEQ ID NO: 35, or SEQ ID NO: 36 and LC1 comprises the amino acid sequence of SEQ ID NO: 8. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment is Contains an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 15. HC2 contains LC2, which has at least 95% identity to the amino acid sequence of SEQ ID NO: 16. In another embodiment, the isolated anti-TRGV9 / anti-CD20 antibody comprises an amino acid sequence having the same identity as the isolated anti-TRGV9 / anti-CD20 antibody. 123 bispecific antibody or antigen-binding fragment comprising the amino acid sequence of SEQ ID NO: 15 HC2 comprises the amino acid sequence of SEQ ID NO:16, and LC2 comprises the amino acid sequence of SEQ ID NO:16.

[0071] Also, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or its antigen-binding flag (a) HC1; (b) HC2; (c) LC1; and (d) ) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is HCDR1 comprising the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively; LC1 comprises HCDR2 and HCDR3, and LC1 comprises SEQ ID NO: 4, SEQ ID NO: 5, and LCDR1, LCDR2, and LCDR3 comprising the amino acid sequence of SEQ ID NO:6. HC1 and HC2 form a binding site for the first antigen that specifically binds to Vγ9, respectively. HCDR1, H, H-L ... CDR2 and HCDR3, and LC2 are SEQ ID NO: 12 and SEQ ID NO: 13, respectively. and LCDR1, LCDR2, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 14. to form a binding site for a second antigen that specifically binds to CD123. In the form of an isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment, The compound has at least 95% identity to the selected amino acid sequence of SEQ ID NO:7. HC1 contains an amino acid sequence having at least one amino acid sequence similar to that of SEQ ID NO: 8, and LC1 contains at least one amino acid sequence similar to that of SEQ ID NO: 8. In another embodiment, the isolated anti-T comprises an amino acid sequence having at least 95% identity to the The RGV9 / anti-CD123 bispecific antibody or antigen-binding fragment has the amino acid sequence of SEQ ID NO: 7. and LC1 comprises the amino acid sequence of SEQ ID NO: 8. In this embodiment, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment is The amino acid sequence of SEQ ID NO: 15 has at least 95% identity to the amino acid sequence of SEQ ID NO: 15. HC2 comprising the sequence of SEQ ID NO: 16, and LC2 comprising at least 9 amino acid sequences of SEQ ID NO: 16. In another embodiment, the isolated anti-TRGV9 antibody comprises an amino acid sequence having 5% identity with the antibody. / Anti-CD123 bispecific antibodies or antigen-binding fragments may be HC2 comprises the amino acid sequence of SEQ ID NO:16, and LC2 comprises the amino acid sequence of SEQ ID NO:16.

[0072] Also, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or its antigen-binding flag (a) HC1; (b) HC2; (c) LC1; and (d) ) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is HCDR1 comprising the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31, respectively , HCDR2, and HCDR3, and LC1 is SEQ ID NO: 4, SEQ ID NO: 5, respectively. and LCDR1, LCDR2, and LCDR3 comprising the amino acid sequence of SEQ ID NO:6. This forms a binding site for the first antigen that specifically binds to Vγ9, and HC2 binds to it. HCDR1 comprising the amino acid sequences of SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11, respectively; HCDR2 and HCDR3, and LC2 are represented by SEQ ID NO: 12 and SEQ ID NO: 1, respectively. 3, and LCDR1, LCDR2, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 14. and forming a binding site for a second antigen that specifically binds to CD123. In embodiments, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding flag The ment has at least 95% identity to the selected amino acid sequence of SEQ ID NO: 34. and LC1 comprises an HC1 having an amino acid sequence having the amino acid sequence of SEQ ID NO: 8. In another embodiment, the isolated The anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment is SEQ ID NO: 34 and LC1 comprises the amino acid sequence of SEQ ID NO: 8. In embodiments, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment is A fragment is an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 15. HC2 contains the amino acid sequence of SEQ ID NO: 16, and LC2 contains at least the amino acid sequence of SEQ ID NO: 16. In another embodiment, the isolated anti-TR antibody comprises an amino acid sequence that has 95% identity with the The GV9 / anti-CD123 bispecific antibody or antigen-binding fragment may be an amino acid sequence of SEQ ID NO: 15. HC2 comprises the amino acid sequence of SEQ ID NO:16, and LC2 comprises the amino acid sequence of SEQ ID NO:16.

[0073] Also, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or its antigen-binding flag (a) HC1; (b) HC2; (c) LC1; and (d) ) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is HCDR1 comprising the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32, respectively , HCDR2, and HCDR3, and LC1 is SEQ ID NO: 4, SEQ ID NO: 5, respectively. and LCDR1, LCDR2, and LCDR3 comprising the amino acid sequence of SEQ ID NO:6. This forms a binding site for the first antigen that specifically binds to Vγ9, and HC2 binds to it. HCDR1 comprising the amino acid sequences of SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11, respectively; HCDR2 and HCDR3, and LC2 are represented by SEQ ID NO: 12 and SEQ ID NO: 1, respectively. 3, and LCDR1, LCDR2, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 14. and forming a binding site for a second antigen that specifically binds to CD123. In embodiments, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding flag The ment has at least 95% identity to the selected amino acid sequence of SEQ ID NO: 35. and LC1 comprises an HC1 having an amino acid sequence having the amino acid sequence of SEQ ID NO: 8. In another embodiment, the isolated The anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment is SEQ ID NO: 35 and LC1 comprises the amino acid sequence of SEQ ID NO: 8. In embodiments, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment is A fragment is an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 15. HC2 contains the amino acid sequence of SEQ ID NO: 16, and LC2 contains at least the amino acid sequence of SEQ ID NO: 16. In another embodiment, the isolated anti-TR antibody comprises an amino acid sequence that has 95% identity with the The GV9 / anti-CD123 bispecific antibody or antigen-binding fragment may be an amino acid sequence of SEQ ID NO: 15. HC2 comprises the amino acid sequence of SEQ ID NO:16, and LC2 comprises the amino acid sequence of SEQ ID NO:16.

[0074] Also, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or its antigen-binding flag (a) HC1; (b) HC2; (c) LC1; and (d) ) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is HCDR1 comprising the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33, respectively , HCDR2, and HCDR3, and LC1 is SEQ ID NO: 4, SEQ ID NO: 5, respectively. and LCDR1, LCDR2, and LCDR3 comprising the amino acid sequence of SEQ ID NO:6. This forms a binding site for the first antigen that specifically binds to Vγ9, and HC2 binds to it. HCDR1 comprising the amino acid sequences of SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11, respectively; HCDR2 and HCDR3, and LC2 are represented by SEQ ID NO: 12 and SEQ ID NO: 1, respectively. 3, and LCDR1, LCDR2, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 14. and forming a binding site for a second antigen that specifically binds to CD123. In embodiments, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding flag The ment has at least 95% identity to the selected amino acid sequence of SEQ ID NO: 36. and LC1 comprises an HC1 having an amino acid sequence having the amino acid sequence of SEQ ID NO: 8. In another embodiment, the isolated The anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment is SEQ ID NO: 36 and LC1 comprises the amino acid sequence of SEQ ID NO: 8. In embodiments, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment is A fragment is an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 15. HC2 contains the amino acid sequence of SEQ ID NO: 16, and LC2 contains at least the amino acid sequence of SEQ ID NO: 16. In another embodiment, the isolated anti-TR antibody comprises an amino acid sequence that has 95% identity with the The GV9 / anti-CD123 bispecific antibody or antigen-binding fragment may be an amino acid sequence of SEQ ID NO: 15. HC2 comprises the amino acid sequence of SEQ ID NO:16, and LC2 comprises the amino acid sequence of SEQ ID NO:16.

[0075] Also, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or its antigen-binding flag (a) HC1; (b) HC2; (c) LC1; and (d) ) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is HCDR1 comprising the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 76, and SEQ ID NO: 3, respectively LC1 comprises SEQ ID NO: 77, HCDR2, and HCDR3, respectively. 5, and LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 6. and HC2 forms a binding site for a first antigen that specifically binds to Vγ9. HCDR1 comprising the amino acid sequences of SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11, respectively. , HCDR2, and HCDR3, and LC2 is SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, S 13, and LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 14. 3 to form a binding site for a second antigen that specifically binds to CD123. In embodiments, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment is The fragment has at least 95% identity to the selected amino acid sequence of SEQ ID NO:65. and LC1 comprises an HC1 having an amino acid sequence having the amino acid sequence of SEQ ID NO: 66. In another embodiment, the isolated polypeptide comprises an amino acid sequence having at least 95% identity to the polypeptide. The anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment is represented by SEQ ID NO: HC1 comprises the amino acid sequence of SEQ ID NO: 65, and LC1 comprises the amino acid sequence of SEQ ID NO: 66. In one embodiment, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding The fragments are at least 95% identical to the selected amino acid sequence of SEQ ID NO:67. HC1 has an amino acid sequence having the same identity as SEQ ID NO: 68, In another embodiment, the amino acid sequence is at least 95% identical to The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment has the sequence HC1 comprises the amino acid sequence of SEQ ID NO: 67, and LC1 comprises the amino acid sequence of SEQ ID NO: 68. In another embodiment, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or anti- The original binding fragment has at least 95% identity to the amino acid sequence of SEQ ID NO: 15. and LC2 comprises an HC2 having an amino acid sequence having the amino acid sequence of SEQ ID NO: 16. In another embodiment, the isolated polypeptide comprises an amino acid sequence having at least 95% identity to the polypeptide. The anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment is represented by SEQ ID NO: HC2 comprises the amino acid sequence of SEQ ID NO: 15, and LC2 comprises the amino acid sequence of SEQ ID NO: 16. .

[0076] Also, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or its antigen-binding flag (a) HC1; (b) HC2; (c) LC1; and (d) ) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is HCDs containing the amino acid sequences of SEQ ID NO: 60, SEQ ID NO: 61, and SEQ ID NO: 62, respectively. LC1 comprises SEQ ID NO: 63, HCDR2, and HCDR3, respectively. LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 64 and SEQ ID NO: 65 DR3 to form a binding site for a first antigen that specifically binds to Vγ9, and HC 2 are H containing the amino acid sequences of SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11, respectively. CDR1, HCDR2, and HCDR3 are represented by SEQ ID NO: 12, LC2, and LC3, respectively. LCDR1 and LCDR2 comprising the amino acid sequences of SEQ ID NO: 13 and SEQ ID NO: 14, and Contains LCDR3 and forms a binding site for a second antigen that specifically binds to CD123 In one embodiment, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen The binding fragments have at least 95% repeat sequence with respect to the selected amino acid sequence of SEQ ID NO:65. comprises HC1 comprising an amino acid sequence having the identity of, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 66 In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO: 65, and LC1 comprises the amino acid sequence of SEQ ID NO: 66 In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC1 comprising an amino acid sequence having at least 9 5% identity to the selected amino acid sequence of SEQ ID NO: 67, and LC1 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 68 In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO: 67, and LC1 comprises the amino acid sequence of SEQ ID NO: 68 In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO: 67, and LC1 comprises the amino acid sequence of SEQ ID NO: 68 In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC2 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 15, and LC2 comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 16 In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises HC2 comprising the amino acid sequence of SEQ ID NO: 15, and LC2 comprises the amino acid sequence of SEQ ID NO: 16 In addition, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or its antigen-binding flag ment is provided herein, (a) HC1, (b) HC2, (c) LC1, (d

[0077] Moreover, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or an antigen-binding fragment thereof is provided herein, (a) HC1, (b) HC2, (c) LC1, (d ) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is HCDs containing the amino acid sequences of SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, respectively LC1 comprises SEQ ID NO: 92, SEQ ID NO: 93, HCDR2, and HCDR3, respectively. LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 93 and SEQ ID NO: 94 DR3 to form a binding site for a first antigen that specifically binds to Vγ9, and HC 2 are H containing the amino acid sequences of SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11, respectively. CDR1, HCDR2, and HCDR3 are represented by SEQ ID NO: 12, LC2, and LC3, respectively. LCDR1 and LCDR2 comprising the amino acid sequences of SEQ ID NO: 13 and SEQ ID NO: 14, and Contains LCDR3 and forms a binding site for a second antigen that specifically binds to CD123 In one embodiment, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen The binding fragments have at least 95% repeat sequence with respect to the selected amino acid sequence of SEQ ID NO: 95. and LC1 comprises an amino acid sequence having identity of the amino acid sequence of SEQ ID NO: 96. In another embodiment, the amino acid sequence has at least 95% identity to the sequence. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises: HC1 comprises the amino acid sequence of SEQ ID NO: 95, and LC1 comprises the amino acid sequence of SEQ ID NO: 96. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or The antigen-binding fragment has at least 95% identity to the amino acid sequence of SEQ ID NO: 15. HC2 has an amino acid sequence having the same identity as SEQ ID NO: 16, and LC2 has the amino acid sequence In another embodiment, the amino acid sequence is at least 95% identical to The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment has the sequence HC2 comprises the amino acid sequence of SEQ ID NO: 15, and LC2 comprises the amino acid sequence of SEQ ID NO: 16. include.

[0078] Also, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or its antigen-binding flag (a) HC1; (b) HC2; (c) LC1; and (d) ) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is HCs containing the amino acid sequences of SEQ ID NO: 98, SEQ ID NO: 99, and SEQ ID NO: 100, respectively. LC1 comprises DR1, HCDR2, and HCDR3, and LC1 comprises SEQ ID NO: 101, LCDR1, LCDR2, and the like comprising the amino acid sequences of SEQ ID NO: 102 and SEQ ID NO: 103 and LCDR3, forming a binding site for a first antigen that specifically binds to Vγ9. HC2 has the amino acid sequences of SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11, respectively. and LC2 comprises HCDR1, HCDR2, and HCDR3 each comprising SEQ ID NO: LCDR1 and LCDR2 containing the amino acid sequences of SEQ ID NO: 12, SEQ ID NO: 13, and SEQ ID NO: 14 and a binding domain for a second antigen that specifically binds to CD123 and includes LCDR3. In one embodiment, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or an antigen-binding fragment having at least one sequence selected from the amino acid sequence of SEQ ID NO: 104. HC1 contains an amino acid sequence having 95% identity with SEQ ID NO: 10. LC1 contains an amino acid sequence having 95% identity with SEQ ID NO: 10. 5. The amino acid sequence of the present invention has at least 95% identity to the amino acid sequence of the present invention. In embodiments, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment is The fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO: 104, and LC1 comprises the amino acid sequence of SEQ ID NO: 1 05. In another embodiment, the isolated anti-TRGV9 / anti-CD123 The bispecific antibody or antigen-binding fragment may have at least one amino acid sequence similar to that of SEQ ID NO: 15. HC2 comprises an amino acid sequence having at least 95% identity with SEQ ID NO: 1; and LC2 comprises an amino acid sequence having at least 95% identity with SEQ ID NO: 1. 6. In embodiments, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment is The fragment comprises HC2 having the amino acid sequence of SEQ ID NO: 15, and LC2 having the amino acid sequence of SEQ ID NO: 16. It contains the amino acid sequence of

[0079] Also, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or its antigen-binding flag (a) HC1; (b) HC2; (c) LC1; and (d) ) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is Containing the amino acid sequences of SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 109, respectively LC1 comprises HCDR1, HCDR2, and HCDR3, each of which is represented by SEQ ID NO: 11. LCDR1 and LCDR2 comprising the amino acid sequences of SEQ ID NO: 111 and SEQ ID NO: 112 and LCDR3, and a binding site for a first antigen that specifically binds to Vγ9. HC2 is formed by the amino acid sequence of SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11, respectively. HCDR1, HCDR2, and HCDR3 each contain the sequence LCDR1, LCDR2, LCDR3, LCDR4, LCDR5, LCDR6, LCDR7, LCDR8, LCDR9, LCDR10, LCDR11, LCDR12, LCDR13, LCDR14, LCDR15, LCDR16, LCDR17, LCDR18, LCDR19 ... R2, and LCDR3, binding to a second antigen that specifically binds to CD123. In one embodiment, an isolated anti-TRGV9 / anti-CD123 bispecific The antibody or antigen-binding fragment may be a fragment of at least one amino acid sequence selected from SEQ ID NO: 113. HC1 comprises an amino acid sequence having at least 95% identity with SEQ ID NO: It contains an amino acid sequence that has at least 95% identity to the 114 amino acid sequence. In another embodiment, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding The fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO: 113, and LC1 comprises the amino acid sequence of SEQ ID NO: No. 114. In another embodiment, the isolated anti-TRGV9 / anti-CD1 23 bispecific antibodies or antigen-binding fragments having a sequence similar to that of SEQ ID NO: 15 HC2 comprises an amino acid sequence having at least 95% identity with SEQ ID NO: The amino acid sequence of SEQ ID NO:16 has at least 95% identity to the amino acid sequence of SEQ ID NO:16. In another embodiment, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding The fragments include HC2, which comprises the amino acid sequence of SEQ ID NO: 15, and LC2, which comprises the amino acid sequence of SEQ ID NO: It contains a sequence of 16 amino acids.

[0080] Also, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or its antigen-binding flag (a) HC1; (b) HC2; (c) LC1; and (d) ) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is Containing the amino acid sequences of SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 119, respectively LC1 comprises HCDR1, HCDR2, and HCDR3, each of which is represented by SEQ ID NO: 12. LCDR1 and LCDR2 comprising the amino acid sequences of SEQ ID NO: 121 and SEQ ID NO: 122 and LCDR3, and a binding site for a first antigen that specifically binds to Vγ9. HC2 is formed by the amino acid sequence of SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11, respectively. HCDR1, HCDR2, and HCDR3 each contain the sequence LCDR1, LCDR2, LCDR3, LCDR4, LCDR5, LCDR6, LCDR7, LCDR8, LCDR9, LCDR10, LCDR11, LCDR12, LCDR13, LCDR14, LCDR15, LCDR16, LCDR17, LCDR18, LCDR19 ... R2, and LCDR3, binding to a second antigen that specifically binds to CD123. In one embodiment, an isolated anti-TRGV9 / anti-CD123 bispecific The antibody or antigen-binding fragment may be a fragment of a nucleic acid sequence selected from the group consisting of: HC1 comprises an amino acid sequence having at least 95% identity with SEQ ID NO: It contains an amino acid sequence that has at least 95% identity to the 124 amino acid sequence. In another embodiment, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding The fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO: 123, and LC1 comprises the amino acid sequence of SEQ ID NO: No. 124. In another embodiment, the isolated anti-TRGV9 / anti-CD1 23 bispecific antibodies or antigen-binding fragments having a sequence similar to that of SEQ ID NO: 15 HC2 comprises an amino acid sequence having at least 95% identity with SEQ ID NO: The amino acid sequence of SEQ ID NO:16 has at least 95% identity to the amino acid sequence of SEQ ID NO:16. In another embodiment, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding The fragments include HC2, which comprises the amino acid sequence of SEQ ID NO: 15, and LC2, which comprises the amino acid sequence of SEQ ID NO: It contains a sequence of 16 amino acids.

[0081] Also, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or its antigen-binding flag (a) HC1; (b) HC2; (c) LC1; and (d) ) LC2, wherein HC1 is related to LC1, HC2 is related to LC2, and HC1 is Containing the amino acid sequences of SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 129, respectively LC1 comprises HCDR1, HCDR2, and HCDR3, each of which is represented by SEQ ID NO: 13. LCDR1 and LCDR2 comprising the amino acid sequences of SEQ ID NO: 131 and SEQ ID NO: 132 and LCDR3, and a binding site for a first antigen that specifically binds to Vγ9. HC2 is formed by the amino acid sequence of SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11, respectively. HCDR1, HCDR2, and HCDR3 each contain the sequence LCDR1, LCDR2, LCDR3, LCDR4, LCDR5, LCDR6, LCDR7, LCDR8, LCDR9, LCDR10, LCDR11, LCDR12, LCDR13, LCDR14, LCDR15, LCDR16, LCDR17, LCDR18, LCDR19 ... R2, and LCDR3, binding to a second antigen that specifically binds to CD123. In one embodiment, an isolated anti-TRGV9 / anti-CD123 bispecific The antibody or antigen-binding fragment may be a fragment of a nucleic acid sequence selected from the group consisting of: HC1 comprises an amino acid sequence having at least 95% identity with SEQ ID NO: It contains an amino acid sequence that has at least 95% identity to the 134 amino acid sequence. In another embodiment, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding The fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO: 133, and LC1 comprises the amino acid sequence of SEQ ID NO: No. 134. In another embodiment, the isolated anti-TRGV9 / anti-CD1 23 bispecific antibodies or antigen-binding fragments having a sequence similar to that of SEQ ID NO: 15 HC2 comprises an amino acid sequence having at least 95% identity with SEQ ID NO: The amino acid sequence of SEQ ID NO:16 has at least 95% identity to the amino acid sequence of SEQ ID NO:16. In another embodiment, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding The fragments include HC2, which comprises the amino acid sequence of SEQ ID NO: 15, and LC2, which comprises the amino acid sequence of SEQ ID NO: It contains a sequence of 16 amino acids.

[0082] In another embodiment, TRGV9 is on the surface of a γδ T cell.

[0083] In another embodiment, CD123 is on the surface of a tumor cell or a CD34+ stem cell.

[0084] In another embodiment, a bispecific antibody against TRGV9 present on the surface of γδ T cells is Binding of the antibody to CD123 on the surface of cancer cells results in potent killing of the cancer cells.

[0085] In another embodiment, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or its anti- The original binding fragments include humanized HC1 and humanized LC1.

[0086] In another embodiment, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding The combined fragments include humanized HC2 and humanized LC2.

[0087] In another embodiment, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or its anti- The original binding fragments are of the IgG1, IgG2, IgG3, or IgG4 isotype. In certain embodiments, the bispecific antibody is of the IgG4 isotype.

[0088] In another embodiment, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or its anti- The original binding fragment has an EC 50 In vitro, γδ in cancer cells Induces T cell-dependent cytotoxicity.

[0089] In another embodiment, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or its anti- The original binding fragment has an EC 50 In vitro, γδ in cancer cells Induces T cell-dependent cytotoxicity.

[0090] In another embodiment, an isolated anti-TRGV9 / anti-CD123 bispecific antibody or its anti- The original binding fragment has an EC 50 In vitro, γδ in cancer cells Induces T cell-dependent cytotoxicity.

[0091] In one embodiment, EC 50 γδ T effector cells and Kasumi3 AML It is evaluated on a mixture of target cells.

[0092] In another embodiment, the effector cell to target cell ratio is from about 0.01:1 to about 5:1. be.

[0093] In yet another embodiment, the ratio of effector cells to target cells is about 0.1:1 to about 2:1 is.

[0094] In certain embodiments, the ratio of effector cells to target cells is about 1:1.

[0095] Also provided herein are isolated anti-TRGV9 / anti-CD123 bispecific antibodies or Provided herein are methods for producing antigen-binding fragments thereof, the methods comprising: anti-TRGV9 / anti-CD123 bilayer under conditions to produce an antibody or antigen-binding fragment thereof Culturing cells containing nucleic acids encoding the bispecific antibody or antigen-binding fragment thereof. and recovering the bispecific antibody or antigen-binding fragment thereof.

[0096] In another aspect, an isolated TRGV9 bispecific antibody or its antigen epitope-binding fragment is provided. A fragment thereof is provided herein, and an isolated TRGV9 bispecific antibody or its antigenic epitope is also provided. The tope-binding fragment comprises a binding site for a first antigen and a binding site for a second antigen. and a binding site for the first antigen that binds to a TRGV9 epitope on γδ T cells. The binding site for the second antigen binds to an epitope of the second antigen on the surface of the target cell. The binding of the TRGV9 epitope on the γδ T cell and the binding of a second antigen epitope on the target cell Binding of the tope results in the killing of the target cell.

[0097] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises: a. HC1 and b. HC2 and c. LC1; d. LC2, and HC1 is associated with LC1, HC2 is associated with LC2, and HC1 is i. SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3, respectively; ii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31, respectively; iii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32, respectively; or iv. comprising the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33, respectively. comprising HCDR1, HCDR2, and HCDR3, LC1 comprises the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. a first antigen-binding site comprising LCDR1, LCDR2, and LCDR3; HC2 and LC2 form a binding site for a second antigen epitope. In embodiments, the TRGV9 bispecific antibody or antigen-binding fragment has the sequence SEQ ID NO: 7, the sequence SEQ ID NO: 34, SEQ ID NO: 35, or SEQ ID NO: 36 HC1 contains an amino acid sequence having 95% identity with SEQ ID NO: 8, and LC1 contains an amino acid sequence having 95% identity with SEQ ID NO: 8. The amino acid sequence may be at least 95% identical to the amino acid sequence. In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment is HC1 comprising an amino acid sequence selected from SEQ ID NO: 34, SEQ ID NO: 35, or SEQ ID NO: 36. LC1 comprises the amino acid sequence of SEQ ID NO:8.

[0098] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises: (a) HC 1, (b) HC2, (c) LC1, and (d) LC2, and HC1 is related to LC1. HC2 is related to LC2, and HC1 is related to SEQ ID NO: 1, SEQ ID NO: 2, and HCDR1, HCDR2, and HCDR3 containing the amino acid sequence of SEQ ID NO: 3, C1 is a LC having the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. DR1, LCDR2, and LCDR3, forming a binding site for a first antigen. HC2 and LC2 form a binding site for a second antigenic epitope. In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises the amino acid sequence of SEQ ID NO: 7. HC1 containing an amino acid sequence having at least 95% identity to the sequence of LC 1 is an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises a sequence: HC1 comprises the amino acid sequence of SEQ ID NO: 7, and LC1 comprises the amino acid sequence of SEQ ID NO: 8. include.

[0099] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises: (a) HC 1, (b) HC2, (c) LC1, and (d) LC2, and HC1 is related to LC1. HC2 is related to LC2, and HC1 is related to SEQ ID NO: 1, SEQ ID NO: 2, and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 31; LC1 includes the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. comprising CDR1, LCDR2, and LCDR3, forming a binding site for a first antigen; HC2 and LC2 form a binding site for a second antigen epitope. In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises the amino acid sequence of SEQ ID NO: 34. HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of LC1 is an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises the sequence comprises an HC1 comprising the amino acid sequence of SEQ ID NO: 34, and an LC1 comprising the amino acid sequence of SEQ ID NO: 8. Contains arrays.

[0100] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises: (a) HC 1, (b) HC2, (c) LC1, and (d) LC2, and HC1 is related to LC1. HC2 is related to LC2, and HC1 is related to SEQ ID NO: 1, SEQ ID NO: 2, and comprising HCDR1, HCDR2, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 32; LC1 includes the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. comprising CDR1, LCDR2, and LCDR3, forming a binding site for a first antigen; HC2 and LC2 form a binding site for a second antigen epitope. In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises the amino acid sequence of SEQ ID NO: 35. HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of LC1 is an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises the sequence comprises an HC1 comprising the amino acid sequence of SEQ ID NO: 35, and an LC1 comprising the amino acid sequence of SEQ ID NO: 8. Contains arrays.

[0101] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises: (a) HC 1, (b) HC2, (c) LC1, and (d) LC2, and HC1 is related to LC1. HC2 is related to LC2, and HC1 is related to SEQ ID NO: 1, SEQ ID NO: 2, and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 33; LC1 includes the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. comprising CDR1, LCDR2, and LCDR3, forming a binding site for a first antigen; HC2 and LC2 form a binding site for a second antigen epitope. In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment has the amino acid sequence of SEQ ID NO: 36. HC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of LC1 is an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises the sequence comprises an HC1 comprising the amino acid sequence of SEQ ID NO: 36, and an LC1 comprising the amino acid sequence of SEQ ID NO: 8. Contains arrays.

[0102] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises: (a) HC 1, (b) HC2, (c) LC1, and (d) LC2, and HC1 is related to LC1. HC2 is related to LC2, and HC1 is related to SEQ ID NO: 1, SEQ ID NO: 76, and SEQ ID NO: 8, respectively. and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 3; LC1 comprises the amino acid sequences of SEQ ID NO: 77, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. a first antigen-binding site comprising LCDR1, LCDR2, and LCDR3; HC2 and LC2 form a binding site for a second antigen epitope. In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment has the antigen of SEQ ID NO: 65. HC1 containing an amino acid sequence having at least 95% identity to the amino acid sequence LC1 is an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 66. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises the amino acid sequence The HC1 comprises the amino acid sequence of SEQ ID NO: 65, and the LC1 comprises the amino acid sequence of SEQ ID NO: 66. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises the amino acid sequence The compound has an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:67. LC1 has at least one amino acid sequence identical to that of SEQ ID NO: 68. In another embodiment, the TRGV9 bispecific The antibody or antigen-binding fragment comprises an HC1 comprising the amino acid sequence of SEQ ID NO: 67, and C1 comprises the amino acid sequence of SEQ ID NO:68.

[0103] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises: (a) HC 1, (b) HC2, (c) LC1, and (d) LC2, and HC1 is related to LC1. HC2 is related to LC2, and HC1 is related to SEQ ID NO: 60, SEQ ID NO: 61, and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 62. LC1 has the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 64, and SEQ ID NO: 6, respectively. and a binding site for a first antigen comprising LCDR1, LCDR2, and LCDR2. HC2 and LC2 form a binding site for a second antigen epitope. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment has the sequence of SEQ ID NO:6 HC1 containing an amino acid sequence having at least 95% identity to the amino acid sequence of 5. LC1 has at least 95% identity to the amino acid sequence of SEQ ID NO: 66. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises an amino acid sequence encoding the The fragment includes HC1 having the amino acid sequence of SEQ ID NO: 65, and LC1 has the amino acid sequence of SEQ ID NO: 6 In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises the amino acid sequence of The fragment has at least 95% identity to the amino acid sequence of SEQ ID NO: 67 HC1 contains the amino acid sequence of SEQ ID NO: 68, and LC1 contains at least one amino acid sequence of SEQ ID NO: 68. In another embodiment, the TRGV9 doublet comprises an amino acid sequence having at least 95% identity. The specific antibody or antigen-binding fragment comprises an HC1 comprising the amino acid sequence of SEQ ID NO:67. LC1 comprises the amino acid sequence of SEQ ID NO:68.

[0104] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises: (a) HC 1, (b) HC2, (c) LC1, and (d) LC2, and HC1 is related to LC1. HC2 is related to LC2, and HC1 is related to SEQ ID NO: 89, SEQ ID NO: 90, and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 91. LC1 has the amino acid sequences of SEQ ID NO: 92, SEQ ID NO: 93, and SEQ ID NO: 94, respectively. a sequence comprising LCDR1, LCDR2, and LCDR3, and a sequence comprising LCDR1, LCDR2, and a sequence comprising ...3, and a sequence comprising LCDR2, and a sequence HC2 and LC2 form a binding site for a second antigen epitope. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment has the sequence set forth in SEQ ID NO: HC containing an amino acid sequence that has at least 95% identity to the 95 amino acid sequence 1, wherein LC1 has at least 95% identity to the amino acid sequence of SEQ ID NO: 96. In another embodiment, the TRGV9 bispecific antibody or antigen-binding The fragment comprises HC1 comprising the amino acid sequence of SEQ ID NO: 95, and LC1 comprises the amino acid sequence of SEQ ID NO: It contains a sequence of 96 amino acids.

[0105] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises: (a) HC 1, (b) HC2, (c) LC1, and (d) LC2, and HC1 is related to LC1. HC2 is related to LC2, and HC1 is related to SEQ ID NO: 98, SEQ ID NO: 99, and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 100. LC1 comprises the sequences of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 103, respectively. and LCDR1, LCDR2, and LCDR3 containing an amino acid sequence, HC2 and LC2 form a binding site for a second antigen epitope. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises: An amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 104 and LC1 comprises an HC1 comprising at least 95 amino acid residues relative to the amino acid sequence of SEQ ID NO: 105. In another embodiment, the TRGV9 bispecific antibody comprises an amino acid sequence having 100% identity to the TRGV9 antibody. or the antigen-binding fragment comprises an HC1 comprising the amino acid sequence of SEQ ID NO: 104, and an LC 1 comprises the amino acid sequence of SEQ ID NO:105.

[0106] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises: (a) HC 1, (b) HC2, (c) LC1, and (d) LC2, and HC1 is related to LC1. HC2 is related to LC2 and HC1 is SEQ ID NO: 107 and SEQ ID NO: 10, respectively. 8, and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 109 3, and LC1 comprises SEQ ID NO: 110, SEQ ID NO: 111, and SEQ ID NO: 112, respectively. a first antigen comprising LCDR1, LCDR2, and LCDR3 having the amino acid sequence HC2 and LC2 form a binding site for a second antigen epitope. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment is an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 113 and LC1 has at least one amino acid sequence corresponding to the amino acid sequence of SEQ ID NO: 114. In another embodiment, the TRGV9 bispecific the antibody or antigen-binding fragment comprises an HC1 comprising the amino acid sequence of SEQ ID NO: 113; LC1 comprises the amino acid sequence of SEQ ID NO:114.

[0107] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises: (a) HC 1, (b) HC2, (c) LC1, and (d) LC2, and HC1 is related to LC1. HC2 is related to LC2 and HC1 is SEQ ID NO: 117 and SEQ ID NO: 11, respectively. 8, and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 119 3, and LC1 comprises SEQ ID NO: 120, SEQ ID NO: 121, and SEQ ID NO: 122, respectively. a first antigen comprising LCDR1, LCDR2, and LCDR3 having the amino acid sequence HC2 and LC2 form a binding site for a second antigen epitope. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment is an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 123 and LC1 has at least one amino acid sequence corresponding to the amino acid sequence of SEQ ID NO: 124. In another embodiment, the TRGV9 bispecific the antibody or antigen-binding fragment comprises an HC1 comprising the amino acid sequence of SEQ ID NO: 123; LC1 comprises the amino acid sequence of SEQ ID NO:124.

[0108] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises: (a) HC 1, (b) HC2, (c) LC1, and (d) LC2, and HC1 is related to LC1. HC2 is related to LC2 and HC1 is SEQ ID NO: 127 and SEQ ID NO: 12, respectively. 8, and HCDR1, HCDR2, and HCDR3 comprising the amino acid sequence of SEQ ID NO: 129 3, and LC1 comprises SEQ ID NO: 130, SEQ ID NO: 131, and SEQ ID NO: 132, respectively. a first antigen comprising LCDR1, LCDR2, and LCDR3 having the amino acid sequence HC2 and LC2 form a binding site for a second antigen epitope. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment is an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 133 and LC1 has at least one amino acid sequence corresponding to the amino acid sequence of SEQ ID NO: 134. In another embodiment, the TRGV9 bispecific the antibody or antigen-binding fragment comprises an HC1 comprising the amino acid sequence of SEQ ID NO: 133; LC1 comprises the amino acid sequence of SEQ ID NO:134.

[0109] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment is humanized H Contains C1 and humanized LC.

[0110] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment binds to CD12 Binds to 3 epitopes.

[0111] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment has the structure of SEQ ID NO: HC containing an amino acid sequence that has at least 95% identity to the 15 amino acid sequence 2, wherein LC2 has at least 95% identity to the amino acid sequence of SEQ ID NO: 16. It includes an amino acid sequence having the following structure:

[0112] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment has the structure of SEQ ID NO: HC2 comprises the amino acid sequence of SEQ ID NO: 15, and LC2 comprises the amino acid sequence of SEQ ID NO: 16. .

[0113] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof is Ig In certain embodiments, the antibodies are of the IgG1, IgG2, and IgG3, or IgG4 isotype. The bispecific antibody or antigen-binding fragment thereof may be an IgG4 isotype. It is Yip.

[0114] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof has a saturation of about 5 EC<0.00pM 50 Induces γδ T cell-dependent cytotoxicity of cancer cells in vitro Lead.

[0115] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof has a saturation of about 3 EC<0.00pM 50 Induces γδ T cell-dependent cytotoxicity of cancer cells in vitro Lead.

[0116] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof has a saturation of about 1 EC<60pM 50 Induces γδ T cell-dependent cytotoxicity of cancer cells in vitro Lead.

[0117] In one embodiment, EC 50 γδ T effector cells and Kasumi3 AML It is evaluated on a mixture of target cells.

[0118] In another embodiment, the effector cell to target cell ratio is from about 0.01:1 to about 5:1. In another embodiment, the ratio of effector cells to target cells is about 0.1:1 to about 2:1. In certain embodiments, the ratio of effector cells to target cells is about 1:1.

[0119] Also provided is an isolated γδ T cell bispecific antibody or antigen-binding fragment thereof. The isolated γδ T cell bispecific antibody or antigen-binding fragment thereof is a binding site for the original epitope and a binding site for the second antigen epitope, The binding site for one antigen epitope binds to a first antigen on a gamma delta T cell and to a second antigen on a gamma delta T cell. The binding site for the antigen epitope binds to an epitope of a second antigen on the surface of a target cell. The binding of a first antigenic epitope on a γδ T cell and a second antigenic epitope on a target cell Binding of the fragment results in the killing of the target cell.

[0120] In another embodiment, a TRGV9 bispecific antibody or antigen-binding fragment thereof is encoded by An isolated nucleic acid is provided herein, as well as an isolated TRGV9 bispecific antibody or its antigen-binding The fragment is a. HC1 and b. HC2 and c. LC1; d. LC2, and HC1 is associated with LC1, HC2 is associated with LC2, and HC1 is i. SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3, respectively; ii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31, respectively; iii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32, respectively; or iv. comprising the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33, respectively. comprising HCDR1, HCDR2, and HCDR3, LC1 comprises the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. a first antigen-binding site comprising LCDR1, LCDR2, and LCDR3; In one embodiment, HC2 and LC2 form a binding site for a second antigen. The isolated nucleic acid is selected from SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36. HC1 containing an amino acid sequence having at least 95% identity to the amino acid sequence of LC1 encodes a TRGV9 bispecific antibody comprising the amino acid sequence of SEQ ID NO: 8, In another embodiment, the isolated nucleic acid comprises an amino acid sequence that has at least 95% identity to the is an amino acid selected from SEQ ID NO: 7, SEQ ID NO: 34, SEQ ID NO: 35, or SEQ ID NO: 36 and LC1 encodes a TRGV9 bispecific antibody comprising HC1 comprising the amino acid sequence of SEQ ID NO: 8. It contains the amino acid sequence of

[0121] In another embodiment, a TRGV9 bispecific antibody or antigen-binding fragment thereof is encoded by An isolated nucleic acid is provided herein, as well as an isolated TRGV9 bispecific antibody or its antigen-binding The fragments are (a) HC1, (b) HC2, (c) LC1, and (d) LC2. HC1 is related to LC1, HC2 is related to LC2, and HC1 is related to LC2. HCDR1 and HCDR2 containing the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, and HCDR3, and LC1 is represented by SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: a first antibody comprising LCDR1, LCDR2, and LCDR3 comprising the amino acid sequence of HC1 and LC2 form a binding site for the first antigen, and HC2 and LC2 form a binding site for the second antigen. In one embodiment, the isolated nucleic acid has a sequence that is at least 95% similar to the amino acid sequence of SEQ ID NO:7. % identity to the TRGV9 bispecific antibody. However, LC1 is an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8. In another embodiment, the isolated nucleic acid comprises the amino acid sequence of SEQ ID NO:7. LC1 encodes a TRGV9 bispecific antibody comprising the amino acid sequence of SEQ ID NO: 8. Includes.

[0122] In another embodiment, a TRGV9 bispecific antibody or antigen-binding fragment thereof is encoded by An isolated nucleic acid is provided herein, as well as an isolated TRGV9 bispecific antibody or its antigen-binding The fragments are (a) HC1, (b) HC2, (c) LC1, and (d) LC2. HC1 is related to LC1, HC2 is related to LC2, and HC1 is related to LC2. HCDR1 and HCDR2 containing the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31 LC1 comprises SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. a first LCDR1, a LCDR2, and an LCDR3 comprising the amino acid sequence of No. 6; HC1 and LC2 form a binding site for a second antigen. In one embodiment, the isolated nucleic acid has at least the amino acid sequence of SEQ ID NO: 34. A TRGV9 bispecific antibody containing HC1 with an amino acid sequence that has 95% identity was created. and LC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:8. In another embodiment, the isolated nucleic acid comprises the amino acid sequence of SEQ ID NO: 34. and LC1 encodes a TRGV9 bispecific antibody comprising an HC1 comprising the amino acid sequence of SEQ ID NO: 8. Contains the acid sequence.

[0123] In another embodiment, a TRGV9 bispecific antibody or antigen-binding fragment thereof is encoded by An isolated nucleic acid is provided herein, as well as an isolated TRGV9 bispecific antibody or its antigen-binding The fragments are (a) HC1, (b) HC2, (c) LC1, and (d) LC2. HC1 is related to LC1, HC2 is related to LC2, and HC1 is related to LC2. HCDR1 and HCDR2 containing the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32 LC1 comprises SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. a first LCDR1, a LCDR2, and an LCDR3 comprising the amino acid sequence of No. 6; HC1 and LC2 form a binding site for a second antigen. In one embodiment, the isolated nucleic acid has at least the amino acid sequence of SEQ ID NO: 35. A TRGV9 bispecific antibody containing HC1 with an amino acid sequence that has 95% identity was created. and LC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:8. In another embodiment, the isolated nucleic acid comprises the amino acid sequence of SEQ ID NO: 35. and LC1 encodes a TRGV9 bispecific antibody comprising an HC1 comprising the amino acid sequence of SEQ ID NO: 8. Contains the acid sequence.

[0124] In another embodiment, a TRGV9 bispecific antibody or antigen-binding fragment thereof is encoded by An isolated nucleic acid is provided herein, as well as an isolated TRGV9 bispecific antibody or its antigen-binding The fragments are (a) HC1, (b) HC2, (c) LC1, and (d) LC2. HC1 is related to LC1, HC2 is related to LC2, and HC1 is related to LC2. HCDR1 and HCDR2 containing the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33 LC1 comprises SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. a first LCDR1, a LCDR2, and an LCDR3 comprising the amino acid sequence of No. 6; HC1 and LC2 form a binding site for a second antigen. In one embodiment, the isolated nucleic acid has at least the amino acid sequence of SEQ ID NO: 36. A TRGV9 bispecific antibody containing HC1 with an amino acid sequence that has 95% identity was created. and LC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:8. In another embodiment, the isolated nucleic acid comprises the amino acid sequence of SEQ ID NO: 36. and LC1 encodes a TRGV9 bispecific antibody comprising an HC1 comprising the amino acid sequence of SEQ ID NO: 8. Contains the acid sequence.

[0125] In another embodiment, a TRGV9 bispecific antibody or antigen-binding fragment thereof is encoded by An isolated nucleic acid is provided herein, as well as an isolated TRGV9 bispecific antibody or its antigen-binding The fragments are (a) HC1, (b) HC2, (c) LC1, and (d) LC2. HC1 is related to LC1, HC2 is related to LC2, and HC1 is related to LC2. HCDR1 and HCDR2 containing the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 76, and SEQ ID NO: 3 LC1 comprises SEQ ID NO: 77, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. LCDR1 and LCDR2 containing the amino acid sequence of No. 6, and LCDR2 containing the first HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated nucleic acid has at least the amino acid sequence of SEQ ID NO:65. and a TRGV9 bispecific antibody containing HC1 having an amino acid sequence with 95% identity. LC1 encodes a polypeptide having at least 95% identity to the amino acid sequence of SEQ ID NO:66. In another embodiment, the isolated nucleic acid comprises an amino acid sequence having the amino acid sequence of SEQ ID NO:65. and LC1 encodes a TRGV9 bispecific antibody comprising HC1 comprising the sequence of SEQ ID NO: 66. In one embodiment, the isolated nucleic acid comprises the amino acid sequence of SEQ ID NO: 67. A TRGV9 double specific antibody containing an HC1 having an amino acid sequence with at least 95% identity to the HC1. and LC1 encodes an isomeric antibody, wherein the LC1 has at least 95% identity to the amino acid sequence of SEQ ID NO: 68. In another embodiment, the isolated nucleic acid comprises an amino acid sequence having an identity of SEQ ID NO: 67. and LC1 encodes a TRGV9 bispecific antibody comprising an HC1 having the amino acid sequence Contains the amino acid sequence numbered 68.

[0126] In another embodiment, a TRGV9 bispecific antibody or antigen-binding fragment thereof is encoded by An isolated nucleic acid is provided herein, as well as an isolated TRGV9 bispecific antibody or its antigen-binding The fragments are (a) HC1, (b) HC2, (c) LC1, and (d) LC2. HC1 is related to LC1, HC2 is related to LC2, and HC1 is related to LC2. HCDR1, HCD containing the amino acid sequences of SEQ ID NO: 60, SEQ ID NO: 61, and SEQ ID NO: 62 LC1 contains SEQ ID NO: 63, SEQ ID NO: 64, and HCDR2, and HCDR3, respectively. and LCDR1, LCDR2, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 6. , form a binding site for the first antigen, and HC2 and LC2 form a binding site for the second antigen. In one embodiment, the isolated nucleic acid has a sequence similar to that of SEQ ID NO:65. TRGV9 bispecific antibodies containing HC1s with amino acid sequences that have at least 95% identity The LC1 encodes an antibody having at least 95% identity to the amino acid sequence of SEQ ID NO: 66. In another embodiment, the isolated nucleic acid comprises an amino acid sequence having the identity of SEQ ID NO: 65. and LC1 encodes a TRGV9 bispecific antibody comprising HC1 having the amino acid sequence of SEQ ID NO: In one embodiment, the isolated nucleic acid comprises the amino acid sequence of SEQ ID NO: 67. TRGV9 containing an HC1 containing an amino acid sequence having at least 95% identity to LC1 encodes a bispecific antibody, wherein LC1 has at least one amino acid sequence similar to the amino acid sequence of SEQ ID NO: 68. In another embodiment, the isolated nucleic acid comprises an amino acid sequence having 95% identity to the amino acid sequence of SEQ ID NO: The TRGV9 bispecific antibody is encoded by HC1, which contains 67 amino acids, and LC1, which contains , comprising the amino acid sequence of SEQ ID NO:68.

[0127] In another embodiment, a TRGV9 bispecific antibody or antigen-binding fragment thereof is encoded by An isolated nucleic acid is provided herein, as well as an isolated TRGV9 bispecific antibody or its antigen-binding The fragments are (a) HC1, (b) HC2, (c) LC1, and (d) LC2. HC1 is related to LC1, HC2 is related to LC2, and HC1 is related to LC2. HCDR1, HCD comprising the amino acid sequences of SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91 LC1 includes SEQ ID NO: 92, SEQ ID NO: 93, and HCDR2, and HCDR3, respectively. and LCDR1, LCDR2, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 94. HC2 and LC2 form a binding site for the first antigen, and HC3 and LC4 form a binding site for the second antigen. In one embodiment, the isolated nucleic acid has a sequence similar to that of SEQ ID NO: 95. TRGV9 bispecific antibody containing HC1 containing an amino acid sequence with at least 95% identity LC1 encodes a human antibody, wherein the human LC1 has at least 95% identity to the amino acid sequence of SEQ ID NO: 96. In another embodiment, the isolated nucleic acid comprises an amino acid sequence having identity to the amino acid sequence of SEQ ID NO: 95. and LC1 encodes a TRGV9 bispecific antibody comprising HC1 having the amino acid sequence No. 96.

[0128] In another embodiment, a TRGV9 bispecific antibody or antigen-binding fragment thereof is encoded by An isolated nucleic acid is provided herein, as well as an isolated TRGV9 bispecific antibody or its antigen-binding The fragments are (a) HC1, (b) HC2, (c) LC1, and (d) LC2. HC1 is related to LC1, HC2 is related to LC2, and HC1 is related to LC2. HCDR1, HCDR2, HCDR3, HCDR4, HCDR5, HCDR6, HCDR7, HCDR8, HCDR9, HCDR10, HCDR11, HCDR12, HCDR13, HCDR14, HCDR15, HCDR16, HCDR17, HCDR18, HCDR19, HCDR119, HCDR111, HCDR19, HC LC1 contains SEQ ID NO: 101, SEQ ID NO: 10, HCDR2, and HCDR3, respectively. 2, and LCDR1, LCDR2, and LCDR3 comprising the amino acid sequence of SEQ ID NO: 103. 2 to form a binding site for a first antigen, and HC2 and LC2 to form a binding site for a second antigen. In one embodiment, the isolated nucleic acid has the amino acid sequence of SEQ ID NO: 104. TRGV containing HC1 containing an amino acid sequence with at least 95% identity to the sequence 9 bispecific antibody, wherein LC1 has at least one amino acid sequence similar to that of SEQ ID NO: 105. In another embodiment, the isolated nucleic acid comprises an amino acid sequence having 95% identity to the sequence A TRGV9 bispecific antibody encoding an HC1 comprising the amino acid sequence of SEQ ID NO: 104, C1 comprises the amino acid sequence of SEQ ID NO:105.

[0129] In another embodiment, a TRGV9 bispecific antibody or antigen-binding fragment thereof is encoded by An isolated nucleic acid is provided herein, as well as an isolated TRGV9 bispecific antibody or its antigen-binding The fragments are (a) HC1, (b) HC2, (c) LC1, and (d) LC2. HC1 is related to LC1, HC2 is related to LC2, and HC1 is related to LC2. HCDR1 comprising the amino acid sequences of SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 109; LC1 contains HCDR2 and HCDR3, and LC1 contains SEQ ID NO: 110 and SEQ ID NO: 111, respectively. 111, and LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 112. DR2 forms a binding site for the first antigen, and HC2 and LC2 form a binding site for the second antigen. In one embodiment, the isolated nucleic acid comprises the amino acid sequence of SEQ ID NO: 113. TR containing HC1 containing an amino acid sequence that has at least 95% identity to the amino acid sequence GV9 bispecific antibody, and LC1 has a low affinity to the amino acid sequence of SEQ ID NO: 114. In another embodiment, the isolated nucleic acid comprises an amino acid sequence having at least 95% identity to the A TRGV9 bispecific antibody encoding an HC1 comprising the amino acid sequence of SEQ ID NO: 113. , LC1 comprises the amino acid sequence of SEQ ID NO:114.

[0130] In another embodiment, a TRGV9 bispecific antibody or antigen-binding fragment thereof is encoded by An isolated nucleic acid is provided herein, as well as an isolated TRGV9 bispecific antibody or its antigen-binding The fragments are (a) HC1, (b) HC2, (c) LC1, and (d) LC2. HC1 is related to LC1, HC2 is related to LC2, and HC1 is related to LC2. HCDR1 comprising the amino acid sequences of SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 119; LC1 contains HCDR2 and HCDR3, and LC1 contains SEQ ID NO: 120 and SEQ ID NO: 130, respectively. 121, and LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 122. DR2 forms a binding site for the first antigen, and HC2 and LC2 form a binding site for the second antigen. In one embodiment, the isolated nucleic acid comprises an amino acid sequence of SEQ ID NO: 123. TR containing HC1 containing an amino acid sequence that has at least 95% identity to the amino acid sequence GV9 bispecific antibody, and LC1 has a low affinity to the amino acid sequence of SEQ ID NO: 124. In another embodiment, the isolated nucleic acid comprises an amino acid sequence having at least 95% identity to the A TRGV9 bispecific antibody encoding an HC1 comprising the amino acid sequence of SEQ ID NO: 123. , LC1 comprises the amino acid sequence of SEQ ID NO:124.

[0131] In another embodiment, a TRGV9 bispecific antibody or antigen-binding fragment thereof is encoded by An isolated nucleic acid is provided herein, as well as an isolated TRGV9 bispecific antibody or its antigen-binding The fragments are (a) HC1, (b) HC2, (c) LC1, and (d) LC2. HC1 is related to LC1, HC2 is related to LC2, and HC1 is related to LC2. HCDR1 comprising the amino acid sequences of SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 129; LC1 contains HCDR2 and HCDR3, and LC1 contains SEQ ID NO: 130 and SEQ ID NO: 140, respectively. 131, and LCDR1, LCDR2, and LCDR3 comprising the amino acid sequences of SEQ ID NO: 132. DR2 forms a binding site for the first antigen, and HC2 and LC2 form a binding site for the second antigen. In one embodiment, the isolated nucleic acid comprises an amino acid sequence of SEQ ID NO: 133. TR containing HC1 containing an amino acid sequence that has at least 95% identity to the amino acid sequence GV9 bispecific antibody, and LC1 has a low affinity to the amino acid sequence of SEQ ID NO: 134. In another embodiment, the isolated nucleic acid comprises an amino acid sequence having at least 95% identity to the A TRGV9 bispecific antibody encoding an HC1 comprising the amino acid sequence of SEQ ID NO: 133. , LC1 comprises the amino acid sequence of SEQ ID NO:134.

[0132] In another embodiment, the isolated nucleic acid comprises a first antigen that binds to TRGV9 on a γδ T cell.

[0023] The present invention encodes a TRGV9 bispecific antibody comprising a binding site comprising:

[0133] In another embodiment, the isolated nucleic acid comprises a second antibody that binds to a cancer antigen present on the surface of a cancer cell. The present invention encodes a TRGV9 bispecific antibody containing a binding site for the antigen.

[0134] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody and Binding of the bispecific antibody to TRGV9 present on the surface of cancer cells and Binding of the present cancer antigens results in the death of the cancer cells.

[0135] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody and comprises HC1 and L C1 is humanized.

[0136] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody and comprises HC2 and L C2 binds to CD123.

[0137] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody. The antibody or antigen-binding fragment thereof may be an IgG1, IgG2, IgG3, or IgG4 antibody. It is a sotype.

[0138] In certain embodiments, the bispecific antibody or antigen-binding fragment thereof is an IgG4 antibody. It is a sotype.

[0139] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody. The antibody or antigen-binding fragment thereof has an EC 50 In vitro Induces gamma delta T cell-dependent cytotoxicity of cancer cells.

[0140] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody. The antibody or antigen-binding fragment thereof has an EC 50 In vitro Induces gamma delta T cell-dependent cytotoxicity of cancer cells.

[0141] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody. The antibody or antigen-binding fragment thereof has an EC 50 In vitro Induces gamma delta T cell-dependent cytotoxicity of cancer cells.

[0142] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody and 50 teeth, Evaluated with a mixture of γδ T effector cells and Kasumi3 AML target cells.

[0143] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody and The ratio of effector cells to target cells is about 0.01:1 to about 5:1. In yet another embodiment, the ratio of target cells to cell population is about 0.1:1 to about 2:1. The vector cell to target cell ratio is approximately 1:1.

[0144] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody. The antibody or antigen-binding fragment thereof is multivalent.

[0145] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody. The antibody or antigen-binding fragment thereof is capable of binding to at least three antigens.

[0146] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody. The antibody or antigen-binding fragment thereof can bind to at least five antigens.

[0147] Also provided are vectors comprising the isolated nucleic acids provided herein.

[0148] Also provided are host cells containing the vectors provided herein.

[0149] Also provided are kits containing the vectors provided herein and packages therefor. It is served.

[0150] A pharmaceutical composition is provided herein, the pharmaceutical composition comprising: (A) an isolated TRGV9 bispecific antibody; an isomeric antibody or antigen-binding fragment thereof, a. HC1 and b. HC2 and c. LC1; d. LC2, and HC1 is associated with LC1, HC2 is associated with LC2, and HC1 is i. SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3, respectively; ii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31, respectively; iii. SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32, respectively; or iv. comprising the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33, respectively. comprising HCDR1, HCDR2, and HCDR3, LC1 comprises the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. a first antigen-binding site comprising LCDR1, LCDR2, and LCDR3; The isolated TRG fragment is composed of HC2 and LC2, which form a binding site for a second antigen. V9 bispecific antibody or an antigen-binding fragment thereof; (B) a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises SEQ ID NO: 7, SEQ ID NO: 34, SEQ ID NO: 35, or SEQ ID NO: 36 HC1, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 8. and LC1 comprising an amino acid sequence having at least 95% identity to the amino acid sequence of In another embodiment, the pharmaceutical composition comprises a bispecific antibody. HC1 comprising an amino acid sequence selected from SEQ ID NO: 35 or SEQ ID NO: 36, and and an LC1 comprising the amino acid sequence of SEQ ID NO:8.

[0151] Also provided herein is a pharmaceutical composition, the pharmaceutical composition comprising: (A) isolated TRGV9; A bispecific antibody or antigen-binding fragment thereof, comprising: (a) HC1; and (b) HC2. and (c) LC1 and (d) LC2, wherein HC1 is related to LC1 and HC2 is related to L C2 and HC1 are amino acids of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively. HCDR1, HCDR2, and HCDR3 each containing the following amino acid sequence: LCDR1 and LCDR2 containing the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6 and LCDR2 to form a binding site for a first antigen, and an isolated TRGV9 bispecific antibody, wherein and (B) a pharmaceutically acceptable carrier. The pharmaceutical composition has at least 95% identity to the amino acid sequence of SEQ ID NO: 7. HC1 containing an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:8 and an LC1 comprising an amino acid sequence having the same identity as the LC1. In the present invention, the pharmaceutical composition comprises HC1 comprising the amino acid sequence of SEQ ID NO: 7 and HC2 comprising the amino acid sequence of SEQ ID NO: 8. and an LC1 comprising the sequence.

[0152] Also provided herein is a pharmaceutical composition, the pharmaceutical composition comprising: (A) isolated TRGV9; A bispecific antibody or antigen-binding fragment thereof, comprising: (a) HC1; and (b) HC2. and (c) LC1 and (d) LC2, wherein HC1 is related to LC1 and HC2 is related to L C2, and HC1 is the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31, respectively. HCDR1, HCDR2, and HCDR3 each contain a nucleotide sequence, and LC1 is , LCDR1, LCDR2, LCDR3, LCDR4, LCDR5, LCDR6, LCDR7, LCDR8, LCDR9, LCDR10, LCDR11, LCDR12, LCDR13, LCDR14, LCDR15, LCDR16, LCDR17, LCDR18, LCDR19, LCDR19, LCDR111, LCDR12, LCDR13, LCDR14, LCDR15, LCDR16, LCDR1 HC2 and LCDR2, which form a binding site for a first antigen, an isolated TRGV9 bispecific antibody or antibody, wherein 2 forms a binding site for a second antigen. (B) an antigen-binding fragment thereof; and (B) a pharmaceutically acceptable carrier. The pharmaceutical composition may comprise a compound having at least 95% identity to the amino acid sequence of SEQ ID NO: 34. HC1 containing an amino acid sequence identical to that of SEQ ID NO: 8, and and an LC1 comprising an amino acid sequence having the identity of In one embodiment, the pharmaceutical composition comprises an HC1 comprising the amino acid sequence of SEQ ID NO: 34 and an HC2 comprising the amino acid sequence of SEQ ID NO: 8. and an LC1 containing the amino acid sequence.

[0153] Also provided herein is a pharmaceutical composition, the pharmaceutical composition comprising: (A) isolated TRGV9; A bispecific antibody or antigen-binding fragment thereof, comprising: (a) HC1; and (b) HC2. and (c) LC1 and (d) LC2, wherein HC1 is related to LC1 and HC2 is related to L C2, and HC1 is the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32, respectively. HCDR1, HCDR2, and HCDR3 each contain a nucleotide sequence, and LC1 is , LCDR1, LCDR2, LCDR3, LCDR4, LCDR5, LCDR6, LCDR7, LCDR8, LCDR9, LCDR10, LCDR11, LCDR12, LCDR13, LCDR14, LCDR15, LCDR16, LCDR17, LCDR18, LCDR19 ...9, LCDR20, LCDR21, LCDR22, LCDR23, LCDR24, LCDR25, LCDR26, LCDR27, LCDR28, LCDR29, LCDR211, LCDR212, LCDR213, LCDR224, LCDR235, LCDR245, LCDR256, LCDR265, LCDR276, LCDR HC2 and LCDR2, which form a binding site for a first antigen, an isolated TRGV9 bispecific antibody or antibody, wherein 2 forms a binding site for a second antigen; (B) an antigen-binding fragment thereof; and (B) a pharmaceutically acceptable carrier. The pharmaceutical composition may comprise a compound having at least 95% identity to the amino acid sequence of SEQ ID NO: 35. HC1 containing an amino acid sequence identical to that of SEQ ID NO: 8, and and an LC1 comprising an amino acid sequence having the identity of In one embodiment, the pharmaceutical composition comprises an HC1 comprising the amino acid sequence of SEQ ID NO: 35 and an HC2 comprising the amino acid sequence of SEQ ID NO: 8. and an LC1 containing the amino acid sequence.

[0154] Also provided herein is a pharmaceutical composition, the pharmaceutical composition comprising: (A) isolated TRGV9; A bispecific antibody or antigen-binding fragment thereof, comprising: (a) HC1; and (b) HC2. and (c) LC1 and (d) LC2, wherein HC1 is related to LC1 and HC2 is related to L C2, and HC1 is the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33, respectively. HCDR1, HCDR2, and HCDR3 each contain a nucleotide sequence, and LC1 is , LCDR1, LCDR2, LCDR3, LCDR4, LCDR5, LCDR6, LCDR7, LCDR8, LCDR9, LCDR10, LCDR11, LCDR12, LCDR13, LCDR14, LCDR15, LCDR16, LCDR17, LCDR18, LCDR19 ...9, LCDR20, LCDR21, LCDR22, LCDR23, LCDR24, LCDR25, LCDR26, LCDR27, LCDR28, LCDR29, LCDR211, LCDR212, LCDR213, LCDR224, LCDR235, LCDR245, LCDR256, LCDR265, LCDR276, LCDR HC2 and LCDR2, which form a binding site for a first antigen, an isolated TRGV9 bispecific antibody or antibody, wherein 2 forms a binding site for a second antigen; (B) an antigen-binding fragment thereof; and (B) a pharmaceutically acceptable carrier. The pharmaceutical composition may comprise a compound having at least 95% identity to the amino acid sequence of SEQ ID NO: 36. HC1 containing an amino acid sequence identical to that of SEQ ID NO: 8, and and an LC1 comprising an amino acid sequence having the identity of In one embodiment, the pharmaceutical composition comprises an HC1 comprising the amino acid sequence of SEQ ID NO: 36 and an HC2 comprising the amino acid sequence of SEQ ID NO: 8. and an LC1 containing the amino acid sequence.

[0155] Also provided herein is a pharmaceutical composition, the pharmaceutical composition comprising: (A) isolated TRGV9; A bispecific antibody or antigen-binding fragment thereof, comprising: (a) HC1; and (b) HC2. and (c) LC1 and (d) LC2, wherein HC1 is related to LC1 and HC2 is related to L C2, and HC1 is the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 76, and SEQ ID NO: 3, respectively. HCDR1, HCDR2, and HCDR3 each contain a nucleotide sequence, and LC1 is , LCDR1, LCDR2, LCDR3, LCDR4, LCDR5, LCDR6, LCDR7, LCDR8, LCDR9, LCDR10, LCDR11, LCDR12, LCDR13, LCDR14, LCDR15, LCDR16, LCDR17, LCDR18, LCDR19 ...11, LCDR12, LCDR13, LCDR14, LCDR15, LCDR1 R2, and LCDR2 form a binding site for a first antigen, and An isolated TRGV9 bispecific antibody, wherein C2 forms a binding site for a second antigen. or an antigen-binding fragment thereof, and (B) a pharmaceutically acceptable carrier. In the present invention, the pharmaceutical composition is a compound having at least 95% identity to the amino acid sequence of SEQ ID NO: 65. HC1 comprising an amino acid sequence having at least 9 amino acids with respect to the amino acid sequence of SEQ ID NO: 66 and LC1, which comprise an amino acid sequence having 5% identity with the LC1. In embodiments, the pharmaceutical composition comprises an HC1 comprising the amino acid sequence of SEQ ID NO: 65 and an HC2 comprising the amino acid sequence of SEQ ID NO: 6 and an LC1 comprising the amino acid sequence of SEQ ID NO:6. The composition contains an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:67. HC1 containing the amino acid sequence of SEQ ID NO: 68 and at least 95% identical to the amino acid sequence of SEQ ID NO: 68 and an LC1 comprising an amino acid sequence having the following functional groups: The pharmaceutical composition comprises an HCl comprising the amino acid sequence of SEQ ID NO: 67 and an HCl comprising the amino acid sequence of SEQ ID NO: 68. and an LC1 comprising an LC2 sequence.

[0156] Also provided herein is a pharmaceutical composition, the pharmaceutical composition comprising: (A) isolated TRGV9; A bispecific antibody or antigen-binding fragment thereof, comprising: (a) HC1; and (b) HC2. and (c) LC1 and (d) LC2, wherein HC1 is related to LC1 and HC2 is related to L C2 and HC1 are SEQ ID NO: 60, SEQ ID NO: 61, and SEQ ID NO: 62, respectively. LC1 comprises HCDR1, HCDR2, and HCDR3 containing amino acid sequences thereof. LCDR1 comprising the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 64, and SEQ ID NO: 6, respectively; a binding site for a first antigen comprising LCDR2 and HC2; and LC2 form the binding site for a second antigen. and (B) a pharmaceutically acceptable carrier. In an embodiment, the pharmaceutical composition comprises a nucleic acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 65. HC1 containing an amino acid sequence having at least one amino acid sequence identical to the amino acid sequence of SEQ ID NO: 66 and LC1, which contains an amino acid sequence having 95% identity with In another embodiment, the pharmaceutical composition comprises an HC1 comprising the amino acid sequence of SEQ ID NO: 65 and an HC2 comprising the amino acid sequence of SEQ ID NO: 66. and an LC1 comprising the amino acid sequence of number 66. The pharmaceutical composition has at least 95% identity to the amino acid sequence of SEQ ID NO: 67. HC1 containing an amino acid sequence having at least 95% repeat activity against the amino acid sequence of SEQ ID NO: 68 and an LC1 comprising an amino acid sequence having the identity of In one embodiment, the pharmaceutical composition comprises an HC1 comprising the amino acid sequence of SEQ ID NO: 67 and an HC2 comprising the amino acid sequence of SEQ ID NO: 68. and LC1 comprising the amino acid sequence.

[0157] Also provided herein is a pharmaceutical composition, the pharmaceutical composition comprising: (A) isolated TRGV9; A bispecific antibody or antigen-binding fragment thereof, comprising: (a) HC1; and (b) HC2. and (c) LC1 and (d) LC2, wherein HC1 is related to LC1 and HC2 is related to L C2 and HC1 are SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, respectively. LC1 comprises HCDR1, HCDR2, and HCDR3 containing amino acid sequences thereof. LCDR1 comprising the amino acid sequences of SEQ ID NO: 92, SEQ ID NO: 93, and SEQ ID NO: 94, respectively. , LCDR2, and LCDR3, forming a binding site for a first antigen; The isolated TRGV9 bispecific antigen, in which LC2 and LC3 form the binding site for a second antigen, (B) a pharmaceutically acceptable carrier. In embodiments, the pharmaceutical composition has a sequence which is at least 95% identical to the amino acid sequence of SEQ ID NO:95. HC1 containing an amino acid sequence having identity to the amino acid sequence of SEQ ID NO: 96 and LC1, which comprises an amino acid sequence having at least 95% identity thereto. In another embodiment, the pharmaceutical composition comprises an HC1 comprising the amino acid sequence of SEQ ID NO: 95 and a and an LC1 comprising the amino acid sequence of SEQ ID NO: 96.

[0158] Also provided herein is a pharmaceutical composition, the pharmaceutical composition comprising: (A) isolated TRGV9; A bispecific antibody or antigen-binding fragment thereof, comprising: (a) HC1; and (b) HC2. and (c) LC1 and (d) LC2, wherein HC1 is related to LC1 and HC2 is related to L C2 and HC1 are SEQ ID NO: 98, SEQ ID NO: 99, and SEQ ID NO: 100, respectively. LC1 comprises HCDR1, HCDR2, and HCDR3 containing the amino acid sequence L comprising the amino acid sequences of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 103, respectively. comprising CDR1, LCDR2, and LCDR3, forming a binding site for a first antigen; and an isolated TRGV in which HC2 and LC2 form a binding site for a second antigen. 9. A bispecific antibody or an antigen-binding fragment thereof, and (B) a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises at least one amino acid sequence selected from the group consisting of SEQ ID NO: 104 and SEQ ID NO: 105. HC1, which contains an amino acid sequence having 95% identity with the amino acid sequence of SEQ ID NO: 105. and LC1, which comprises an amino acid sequence having at least 95% identity to In another embodiment, the pharmaceutical composition comprises an isomeric antibody comprising the amino acid sequence of SEQ ID NO: 104. and LC1 comprising the amino acid sequence of SEQ ID NO: 105. nothing.

[0159] Also provided herein is a pharmaceutical composition, the pharmaceutical composition comprising: (A) isolated TRGV9; A bispecific antibody or antigen-binding fragment thereof, comprising: (a) HC1; and (b) HC2. and (c) LC1 and (d) LC2, wherein HC1 is related to LC1 and HC2 is related to L C2 and HC1 are SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 1, respectively. HCDR1, HCDR2, and HCDR3 contain the amino acid sequence of 09, and LC1 is , containing the amino acid sequences of SEQ ID NO: 110, SEQ ID NO: 111, and SEQ ID NO: 112, respectively. a first antigen-binding site comprising LCDR1, LCDR2, and LCDR3; and HC2 and LC2 form a binding site for a second antigen. (B) a pharmaceutically acceptable carrier; and In one embodiment, the pharmaceutical composition comprises at least one amino acid sequence selected from the group consisting of: HC1 containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 114 and LC1, which contains an amino acid sequence having at least 95% identity to the sequence In another embodiment, the pharmaceutical composition comprises a bispecific antibody having the amino acid sequence of SEQ ID NO: 113. and an LC1 comprising the amino acid sequence of SEQ ID NO: 114. Includes:

[0160] Also provided herein is a pharmaceutical composition, the pharmaceutical composition comprising: (A) isolated TRGV9; A bispecific antibody or antigen-binding fragment thereof, comprising: (a) HC1; and (b) HC2. and (c) LC1 and (d) LC2, wherein HC1 is related to LC1 and HC2 is related to L C2 and HC1 are SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 1 LC1 contains HCDR1, HCDR2, and HCDR3, which contain 19 amino acid sequences. , which contain the amino acid sequences of SEQ ID NO: 120, SEQ ID NO: 121, and SEQ ID NO: 122, respectively. a first antigen-binding site comprising LCDR1, LCDR2, and LCDR3; and HC2 and LC2 form a binding site for a second antigen. (B) a pharmaceutically acceptable carrier; and In one embodiment, the pharmaceutical composition comprises at least one amino acid sequence selected from the group consisting of: HC1 containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 124 and LC1, which contains an amino acid sequence having at least 95% identity to the sequence In another embodiment, the pharmaceutical composition comprises a bispecific antibody having the amino acid sequence of SEQ ID NO: 123. and an LC1 comprising the amino acid sequence of SEQ ID NO: 124. Includes.

[0161] Also provided herein is a pharmaceutical composition, the pharmaceutical composition comprising: (A) isolated TRGV9; A bispecific antibody or antigen-binding fragment thereof, comprising: (a) HC1; and (b) HC2. and (c) LC1 and (d) LC2, wherein HC1 is related to LC1 and HC2 is related to L C2, and HC1 are SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 1, respectively. LC1 contains HCDR1, HCDR2, and HCDR3, each containing 29 amino acids. , containing the amino acid sequences of SEQ ID NO: 130, SEQ ID NO: 131, and SEQ ID NO: 132, respectively. a first antigen-binding site comprising LCDR1, LCDR2, and LCDR3; and HC2 and LC2 form a binding site for a second antigen. (B) a pharmaceutically acceptable carrier; and In one embodiment, the pharmaceutical composition comprises at least one amino acid sequence selected from the group consisting of: HC1 containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 134 and LC1, which contains an amino acid sequence having at least 95% identity to the sequence In another embodiment, the pharmaceutical composition comprises a bispecific antibody having the amino acid sequence of SEQ ID NO: 133. and an LC1 comprising the amino acid sequence of SEQ ID NO: 134. Includes.

[0162] In another embodiment, the pharmaceutical composition comprises a first antigen that binds to TRGV9 on γδ T cells. The present invention also includes bispecific antibodies that contain binding sites for

[0163] In another embodiment, the pharmaceutical composition comprises a bispecific antibody, The site binds to a cancer antigen present on the surface of cancer cells.

[0164] In another embodiment, the pharmaceutical composition comprises a bispecific antibody present on the surface of a γδ T cell. Binding of bispecific antibodies to TRGV9 present on the surface of cancer cells and cancer antigens present on the surface of cancer cells Binding of the agonist results in the death of the cancer cells.

[0165] In another embodiment, the pharmaceutical composition comprises a bispecific antibody, wherein HC1 and LC1 are human It has been turned into

[0166] In another embodiment, the pharmaceutical composition comprises a bispecific antibody, wherein HC2 and LC2 are Binds to 123.

[0167] In another embodiment, the pharmaceutical composition comprises a bispecific antibody, The original binding fragments are of the IgG1, IgG2, IgG3, or IgG4 isotype. do.

[0168] Also provided is a method of directing Vγ9-expressing γδ T cells to cancer cells, the method comprising: contacting Vγ9-expressing γδ T cells with a pharmaceutical composition provided herein. Contacting Vγ9-expressing γδ T cells with the pharmaceutical composition induces Vγ9-expressing γδ T cells to target cancer cells. To direct.

[0169] Also provided are methods for inhibiting the growth or proliferation of cancer cells that express cancer antigens on their cell surface. The method includes contacting a cancer cell with a pharmaceutical composition provided herein, Contacting with the pharmaceutical composition inhibits the growth or proliferation of the cancer cells.

[0170] In one embodiment, the cancer cells are infected with an anti-TRGV9 bispecific antibody or an antigen-binding fragment thereof. During contact with the patient, the patient is in the presence of Vγ9-expressing γδ T cells.

[0171] Also provided is a method for treating cancer in a subject in need thereof, the method comprising: a. Identifying a subject in need of cancer treatment; and b. administering a pharmaceutical composition provided herein to a subject in need thereof; Including, Administering the pharmaceutical composition to a subject in need thereof treats cancer in the subject.

[0172] Also provided is a method of activating Vγ9-expressing γδ T cells, the method comprising: contacting T cells with a pharmaceutical composition provided herein, Contacting T cells with the pharmaceutical composition increases CD40 expression compared to control Vγ9-expressing γδ T cells. 69, resulting in increased CD25, and / or granzyme B expression.

[0173] Also provided are methods of producing the pharmaceutical compositions provided herein, the methods comprising: The antibody or antigen-binding fragment thereof may be combined with a pharmaceutically acceptable carrier to form a pharmaceutical obtaining a composition. [Brief explanation of the drawings]

[0174] The foregoing summary, as well as the following detailed description of certain embodiments of the present application, is taken in conjunction with the accompanying drawings. The present application will be better understood when read together. It should be understood that the present invention is not limited to the precise embodiments shown. [Figure 1] FIG. 1 shows a schematic demonstrating the binding of an anti-TRGV9 / anti-tumor-associated antigen (TAA) bispecific antibody to recruit γδ T cells to cancer cells and induce cancer cell death. [Figure 2] FIG. 1 shows a graph demonstrating that zoledronic acid selectively expands Vy9V52 T cells from whole peripheral blood mononuclear cells (PBMCs). [Figure 3A] Phenotypic characterization of Vγ9+ γδ T cells. A schematic diagram of the gates used to describe γδ T cell differentiation is shown (left). Representative FACS dot plots show the differentiation profile of Vγ9+ γδ T cells from fresh PBMCs (left) and PBMCs cultured ex vivo with zoledronic acid, IL-2, and IL-15 for 14 days (right). Quadrant numbers reflect the frequency (mean ± SEM) of each population between fresh and activated Vγ9+ γδ T cells. Data presented are the mean (± SEM) of five donors (n = 5) from a single experiment. [Figure 3B] Phenotypic characterization of Vγ9+ γδ T cells is shown. Representative dot plots reflecting the frequency (mean ± SEM) of Vγ9+ γδ T cells positive for each activation marker are shown from either fresh PBMCs (top row) or PBMCs cultured for 14 days with zoledronic acid, IL-2, and IL-15 (bottom row). Data presented are the mean (± SEM) of seven donors (n = 7) for CD62L, CD69, and CD44 expression data from two independent experiments. n is five donors for NKG2D expression data and two donors each for CD45RO and CD71 expression data from a single experiment. [Figure 3C]Figure 1 shows phenotypic characterization of Vy9+ γδ T cells. The numbers above the gate in a dot plot showing the frequency (mean ± SEM) of V59+ γδ T cells positive for each inhibitory receptor surface expression from either fresh PBMCs (top row) or PBMCs cultured for 14 days with zoledronic acid + IL-2 + IL-15 (bottom row). Data shown here are the mean (± SEM) of five donors (n = 5) for PD1, CTLA4, TIGIT, and LAG3 surface expression, and seven donors (n = 7) for 2B4 and TIM3 surface expression data from two independent experiments. [Figure 3D]

[0033] Figure 1 shows phenotypic characterization of Vy9+ γδ T cells. Representative FACS dot plots demonstrating the frequency (mean ± SEM) of Vδ9+ γδ T cells expressing intracellular granzyme B (left column) and perforin (right column) from fresh PBMCs (top row) and PBMCs cultured ex vivo with zoledronic acid + IL-2 + IL-15 for 14 days (bottom row). Data shown are the mean (± SEM) of four (n = 4) and seven (n = 7) donors for granzyme B and perforin data, respectively, from two independent experiments. [Figure 3E]

[0023] Figure 1 shows phenotypic characterization of Vγ9+ γδ T cells. Bar graphs depicting mean (±SEM) concentrations (pg / mL) of cytokines in cell culture supernatants on days 0 and 14 of PBMC culture with zoledronic acid, IL-2, and IL-15. Data presented are the mean (±SEM) of four wells (n=4) from a single donor. [Figure 4] 1 shows histograms demonstrating that VG1 (anti-TRGV9 / anti-CD123 bispecific antibody) recruits Vγ9+ T cells, as evidenced by conjugate formation between γδ T cells and Kasumi-3 cells. [Figure 5A] Graphs demonstrating VG1 (anti-TRGV9 / anti-CD123 bispecific antibody) bispecific-mediated γδ T cell cytotoxicity against Kasumi-3 cells at different effector-to-target cell ratios (1:1 for FIG. 5A). [Figure 5B]Graphs demonstrating VG1 (anti-TRGV9 / anti-CD123 bispecific antibody) bispecific-mediated γδ T cell cytotoxicity against Kasumi-3 cells at different effector to target cell ratios (5:1 for 5B). [Figure 5C] Graphs demonstrating VG1 (anti-TRGV9 / anti-CD123 bispecific antibody) bispecific-mediated γδ T cell cytotoxicity against Kasumi-3 cells at different effector-to-target cell ratios (10:1 for FIG. 5C). [Figure 6A] 6A shows a graph demonstrating the expression of CD69 (FIG. 6A) 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] 6B shows a graph demonstrating the expression of CD25 (FIG. 6B) 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] A graph demonstrating the expression of granzyme B (FIG. 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 is shown. [Figure 7] Selective cell binding of anti-TAA1 (TAA mIgG2a, TAA1B1) to transfected Jurkat cells is shown. The EC50 of binding was ~1-2 nM. TAA1B1 did not show any significant binding to an ALL cell line that endogenously expresses an unrelated protein (TAA1-NULL) but does not express TAA1. [Figure 8] Selective protein binding of anti-TAA1 (TAA1 mIgG2a, TAA1B1) to recombinant TAA1 protein (TAA1W16) is shown. TAA1B1 did not show significant binding to an unrelated protein (TAA1-NULL-W16). [Figure 9]Figure 1 shows the phenotype of Vg9+ cells used in cytotoxicity testing of TAA1 x Vγ9 bispecific (TAA1B50) from healthy donors. [Figure 10] We show that anti-TRGV9 / anti-TAA1 bispecific antibodies mediate γδ T cell cytotoxicity against TAA1-expressing Jurkat cells in vitro. Cytotoxicity values ​​presented here are subtracted from the basal cytotoxicity observed in the absence of bispecific antibodies. EC50 values ​​were calculated as described in the Methods. Representative data shown here are from a single experiment. [Figure 11] Figure 1 shows bispecific antibody-mediated cytotoxicity. Expanded and enriched Vy9V52 T cells from different donors were used to induce cytotoxicity in Jurkat cell lines in the presence of Vy9xTAA1 at the concentrations indicated (E:T ratio 1:1). Assays were performed for 16 hours. The percentage of dead target cells for the various conditions is shown in the figure. [Figure 12] Figure 1 shows that the anti-TRGV9 / anti-TAA2 bispecific antibody (TAA2V9B106(B3)) binds to γδ T cells (left panel) and mediates γδ T cell cytotoxicity against TAA2-expressing H929 cells in vitro (right panel). EC50 values ​​were calculated as described in the Methods. Representative data shown here are from a single experiment. [Figure 13] Figure 1 shows that anti-TRGV9 / anti-TAA2 bispecific antibody (HC1:VG9B420-LH-scFv; HC2:TAA2-Fab(TAA2V9B71.001)) binds to γδ T cells (left panel) and mediates γδ T cell cytotoxicity against TAA2-expressing H929 cells in vitro (right panel). EC50 values ​​were calculated as described in Methods. Representative data shown here are from a single experiment. [Figure 14]Figure 1 shows that the anti-TRGV9 / anti-TAA2 bispecific antibody (VG9SB10SC1087_P18_D08-Fab RF, TAA2-scFv(TAA2V9B100.001)) binds to γδ T cells (left panel) and mediates γδ T cell cytotoxicity against TAA2-expressing H929 cells in vitro (right panel). EC50 values ​​were calculated as described in the Methods. Representative data shown here are from a single experiment. [Figure 15] Figure 1 shows that the anti-TRGV9 / anti-TAA2 bispecific antibody (VG9SB10SC1087_P18_C12-Fab RF, TAA2-scFv(TAA2V9B101.001)) binds to γδ T cells (left panel) and mediates γδ T cell cytotoxicity against TAA2-expressing H929 cells in vitro (right panel). EC50 values ​​were calculated as described in the Methods. Representative data shown here are from a single experiment. [Figure 16] Figure 1 shows that the anti-TRGV9 / anti-TAA2 bispecific antibody (VG9SB10SC1087_P19_C03-Fab RF, TAA2-scFv(TAA2V9B103.001)) binds to γδ T cells (left panel) and mediates γδ T cell cytotoxicity against TAA2-expressing H929 cells in vitro (right panel). EC50 values ​​were calculated as described in the Methods. Representative data shown here are from a single experiment. DETAILED DESCRIPTION OF THE INVENTION

[0175] Various publications, articles and patents are cited or referenced in the Background and throughout this specification. Each of these references is incorporated herein by reference in its entirety. Any discussion of documents, operations, materials, devices, articles or the like which is included in the specification is indicative of the context of this invention. Such discussion is intended to provide a basis for understanding whether any or all of these matters are disclosed or implied. is admitted to be part of the prior art to any claimed invention. isn't it.

[0176] Unless otherwise defined, all technical and scientific terms used herein refer to the It has the same meaning as commonly understood by one of ordinary skill in the art to which it pertains. Certain terms used herein have the meanings set forth herein.

[0177] As used in this specification and the appended claims, the singular forms "a," "an," and " It should be noted that "the" includes multiple referents unless the context makes clear otherwise. There is.

[0178] Unless otherwise specified, any numerical values, such as concentrations or concentration ranges, described herein are In all cases, the terms "about" and "about" should be understood as being modified. 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, 1% to 10 The concentration range of % (w / v) includes 0.9% (w / v) to 11% (w / v). When used, the use of a numerical range shall be interpreted as including that range unless the context clearly indicates otherwise. All possible subranges, including integers and fractions of values, and all individual numbers within that range Explicitly included.

[0179] Unless otherwise indicated, the term "at least" preceding a series of elements refers to every element in the series. It should be understood that the present invention refers to elements of the present invention. The reader will recognize many equivalents to the specific embodiments described herein, or Such equivalents are intended to be encompassed by this invention. will be done.

[0180] As used herein, the terms "comprises," "comprising," "includes," "including," "has," "having ), "contains," or "containing," or any of these terms Other variations of the stated integer or groups of integers are intended, but are not limited to these. It does not exclude any other integer or group of integers other than , and is non-exclusive or non-limiting. It will be understood that the present invention is intended to encompass, for example, compositions, mixtures, processes, The method, article, or apparatus is not necessarily limited to only those elements, but is expressly This document does not include any compositions, mixtures, processes, methods, articles, or devices not listed in this document. Furthermore, unless expressly stated to the contrary, "or" may refer to any element other than the element "or" that is not present in the original text. " refers to an inclusive "or" and not an exclusive "or." For example, ,Condition A or B is A true (or exists) and B false (or does not exist) If A is false (or does not exist) and B is true (or exists), then If both A and B are true (or exist), then it is satisfied by either one of

[0181] As used herein, the conjunctive term "and / or" between multiple listed elements means It is understood to encompass both individual and combined options. For example, When elements are connected by "and / or," the first option may be selected without the second option. The first option indicates that the second option is applicable without the first option. The third option is that the first and second elements are applicable together. Any one of these options is included in the meaning and therefore As used in the specification, it is understood that the requirements of the term "and / or" are met. The simultaneous applicability of two or more of the following is also included in the meaning, and therefore the term "and / or" It is understood that the requirements of

[0182] As used herein, the terms "consists of" or "consist" Variations such as "of" or "consisting of" are used throughout the specification and claims. When used throughout the range, it includes any enumerated integer or group of integers, but does not include additional Indicates that no integer or group of integers is added to the specified method, structure, or composition.

[0183] As used herein, the term "consists essentially of" or "consist essentially of" or "consist essentially of" Variations such as "isting essentially of" and "is not" are used throughout the specification and claims. When used, it encompasses any enumerated integer or group of integers, and optionally includes the specified method, structure, or any enumerated integer or that does not materially alter the basic or novel characteristics of the composition. Indicates inclusion of the group of integers. See MPEP §2111.03.

[0184] As used herein, a "subject" refers to any animal, e.g., a mammal, e.g., a human. As used herein, the term "mammal" includes all mammals. Examples of mammals include, but are not limited to, cattle, horses, sheep, pigs, cats, dogs, mice, rats, rabbits, guinea pigs, monkeys, humans, etc., or e.g. , and humans.

[0185] As used herein, the terms "about," "approximately," and "approximately" refer to dimensions or characteristics of components. The terms "approximately," "substantially," and similar terms, as understood by those skilled in the art, are used to describe dimensions. / The characteristics are not strict boundaries or parameters, but functionally the same or similar, It should also be understood that this does not exclude minor differences. Such references involving numerical parameters are to be understood as including within the art accepted mathematical conventions. using economic and industrial principles (e.g., rounding, measurement, or other systematic errors, manufacturing tolerances, etc.) When used, the least significant figure will include the variant that does not change.

[0186] The terms "identical" or percent "identity" refer to the degree to which two or more nucleic acids or polypeptides peptide sequences (e.g., anti-TRGV9 / anti-cancer-associated antigen bispecific antibodies and peptide sequences encoding same) Polynucleotides encoding the same, anti-TRGV9 / anti-CD123 bispecific antibodies Polynucleotides encoding TRGV9, TRGV9 polypeptides and TRGV9 polypeptides encoding the same / Polynucleotides, CD123 polypeptides and CD123 polypeptides encoding same nucleotides) using one of the following sequence comparison algorithms: When compared and aligned to maximize agreement as measured by visual inspection amino acid residues or nucleotides that are identical to or a specific percentage of identical to It refers to two or more sequences or subsequences having the following structure:

[0187] For sequence comparison, typically one sequence serves as a reference sequence, to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are input into a computer If necessary, subsequence coordinates are specified and the sequence algorithm program parameters are entered. The sequence comparison algorithm is then run using the designated program parameters. Based on the data, the percent sequence identity of the test sequence relative to the reference sequence is calculated.

[0188] Optimal alignment of sequences for comparison can be achieved by, for example, Smith & Waterman, Adv. Appl. Math. 2:482 (1981) Local Homology Algorithm, Ne Edleman & Wunsch, J. Mol. Biol. 48:443 (1970) Same-sex alignment algorithm, Pearson & Lipman, Proc. Nat' Acad.Sci.USA 85:2444 (1988) similarity search method, these A computerized implementation of the algorithm (Wisconsin Genetics Society) ftware Package,Genetics Computer Group,5 GAP, BESTFIT at 75 Science Dr., Madison, WI , FASTA, and TFASTA), or visual inspection (typically Current Pro tocols in Molecular Biology,FMAusubel et al., eds., Current Protocols, a joint ve nature between Greene Publishing Associates es, Inc. and John Wiley & Sons, Inc., (1995 Su This can be done by means of a fusion (see Ausubel).

[0189] Examples of suitable algorithms for determining percent sequence identity and sequence similarity are ltschul et al. (1990) J.Mol.Biol.215:403-4 10, and Altschul et al. (1997) Nucleic Acids Res. 25:3389-3402, respectively. The software used to perform the BLAST analysis is the National Center for Biotechnology Information. Publicly available through the National Center for Biotechnology Information The algorithm first finds words and alphanumeric sequences of the same length in the database sequence. Either they match when aligned or they meet some positive threshold score T. High scores are obtained by identifying short words of length W in the query sequence. T is the neighborhood word score threshold (Altschul et al., 2011). These initial neighborhood word hits are then used to compile the nucleotide sequences containing the word. It then serves as a seed to start a search to find longer HSPs. , word hits are added along each sequence as far as possible to increase the cumulative alignment score. Extend the pole in both directions.

[0190] For nucleotide sequences, the parameter M (reward for a pair of matching residues) Uses core (always > 0) and N (penalty score for mismatched residues, always < 0) For amino acid sequences, a scoring matrix is ​​used to calculate the cumulative score. The cumulative score is calculated by subtracting the cumulative alignment score from its maximum score by an amount X. When the alignment is negatively scored, the accumulation of one or more negatively scoring residues results in When the cumulative score becomes zero or less, or when the end of either sequence is reached, each direction The BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment. For the octide sequence, the default is word length (W) 11, expected value 10, M=5 For amino acid sequences, use BLASTP. The program defaults to a word length (W) of 3, an expected value (E) of 10, and a BLOSU Use the M62 scoring matrix (Henikoff & Henikoff, P roc. Natl. Acad. Sci. USA 89:10915 (1989) .

[0191] In addition to calculating percent sequence identity, the BLAST algorithm also calculates the percent sequence identity between two sequences. Statistical analysis of similarities between columns is also performed (e.g., Karlin & Altschul, Proc. See 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 means that a match between two nucleotide or amino acid sequences occurs by chance. For example, a nucleic acid provides an indication of the probability that a test nucleic acid will be detected by the smallest match in a comparison of the test nucleic acid and the reference nucleic acid. If the total probability is less than about 0.1, less than about 0.01, or less than about 0.001, the reference sequence is considered to be similar to

[0192] Further indications that two nucleic acid sequences or polypeptides are substantially identical include the following: As described above, the polypeptide encoded by the first nucleic acid is encoded by the second nucleic acid. Therefore, the polypeptide is immunologically cross-reactive with the polypeptide to be administered. A polypeptide is typically substantially identical to a second polypeptide, e.g., two peptides Another indication that two nucleic acid sequences are substantially identical is The hybridization of two molecules to each other under stringent conditions.

[0193] As used herein, the term "polynucleotide" is used interchangeably with "nucleic acid molecule." , also called "nucleotides" or "nucleic acids," and may be unmodified RNA or DNA or modified RNA or DNA. Any polyribonucleotide or polydeoxyribonucleotide, which may be NA or DNA. "Polynucleotide" refers to a nucleotide, but is not limited to these. , single-stranded and double-stranded DNA, DNA that is a mixture of single-stranded and double-stranded regions, single-stranded and Double-stranded RNA, as well as RNA that is a mixture of single-stranded and double-stranded regions, single-stranded or more typically Contains DNA and RNA which may typically be double-stranded or a mixture of single- and double-stranded regions. In addition, "polynucleotide" refers to a molecule that is a hybrid of RNA or DNA. The term polynucleotide refers to a triple-stranded region containing both RNA and DNA. , DNA or RNA containing one or more modified bases, and Also included are DNA or RNA with backbones that have been modified by any suitable method. , tritylated bases and unusual bases, e.g., inosine. Various modifications can be made to DNA and R Thus, a "polynucleotide" is a nucleic acid that is typically found in nature. Chemically, enzymatically or metabolically modified forms of polynucleotides, as well as viruses and "Polynucleotides" encompass chemical forms characteristic of DNA and RNA in living cells. also encompasses relatively short nucleic acid strands, often called oligonucleotides.

[0194] As used herein, the term "vector" refers to a vector that operably carries another nucleic acid segment. A replicon into which a segment can be inserted to replicate or express that segment. And so.

[0195] As used herein, the term "host cell" refers to a cell that can be used to express the nucleic acid molecules provided herein. A "host cell" refers to a cell comprising, for example, a primary cell, a cell in culture, or a cell line. In one embodiment, a "host cell" is a cell of any type, including, but not limited to, any of the cells of the present invention. In another embodiment, the host cell is a cell transfected with a nucleic acid molecule provided herein. "Main cells" are the progeny or potential progeny of such transfected cells. The progeny of the cells may be affected by, for example, mutations or environmental influences that may occur in subsequent generations, or by the host cell genome. Depending on the incorporation of the nucleic acid molecule into the cell, the cell may or may not be identical to the parent cell.

[0196] As used herein, the term "expression" refers to the biosynthesis of a gene product. The term includes the transcription of a gene into RNA. The translation of the polypeptides into the above-mentioned polypeptides, including all naturally occurring post-transcriptional and post-translational modifications thereof, is also included. The expressed bispecific antibody may be expressed in the cytoplasm of a host cell, in the growth medium of a cell culture, etc. They may be present in the extracellular environment of the cell or may be anchored in the cell membrane.

[0197] As used herein, the terms "peptide," "polypeptide," or "protein" can refer to molecules composed of amino acids and recognized by those skilled in the art as proteins. In this specification, the conventional one-letter or three-letter codes for amino acid residues are used. The terms "peptide," "polypeptide," and "protein" refer to any length of amino acids. can be used interchangeably herein to refer to a polymer of It may be straight or branched chain, may contain modified amino acids, and may be intermediated by non-amino acids. The term also refers to compounds that have been modified naturally or by intervention. Amino acid polymers include, for example, disulfide bond formation, glycosylation, lipidation, Acetylation, phosphorylation, or any other manipulation or modification, e.g., coupling with a labeling component. The definition also includes, for example, one or more analogs of an amino acid (e.g., and polypeptides containing amino acids that are well known in the art. Other known modifications are included.

[0198] The peptide sequences described herein are written according to the usual convention and include the N-terminal region of the peptide. The C-terminal region is on the left and the C-terminal region is on the right. The isomeric forms of the amino acids are known, but are not shown separately. Unless explicitly stated, it is the L-form of the amino acid that is shown.

[0199] antibody Anti-TRGV9 antibodies or antigen-binding fragments thereof, nucleic acids encoding the antibodies, and expression vectors Provided herein are antibodies, recombinant cells containing the vectors, and compositions containing the antibodies. In addition, the present invention relates to a method for producing an anti-TRGV9 bispecific antibody or an antigen-binding fragment thereof, ... Nucleic acids and expression vectors, recombinant cells containing the vectors, and compositions comprising bispecific antibodies Also provided herein are anti-TRGV9 / anti-CD123 bispecific antibodies or compositions thereof. Nucleic acids and expression vectors encoding antigen-binding fragments and bispecific antibodies of Provided herein are recombinant cells containing the antibody, as well as compositions comprising the bispecific antibody. Methods for producing the antibodies and for using the antibodies to treat diseases, including cancer, are also provided. The antibodies disclosed herein exhibit high affinity binding to TRGV9 and / or CD123. High affinity binding to TRGV9, high specificity to TRGV9 and / or high specificity to CD123 and its high specificity and efficacy in treating or preventing cancer when administered alone or in combination with other anti-cancer therapies. possess one or more desirable functional properties, including but not limited to the ability to prevent do.

[0200] As used herein, the term "antibody" is used broadly and includes immunoglobulins, or monoclonal antibodies. Antibodies, including human, humanized, composite, and chimeric antibodies, which may be monoclonal or polyclonal. Generally, antibodies are molecules that bind to specific antigens, and include antibody fragments. An immunoglobulin is a protein or peptide chain that exhibits specificity. The structure of an antibody is known. IgA antibodies are divided into five major classes depending on the amino acid sequence of the heavy chain constant domain: IgA and IgG can be assigned to different classes of antibodies. are of the isotypes IgA1, IgA2, IgG1, IgG2, IgG3 and IgG4. Thus, the antibodies provided herein are classified into five major classes: or any of the corresponding subclasses. The antibodies provided herein are IgG1. In some embodiments, the antibodies provided herein are In some embodiments, the antibody provided herein is an IgG2. In some embodiments, the antibodies provided herein are IgG4, IgG5, or IgG6. Antibody light chains from vertebrate species are classified into two distinct groups based on the amino acid sequence of their constant domains. can be assigned to one of different types, i.e., κ and λ. The antibodies provided herein can contain a kappa or lambda light chain constant domain. According to certain embodiments, the antibodies provided herein are derived from rat or human antibodies. The heavy and / or light chain constant regions of

[0201] In addition to heavy and light constant domains, antibodies contain antigen-specific domains consisting of a light chain variable region and a heavy chain variable region. Each of these contains three domains (i.e., complementarity determining regions 1-3) ; CDR1, CDR2, and CDR3). "CDR" refers to the sequence of an immunoglobulin (I). g or antibody) Three hypervariable regions within the non-framework region of the VH β-sheet framework one of the regions (HCDR1, HCDR2, or HCDR3), or the antibody VL β - one of the three hypervariable regions within the non-framework region of the sheet framework (L Therefore, the CDR refers to the frame The CDR regions are variable region sequences interspersed within the work region sequences. For example, Kabat identifies the most hypervariable regions within antibody variable (V) domains as (Kabat et al., J. Biol. Chem. 252:66 09-6616(1977), Kabat,Adv.Prot.Chem.32:1-7 5 (1978)). The CDR region sequences also form part of the conserved β-sheet framework. are structurally defined by Chothia as residues that are not Chothia and Lesk, J. Mol. Biol. 196:901-917 (1987)). Both terms are used in the art. CDR region sequences are also well recognized as AbM, Contact, and IM. Exemplary CDR region sequences are provided herein, e.g., in the Sequence Listing. and are illustrated in the table provided in the Examples below. The position is determined by the non-nuclear structure of many structures (Al-Lazikani et al. ., J. Mol. Biol. 273:927-948 (1997), Morea et al. al., Methods 20:267-279 (2000)). The number of additional residues for the canonical positions is conventionally determined by the standard because the number varies in different antibodies. A typical variable region numbering scheme (Al-Lazikani et al., supra (1999) 7)) followed by the residue number a, b, c, etc. Such nomenclature is well known in the art. It is well known to those who

[0202] The light chain variable region CDR1 domain is referred to herein as LCDR1 or VL CDR1 The light chain variable region CDR2 domain is referred to herein as LCDR2. The light chain variable region CDR3 domain is referred to herein as a CDR2 domain or VL CDR2. In this context, it is interchangeably referred to as LCDR3 or VL CDR3. The heavy chain CDR1 is referred to herein interchangeably as HCDR1 or VH CDR1. The variable region CDR2 domain is referred to herein interchangeably as HCDR2 or VH CDR2. The heavy chain variable region CDR1 domain is referred to herein as HCDR3 or VH It is referred to interchangeably as CDR3.

[0203] As used herein, the term "hypervariable region" such as VH or VL refers to a region that is hypervariable in sequence. Refers to the regions of an antibody variable region that are variable and / or form structurally defined loops Generally, antibodies consist of six hypervariable regions: VH (HCDR1, HCDR2, HCDR3). R3) and VL (LCDR1, LCDR2, LCDR3). Hypervariable region delineations are used and encompassed herein. "Kabat" CDRs are: are based on sequence variability and are the most commonly used (e.g., Kabat et al. al.,Sequences of Proteins of Immunologic al Interest,5th Ed.Public Health Service ,National Institutes of Health,Bethesda, (See MD. (1991)). "Chothia" instead uses the structural loop Refers to the location (e.g., Chothia and Lesk, J. Mol. Biol. 1999 6:901-917 (1987). The ends of the Chothia CDR-HCDR1 loop, as numbered, correspond to the length of the loop. It varies from H32 to H34 depending on the size (this is because the Kabat numbering scheme This is to place an insertion in H35A and H35B. If neither H35A nor H35B is present, The loop ends at 32, and if only 35A is present, the loop ends at 33, and 35A and 3 (If both 5B and 5B are present, the loop ends at 34.) The "AbM" hypervariable region is at represents a compromise between the CDR and the Chothia structural loop, and Oxford Mole used by AbM antibody modeling software in MRI (e.g., Mart in,in Antibody Engineering,Vol.2,Chapter 3, Springer Verlag). "Contact" hypervariable domain The range is based on an analysis of available complex crystal structures.

[0204] Recently, a universal numbering system has been developed and widely adopted (ImMunoGe neTics (IMGT) Information System (registered trademark) (Laf ranc et al.,Dev.Comp.Immunol.27(1):55-77 (2003)). IMGT is immunoglobulin (IG), T cell receptor The T cell receptor (TR) and the major histocompatibility complex (MAH) in humans and other vertebrates or histocompatibility complex (MHC)) is an integrated information system specializing in the In this context, the CDRs are defined as those that are identical in both amino acid sequence and position in the light or heavy chain. It is meant that the "position" of the CDRs within the structure of the immunoglobulin variable domain is conserved between species. The variable domain sequences are arranged in a structure called a loop. By using a consistent numbering system, CDR and framework residues can be easily identified. This information is used to identify CDR residues from immunoglobulins of one species, typically can be used to graft and replace into an acceptor framework from a human antibody An additional numbering system (AHon) is proposed by Honegger and Pluckth Developed by un, J. Mol. Biol. 309:657-670 (2001) For example, numbering systems, including Kabat numbering and the IMGT specific numbering system, Correspondence between systems is well known to those skilled in the art (e.g., Kabat, supra; Chothia and Lesk, supra; Martin, supra; Lefranc et al., supra (See Kabat and Choth, 2001). It combines ia.

[0205] [Table 1]

[0206] The hypervariable region may also include an "extended hypervariable region" such as: 24-36 or 24-34 (LCDR1), 46-56 or 50-56 (LCDR2), and 89-9 7 or 89-96 (LCDR3), and 26-35 or 26-35A in VH (HCD R1), 50-65 or 49-65 (HCDR2), and 93-102, 94-102, or 95-102 (HCDR3). CDR sequences reflecting this are provided herein.

[0207] The term "constant region" or "constant domain" refers to a region of an antibody that is not directly involved in binding to an antigen. However, the carbohydrate moieties of the light and heavy chains exhibit various effector functions, such as interaction with Fc receptors. The term refers to the hydroxy-terminal portion of an immunoglobulin, which is the variable region that contains the antigen-binding site. A portion of an immunoglobulin molecule that has a more conserved amino acid sequence than other portions of the molecule The constant region refers to the CH1, CH2, and CH3 regions of the heavy chain and the CL region of the light chain. It may contain.

[0208] The term "framework" or "FR" residues refers to the variable region residues that flank the CDRs. FR residues are useful in, for example, chimeric antibodies, human antibodies, human domain antibodies, diabodies, linear antibodies, FR residues are present in antibodies, monoclonal antibodies, and bispecific antibodies. are the variable domain residues of

[0209] As used herein, the term "isolated antibody" refers to an antibody that is isolated from other antibodies with different antigen specificities. (e.g., an isolated antibody that specifically binds TRGV9 is an antibody that is substantially free of V An isolated antibody that specifically binds to CD123 and is substantially free of antibodies that do not bind to γ9 is (Isolated antibodies are substantially free of antibodies that do not bind to CD123.) Furthermore, isolated antibodies are free of other cellular material and and / or chemicals are substantially free.

[0210] As used herein, the term "monoclonal antibody" refers to a substantially homogeneous population of antibodies. The individual antibodies that make up the population are antibodies obtained from the autoantibodies that may be present in trace amounts. The monoclonal antibodies provided herein are identical except for naturally occurring mutations. Doma method, phage display technology, single lymphocyte gene cloning technology, or recombinant For example, monoclonal antibodies can be produced by transgenic DNA techniques. B cells obtained from a transgenic non-human animal, e.g., a transgenic mouse or rat. and can be produced by a hybridoma containing a human heavy chain transgene and a human light chain transgene. It has a genome that includes

[0211] As used herein, the term "antigen-binding fragment" refers to, for example, a diabody, Fab, Fab', F(ab')2, Fv fragments, disulfide-stabilized Fv flag ment (dsFv), (dsFv)2, bispecific dsFv (dsFv-dsFv'), Disulfide-stabilized diabodies (ds diabodies), single-chain antibody molecules (scFv), single Single domain antibody (sdAb) scFv dimers (bivalent diabodies), one or more Multispecific antibodies formed from portions of antibodies containing CDRs, camelized single domain antibodies, Nanobodies, domain antibodies, bivalent domain antibodies, or antibodies that bind to an antigen but do not retain the complete antibody structure It refers to an antibody fragment such as any other antibody fragment that does not contain an antigen-binding fragment. The antibody can bind to the same antigen as the parent antibody or parent antibody fragment. According to certain embodiments, the antigen-binding fragment comprises a light chain variable region, a light chain constant region, and a heavy chain variable region. According to another particular embodiment, the antigen-binding fragment comprises an Fd fragment of the F chain. ab and F(ab').

[0212] As used herein, the term "single chain antibody" refers to a short peptide of about 15 to about 20 amino acids. The present invention relates to a method for producing a variable region comprising a heavy chain variable region and a light chain variable region connected by a peptide. As used herein, the term "single domain antibody" refers to a single chain antibody comprising a heavy chain variable region. The conventional single-stranded antibody in the art includes both a heavy chain constant region and a heavy chain constant region, or includes only a heavy chain variable region. Refers to a single domain antibody.

[0213] As used herein, the term "human antibody" refers to an antibody produced by a human or Human-produced antibodies made using any technique known in the art This definition of a human antibody refers to an antibody having an amino acid sequence corresponding to an intact or or full-length antibodies, fragments thereof, and / or at least one human heavy chain and / or a human or antibodies comprising a light chain polypeptide.

[0214] As used herein, the term "humanized antibody" refers to an antibody in which the antigen-binding properties of the antibody are retained. However, the sequence homology of the human antibody is modified to reduce the antigenicity of the antigen in the human body. It refers to a non-human antibody raised against it.

[0215] As used herein, the term "chimeric antibody" refers to an antibody having an amino acid sequence similar to that of an immunoglobulin molecule. The variable regions of both the light and heavy chains are often In this case, a mammalian species (e.g., a mouse) with the desired specificity, affinity, and potency is selected. The variable regions correspond to antibodies derived from the same species (e.g., rat, rabbit, etc.), while the constant regions correspond to antibodies derived from the same species (e.g., rat, rabbit, etc.). To avoid eliciting an immune response in the host, it is advisable to use a mammal derived from another species (e.g., a human). The sequence corresponds to the antibody sequence.

[0216] As used herein, the term "multispecific antibody" refers to an antibody that contains multiple immunoglobulin variable domains. The term "antibody" refers to an antibody comprising a plurality of immunoglobulin variable domain sequences, wherein the first immunoglobulin variable domain sequence of the plurality is a first immunoglobulin variable domain sequence. a second immunoglobulin variable domain having binding specificity for one epitope and In one embodiment, the first and second epitopes have binding specificity for a second epitope. The first and second epitopes do not overlap or do not substantially overlap. The first and second epitopes may be located on different antigens, e.g., different proteins (or different multimers). In one embodiment, the multispecific antibody comprises a third, fourth, or fifth subunit of a protein. In one embodiment, the multispecific antibody comprises a first, second, third, fourth, or fifth immunoglobulin variable domain. is a bispecific antibody molecule, a trispecific antibody molecule, or a tetraspecific antibody molecule.

[0217] As used herein, the term "bispecific antibody" refers to an antibody that binds to no more than two epitopes or two A bispecific antibody refers to a multispecific antibody that binds to the following antigens: For example, a first immunoglobulin having binding specificity to an epitope on the TRGV9 antigen. a nucleotide variable domain sequence, and a second epitope (e.g., a tumor-associated antigen (e.g., CD12 a second immunoglobulin variable domain having binding specificity for an epitope on an antigen (antigen); In one embodiment, the first and second epitopes are characterized by different sequences. antigens, e.g., on different proteins (or subunits of different multimeric proteins) In certain embodiments, a bispecific antibody has binding specificity for a first epitope. heavy chain variable domain sequences and light chain variable domain sequences that bind to a second epitope In some embodiments, the antibody comprises a heavy chain variable domain sequence and a light chain variable domain sequence having specificity. In this context, a bispecific antibody is a half antibody or its derivatives that has binding specificity for a first epitope. a half antibody or fragment thereof having binding specificity for a second epitope; In one embodiment, the bispecific antibody comprises a first epitope and a second epitope. scFv or fragment thereof having the same binding specificity to a second epitope and an scFv or fragment thereof having the first epitope. In one embodiment, the first epitope is located in TRGV9 and the second epitope is located in CD123. The first epitope is located on TRGV9, and the second epitope is located on PD-1, PD-L1, and C. TLA-4, EGFR, HER-2, CD19, CD20, CD3, and / or other cancer-related Related immunosuppressive factors or surface antigens are located on the surface of the thymocytes.

[0218] As used herein, the term "half antibody" refers to a single antibody associated with one immunoglobulin light chain. An exemplary half antibody is shown in SEQ ID NO: 17. If so, half antibodies may encompass fragments thereof, e.g., single antibodies from Camelidae. It will be readily apparent that an antigen-binding domain may also be comprised of a variable domain of There will be.

[0219] As used herein, the term "TRGV9" refers to a γ It refers to a polypeptide that can form a γδ T cell receptor. These cells are the first T cells to develop in the human fetus and are the predominant gamma-positive T cells in healthy adult peripheral blood cells. δ T cell subset. The term "TRGV9" refers to It may be expressed naturally by a gene or cDNA encoding the polypeptide. Any TRGV9 variant, isoform, or variant that can be expressed on transfected cells. Unless otherwise specified, TRGV9 is, in certain embodiments, The human TRGV9 amino acid sequence is available from GenBank accession no. This document is provided by application number NG_001336.2.

[0220] The term "CD123" refers to the soluble cytokine interferon-1, which is important in the immune system. CD12 refers to a molecule found on cells that helps transmit the leukin-3 signal. Interleukin-3 may also be referred to as the "interleukin-3 receptor." The receptor is a type I cytokine receptor. They belong to the receptor family and are paired with a common beta subunit (beta c or CD131). The CD123 receptor is a heterodimer with a unique alpha chain. It can be found on cells, induces tyrosine phosphorylation within cells, and promotes proliferation and differentiation in hematopoietic cell lines. CD123 can also promote the progression of acute myeloid leukemia (AML). The term "CD123" refers to a cellular subtype, unless otherwise specified. Genes naturally expressed by or encoding polypeptides of T cells (including T cells) Any CD12 that can be expressed on cells transfected with the gene or cDNA 3 variants, isoforms, and species homologs, and in certain embodiments, "CD12 "3" is human CD123. The human CD123 amino acid sequence is available from GenBank Accession No. This document is provided by session number AY789109.1.

[0221] As used herein, an antibody that "specifically binds to TRGV9" refers to an antibody that specifically binds to TRGV9, For example, for human TRGV9, 1 × 10 -7 M or less, e.g., 1×10 -8 M or less, 5×1 0 -9 M or less, 1×10 -9 M or less, 5×10 -10 M or less, or 1 x 10 -10 M or less The term "KD" refers to an antibody that binds with a KD of 0.01 to 0.02. The term "KD" refers to the ratio of Kd to Ka (i.e., Kd / Ka). The KD value of an antibody refers to the dissociation constant, which is obtained from the ratio and expressed as a molar concentration (M). For example, the K D can be determined by using surface plasmon resonance, e.g., Biacore® ) system, or by using a biosensor system such as the Octet R By using biolayer interferometry technology such as the ED96 system, You can ask for this.

[0222] As used herein, an antigen-binding domain or domains that "specifically bind to a tumor-associated antigen" The antigen-binding fragment is a fragment of the tumor-associated antigen, which is expressed as 1 × 10 -7 M or less, e.g., 1×10 - 8 M or less, 5×10 -9 M or less, 1×10 -9 M or less, 5×10 -10 M or less, or 1x 10 -10 An antigen-binding domain or antigen-binding fragment that binds with a KD of M or less.

[0223] The term "KD" is derived from the ratio of Kd to Ka (i.e., Kd / Ka) and is expressed as molar concentration (M The KD value of an antibody refers to the dissociation constant, expressed as the KD (kappa-like dissociation constant). For example, the antigen-binding domain or antigen-binding flag can be determined by a method described in The KD of the ment can be determined by using surface plasmon resonance, e.g., Biacore (registered trademark) system, or by using a biosensor system of the Oc Using biolayer interferometry technology such as the tet RED96 system It can be found by

[0224] As used herein, an antibody that "specifically binds to CD123" refers to an antibody that specifically binds to CD123, For example, for human CD123, 1 x 10 -7 M or less, e.g., 1×10 -8 M or less, 5×1 0 -9 M or less, 1×10 -9 M or less, 5×10 -10 M or less, or 1 x 10 -10 M or less The term "KD" refers to an antibody that binds with a KD of 0.01 to 0.02. The term "KD" refers to the ratio of Kd to Ka (i.e., Kd / Ka). The KD value of an antibody refers to the dissociation constant, which is obtained from the ratio and expressed as a molar concentration (M). For example, the K D can be determined by using surface plasmon resonance, e.g., Biacore® ) system, or by using a biosensor system such as the Octet R By using biolayer interferometry technology such as the ED96 system, You can ask for this.

[0225] The smaller the KD value of an antibody, the higher the affinity with which the antibody binds to its target antigen.

[0226] In one aspect, provided herein are antibodies that bind to TRGV9. In some embodiments, the antibody comprises a heavy chain variable region and a light chain variable region. The V9 antibody is not a single domain antibody or a nanobody. The GV1 antibody is a humanized antibody.

[0227] In certain embodiments, the VH region, ... L area, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL C Anti-TRGV9 antibodies comprising VL CDR2, VL CDR3, and / or VL CDR4 are provided herein. In some embodiments, the antibody comprises a VH region of any one of the antibodies described herein. Provided herein are anti-TRGV9 antibodies, including those described herein. Also provided herein are anti-TRGV9 antibodies comprising the VL region of any one of the antibodies described above. In some embodiments, the VH of any one of the antibodies described herein an anti-TRG antibody comprising the VL region and the VL region of any one of the antibodies described herein; Provided herein is a V9 antibody. In some embodiments, the antibody described herein an antibody comprising VH CDR1, VH CDR2, and VH CDR3 of any one of TRGV9 antibodies are provided herein. In some embodiments, the antibodies described herein VL CDR1, VL CDR2, and VL CDR3 of any one of the antibodies In some embodiments, an anti-TRGV9 antibody comprising the antibody described herein is provided. VH CDR1, VH CDR2, and VH CDR of any one of the antibodies described R3 and VL CDR1, VL CDR2, VL CDR3 of any one of the antibodies described herein. Provided herein are anti-TRGV9 antibodies comprising a VL CDR1, a VL CDR2, and a VL CDR3. The VH CDR1, VH CDR2, VH CDR3, and VH CDR4 of the TRGV9 antibody provided herein Representative VH including VL CDR1, VL CDR2, and VL CDR3 amino acid sequences and VL amino acid sequences are provided in the Sequence Listing and Tables 1-31.

[0228] In certain embodiments, the VH region, ... L area, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL C A binding domain that binds to TRGV9 having a VL CDR2, and / or a VL CDR3, Provided herein are anti-TRGV9 bispecific antibodies. In some embodiments, the Binding to TRGV9 having any one of the VH regions of the antibodies described herein. Provided herein are anti-TRGV9 bispecific antibodies comprising the domains. In one embodiment, a TRGV having a VL region of any one of the antibodies described herein. Provided herein are anti-TRGV9 bispecific antibodies comprising a binding domain that binds to TRGV9. In some embodiments, the VH region of any one of the antibodies described herein and a VL region of any one of the antibodies described herein. Provided herein are anti-TRGV9 bispecific antibodies comprising binding domains that bind to In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VH CDR4, VH CDR5, VH CDR6, VH CDR7, VH CDR8, VH CDR9, VH CDR10, VH CDR11, VH CDR12, VH CDR13, VH CDR14, VH CDR15, VH CDR16, VH CDR17, VH CDR18, VH CDR1 an anti-T comprising a binding domain that binds to TRGV9 having a VH CDR2 and a VH CDR3; Provided herein are RGV9 bispecific antibodies. In some embodiments, the antibodies provided herein VL CDR1, VL CDR2, and VL CDR3 of any one of the antibodies described Anti-TRGV9 bispecific antibodies containing binding domains that bind to DR3-bearing TRGV9 In some embodiments, the antibodies described herein are Any one of VH CDR1, VH CDR2, and VH CDR3 and the VH CDR1, VH CDR2, and VH CDR3 described herein and VL CDR1, VL CDR2, and VL CDR3 of any one of the antibodies described above. The present invention provides an anti-TRGV9 bispecific antibody comprising a binding domain that binds to TRGV9 having the following structure: provided in the book.

[0229] In certain embodiments, the anti-TRGV9 antibody is a bispecific antibody. In some embodiments, the anti-TRGV9 bispecific antibody may comprise a VH of an anti-CD123 antibody provided herein. area, VL area, VH CDR1, VH CDR2, VH CDR3, VL CDR1, a second binding domain that binds to CD123 having VL CDR2 and / or VL CDR3; In some embodiments, the anti-TRGV9 bispecific antibody further comprises a domain. A second binding domain that binds to CD123 and has the VH region of the anti-CD123 antibody provided herein. In some embodiments, the anti-TRGV9 bispecific antibody further comprises a domain. A second binding domain that binds to CD123 and has the VL region of the anti-CD123 antibody provided herein. In some embodiments, the anti-TRGV9 bispecific antibody further comprises a domain. The VH regions of the anti-CD123 antibodies provided herein and the VH regions of the anti-CD123 antibodies provided herein and a VL region of In embodiments, the anti-TRGV9 bispecific antibody is an anti-CD123 antibody provided herein. VH CDR1, VH CDR2, and VH CDR3 of the same antibody that binds to CD123. In some embodiments, the anti-TRGV9 bispecific antibody further comprises a second binding domain. The antibody may comprise the VL CDR1, VL CDR2, and VL CDR3 of an anti-CD123 antibody provided herein. and a second binding domain that binds to CD123 having a VL CDR3. In some embodiments, the anti-TRGV9 bispecific antibody is an anti-CD12 antibody provided herein. VH CDR1, VH CDR2, and VH CDR3 of the three antibodies provided herein. and VL CDR1, VL CDR2, and VL CDR3 of an anti-CD123 antibody. It further comprises a second binding domain that binds to CD123.

[0230] In certain embodiments, anti-TRGV9 antibodies are provided that are intact antibodies. In embodiments, an anti-TRGV9 antibody is provided, and an antigen-binding fragment of the anti-TRGV9 antibody is In some embodiments, the antigen-binding fragment of an anti-TRGV9 antibody has the following function: In some embodiments, the antigen-binding fragment is a diabodies. In some embodiments, the antigen-binding fragment is a Fab. In some embodiments, the antigen-binding fragment is a Fab'. In some embodiments, the antigen-binding fragment is F(ab'). The fragment is an Fv fragment. In some embodiments, the antigen-binding fragment The compound is a disulfide-stabilized Fv fragment (dsFv). In some embodiments, the antigen-binding fragment is a (dsFv)2. In some embodiments, the antigen-binding fragment is a bispecific dsFv (dsFv-ds In some embodiments, the antigen-binding fragment is a disulfide-stabilized Fv'. In some embodiments, the antigen-binding flag The antibody fragment is a single-chain antibody molecule (scFv). In some embodiments, the antigen-binding fragment is a single domain antibody. In some embodiments, the antigen-binding fragment is an scFv fragment. In some embodiments, the antigen-binding fragment is a divalent diabody. A multispecific antibody is 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. The binding fragment is a bivalent domain antibody. In some embodiments, the antigen-binding fragment A fragment is an antibody fragment that binds to an antigen but does not contain the entire antibody structure.

[0231] In certain embodiments, the anti-TRGV9 antibody comprises a VH region and a VL region. In embodiments, the anti-TRGV9 antibody is not a single chain antibody. The RGV9 antibody is not a single domain antibody. In some embodiments, the anti-TRGV9 antibody In certain embodiments, the anti-TRGV9 antibody is not a VHH antibody. In certain embodiments, the anti-TRGV9 antibody is not a llama antibody. In some embodiments, the anti-TRGV9 bispecific antibody does not include a single chain antibody. In certain embodiments, anti-TRGV9 bispecific antibodies do not include single domain antibodies. Anti-TRGV9 bispecific antibodies do not include nanobodies. V9 bispecific antibodies do not include VHH antibodies. In certain embodiments, anti-TRGV9 bispecific antibodies Specific antibodies do not include llama antibodies. In some embodiments, the anti-TRGV9 antibody is a polyclonal antibody. Bispecific Antibodies In other embodiments, the anti-TRGV9 antibody is a bispecific antibody. In certain embodiments, the multispecific antibody is an antibody that binds to the antigen of the anti-TRGV9 antibody provided herein. In other embodiments, the bispecific antibody comprises a binding fragment of any of the antibodies provided herein. In some embodiments, the antibody comprises an antigen-binding fragment of an anti-TRGV9 antibody. In certain embodiments, the anti-TRGV9 antibody is an agonist antibody. Activates cells. In other embodiments, the anti-TRGV9 antibody is an antagonist antibody. In certain embodiments, the anti-TRGV9 antibody inactivates γδ T cells. In embodiments, the anti-TRGV9 antibody blocks the activation of γδ T cells. In some embodiments, the anti-TRGV9 antibody modulates the activity of γδ T cells. Therefore, anti-TRGV9 antibodies neither activate nor inactivate the activity of γδ T cells. In certain embodiments, the γδ T cells are human γδ T cells. Bispecific antibodies comprising the TRGV9 antibodies provided herein in a knob-in-hole format. In some embodiments, the anti-TRGV9 antibodies provided herein are In some embodiments, the anti-TR antibody provided herein may be comprised in a bispecific antibody. The GV9 bispecific antibody may be included in a multispecific antibody. The bispecific antibodies provided herein bind to a first TRGV9 epitope. Provided are anti-TRGV9 antibodies comprising a first binding domain and a second TRGV9 epitope. and a second binding domain comprising an anti-TRGV9 antibody provided herein that binds to The first TRGV9 epitope and the second TRGV9 epitope are not the same. In embodiments, the TRGV9 antibodies or antigen-binding fragments thereof provided herein are In certain embodiments, the antibodies provided herein specifically bind to TRGV9. The antibody or antigen-binding fragment thereof does not bind to an epitope on V52.

[0232] In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) a sequence Amino acids of VH CDR1, VH CDR2, and VH CDR3, respectively, of No. 34 a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the sequence (ii) VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 8, respectively and VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of In another aspect, provided herein is an antibody that binds to TRGV9, comprising the antibody (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1, a 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) a VL CDR1 having the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 5. and a VL CDR2 having the amino acid sequence of SEQ ID NO: 6. In another embodiment, an antibody that binds to TRGV9 is described herein. and (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 196, the sequence VH CDR2 having the amino acid sequence of SEQ ID NO: 197, and the amino acid sequence of SEQ ID NO: 198 and (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 199. VL CDR1 having the amino acid sequence of SEQ ID NO: 200, VL CDR2 having the amino acid sequence of SEQ ID NO: 201, and VL CDR3 having the amino acid sequence of SEQ ID NO: 202. and a VL comprising a VL CDR3 having the amino acid sequence of SEQ ID NO: 201. Provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) an amino acid sequence of SEQ ID NO: 202; VH CDR1 having the amino acid sequence of SEQ ID NO: 203 2, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 204; and (ii) ) VL CDR1 having the amino acid sequence of SEQ ID NO: 205, VL CDR2 having the amino acid sequence of SEQ ID NO: 206 VL CDR2 having the amino acid sequence of SEQ ID NO: 207, and VL CDR3 having the amino acid sequence of SEQ ID NO: 208. In another aspect, provided herein is an antibody that binds to TRGV9. , the antibody comprises (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 208, a VH CDR2 having the amino acid sequence of SEQ ID NO: 20 VH CDR2 having the amino acid sequence of SEQ ID NO: 9, and VH CDR3 having the amino acid sequence of SEQ ID NO: 210 (ii) a VH comprising a VH CDR3; and (iii) a VL having the amino acid sequence of SEQ ID NO: 211. CDR1, VL CDR2 having the amino acid sequence of SEQ ID NO: 212, and SEQ ID NO: 213 and a VL comprising a VL CDR3 having the amino acid sequence of Provided herein is an antibody that binds to 9, the antibody comprising (i) the amino acid sequence of SEQ ID NO: 214. a VH CDR1 having the amino acid sequence of SEQ ID NO: 215; and a VH CDR2 having the amino acid sequence of SEQ ID NO: 216. (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 216; and 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 a VL CDR2 having the amino acid sequence of SEQ ID NO: 219, In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 214, VH CDR2 having the amino acid sequence of SEQ ID NO: 703, and VH CDR3 having the amino acid sequence of SEQ ID NO: 704. (ii) a VH CDR1 having the amino acid sequence of SEQ ID NO: 217, , a VL CDR2 having the amino acid sequence of SEQ ID NO: 218, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 219 In another embodiment, the VL comprises a VL CDR3 having the sequence Provided herein is an antibody having (i) the amino acid sequence of SEQ ID NO: 220. VH CDR1, 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. (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 223; VL CDR1 having the amino acid sequence of SEQ ID NO: 224 and a VL comprising a VL CDR2 and a VL CDR3 having the amino acid sequence of SEQ ID NO: 225. In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 226, the amino acid sequence of SEQ ID NO: 227 and a VH CDR3 having the amino acid sequence of SEQ ID NO: 228. and (ii) a 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 a VL comprising a VL CDR3 having SEQ ID NO: In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 34. The antibody comprises a VL having the amino acid sequence of SEQ ID NO: 34. and a VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody is 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 a VH comprising the amino acid sequence of SEQ ID NO: 8. Some VLs include those containing an amino acid sequence that has at least 95% identity to In embodiments, the antibody has at least 95% identity to the amino acid sequence of SEQ ID NO: 34. and a VH comprising an amino acid sequence having at least 9 amino acids relative to the amino acid sequence of SEQ ID NO: 8. VL, which contains an amino acid sequence with 5% identity.

[0233] In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) a sequence Amino acids of VH CDR1, VH CDR2, and VH CDR3, respectively, of No. 35 a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the sequence (ii) VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 8, respectively and VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of In another aspect, provided herein is an antibody that binds to TRGV9, comprising the antibody (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1, a 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) a VL CDR1 having the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 5. and a VL CDR2 having the amino acid sequence of SEQ ID NO: 6. In another embodiment, an antibody that binds to TRGV9 is described herein. and (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 232, the sequence VH CDR2 having the amino acid sequence of SEQ ID NO: 233, and the amino acid sequence of SEQ ID NO: 234 and (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 235. VL CDR1 having the amino acid sequence of SEQ ID NO: 236, VL CDR2 having the amino acid sequence of SEQ ID NO: 237, and VL CDR3 having the amino acid sequence of SEQ ID NO: 238. and a VL comprising a VL CDR3 having the amino acid sequence of SEQ ID NO:237. Provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) an amino acid sequence of SEQ ID NO: 238; VH CDR1 having the amino acid sequence of SEQ ID NO: 239 2, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 240; and (ii) 241, VL CDR1 having the amino acid sequence of SEQ ID NO: 242, VL CDR2 having the amino acid sequence of SEQ ID NO: 243, and VL CDR3 having the amino acid sequence of SEQ ID NO: 243. In another aspect, provided herein is an antibody that binds to TRGV9. , the antibody comprises (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 244; VH CDR2 having the amino acid sequence of SEQ ID NO: 5, and VH CDR3 having the amino acid sequence of SEQ ID NO: 246 (ii) a VH comprising a VH CDR3; and (iii) a VL having the amino acid sequence of SEQ ID NO: 247. CDR1, VL CDR2 having the amino acid sequence of SEQ ID NO: 248, and SEQ ID NO: 249 and a VL comprising a VL CDR3 having the amino acid sequence of Provided herein is an antibody that binds to 9, the antibody comprising (i) the amino acid sequence of SEQ ID NO: 250. a VH CDR1 having the amino acid sequence of SEQ ID NO: 251; and a VH CDR2 having the amino acid sequence of SEQ ID NO: 252. (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 252; and 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 a VL CDR2 having the amino acid sequence of SEQ ID NO: 255, In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 250, VH CDR2 having the amino acid sequence of SEQ ID NO: 705, and VH CDR3 having the amino acid sequence of SEQ ID NO: 706. (ii) a VH CDR1 having the amino acid sequence of SEQ ID NO: 253, , a VL CDR2 having the amino acid sequence of SEQ ID NO: 254, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 255 In another embodiment, the VL comprises a VL CDR3 having the sequence Provided herein is an antibody having (i) the amino acid sequence of SEQ ID NO: 256. VH CDR1, 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. (ii) a VH comprising a VH CDR3 having an amino acid sequence of SEQ ID NO: 259; VL CDR1 having the amino acid sequence of SEQ ID NO: 260 and a VL comprising a VL CDR2 and a VL CDR3 having the amino acid sequence of SEQ ID NO: 261. In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 262, the amino acid sequence of SEQ ID NO: 263 and a VH CDR3 having the amino acid sequence of SEQ ID NO: 264. and (ii) a 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 CDR2 having the amino acid sequence of SEQ ID NO: 267 In some embodiments, the antibody comprises a VL comprising a VL CDR3 having SEQ ID NO: In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 35. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO: 35. and a VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody has a sequence identity that is at least 95% identical to the amino acid sequence of SEQ ID NO:35. In some embodiments, the antibody comprises a VH comprising an amino acid sequence having identity to the VH. Contains an amino acid sequence having at least 95% identity to the amino acid sequence of sequence number 8 In some embodiments, the antibody comprises a VL sequence similar to that of SEQ ID NO: 35. VH and the amino acid sequence of SEQ ID NO: 8, which comprises an amino acid sequence having at least 95% identity. and VL, which comprises an amino acid sequence having at least 95% identity to the sequence.

[0234] In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) a sequence Amino acids of VH CDR1, VH CDR2, and VH CDR3 of No. 36, respectively a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the sequence (ii) VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 8, respectively and VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of In another aspect, provided herein is an antibody that binds to TRGV9, comprising the antibody (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1, a VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 33. and (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO: 4, SEQ ID NO: 5. and a VL CDR2 having the amino acid sequence of SEQ ID NO: 6. In another embodiment, an antibody that binds to TRGV9 is described herein. and (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 268, the sequence VH CDR2 having the amino acid sequence of SEQ ID NO: 269, and the amino acid sequence of SEQ ID NO: 270 and (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 271. VL CDR1 having the amino acid sequence of SEQ ID NO: 272, VL CDR2 having the amino acid sequence of SEQ ID NO: 273, and VL CDR3 having the amino acid sequence of SEQ ID NO: 274. and a VL comprising a VL CDR3 having the amino acid sequence of SEQ ID NO:273. Provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) an amino acid sequence of SEQ ID NO: 274; VH CDR1 having the amino acid sequence of SEQ ID NO: 275 2, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 276; and (ii) ) VL CDR1 having the amino acid sequence of SEQ ID NO: 277, VL CDR2 having the amino acid sequence of SEQ ID NO: 278 VL CDR2 having the amino acid sequence of SEQ ID NO: 279, and VL CDR3 having the amino acid sequence of SEQ ID NO: 279. In another aspect, provided herein is an antibody that binds to TRGV9. , the antibody comprises (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 280, a VH CDR2 having the amino acid sequence of SEQ ID NO: 28 VH CDR2 having the amino acid sequence of SEQ ID NO: 1, and VH CDR3 having the amino acid sequence of SEQ ID NO: 282 (ii) a VH comprising a VH CDR3; and (iii) a VL having the amino acid sequence of SEQ ID NO: 283. CDR1, VL CDR2 having the amino acid sequence of SEQ ID NO: 284, and SEQ ID NO: 285 and a VL comprising a VL CDR3 having the amino acid sequence of Provided herein is an antibody that binds to 9, the antibody comprising (i) the amino acid sequence of SEQ ID NO: 286. a VH CDR1 having the amino acid sequence of SEQ ID NO: 287; and a VH CDR2 having the amino acid sequence of SEQ ID NO: 287. (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 288; and 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 a VL CDR2 having the amino acid sequence of SEQ ID NO: 291, In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 286, VH CDR2 having the amino acid sequence of SEQ ID NO: 707, and VH CDR3 having the amino acid sequence of SEQ ID NO: 708. (ii) a VH having a CDR3 and (iii) a VL CDR1 having the amino acid sequence of SEQ ID NO: 289; , a VL CDR2 having the amino acid sequence of SEQ ID NO: 290, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 291 In another embodiment, the VL comprises a VL CDR3 having the sequence Provided herein is an antibody having (i) the amino acid sequence of SEQ ID NO: 292. VH CDR1, VH CDR2 having the amino acid sequence of SEQ ID NO: 293, and VH CDR3 having the amino acid sequence of SEQ ID NO: (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 295; VL CDR1 having the amino acid sequence of SEQ ID NO: 296 and a VL comprising a VL CDR2 and a VL CDR3 having the amino acid sequence of SEQ ID NO: 297. In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 298, the amino acid sequence of SEQ ID NO: 299 and a VH CDR3 having the amino acid sequence of SEQ ID NO: 300. and (ii) a 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 a VL comprising a VL CDR3 having SEQ ID NO: In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 36. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO: 36. and a VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody has a sequence identity that is at least 95% identical to the amino acid sequence of SEQ ID NO:36. In some embodiments, the antibody comprises a VH comprising an amino acid sequence having identity to the VH. Contains an amino acid sequence having at least 95% identity to the amino acid sequence of sequence number 8 In some embodiments, the antibody comprises a VL sequence similar to that of SEQ ID NO: 36. VH and the amino acid sequence of SEQ ID NO: 8, which comprises an amino acid sequence having at least 95% identity. and VL, which comprises an amino acid sequence having at least 95% identity to the sequence.

[0235] In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) a sequence Amino acids of VH CDR1, VH CDR2, and VH CDR3, respectively, of No. 65 a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the sequence (ii) VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 66, respectively VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of VL CDR3. In another aspect, provided herein is an antibody that binds to TRGV9, comprising an anti- The antibody comprises (i) a VH CDR1, a VH CDR2, and a VH CDR3 of SEQ ID NO: 67, respectively. VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of CDR3 and (ii) a VL CDR1 and a VL CDR2, respectively, of SEQ ID NO: 68. and VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of In another embodiment, an antibody that binds to TRGV9 comprises a VL comprising a VL CDR3. and (i) a 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) a VH having the amino acid sequence of SEQ ID NO: 77, VL CDR1 having the amino acid sequence of SEQ ID NO: 5, and VL CDR2 having the amino acid sequence of SEQ ID NO: 6 In another embodiment, the VL comprises a VL CDR3 having the sequence Provided herein is an antibody comprising: (i) a V having the amino acid sequence of SEQ ID NO: 60; VH CDR1 having the amino acid sequence of SEQ ID NO: 61, VH CDR2 having the amino acid sequence of SEQ ID NO: 62 and (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 63. VL CDR1 having the amino acid sequence of SEQ ID NO: 64, VL CDR2 having the amino acid sequence of SEQ ID NO: 64, and a VL comprising a VL CDR3 having the amino acid sequence of SEQ ID NO: 6. Provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) a polypeptide selected from the group consisting of SEQ ID NO: 304; VH CDR1 having the amino acid sequence of SEQ ID NO: 305 a VH comprising a VH CDR2 and a VH CDR3 having the amino acid sequence of SEQ ID NO: 306; (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO: 307, an amino acid sequence of SEQ ID NO: 308, VL CDR2 having the amino acid sequence of SEQ ID NO: 309, and VL CDR3 having the amino acid sequence of SEQ ID NO: 309. In another embodiment, the antibody that binds to TRGV9 is provided herein. The antibody comprises (i) a 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) a VH having the amino acid sequence of SEQ ID NO: 313, VL CDR1, 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. and a VL comprising a VL CDR3 having an amino acid sequence of 315. Provided herein is an antibody that binds to RGV9, the antibody comprising (i) the amino acid sequence of SEQ ID NO: 316. VH CDR1 having the amino acid sequence of SEQ ID NO: 317, VH CDR2 having the amino acid sequence of SEQ ID NO: 318 and a VH CDR3 having the amino acid sequence of SEQ ID NO: 318; and (ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 319, the amino acid sequence of SEQ ID NO: 320 and a VL CDR3 having the amino acid sequence of SEQ ID NO: 321. In another aspect, provided herein is an antibody that binds to TRGV9, comprising: The antibody comprises (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 322, a VH CDR2 having the amino acid sequence of SEQ ID NO: 323, and VH CDR2 having the amino acid sequence of SEQ ID NO: 324. (ii) a VH comprising a H CDR3 and a VL C having the amino acid sequence of SEQ ID NO: 325; DR1, 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 and a VL comprising a VL CDR3 having the amino acid sequence TRGV9. Provided herein is an antibody that binds to VH CDR1 having the amino acid sequence of SEQ ID NO: 708, VH CDR2 having the amino acid sequence of SEQ ID NO: 709, and (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 709; VL CDR1 having the amino acid sequence of SEQ ID NO: 325, VL CDR2 having the amino acid sequence of SEQ ID NO: 326 VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NO: 327. In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 328, an amino acid sequence of SEQ ID NO: 329, VH CDR2 having the amino acid sequence of SEQ ID NO: 330, and VH CDR3 having the amino acid sequence of SEQ ID NO: 331. and (ii) a 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 the amino acid sequence of SEQ ID NO: 333 In another embodiment, a VL that binds to TRGV9 comprises a VL CDR3 having the sequence Provided herein is an antibody comprising: (i) a V having the amino acid sequence of SEQ ID NO: 334; VH CDR1 having the amino acid sequence of SEQ ID NO: 335, VH CDR2 having the amino acid sequence of SEQ ID NO: 3 (ii) a VH comprising a VH CDR3 having an amino acid sequence of SEQ ID NO: 337; VL CDR1 having the amino acid sequence of SEQ ID NO: 338 and a VL comprising a VL CDR2 and a VL CDR3 having the amino acid sequence of SEQ ID NO: 339. In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) a sequence 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 a VH CDR3 having the amino acid sequence of SEQ ID NO: 342. (ii) a VH having the amino acid sequence of SEQ ID NO: 343; and (iii) a VL CDR1 having the amino acid sequence of SEQ ID NO: 344. 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, the antibody that binds to TRGV9 comprises a VL comprising a VL CDR3 that As provided herein, the antibody comprises: (i) a VH CD having the amino acid sequence of SEQ ID NO: 346; R1, a VH CDR2 having the amino acid sequence of SEQ ID NO: 347, and an amino acid sequence of SEQ ID NO: 348 (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 349; VL CDR1 having the sequence of SEQ ID NO: 350; VL CDR2 having the amino acid sequence of SEQ ID NO: 350; and a VL comprising a VL CDR3 having the amino acid sequence of SEQ ID NO: 351. In an aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) a polypeptide selected from the group consisting of SEQ ID NO: 3 VH CDR1 having the amino acid sequence of SEQ ID NO: 52, VH CDR2 having the amino acid sequence of SEQ ID NO: 353 a VH comprising a VH CDR2 and a VH CDR3 having the amino acid sequence of SEQ ID NO: 354; and (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO: 355, a VL CDR2 having the amino acid sequence of SEQ ID NO: 356 VL CDR2 having the amino acid sequence of SEQ ID NO: 357, and VL CDR3 having the amino acid sequence of SEQ ID NO: 358. In another embodiment, an antibody that binds to TRGV9 is described herein. and the antibody comprises (i) a 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 the amino acid sequence of SEQ ID NO: 360 and (ii) a VH having the amino acid sequence of SEQ ID NO: 361. a VL CDR1 having the amino acid sequence of SEQ ID NO: 362, a VL CDR2 having the amino acid sequence of SEQ ID NO: 363, and a VL CDR3 having the sequence and a VL comprising a VL CDR3 having the amino acid sequence of 363.

[0013] Provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) an antibody of SEQ ID NO: 358 VH CDR1 having the amino acid sequence of SEQ ID NO: 710 R2, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 711; i) VL CDR1 having the amino acid sequence of SEQ ID NO: 361, the amino acid sequence of SEQ ID NO: 362 VL CDR2 having the amino acid sequence of SEQ ID NO: 363 3. In another aspect, provided herein is an antibody that binds to TRGV9. The antibody comprises (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 364, VH CDR2 having the amino acid sequence of SEQ ID NO: 366, and (ii) a VH having the amino acid sequence of SEQ ID NO: 367, CDR1, VL CDR2 having the amino acid sequence of SEQ ID NO: 368, and SEQ ID NO: 36 and a VL comprising a VL CDR3 having an amino acid sequence of 16 to 19. Provided herein are antibodies that bind to V9, the antibodies having (i) the amino acid sequence of SEQ ID NO: 370. VH CDR1 having the amino acid sequence of SEQ ID NO: 371, VH CDR2 having the amino acid sequence of SEQ ID NO: 372, and and a VH CDR3 having the amino acid sequence of SEQ ID NO: 372; and (ii) a VH having the sequence 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 a VL CDR3 having the amino acid sequence of SEQ ID NO: 375. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO: 65. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 66. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO: 65. and a VL having the amino acid sequence of SEQ ID NO: 66. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 67. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO: 68. , VH having the amino acid sequence of SEQ ID NO: 67 and V having the amino acid sequence of SEQ ID NO: 68 In some embodiments, the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 71. In some embodiments, the antibody comprises a light chain having the amino acid sequence of SEQ ID NO: 72. In some embodiments, the antibody comprises 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 , SEQ ID NO: 70. In some embodiments, the antibody comprises the amino acid sequence of SEQ ID NO: 74 In some embodiments, the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 75. In some embodiments, the antibody comprises a light 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 comprises the amino acid sequence of SEQ ID NO: 73. The antibody may be an antibody having at least 95% identity to the amino acid sequence of SEQ ID NO:65. In some embodiments, the antibody comprises a VH comprising the amino acid sequence of SEQ ID NO: 66. The VL comprises an amino acid sequence having at least 95% identity to the amino acid sequence of the VL. In some embodiments, the antibody has a sequence identical to that of SEQ ID NO: 65, but is at least 95% identical to that of SEQ ID NO: 65. % identity to the amino acid sequence of SEQ ID NO: 66. and VL, which comprises an amino acid sequence having at least 95% identity. In one embodiment, the antibody has at least 95% identity to the amino acid sequence of SEQ ID NO:67. In some embodiments, the antibody comprises a VH comprising an amino acid sequence comprising SEQ ID NO: 68. VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of In some embodiments, the antibody comprises at least one antibody fragment that is directed against the amino acid sequence of SEQ ID NO:67. VH, which contains an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 68. and VL, which comprises an amino acid sequence having at least 95% identity to In one embodiment, the antibody has a sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 71. In some embodiments, the antibody comprises a heavy chain comprising an amino acid sequence having the sequence number comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:72; Light In some embodiments, the antibody comprises at least one amino acid sequence selected from the group consisting of SEQ ID NO: 71 and SEQ ID NO: 72. a heavy chain comprising an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 72; and a light chain comprising an amino acid sequence having at least 95% identity to the sequence. In some embodiments, the antibody comprises the amino acid sequence of SEQ ID NO: 70. The antibody has at least 95% identity to the amino acid sequence of SEQ ID NO: 74. In some embodiments, the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 75. a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of In some embodiments, the antibody has at least 9 amino acid residues to the amino acid sequence of SEQ ID NO: 74. 5% identity to the amino acid sequence of SEQ ID NO: 75. and a light chain comprising an amino acid sequence having at least 95% identity with the In embodiments, the antibody comprises the amino acid sequence of SEQ ID NO:73.

[0236] In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) a sequence The amino acids of VH CDR1, VH CDR2, and VH CDR3 of No. 104, respectively, are VH and VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence (ii) VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 105, respectively. VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of CDR3 In another aspect, provided herein is an antibody that binds to TRGV9. The antibody comprises (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 98, a VH CDR2 having the amino acid sequence of SEQ ID NO: 99, VH CDR2 having the amino acid sequence of SEQ ID NO: 100 (ii) a VH comprising CDR3 and a VL CD having the amino acid sequence of SEQ ID NO: 101; R1, a VL CDR2 having the amino acid sequence of SEQ ID NO: 102, and an amino acid sequence of SEQ ID NO: 103 In another embodiment, the VL comprises a VL CDR3 having the amino acid sequence Provided herein are antibodies that bind to the antibody, the antibody having (i) the amino acid sequence of SEQ ID NO: 412. a VH CDR1 having the amino acid sequence of SEQ ID NO: 413, a VH CDR2 having the sequence (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 414; and VL CDR1 having the amino acid sequence of SEQ ID NO: 15, VL CDR2 having the amino acid sequence of SEQ ID NO: 416 a VL CDR2, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 417; In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: i) VH CDR1 having the amino acid sequence of SEQ ID NO: 418, amino acid sequence of SEQ ID NO: 419 VH CDR2 having the sequence of SEQ ID NO: 420, and VH CDR3 having the amino acid sequence of SEQ ID NO: 421. 3, and (ii) a 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 the amino acid sequence of SEQ ID NO: 423 In another embodiment, the VL comprises a VL CDR3 having a sequence similar to that of the VL CDR1. Provided herein is an antibody, the antibody comprising: (i) a VH having the amino acid sequence of SEQ ID NO: 424; CDR1, VH CDR2 having the amino acid sequence of SEQ ID NO: 425, and SEQ ID NO: 42 (ii) a VH comprising a VH CDR3 having an amino acid sequence of SEQ ID NO: 427; VL CDR1 having the amino acid sequence of SEQ ID NO: 428 R2, and a VL comprising a VL CDR3 having the amino acid sequence of SEQ ID NO: 429. In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) a sequence 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 a VH CDR3 having the amino acid sequence of SEQ ID NO: 432. , VH, and (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO: 433, SEQ ID NO: 4 VL CDR2 having the amino acid sequence of SEQ ID NO: 34, and VL CDR3 having the amino acid sequence of SEQ ID NO: 435 In another embodiment, the antibody that binds to TRGV9 comprises a VL comprising a VL CDR3 comprising the VL CDR3 of the present invention. As provided herein, the antibody comprises: (i) a VH CDR having the amino acid sequence of SEQ ID NO: 430; 1. VH CDR2 having the amino acid sequence of SEQ ID NO: 714 and the amino acid sequence of SEQ ID NO: 715 (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 433; VL CDR1 having the amino acid sequence of SEQ ID NO: 434, VL CDR2 having the amino acid sequence of SEQ ID NO: 435, and and a VL comprising a VL CDR3 having the amino acid sequence of SEQ ID NO: 435. In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) a polypeptide selected from the group consisting of SEQ ID NO: 43 VH CDR1 having the amino acid sequence of SEQ ID NO: 6, VH CDR2 having the amino acid sequence of SEQ ID NO: 437 a VH comprising a VH CDR2 and a VH CDR3 having the amino acid sequence of SEQ ID NO: 438; (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO: 439, and a VL CDR2 having the amino acid sequence of SEQ ID NO: 440 VL CDR2 having the amino acid sequence of SEQ ID NO: 441, and VL CDR3 having the amino acid sequence of SEQ ID NO: 442. In another embodiment, an antibody that binds to TRGV9 is described herein. and (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 442, the sequence VH CDR2 having the amino acid sequence of SEQ ID NO: 443, and the amino acid sequence of SEQ ID NO: 444 and (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 445. VL CDR1 having the amino acid sequence of SEQ ID NO: 446, VL CDR2 having the amino acid sequence of SEQ ID NO: and a VL CDR3 having the amino acid sequence of SEQ ID NO: 447. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 104. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO: 105. In one embodiment, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 104 and a VH having the amino acid sequence of SEQ ID NO: 105. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO: 106. In some embodiments, the antibody comprises the amino acid sequence of SEQ ID NO: 104. VH, which comprises an amino acid sequence having at least 95% identity to In this embodiment, the antibody has at least 95% identity to the amino acid sequence of SEQ ID NO: 105. In some embodiments, the antibody comprises a VL comprising an amino acid sequence having the sequence Contains an amino acid sequence having at least 95% identity to the amino acid sequence of No. 104. and VH, having at least 95% identity to the amino acid sequence of SEQ ID NO: 105. and a VL comprising the amino acid sequence SEQ ID NO: 106. It contains the amino acid sequence of

[0237] In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) a sequence The amino acids of VH CDR1, VH CDR2, and VH CDR3 of No. 113, respectively, are VH and VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence (ii) VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 114, respectively. VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of CDR3 In another aspect, provided herein is an antibody that binds to TRGV9. , the antibody comprises (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 107, a VH CDR2 having the amino acid sequence of SEQ ID NO: 10 VH CDR2 having the amino acid sequence of SEQ ID NO: 109, and VH CDR3 having the amino acid sequence of SEQ ID NO: 110. (ii) a VH comprising a VH CDR3; and (iii) a VL having the amino acid sequence of SEQ ID NO: 110. CDR1, VL CDR2 having the amino acid sequence of SEQ ID NO: 111, and SEQ ID NO: 112 and a VL comprising a VL CDR3 having the amino acid sequence of Provided herein is an antibody that binds to 9, the antibody comprising (i) the amino acid sequence of SEQ ID NO: 448. a VH CDR1 having the amino acid sequence of SEQ ID NO: 449; and (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 450; and 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 a VL CDR2 having the amino acid sequence of SEQ ID NO: 453, In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 454, VH CDR2 having the amino acid sequence of SEQ ID NO: 456 (ii) a VH having a CDR3 and (iii) a VL CDR1 having the amino acid sequence of SEQ ID NO: 457; , a VL CDR2 having the amino acid sequence of SEQ ID NO: 458, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 459 In another embodiment, the VL comprises a VL CDR3 having the sequence Provided herein is an antibody having (i) the amino acid sequence of SEQ ID NO: 460. VH CDR1, 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. (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 463; VL CDR1 having the amino acid sequence of SEQ ID NO: 464 and a VL comprising a VL CDR2 and a VL CDR3 having the amino acid sequence of SEQ ID NO: 465. In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 466, the amino acid sequence of SEQ ID NO: 467 and a VH CDR3 having the amino acid sequence of SEQ ID NO: 468. and (ii) a 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, the antibody binds to TRGV9 and comprises a VL comprising a VL CDR3 having provided herein, the antibody comprises: (i) a VH C having the amino acid sequence of SEQ ID NO: 466; DR1 having the amino acid sequence of SEQ ID NO: 716, and VH CDR2 having the amino acid sequence of SEQ ID NO: 717 (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 469; VL CDR1 having the amino acid sequence of SEQ ID NO: 470, VL CDR2 having the amino acid sequence of SEQ ID NO: 470 and a VL comprising a VL CDR3 having the amino acid sequence of SEQ ID NO: 471. In one aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) a sequence selected from the group consisting of SEQ ID NO: VH CDR1 having the amino acid sequence of SEQ ID NO: 472, VH CDR2 having the amino acid sequence of SEQ ID NO: 473 VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 474. H, and (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO: 475, SEQ ID NO: 476 and VL CDR2 having the amino acid sequence of SEQ ID NO: 477. In another embodiment, an antibody that binds to TRGV9 comprises a VL comprising a VL CDR3. and (i) a 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 the amino acid sequence of SEQ ID NO: 480 and (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 481. a VL CDR1 having the amino acid sequence of SEQ ID NO: 482, a VL CDR2 having the amino acid sequence of SEQ ID NO: 483, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 484. and a VL having a VL CDR3 having the amino acid sequence of SEQ ID NO: 483. In embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 113. In embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO: 114. In embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 113 and a VH having the amino acid sequence of SEQ ID NO: 114 and a VL having the amino acid sequence of SEQ ID NO: 11. In some embodiments, the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 11. In some embodiments, the antibody comprises a light chain having the amino acid sequence of SEQ ID NO: 11. 5 and a light chain having the amino acid sequence of SEQ ID NO: 116. In some embodiments, the antibody has at least one amino acid sequence that is identical to that of SEQ ID NO: 113. In some embodiments, the antibody comprises a VH comprising an amino acid sequence having 95% identity. The antibody is 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 a VL comprising the amino acid sequence of SEQ ID NO: 113. VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: Contains an amino acid sequence that is at least 95% identical to the amino acid sequence of No. 114 In some embodiments, the antibody comprises a VL and a VL. The heavy chain contains an amino acid sequence that has at least 95% identity to the In some embodiments, the antibody has at least 95% identity to the amino acid sequence of SEQ ID NO: 116. In some embodiments, the antibody comprises a light chain comprising an amino acid sequence having SEQ ID NO: 115 amino acid sequence having at least 95% identity to the amino acid sequence of heavy chain and an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:116. and a light chain comprising the amino acid sequence.

[0238] In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) a sequence The amino acids of VH CDR1, VH CDR2, and VH CDR3 of No. 123, respectively, are VH and VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence (ii) VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 124, respectively. VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of CDR3 In another aspect, provided herein is an antibody that binds to TRGV9. , the antibody comprises (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 117, a VH CDR2 having the amino acid sequence of SEQ ID NO: 11 VH CDR2 having the amino acid sequence of SEQ ID NO: 119, and VH CDR3 having the amino acid sequence of SEQ ID NO: 120. (ii) a VH comprising a VH CDR3; and (iii) a VL having the amino acid sequence of SEQ ID NO: 120. CDR1, VL CDR2 having the amino acid sequence of SEQ ID NO: 121, and SEQ ID NO: 122 and a VL comprising a VL CDR3 having the amino acid sequence of Provided herein is an antibody that binds to 9, the antibody comprising (i) the amino acid sequence of SEQ ID NO: 484. a VH CDR1 having the amino acid sequence of SEQ ID NO: 485; and a VH CDR2 having the amino acid sequence of SEQ ID NO: 485. (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 486; and 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 a VL CDR2 having the amino acid sequence of SEQ ID NO: 489, In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 490, VH CDR2 having the amino acid sequence of SEQ ID NO: 492, and VH CDR3 having the amino acid sequence of SEQ ID NO: 493. (ii) a VH having a CDR3 and (iii) a VL CDR1 having the amino acid sequence of SEQ ID NO: 493 , a VL CDR2 having the amino acid sequence of SEQ ID NO: 494, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 495 In another embodiment, the VL comprises a VL CDR3 having the sequence Provided herein is an antibody having (i) the amino acid sequence of SEQ ID NO: 496. VH CDR1, VH CDR2 having the amino acid sequence of SEQ ID NO: 497, and VH CDR3 having the amino acid sequence of SEQ ID NO: (ii) a VH comprising a VH CDR3 having an amino acid sequence of SEQ ID NO: 499; VL CDR1 having the amino acid sequence of SEQ ID NO: 500 and a VL comprising a VL CDR2 and a VL CDR3 having the amino acid sequence of SEQ ID NO: 501. In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 502, the amino acid sequence of SEQ ID NO: 503 and a VH CDR3 having the amino acid sequence of SEQ ID NO: 504. and (ii) a 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, the antibody binds to TRGV9 and comprises a VL comprising a VL CDR3 having provided herein, the antibody comprises: (i) a VH C having the amino acid sequence of SEQ ID NO: 502; DR1, 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 (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 505; VL CDR1 having the amino acid sequence of SEQ ID NO: 506, VL CDR2 having the amino acid sequence of SEQ ID NO: 507 and a VL comprising a VL CDR3 having the amino acid sequence of SEQ ID NO: 507. In one aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) a sequence selected from the group consisting of SEQ ID NO: VH CDR1 having the amino acid sequence of SEQ ID NO: 508, VH CDR2 having the amino acid sequence of SEQ ID NO: 509 VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 510. H, and (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO: 511, SEQ ID NO: 512 and VL CDR2 having the amino acid sequence of SEQ ID NO: 513. In another embodiment, an antibody that binds to TRGV9 comprises a VL comprising a VL CDR3. and (i) a 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 the amino acid sequence of SEQ ID NO: 516 and (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 517. a VL CDR1 having the amino acid sequence of SEQ ID NO: 518, a VL CDR2 having the amino acid sequence of SEQ ID NO: 519, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 520. and a VL having a VL CDR3 having the amino acid sequence of SEQ ID NO: 519. In embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 123. In embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO: 124. In embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 123 and a VH having the amino acid sequence of SEQ ID NO: 124 and a VL having the amino acid sequence of SEQ ID NO: 12. In some embodiments, the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 12. In some embodiments, the antibody comprises a light chain having the amino acid sequence of SEQ ID NO: 12. 5 and a light chain having the amino acid sequence of SEQ ID NO: 126. In some embodiments, the antibody has at least one amino acid sequence identical to that of SEQ ID NO: 123. In some embodiments, the antibody comprises a VH comprising an amino acid sequence having 95% identity. The antibody is 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 VL comprising the amino acid sequence of SEQ ID NO: 123. VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: Contains an amino acid sequence that is at least 95% identical to the amino acid sequence of No. 124 In some embodiments, the antibody comprises a VL and a VL. The heavy chain contains an amino acid sequence that has at least 95% identity to the In some embodiments, the antibody has at least 95% identity to the amino acid sequence of SEQ ID NO: 126. In some embodiments, the antibody comprises a light chain comprising an amino acid sequence having SEQ ID NO: 125 amino acid sequence having at least 95% identity to the amino acid sequence, heavy chain and an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 126. and a light chain comprising the amino acid sequence.

[0239] In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) a sequence The amino acids of VH CDR1, VH CDR2, and VH CDR3 of No. 133, respectively, are VH and VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence (ii) VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 134, respectively. VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of CDR3 In another aspect, provided herein is an antibody that binds to TRGV9. , the antibody comprises (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 127, a VH CDR2 having the amino acid sequence of SEQ ID NO: 12 VH CDR2 having the amino acid sequence of SEQ ID NO: 129, and VH CDR3 having the amino acid sequence of SEQ ID NO: 130. (ii) a VH comprising a VH CDR3; and (iii) a VL having the amino acid sequence of SEQ ID NO: 130. CDR1, VL CDR2 having the amino acid sequence of SEQ ID NO: 131, and SEQ ID NO: 132 and a VL comprising a VL CDR3 having the amino acid sequence of Provided herein is an antibody that binds to 9, the antibody comprising (i) the amino acid sequence of SEQ ID NO: 520. a VH CDR1 having the amino acid sequence of SEQ ID NO: 521; and a VH CDR2 having the amino acid sequence of SEQ ID NO: 522. (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 522; and 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 a VL CDR2 having the amino acid sequence of SEQ ID NO: 525, In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 526, VH CDR2 having the amino acid sequence of SEQ ID NO: 528, and VH CDR3 having the amino acid sequence of SEQ ID NO: 529. (ii) a VH CDR1 having the amino acid sequence of SEQ ID NO: 529, , a VL CDR2 having the amino acid sequence of SEQ ID NO: 530, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 531 In another embodiment, the VL comprises a VL CDR3 having the sequence Provided herein is an antibody having (i) the amino acid sequence of SEQ ID NO: 532. VH CDR1, 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. (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 535; VL CDR1 having the amino acid sequence of SEQ ID NO: 536 and a VL comprising a VL CDR2 and a VL CDR3 having the amino acid sequence of SEQ ID NO: 537. In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) VH CDR1 having the amino acid sequence of SEQ ID NO: 538, the amino acid sequence of SEQ ID NO: 539 and a VH CDR3 having the amino acid sequence of SEQ ID NO: 540. and (ii) a 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, the antibody binds to TRGV9 and comprises a VL comprising a VL CDR3 having provided herein, the antibody comprises: (i) a VH C having the amino acid sequence of SEQ ID NO: 538; DR1 having the amino acid sequence of SEQ ID NO: 720, and VH CDR2 having the amino acid sequence of SEQ ID NO: 721 (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 541; VL CDR1 having the amino acid sequence of SEQ ID NO: 542, VL CDR2 having the amino acid sequence of SEQ ID NO: 543 and a VL comprising a VL CDR3 having the amino acid sequence of SEQ ID NO: 543. In one aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) a sequence selected from the group consisting of SEQ ID NO: VH CDR1 having the amino acid sequence of SEQ ID NO: 544, VH CDR2 having the amino acid sequence of SEQ ID NO: 545 VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 546. H, and (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO: 547, SEQ ID NO: 548 and a VL CDR2 having the amino acid sequence of SEQ ID NO: 549. In another embodiment, an antibody that binds to TRGV9 comprises a VL comprising a VL CDR3. and (i) a 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 the amino acid sequence of SEQ ID NO: 552 and (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 553. a VL CDR1 having the amino acid sequence of SEQ ID NO: 554, a VL CDR2 having the amino acid sequence of SEQ ID NO: 555, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 556. and a VL having a VL CDR3 having the amino acid sequence of SEQ ID NO: 555. In embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 133. In embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO: 134. In embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 133 and a VH having the amino acid sequence of SEQ ID NO: 134 and a VL having the amino acid sequence of SEQ ID NO: 13. In some embodiments, the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 13. In some embodiments, the antibody comprises a light chain having the amino acid sequence of SEQ ID NO: 13. 5 and a light chain having the amino acid sequence of SEQ ID NO: 136. In some embodiments, the antibody has at least one amino acid sequence identical to that of SEQ ID NO: 133. In some embodiments, the antibody comprises a VH comprising an amino acid sequence having 95% identity. The antibody is 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 a VL comprising the amino acid sequence of SEQ ID NO: 133. VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: Contains an amino acid sequence that is at least 95% identical to the amino acid sequence of No. 134 In some embodiments, the antibody comprises a VL that is directed against the amino acid sequence of SEQ ID NO: 135. The heavy chain contains an amino acid sequence that has at least 95% identity to the In some embodiments, the antibody has at least 95% identity to the amino acid sequence of SEQ ID NO: 136. In some embodiments, the antibody comprises a light chain comprising an amino acid sequence having SEQ ID NO: 135 amino acid sequence having at least 95% identity to the amino acid sequence of heavy chain and an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 136. and a light chain comprising the amino acid sequence.

[0240] In some embodiments, the anti-TRGV9 antibody is not a single chain antibody. In some embodiments, the anti-TRGV9 antibody is not a single domain antibody. The TRGV9 antibody is not a nanobody. In certain embodiments, the anti-TRGV9 antibody is a V Not an HH antibody. In certain embodiments, the anti-TRGV9 antibody is not a llama antibody.

[0241] In some embodiments, the anti-TRGV9 antibodies provided herein each comprise the sequence VH CDR1, VH CDR2, VH CDR3, VH CDR4, VH CDR5, VH CDR6, VH CDR7, VH CDR8, VH CDR9, VH CDR10, VH CDR11, VH CDR12, VH CDR13, VH CDR14, VH CDR15, VH CDR16, VH CDR17, VH CDR18, VH CDR19, VH C In some embodiments, the antibodies provided herein comprise a VH CDR1, a VH CDR2, and a VH CDR3. The TRGV9 antibodies have the amino acid sequences of SEQ ID NOs: 733, 734, and 735, respectively. In some embodiments, the VH CDR1, VH CDR2, and VH CDR3 do not contain the corresponding VH CDR1, VH CDR2, and VH CDR3. In some embodiments, the anti-TRGV9 antibodies provided herein are those represented by SEQ ID NOs: 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747, 748, 749, 750, 751, 752, 753, 754, 755, 75 VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of 7 and 738, respectively. In some embodiments, the anti-TRGV9 antibodies provided herein do not contain DR3. , VH CDRs having the amino acid sequences of SEQ ID NOs: 739, 740, and 741, respectively In some embodiments, the VH CDRs described herein do not include VH CDR1, VH CDR2, and VH CDR3. The anti-TRGV9 antibodies provided herein are those set forth in SEQ ID NOs: 742, 743, and 744, respectively. does not contain VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence In some embodiments, the anti-TRGV9 antibodies provided herein each have the sequence VH CDR1, VH CDR2, VH CDR3, VH CDR4, VH CDR5, VH CDR6, VH CDR7, VH CDR8, VH CDR9, VH CDR10, VH CDR11, VH CDR12, VH CDR13, VH CDR14, VH CDR15, VH CDR16, VH CDR17, VH CDR18, VH CDR19, VH C In some embodiments, the antibodies provided herein comprise a VH CDR1, a VH CDR2, and a VH CDR3. The TRGV9 antibodies have the amino acid sequences of SEQ ID NOs: 748, 749, and 750, respectively. In some embodiments, the VH CDR1, VH CDR2, and VH CDR3 do not contain the corresponding VH CDR1, VH CDR2, and VH CDR3. In one embodiment, the anti-TRGV9 antibody provided herein has the amino acid sequence of SEQ ID NO: 751. In some embodiments, the anti-TR antibody provided herein does not comprise a VH domain having The GV9 antibody does not contain a VH domain having the amino acid sequence of SEQ ID NO: 752. In some embodiments, the anti-TRGV9 antibodies provided herein comprise the amino acid sequence of SEQ ID NO: 753. In some embodiments, the VH domain does not comprise a VH domain having the sequence The anti-TRGV9 antibody does not contain a VH domain having the amino acid sequence of SEQ ID NO: 754. In some embodiments, the anti-TRGV9 antibody provided herein is selected from the group consisting of SEQ ID NO: 755 In some embodiments, the VH domain does not comprise a VH domain having an amino acid sequence of The provided anti-TRGV9 antibody comprises a VH domain having the amino acid sequence of SEQ ID NO: 756. In some embodiments, the anti-TRGV9 antibodies provided herein do not include SEQ ID NO: It does not contain a VH domain having the amino acid sequence of No. 757.

[0242] In another embodiment, a V has the amino acid sequence of APNxGzYTbDF (SEQ ID NO: 758). Provided herein are anti-TRGV9 antibodies comprising a VH domain comprising a H CDR3, wherein x is Y or M, z is M or D, and b is I or L. The present invention relates to an anti-TRGV9 antibody comprising a VH domain comprising the amino acid sequence of SEQ ID NO: 758. In another embodiment, the amino acid sequence of GxTFzz (SEQ ID NO: 761) is provided herein. Provided herein are anti-TRGV9 antibodies comprising a VH domain comprising a VH CDR1 comprising , where x is F, D, or G and z is S or N. In another embodiment, Provided herein is an anti-TRGV9 antibody comprising a VH domain comprising the amino acid sequence of SEQ ID NO:761. In another embodiment, a VL having the amino acid sequence of RxSQSz (SEQ ID NO: 762) Provided herein is an anti-TRGV9 antibody comprising a VL domain comprising CDR1, wherein: x is A or S and Z is V or L. In another embodiment, the amino acid sequence of SEQ ID NO: 761 is Provided herein are anti-TRGV9 antibodies comprising a VL domain comprising a nucleotide sequence.

[0243] In another aspect, provided herein is an antibody that binds to TRGV9, the antibody comprising: (i) a VH (ii) a VH comprising CDR1, VH CDR2, and VH CDR3; and and a VL comprising R1, VL CDR2, and VL CDR3. In some embodiments, the VH CDR1 comprises a first polar amino acid. CDR1 comprises the last polar, uncharged amino acid. In some embodiments, the VH CDR In some embodiments, VH CDR1 comprises at least one tyrosine. In some embodiments, the VH CDR1 comprises at least 20% hydrophobic amino acids. and at least two hydrophobic amino acids. In some embodiments, the VH CDR1 In some embodiments, the VH CDRs comprise at least about 40% hydrophobic amino acids. 1 comprises a VH CDR1 comprising 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 The structure of VH CDR1 shown above contains at least about 40% hydrophobic amino acids. Any combination of two or more of the features is also contemplated. In some embodiments, the VH CDR2 comprises a polar amino acid at residue 13. In some embodiments, the VH CDR2 comprises a hydrophobic amino acid at amino acid position 15. DR2 has phenylalanine (F) or leucine (L) at position 15. In some embodiments, the VH CDR2 comprises a polar amino acid at position 14. In some embodiments, the VH CDR2 has a lysine (K) or serine at position 14. In some embodiments, the VH CDR2 comprises a hydrophobic amino acid at position 2 (serine, S). In some embodiments, the VH CDR2 comprises a hydrophobic amino acid at position 3. In some embodiments, the VH CDR2 comprises the polar penultimate amino acid In some embodiments, the VH CDR2 contains a polar amino acid at residue 13, a hydrophobic amino acid at position 15, a polar amino acid, phenylalanine (F) or leucine (L) at position 15, a polar amino acid at position 14 acid, lysine (K) or serine (S) at position 14, a hydrophobic amino acid at position 2 or 3, and a polar containing the penultimate amino acid, two of the structural features of VH CDR2 listed above, or Any combination of three or more is also contemplated. In some embodiments, the VH CDR3 is In some embodiments, the VH CDR3 has a sequence of 7 In some embodiments, the VH CDR3 comprises a hydrophobic or polar charged amino acid at position In some embodiments, the VH CDR3 comprises a polar, uncharged, or hydrophobic amino acid at position 6. does not contain a polar charged amino acid at position 3, a hydrophobic or polar charged amino acid at position 7, and a Contains polar, uncharged or hydrophobic amino acids. Two of the structural features of VH CDR3 listed above or any combination of three or more are also contemplated. In some embodiments, VL CDR1 contains a polar amino acid at position 4. In some embodiments, the VL CDR1 comprises a first amino acid at position 2 that is polar. In some embodiments, the VL CDR1 comprises a non-charged or hydrophobic amino acid at position 3. In some embodiments, the VL CDR1 contains a polar amino acid at position 5. In some embodiments, the VL CDR1 comprises a hydrophobic amino acid at position 6. In some embodiments, the VL CDR1 has a polar amino acid at position 4, a first amino acid that is polar charged, and a second amino acid that is polar charged. a polar uncharged or hydrophobic amino acid at position 2, a serine at position 3, a polar amino acid at position 5, and Contains a hydrophobic amino acid at position 6. Two or three of the structural features of VL CDR1 listed above Any combination of the above is also contemplated. In some embodiments, the VL CDR2 is In some embodiments, the VL CDR2 contains a polar charged amino acid at position 6. or a hydrophobic amino acid. In some embodiments, the VL CDR2 comprises a polar charged amino acid at position 3. In some embodiments, the VL CDR2 comprises a polar uncharged amino acid at position 4. In some embodiments, the VL CDR2 comprises a hydrophobic amino acid at position 2. In some embodiments, the VL CDR2 contains a polar amino acid at position 7, a polar charged or is a hydrophobic amino acid, a polar charged amino acid at position 3, a polar uncharged amino acid at position 4, and a hydrophobic amino acid at position 2. Contains hydrophilic amino acids. Any two or more of the structural features of VL CDR2 listed above Any combination is contemplated. In some embodiments, the VL CDR3 has a hydrophobic tail. In some embodiments, the VL CDR3 comprises a terminal tyrosine. In some embodiments, the VL CDR3 comprises a polar, uncharged amino acid at position 5. In some embodiments, the VL CDR3 comprises a polar amino acid at position 2. In some embodiments, the VL CDR3 contains a polar, uncharged or hydrophobic amino acid at position 1. In some embodiments, the VL CDR3 comprises a hydrophobic amino acid at position 3. The L CDR3 comprises a hydrophilic or polar uncharged amino acid at position 6. In some embodiments, In some embodiments, the VL CDR3 does not contain a polar or hydrophobic amino acid at position 7. VL CDR3 has a hydrophobic terminal amino acid, a terminal tyrosine, and 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, Contains a hydrophilic or polar uncharged amino acid at position 6 and no polar or hydrophobic amino acid at position 7 Any combination of two or more of the above VL CDR3 structural features is also contemplated. In certain embodiments, the residue position numbering follows the exemplary numbering.

[0244] In some embodiments, the anti-TRGV9 antibody is a multispecific antibody. In certain embodiments, the anti-TRGV9 antibody is a bispecific antibody. The antibodies include antigen-binding fragments of the anti-TRGV9 antibodies provided herein. In this embodiment, the multispecific antibody comprises a first binding epitope that binds to a first TRGV9 epitope. a first T domain and a second domain that binds to a second TRGV9 epitope; The TRGV9 epitope and the second TRGV9 epitope are different. The bispecific antibody further comprises a third binding domain that binds to a target that is not TRGV9.

[0245] In another embodiment, (a) a first binding domain that binds to TRGV9; and (b) a TRGV9 and a second binding domain that binds to a second target that is not a will be provided to.

[0246] In some embodiments, the bispecific 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 comprises a heavy chain variable region and a light chain variable region. and the second binding domain comprises a heavy chain variable region and a light chain variable region. In some embodiments, the TRGV9 antibody is not a single domain antibody or a nanobody.

[0247] In another aspect, provided herein is a bispecific antibody, the antibody (a) binding to TRGV9. (b) a first binding domain that binds to a second target that is not TRGV9; and a first binding domain comprising (i) a VH C domain of SEQ ID NO: 7, VH CDR1 having the amino acid sequences of DR1, VH CDR2, and VH CDR3; (ii) a VH comprising a VH CDR2, and a VH CDR3, and (iii) a VH of SEQ ID NO: 8, respectively; , VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3. and a VL comprising CDR1, VL CDR2, and VL CDR3. Provided herein are bispecific antibodies, the antibodies comprising: (a) a first binding domain that binds to TRGV9; and (b) a second binding domain that binds to a second target that is not TRGV9. the first binding domain comprises (i) a 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) a VL having the amino acid sequence of SEQ ID NO: 4. VL CDR1 having the amino acid sequence of SEQ ID NO: 5, and VL CDR2 having the amino acid sequence of SEQ ID NO: 6 and a VL comprising a VL CDR3 having the sequence As provided herein, the antibody comprises: (a) a first binding domain that binds to TRGV9; a second binding domain that binds to a second target that is not TRGV9, The main group consists of (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 160, a VH CDR2 having the amino acid sequence of SEQ ID NO: 16 VH CDR2 having the amino acid sequence of SEQ ID NO: 1, and VH CDR3 having the amino acid sequence of SEQ ID NO: 162 (ii) a VH comprising a VH CDR3; and (iii) a VL having the amino acid sequence of SEQ ID NO: 163. CDR1, VL CDR2 having the amino acid sequence of SEQ ID NO: 164, and SEQ ID NO: 165 and a VL comprising a VL CDR3 having the amino acid sequence Provided herein are specific antibodies, the antibodies comprising: (a) a first binding domain that binds to TRGV9; and (b) a second binding domain that binds to a second target that is not TRGV9, The binding domain of the present invention comprises (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 166, a VH CDR2 having the sequence VH CDR2 having the amino acid sequence of SEQ ID NO: 167, and the amino acid sequence of SEQ ID NO: 168 and (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 169. VL CDR1 having the amino acid sequence of SEQ ID NO: 170, VL CDR2 having the amino acid sequence of SEQ ID NO: and a VL comprising a VL CDR3 having the amino acid sequence of SEQ ID NO:171. Provided herein are bispecific antibodies, the antibodies comprising: (a) a first binding domain that binds to TRGV9; and (b) a second binding domain that binds to a second target that is not TRGV9. the first binding domain comprises (i) a VH CDR having the amino acid sequence of SEQ ID NO: 172; 1. VH CDR2 having the amino acid sequence of SEQ ID NO: 173 and the amino acid sequence of SEQ ID NO: 174 (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 175; VL CDR1 having the amino acid sequence of SEQ ID NO: 176, VL CDR2 having the amino acid sequence of SEQ ID NO: 177, and and a VL comprising a VL CDR3 having the amino acid sequence of SEQ ID NO: 177. In one embodiment, a bispecific antibody is provided herein, the antibody comprising: (a) a first antibody that binds to TRGV9; (b) a second binding domain that binds to a second target that is not TRGV9. and a first binding domain comprising (i) a VH having the amino acid sequence of SEQ ID NO: 178. CDR1, VH CDR2 having the amino acid sequence of SEQ ID NO: 179, and SEQ ID NO: 18 and (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 181. VL CDR1 having the amino acid sequence of SEQ ID NO: 182, VL CDR2 having the amino acid sequence of SEQ ID NO: 183 R2, and a VL comprising a VL CDR3 having the amino acid sequence of SEQ ID NO: 183. In another aspect, provided herein is a bispecific antibody, the antibody (a) binding to TRGV9; (b) a first binding domain that binds to a second target that is not TRGV9; a first binding domain having (i) the amino acid sequence of SEQ ID NO: 178; a VH CDR1 having the amino acid sequence of SEQ ID NO: 700, a VH CDR2 having the sequence (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 1; VL CDR1 having the amino acid sequence of SEQ ID NO: 181, VL CDR2 having the amino acid sequence of SEQ ID NO: 182 a VL CDR2, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 183; In another aspect, provided herein is a bispecific antibody, the antibody comprising: (a) TRG (b) a first binding domain that binds to V9 and (b) a second binding domain that binds to a second target that is not TRGV9 and a second binding domain, the first binding domain comprising: (i) the amino acid sequence of SEQ ID NO: 184 VH CDR1 having the sequence: VH CDR2 having the amino acid sequence of SEQ ID NO: 185; and a VH CDR3 having the amino acid sequence of SEQ ID NO: 186; and (ii) a VH having the sequence 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 a VL CDR3 having the amino acid sequence of SEQ ID NO: 189. In another aspect, a bispecific antibody is provided herein, the antibody comprising: ) a first binding domain that binds to TRGV9 and (b) a second binding domain that binds to a non-TRGV9 target. and a second binding domain that binds to the first binding domain, the first binding domain comprising: (i) a nucleic acid sequence of SEQ ID NO: 190 VH CDR1 having the amino acid sequence of SEQ ID NO: 191 a VH comprising a VH CDR2 and a VH CDR3 having the amino acid sequence of SEQ ID NO: 192; ii) VL CDR1 having the amino acid sequence of SEQ ID NO: 193, VL CDR2 having the amino acid sequence of SEQ ID NO: 195, and VL CDR3 having the amino acid sequence of SEQ ID NO: 196. In some embodiments, the first binding domain comprises a VL comprising R3. In some embodiments, the first binding domain comprises a VH having an amino acid sequence of and a VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding The domains are VH having the amino acid sequence of SEQ ID NO: 7 and VH having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises an amino acid sequence of SEQ ID NO: 23 and a VL comprising the amino acid sequence of SEQ ID NO: 23. In some embodiments, the first binding domain comprises a heavy chain having the amino acid sequence In some embodiments, the first binding domain comprises a light chain having an amino acid sequence of The antibody has a heavy chain having the amino acid sequence of SEQ ID NO: 23 and a non-human IgG antibody having the amino acid sequence of SEQ ID NO: 24. In some embodiments, the first binding domain comprises an amino acid sequence of SEQ ID NO: 17 and a light chain comprising an amino acid sequence of SEQ ID NO: 18. In some embodiments, the first binding domain comprises the amino acid sequence of SEQ ID NO: 69. In some embodiments, the first binding domain comprises a heavy chain having the amino acid sequence In some embodiments, the first binding domain comprises a light chain having an amino acid sequence of The antibody has a heavy chain having the amino acid sequence of SEQ ID NO: 69 and a non-human IgG antibody having the amino acid sequence of SEQ ID NO: 24. In some embodiments, the first binding domain comprises an amino acid sequence of SEQ ID NO: 7 and a light chain comprising an amino acid sequence of SEQ ID NO: 7. The VH comprises an amino acid sequence having at least 95% identity to the amino acid sequence of the VH. In some embodiments, the first binding domain has at least one amino acid sequence similar to that of SEQ ID NO:8. In some embodiments, the VL comprises an amino acid sequence having at least 95% identity to the VL. In the present invention, the first binding domain has at least 95% identity to the amino acid sequence of SEQ ID NO: 7. and a VH comprising an amino acid sequence having at least one amino acid sequence identical to the amino acid sequence of SEQ ID NO: 8. In some embodiments, the VL comprises an amino acid sequence having at least 95% identity with the VL. , the first binding domain has at least 95% identity to the amino acid sequence of SEQ ID NO: 23 In some embodiments, the first binding domain comprises a heavy chain comprising an amino acid sequence having a The amino acid sequence of SEQ ID NO:24 is an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:24. In some embodiments, the first binding domain comprises a light chain comprising the sequence of SEQ ID NO: 23 amino acid sequences having at least 95% identity to the amino acid sequence of and an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the first binding domain comprises a light chain comprising the sequence SEQ ID NO: In some embodiments, the first binding domain comprises a sequence of 17 amino acids. 69 amino acid sequence having at least 95% identity to the amino acid sequence of In some embodiments, the first binding domain comprises the amino acid sequence of SEQ ID NO:24. The light chain comprises an amino acid sequence having at least 95% identity to the sequence. In some embodiments, the first binding domain has at least one amino acid sequence similar to that of SEQ ID NO: 69. a heavy chain comprising an amino acid sequence having 95% identity with the amino acid sequence of SEQ ID NO: 24; and a light chain comprising an amino acid sequence having at least 95% identity to

[0248] In another aspect, provided herein is a bispecific antibody, the antibody (a) binding to TRGV9. (b) a first binding domain that binds to a second target that is not TRGV9; and a first binding domain comprising (i) a VH VH CDR1 having the amino acid sequences of CDR1, VH CDR2, and VH CDR3 , VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 8; and (ii) a VH comprising: and a VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3. and a VL comprising VL CDR1, VL CDR2, and VL CDR3.

[0006] Provided herein are bispecific antibodies, the antibodies comprising: (a) a first binding domain that binds to TRGV9; and (b) a second binding domain that binds to a second target that is not TRGV9. the first binding domain comprises (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1; , a VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and an amino acid sequence of SEQ ID NO: 31 and (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 4. VL CDR1 having the amino acid sequence of SEQ ID NO: 5, VL CDR2 having the amino acid sequence of SEQ ID NO: 6 In another embodiment, the bispecific antibody comprises a VL comprising a VL CDR3 having the amino acid sequence Provided herein are antibodies, the antibodies comprising: (a) a first binding domain that binds to TRGV9; and (b) a second binding domain that binds to a second target that is not TRGV9, The binding domains include (i) a 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. (ii) a VH having the amino acid sequence of SEQ ID NO: 199, L CDR1, VL CDR2 having the amino acid sequence of SEQ ID NO: 200, and SEQ ID NO: 2 and a VL comprising a VL CDR3 having the amino acid sequence of SEQ ID NO: 01.

[0006] Provided herein are specific antibodies, the antibodies comprising: (a) a first binding domain that binds to TRGV9; and (b) a second binding domain that binds to a second target that is not TRGV9; The first binding domain comprises: (i) a 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 the amino acid sequence of SEQ ID NO: 204 and (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 205. a VL CDR1 having the amino acid sequence of SEQ ID NO: 206, a VL CDR2 having the amino acid sequence of SEQ ID NO: 207, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 209. and a VL comprising a VL CDR3 having the amino acid sequence of SEQ ID NO: 207. Provided herein are bispecific antibodies, the antibodies comprising: (a) a first antibody that binds to TRGV9; (b) a second binding domain that binds to a second target that is not TRGV9; and the first binding domain comprises (i) a VH C having the amino acid sequence of SEQ ID NO: 208. DR1, 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 (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 211; VL CDR1 having the amino acid sequence of SEQ ID NO: 212, VL CDR2 having the amino acid sequence of SEQ ID NO: 213 and a VL comprising a VL CDR3 having the amino acid sequence of SEQ ID NO: 213. In one aspect, provided herein is a bispecific antibody, the antibody (a) binding to TRGV9. (b) a first binding domain that binds to a second target that is not TRGV9; and a first binding domain having (i) the amino acid sequence of SEQ ID NO: 214. VH CDR1, 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. (ii) a VH comprising a VH CDR3 having an amino acid sequence of SEQ ID NO: 217; VL CDR1 having the amino acid sequence of SEQ ID NO: 218 and a VL comprising a VL CDR2 and a VL CDR3 having the amino acid sequence of SEQ ID NO: 219. In another aspect, provided herein is a bispecific antibody, the antibody comprising: (a) TRGV9 and (b) a first binding domain that binds to a second target that is not TRGV9. and a binding domain of: (i) the amino acid sequence of SEQ ID NO: 214 a VH CDR1 having the amino acid sequence of SEQ ID NO: 702; and (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 703; and 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 a VL CDR2 having the amino acid sequence of SEQ ID NO: 219, In another aspect, provided herein is a bispecific antibody, the antibody comprising (a) T (b) a first binding domain that binds to RGV9 and (b) a second binding domain that binds to a non-TRGV9 target and a second binding domain binding to the amino acid sequence of SEQ ID NO: 220, VH CDR1 having the amino acid sequence of SEQ ID NO: 221 2, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 222; and (ii) 223, VL CDR1 having the amino acid sequence of SEQ ID NO: 224, VL CDR2 having the amino acid sequence of SEQ ID NO: 225, and VL CDR3 having the amino acid sequence of SEQ ID NO: 225. In another aspect, provided herein is a bispecific antibody, wherein the antibody comprises: (a) a first binding domain that binds to TRGV9 and (b) a second target that is not TRGV9. and a second binding domain that specifically binds to the first binding domain, the first binding domain comprising: (i) SEQ ID NO: 22 VH CDR1 having the amino acid sequence of SEQ ID NO: 6, VH CDR2 having the amino acid sequence of SEQ ID NO: 227 a VH comprising a VH CDR2 and a VH CDR3 having the amino acid sequence of SEQ ID NO: 228; (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO: 229, and an amino acid sequence of SEQ ID NO: 230 VL CDR2 having the amino acid sequence of SEQ ID NO: 231, and VL CDR3 having the amino acid sequence of SEQ ID NO: 232. In some embodiments, the first binding domain comprises a VL comprising a CDR3. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 34. In some embodiments, the first antibody comprises a VL having the amino acid sequence of SEQ ID NO: 8. The binding domain of the present invention comprises a VH having the amino acid sequence of SEQ ID NO: 34 and a VH having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises a VL having the sequence SEQ ID NO: V, comprising an amino acid sequence having at least 95% identity to the amino acid sequence of 34; In some embodiments, the first binding domain comprises the amino acid sequence of SEQ ID NO: 8. Some VLs include those containing an amino acid sequence having at least 95% identity to In this embodiment, the first binding domain has at least one amino acid sequence selected from the group consisting of SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 4 VH containing an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 8 and VL, which comprises an amino acid sequence having at least 95% identity with the VL.

[0249] In another aspect, provided herein is a bispecific antibody, the antibody (a) binding to TRGV9. (b) a first binding domain that binds to a second target that is not TRGV9; and a first binding domain comprising (i) a VH domain of SEQ ID NO: 35, VH CDR1 having the amino acid sequences of CDR1, VH CDR2, and VH CDR3 , VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 8; and (ii) a VH comprising: and a VL having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3. and a VL comprising VL CDR1, VL CDR2, and VL CDR3.

[0006] Provided herein are bispecific antibodies, the antibodies comprising: (a) a first binding domain that binds to TRGV9; and (b) a second binding domain that binds to a second target that is not TRGV9. the first binding domain comprises (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1; , a VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and an amino acid sequence of SEQ ID NO: 32 and (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 4. VL CDR1 having the amino acid sequence of SEQ ID NO: 5, VL CDR2 having the amino acid sequence of SEQ ID NO: 6 In another embodiment, the bispecific antibody comprises a VL comprising a VL CDR3 having the amino acid sequence Provided herein are antibodies, the antibodies comprising: (a) a first binding domain that binds to TRGV9; and (b) a second binding domain that binds to a second target that is not TRGV9, The binding domains include (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 232, a VH CDR2 having the amino acid sequence of SEQ ID NO: 233, a VH CDR3 having the amino acid sequence of SEQ ID NO: 234, a VH CDR4 having the amino acid sequence of SEQ ID NO: 235, a VH CDR5 having the amino acid sequence of SEQ ID NO: 236, a VH CDR6 having the amino 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) a VH having the amino acid sequence of SEQ ID NO: 235. L CDR1, VL CDR2 having the amino acid sequence of SEQ ID NO: 236, and SEQ ID NO: 2 and a VL comprising a VL CDR3 having a sequence of 37 amino acids.

[0006] Provided herein are specific antibodies, the antibodies comprising: (a) a first binding domain that binds to TRGV9; and (b) a second binding domain that binds to a second target that is not TRGV9; The first binding domain comprises: (i) a 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 the amino acid sequence of SEQ ID NO: 240 and (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 241. a VL CDR1 having the amino acid sequence of SEQ ID NO: 242, a VL CDR2 having the amino acid sequence of SEQ ID NO: 243, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 244. and a VL comprising a VL CDR3 having the amino acid sequence of SEQ ID NO: 243. Provided herein are bispecific antibodies, the antibodies comprising: (a) a first antibody that binds to TRGV9; (b) a second binding domain that binds to a second target that is not TRGV9; and the first binding domain comprises (i) a VH C having the amino acid sequence of SEQ ID NO: 244. DR1, 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 (ii) a VH comprising a VH CDR3 having the amino acid sequence of SEQ ID NO: 247; VL CDR1 having the amino acid sequence of SEQ ID NO: 248, VL CDR2 having the amino acid sequence of SEQ ID NO: 248 and a VL comprising a VL CDR3 having the amino acid se...

Claims

1. 1. An antibody that binds to T cell receptor gamma variable 9 (TRGV9), the antibody comprising a heavy chain An antibody comprising a variable region (VH) and a light chain variable region (VL).

2. The antibody is (i) a VH complementarity determining region (CDR) 1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 31, and VH CDR3 having the amino acid sequence of SEQ ID NO:

32. VH comprising a H CDR3; (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO:4, a VL CDR2 having the amino acid sequence of SEQ ID NO:5 and a VL CDR2 having the amino acid sequence of SEQ ID NO:

6. The antibody of claim 1 , comprising:

3. The antibody of claim 2, wherein the antibody comprises a VH having the amino acid sequence of SEQ ID NO:

34. .

4. The antibody of claim 2, wherein the antibody comprises a VL having the amino acid sequence of SEQ ID NO:

8.

5. The antibody comprises a VH having the amino acid sequence of SEQ ID NO:34 and a VH having the amino acid sequence of SEQ ID NO:

8. and a VL having the following structure:

6. The antibody is (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1, and the amino acid sequence of SEQ ID NO: 2 and a VH CDR3 having the amino acid sequence of SEQ ID NO:

32. Hmm, VH and (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO:4, a VL CDR2 having the amino acid sequence of SEQ ID NO:5 and a VL CDR2 having the amino acid sequence of SEQ ID NO:

6. The antibody of claim 1 , comprising:

7. The antibody of claim 6, wherein the antibody comprises a VH having the amino acid sequence of SEQ ID NO:

35. .

8. The antibody of claim 6, wherein the antibody comprises a VL having the amino acid sequence of SEQ ID NO:

8.

9. The antibody comprises a VH having the amino acid sequence of SEQ ID NO:35 and a VH having the amino acid sequence of SEQ ID NO:

8. and a VL having the following structure:

10. The antibody is (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1, and the amino acid sequence of SEQ ID NO: 2 and a VH CDR3 having the amino acid sequence of SEQ ID NO:

33. Hmm, VH and (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO:4, a VL CDR2 having the amino acid sequence of SEQ ID NO:5 and a VL CDR2 having the amino acid sequence of SEQ ID NO:

6. The antibody of claim 1 , comprising:

11. The antibody of claim 10, wherein the antibody comprises a VH having the amino acid sequence of SEQ ID NO:

36. body.

12. The antibody of claim 10, wherein the antibody comprises a VL having the amino acid sequence of SEQ ID NO:

8. .

13. The antibody comprises a VH having the amino acid sequence of SEQ ID NO:36 and a VH having the amino acid sequence of SEQ ID NO:

8. and a VL having the following structure:

14. The antibody is (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1, a VH CDR2 having the amino acid sequence of SEQ ID NO: 76 and VH CDR2 having the amino acid sequence of SEQ ID NO:

3. Hmm, VH and (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO: 77, and the amino acid sequence of SEQ ID NO: 5 and a VL CDR2 having the amino acid sequence of SEQ ID NO:

6. The antibody of claim 1 , comprising:

15. The antibody is (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 60, and an amino acid sequence of SEQ ID NO: 61 VH CDR2 having the sequence of SEQ ID NO: 62 and VH CDR3 having the amino acid sequence of SEQ ID NO:

63. VH comprising (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO:63, VL CDR2 having the amino acid sequence of SEQ ID NO:6, and VL CDR3 having the amino acid sequence of SEQ ID NO:

7.

2. The antibody of claim 1 , comprising:

16. 16. The antibody of claim 14 or 15, wherein the antibody comprises a VH having the amino acid sequence of SEQ ID NO:

65. The antibody described.

17. 16. The antibody of claim 14 or 15, wherein the antibody comprises a VL having the amino acid sequence of SEQ ID NO:

66. The antibody described.

18. The antibody comprises a VH having the amino acid sequence of SEQ ID NO:65 and a VH having the amino acid sequence of SEQ ID NO:

66. and a VL having a sequence of:

19. 16. The antibody of claim 14 or 15, wherein the antibody comprises a VH having the amino acid sequence of SEQ ID NO:

67. The antibody described.

20. The antibody of claim 14 or 15, wherein the antibody comprises a VL having the amino acid sequence of SEQ ID NO:

68. The antibody described.

21. The antibody comprises a VH having the amino acid sequence of SEQ ID NO:67 and a VH having the amino acid sequence of SEQ ID NO:

68. and a VL having a sequence of:

22. The antibody is (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 98, and the amino acid sequence of SEQ ID NO: 99 VH CDR2 having the sequence of SEQ ID NO: 100, and VH CDR3 having the amino acid sequence of SEQ ID NO:

101. VH, including 3; (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO: 101, VL CDR2 having the amino acid sequence of SEQ ID NO: 103, 2. The antibody of claim 1, comprising: a VL comprising CDR3;

23. 23. The antibody of claim 22, wherein the antibody comprises a VH having the amino acid sequence of SEQ ID NO:

104. antibody.

24. 23. The antibody of claim 22, wherein the antibody comprises a VL having the amino acid sequence of SEQ ID NO:

105. antibody.

25. The antibody comprises a VH having the amino acid sequence of SEQ ID NO: 104 and a VH having the amino acid sequence of SEQ ID NO:

105. and a VL having the sequence of

26. The antibody is (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 107, an amino acid sequence of SEQ ID NO: 108, VH CDR2 having the amino acid sequence of SEQ ID NO: 109, and VH CDR3 having the amino acid sequence of SEQ ID NO:

110. VH, comprising DR3; (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO: 110, VL CDR2 having the amino acid sequence of SEQ ID NO: 112, 2. The antibody of claim 1, comprising: a VL comprising CDR3;

27. 27. The antibody of claim 26, wherein the antibody comprises a VH having the amino acid sequence of SEQ ID NO:

113. antibody.

28. 27. The antibody of claim 26, wherein the antibody comprises a VL having the amino acid sequence of SEQ ID NO:

114. antibody.

29. The antibody comprises a VH having the amino acid sequence of SEQ ID NO:113 and a VH having the amino acid sequence of SEQ ID NO:

114. and a VL having the sequence of .

30. The antibody is (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 117, an amino acid sequence of SEQ ID NO: 118, VH CDR2 having the amino acid sequence of SEQ ID NO: 119, and VH CDR3 having the amino acid sequence of SEQ ID NO:

120. VH, comprising DR3; (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO: 120, VL CDR2 having the amino acid sequence of SEQ ID NO: 122, and VL CDR3 having the amino acid sequence of SEQ ID NO:

123.

2. The antibody of claim 1, comprising: a VL comprising CDR3;

31. 31. The antibody of claim 30, wherein the antibody comprises a VH having the amino acid sequence of SEQ ID NO:

123. antibody.

32. 31. The antibody of claim 30, wherein the antibody comprises a VL having the amino acid sequence of SEQ ID NO:

124. antibody.

33. The antibody comprises a VH having the amino acid sequence of SEQ ID NO: 123 and a VH having the amino acid sequence of SEQ ID NO:

124. and a VL having the sequence of .

34. The antibody is (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 127, an amino acid sequence of SEQ ID NO: 128, VH CDR2 having the amino acid sequence of SEQ ID NO: 129, and VH CDR3 having the amino acid sequence of SEQ ID NO:

130. VH, comprising DR3; (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO: 130, VL CDR2 having the amino acid sequence of SEQ ID NO: 132, and VL CDR3 having the amino acid sequence of SEQ ID NO:

133.

2. The antibody of claim 1, comprising: a VL comprising CDR3;

35. 35. The antibody of claim 34, wherein the antibody comprises a VH having the amino acid sequence of SEQ ID NO:

133. antibody.

36. 35. The antibody of claim 34, wherein the antibody comprises a VL having the amino acid sequence of SEQ ID NO:

134. antibody.

37. The antibody comprises a VH having the amino acid sequence of SEQ ID NO: 133 and a VH having the amino acid sequence of SEQ ID NO:

134. and a VL having the sequence of .

38. 38. Any one of claims 1 to 37, wherein the TRGV9 is present on the surface of a γδ T cell. The antibody described in

39. The antibody of any one of claims 1 to 38, wherein the antibody is a humanized antibody.

40. The antibody of any one of claims 1 to 39, wherein the antibody is an IgG antibody.

41. 2. The method of claim 1 , wherein the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody.

40. The antibody described in 40.

42. The antibody of any one of claims 1 to 41, wherein the antibody is multivalent.

43. The antibody of claim 42, wherein the antibody is capable of binding to at least three antigens. .

44. The antibody of claim 42, wherein the antibody is capable of binding to at least five antigens. .

45. A nucleic acid encoding an antibody according to any one of claims 1 to 44.

46. A vector comprising the nucleic acid of claim 45.

47. A host cell comprising the vector of claim 45.

48. 46. ​​A kit comprising the vector of claim 45 and a package therefor.

49. A pharmaceutical composition comprising the antibody according to any one of claims 1 to 44 and a pharma- ceutically acceptable carrier. Pharmaceutical composition.

50. 50. A method for producing the pharmaceutical composition of claim 49, comprising administering the antibody to a pharma- ceutical acceptable carrier. combining said carrier with said pharmaceutical composition.

51. A method of activating γδ T cells expressing TRGV9, comprising: A method comprising contacting with an antibody according to any one of claims 1 to 44.

52. The contacting increases the expression of CD69 T cells relative to a control γδ T cell expressing TRGV9.

52. The method of claim 51, which results in increased expression of CD25, and / or Granzyme B. .

53. A bispecific antibody, (a) a first binding domain that binds to TRGV9; (b) a second binding domain that binds to a second target that is not TRGV9. Specific antibodies.

54. The first binding domain comprises: (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1, and the amino acid sequence of SEQ ID NO: 2 and a VH CDR3 having the amino acid sequence of SEQ ID NO:

3. , VH, and (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO:4, a VL CDR2 having the amino acid sequence of SEQ ID NO:5 and a VL CDR2 having the amino acid sequence of SEQ ID NO:

6.

54. The bispecific antibody of claim 53, comprising:

55. 5. The first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:

7.

5. A bispecific antibody according to claim 4.

56. 5. The first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:

8.

5. A bispecific antibody according to claim 4.

57. The first binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 7 and a VH having the amino acid sequence of SEQ ID NO:

8. and a VL having the amino acid sequence:

58. The first binding domain comprises: (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1, and the amino acid sequence of SEQ ID NO: 2 and a VH CDR2 having the amino acid sequence of SEQ ID NO:

31. Hmm, VH and (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO:4, a VL CDR2 having the amino acid sequence of SEQ ID NO:5 and a VL CDR2 having the amino acid sequence of SEQ ID NO:

6.

54. The bispecific antibody of claim 53, comprising:

59. The first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:

34.

59. The bispecific antibody according to 58.

60. 5. The first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:

8.

9. The bispecific antibody according to claim 8.

61. The first binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 34 and a VH having the amino acid sequence of SEQ ID NO: 8 and a VL having the amino acid sequence of:

62. The first binding domain comprises: (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1, and the amino acid sequence of SEQ ID NO: 2 and a VH CDR3 having the amino acid sequence of SEQ ID NO:

32. Hmm, VH and (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO:4, a VL CDR2 having the amino acid sequence of SEQ ID NO:5 and a VL CDR2 having the amino acid sequence of SEQ ID NO:

6.

54. The bispecific antibody of claim 53, comprising:

63. The first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:

35.

63. A bispecific antibody according to claim 62.

64. 7. The method of claim 6, wherein the first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:

8.

3. A bispecific antibody according to claim 2.

65. The first binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 35 and a VH having the amino acid sequence of SEQ ID NO: 8 and a VL having an amino acid sequence of:

66. The first binding domain comprises: (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1, and the amino acid sequence of SEQ ID NO: 2 and a VH CDR3 having the amino acid sequence of SEQ ID NO:

33. Hmm, VH and (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO:4, a VL CDR2 having the amino acid sequence of SEQ ID NO:5 and a VL CDR2 having the amino acid sequence of SEQ ID NO:

6.

54. The bispecific antibody of claim 53, comprising:

67. The first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:

36.

67. A bispecific antibody according to claim 66.

68. 7. The method of claim 6, wherein the first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:

8.

7. A bispecific antibody according to claim 6.

69. The first binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 36 and a VH having the amino acid sequence of SEQ ID NO: 8 and a VL having the amino acid sequence of:

70. The first binding domain comprises: (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 1, a VH CDR2 having the amino acid sequence of SEQ ID NO: 76 and VH CDR2 having the amino acid sequence of SEQ ID NO:

3. Hmm, VH and (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO: 77, and the amino acid sequence of SEQ ID NO: 5 and a VL CDR2 having the amino acid sequence of SEQ ID NO:

6.

54. The bispecific antibody of claim 53, comprising:

71. The first binding domain comprises: (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 60, and an amino acid sequence of SEQ ID NO: 61 VH CDR2 having the sequence of SEQ ID NO: 62 and VH CDR3 having the amino acid sequence of SEQ ID NO:

63. VH comprising (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO:63, VL CDR2 having the amino acid sequence of SEQ ID NO:6, and VL CDR3 having the amino acid sequence of SEQ ID NO:

7. and a VL comprising:

72. The first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:

65.

72. A bispecific antibody according to claim 70 or 71.

73. The first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:

66.

72. A bispecific antibody according to claim 70 or 71.

74. The first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:65 and a VH having the amino acid sequence of SEQ ID NO:6 72. The bispecific antibody of claim 70 or 71, comprising a VL having an amino acid sequence of:

75. The first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:

67.

72. A bispecific antibody according to claim 70 or 71.

76. The first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:

68.

72. A bispecific antibody according to claim 70 or 71.

77. the first binding domain, a VH having the amino acid sequence of SEQ ID NO:67, and a VH having the amino acid sequence of SEQ ID NO:6 72. A bispecific antibody as described in claim 70 or 71, wherein the VL has an amino acid sequence of 8.

78. The first binding domain comprises: (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 89, and an amino acid sequence of SEQ ID NO: 90 VH CDR2 having the sequence of SEQ ID NO: 91 and VH CDR3 having the amino acid sequence of SEQ ID NO:

92. VH comprising (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO:92, VL CDR2 having the amino acid sequence of SEQ ID NO:94, and VL CDR3 having the amino acid sequence of SEQ ID NO:

95.

3. The bispecific antibody of claim 53 , comprising:

79. The first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:

95.

79. A bispecific antibody according to claim 78.

80. The first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:

96.

79. A bispecific antibody according to claim 78.

81. The first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:95 and a VH having the amino acid sequence of SEQ ID NO:9 79. The bispecific antibody of claim 78, comprising a VL having an amino acid sequence of:

82. The first binding domain comprises: (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 98, and the amino acid sequence of SEQ ID NO: 99 VH CDR2 having the sequence of SEQ ID NO: 100, and VH CDR3 having the amino acid sequence of SEQ ID NO:

101. VH, including 3; (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO: 101, VL CDR2 having the amino acid sequence of SEQ ID NO: 103, 54. The bispecific antibody of claim 53, comprising:

83. The first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:

104.

83. The bispecific antibody according to claim 82.

84. The first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:

105.

83. The bispecific antibody according to claim 82.

85. The first binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 104 and a VH having the amino acid sequence of SEQ ID NO: and a VL having an amino acid sequence of 105.

86. The first binding domain comprises: (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 107, an amino acid sequence of SEQ ID NO: 108, VH CDR2 having the amino acid sequence of SEQ ID NO: 109, and VH CDR3 having the amino acid sequence of SEQ ID NO:

110. VH, comprising DR3; (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO: 110, VL CDR2 having the amino acid sequence of SEQ ID NO: 112, 54. The bispecific antibody of claim 53, comprising:

87. The first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:

113.

87. The bispecific antibody according to claim 86.

88. The first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:

114.

87. The bispecific antibody according to claim 86.

89. The first binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 113 and a VH having the amino acid sequence of SEQ ID NO: and a VL having an amino acid sequence of 114.

90. The first binding domain comprises: (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 117, an amino acid sequence of SEQ ID NO: 118, VH CDR2 having the amino acid sequence of SEQ ID NO: 119, and VH CDR3 having the amino acid sequence of SEQ ID NO:

120. VH, comprising DR3; (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO: 120, VL CDR2 having the amino acid sequence of SEQ ID NO: 122, and VL CDR3 having the amino acid sequence of SEQ ID NO:

123.

54. The bispecific antibody of claim 53, comprising:

91. The first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:

123.

91. The bispecific antibody according to item 90.

92. The first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:

124.

91. The bispecific antibody according to item 90.

93. The first binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 123 and a VH having the amino acid sequence of SEQ ID NO: and a VL having an amino acid sequence of 124.

94. The first binding domain comprises: (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 127, an amino acid sequence of SEQ ID NO: 128, VH CDR2 having the amino acid sequence of SEQ ID NO: 129, and VH CDR3 having the amino acid sequence of SEQ ID NO:

130. VH, comprising DR3; (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO: 130, VL CDR2 having the amino acid sequence of SEQ ID NO: 132, and VL CDR3 having the amino acid sequence of SEQ ID NO:

133.

54. The bispecific antibody of claim 53, comprising:

95. The first binding domain comprises a VH having the amino acid sequence of SEQ ID NO:

133.

95. The bispecific antibody of claim 94.

96. The first binding domain comprises a VL having the amino acid sequence of SEQ ID NO:

134.

95. The bispecific antibody of claim 94.

97. The first binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 133 and a VH having the amino acid sequence of SEQ ID NO: and a VL having an amino acid sequence of 134.

98. The method according to any one of claims 53 to 97, wherein the second target is a cancer antigen present on the surface of a cancer cell. The bispecific antibody according to any one of claims 1 to 4.

99. The antigen on the surface of the cancer cell is a tumor-specific antigen, a tumor-associated antigen, or a neoantigen.

99. The bispecific antibody of claim 98.

100. The method of any one of claims 53 to 99, wherein the second target is CD123. Specific antibodies.

101. The second binding domain comprises: (i) a VH CDR1 having the amino acid sequence of SEQ ID NO: 9, a VH CDR2 having the amino acid sequence of SEQ ID NO: 10 and VH CDR3 having the amino acid sequence of SEQ ID NO:

11. VH and (ii) a VL CDR1 having the amino acid sequence of SEQ ID NO: 12, VL CDR2 having the amino acid sequence of SEQ ID NO: 14, and VL CDR3 having the amino acid sequence of SEQ ID NO:

15.

101. The bispecific antibody of claim 100, comprising:

102. The second binding domain comprises a VH having the amino acid sequence of SEQ ID NO:

15.

101. A bispecific antibody according to claim 101.

103. The second binding domain comprises a VL having the amino acid sequence of SEQ ID NO:

16.

101. A bispecific antibody according to claim 101.

104. The second binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 15 and a VH having the amino acid sequence of SEQ ID NO: 1 102. The bispecific antibody of claim 101, comprising a VL having an amino acid sequence of:

105. Any of claims 53 to 104, wherein the TRGV9 is present on the surface of a γδ T cell.

1. A bispecific antibody according to claim 1.

106. The TRGV9 is present on the surface of a γδ T cell and the second target is The method according to any one of claims 53 to 104, wherein the antigen is a cancer antigen expressed on the surface of a cell. Bispecific antibodies.

107. The bispecific antibody binds to the TRGV9 on the surface of the γδ T cell and to the cancer cell 107. The method of claim 106, wherein binding to the antigen on the surface of the cell kills the cancer cell. Bispecific antibodies.

108. The first binding domain is humanized or the second binding domain is humanized. or both the first binding domain and the second binding domain are human. The bispecific antibody according to any one of claims 53 to 107,

109. The bispecific antibody according to any one of claims 53 to 108, wherein the bispecific antibody is an IgG antibody. Bispecific antibodies.

110. 2. The method of claim 1 , wherein the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody.

109. A bispecific antibody according to claim 109.

111. A bispecific antibody according to any one of claims 53 to 110 and a pharma- ceutically acceptable carrier. and

112. A method for directing γδ T cells expressing TRGV9 to cancer cells, comprising: Contacting a cell with a bispecific antibody according to any one of claims 53 to 110 wherein said contacting directs said γδ T cells to said cancer cells.

113. 1. A method for inhibiting the growth or proliferation of a cancer cell that expresses a cancer antigen on the cell surface, comprising: Contacting a cell with a bispecific antibody according to any one of claims 53 to 110 and contacting said cancer cells with said pharmaceutical composition inhibits the growth or proliferation of said cancer cells. To harm, a method.

114. While the cancer cells are in contact with the bispecific antibody, The method of claim 113, in the presence of cells.

115. A method for eliminating cancer cells in a subject, comprising administering to a subject an effective amount of any one of claims 53 to 110. Administering to said subject the bispecific antibody of any one of claims 1 to 5.

116. 116. The method of claim 115, wherein the subject is a subject in need of the method.

117. 117. The method of claim 115 or 116, wherein the subject is a human.

118. A method of activating γδ T cells expressing TRGV9, comprising: A method comprising contacting a subject with a bispecific antibody according to any one of claims 53 to 110. Law.

119. An isolated TRGV9 bispecific antibody or antigen-binding fragment thereof, comprising: The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises: a. a first heavy chain (HC1); and b. a second heavy chain (HC2); and c. the first light chain (LC1); d. a second light chain (LC2), HC1 is associated with LC1, HC2 is associated with LC2, (A) HC1 is i. SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3, respectively; ii. SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:31, respectively; iii. SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:32, respectively; or iv. the amino acid sequences of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:33, respectively; heavy chain complementarity determining region 1 (HCDR1), HCDR2, and HCDR3; LC1 has the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. light chain complementarity determining region 1 (LCDR1), LCDR2, and LCDR3, HC1 and LC2 form a binding site for a first antigen, and HC2 and LC2 form a binding site for a second antigen. or (B) HC1 is the amino acid sequence of SEQ ID NO:1, SEQ ID NO:76, and SEQ ID NO:3, respectively. HCDR1, HCDR2, and HCDR3 comprising the sequences LC1 has the amino acid sequences of SEQ ID NO:77, SEQ ID NO:5, and SEQ ID NO:6, respectively. A binding site for a first antigen comprising LCDR1, LCDR2, and LCDR3 comprising: and HC2 and LC2 form a binding site for a second antigen; (C) HC1 is an amine of SEQ ID NO: 60, SEQ ID NO: 61, or SEQ ID NO: 62, respectively. HCDR1, HCDR2, and HCDR3 each containing the amino acid sequence LC1 has the amino acid sequence of SEQ ID NO:63, SEQ ID NO:64, and SEQ ID NO:6, respectively. and a LCDR1, LCDR2, and LCDR3 that comprise a sequence that binds to a first antigen. and HC2 and LC2 form a binding site for a second antigen; or (D) HC1 is an amine of SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, respectively. HCDR1, HCDR2, and HCDR3 each containing the amino acid sequence LC1 is the amino acid sequence of SEQ ID NO:92, SEQ ID NO:93, and SEQ ID NO:94, respectively. The LCDR1, LCDR2, and LCDR3 have the sequence a binding site for a second antigen, and HC2 and LC2 form a binding site for a second antigen; (E) HC1 is selected from the group consisting of SEQ ID NO: 98, SEQ ID NO: 99, and SEQ ID NO: 100, respectively. HCDR1, HCDR2, and HCDR3 each containing an amino acid sequence; LC1 is the sequence of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 103, respectively. and an LCDR1, LCDR2, and LCDR3 each including an amino acid sequence, and HC2 and LC2 form a binding site for a second antigen. , (F) HC1 is SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 109, respectively. and a HCDR1, a HCDR2, and a HCDR3 comprising the amino acid sequence LC1 is the sequence of SEQ ID NO: 110, SEQ ID NO: 111, and SEQ ID NO: 112, respectively. and an LCDR1, LCDR2, and LCDR3 each including an amino acid sequence, and HC2 and LC2 form a binding site for a second antigen. , (G) HC1 is SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 119, respectively. and a HCDR1, a HCDR2, and a HCDR3 comprising the amino acid sequence LC1 is the sequence of SEQ ID NO: 120, SEQ ID NO: 121, and SEQ ID NO: 122, respectively. and an LCDR1, LCDR2, and LCDR3 each including an amino acid sequence, and HC2 and LC2 form a binding site for a second antigen. or (H) HC1 is SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 129, respectively. and a HCDR1, a HCDR2, and a HCDR3 comprising the amino acid sequence LC1 is the sequence of SEQ ID NO: 130, SEQ ID NO: 131, and SEQ ID NO: 132, respectively. and an LCDR1, LCDR2, and LCDR3 each including an amino acid sequence, and HC2 and LC2 form a binding site for a second antigen. An isolated TRGV9 bispecific antibody or antigen-binding fragment thereof.

120. (A) HC1 is selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 34, SEQ ID NO: 35, and SEQ ID NO:

36. an amino acid sequence having at least 95% identity to the amino acid sequence of , an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8 Includes or (B) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

65. and LC1 has an amino acid sequence which is at least 9 times the amino acid sequence of SEQ ID NO:

66. Contains an amino acid sequence with 5% identity (C) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

67. and LC1 has an amino acid sequence which is at least 9 times the amino acid sequence of SEQ ID NO:

68. Contains an amino acid sequence with 5% identity (D) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

95. and LC1 has an amino acid sequence which is at least 90% identical to the amino acid sequence of SEQ ID NO:

96. Contains an amino acid sequence with 5% identity (E) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

104. and LC1 has at least one amino acid sequence having the amino acid sequence of SEQ ID NO:

105. or (F) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

113. and LC1 has an amino acid sequence having at least one amino acid sequence similar to that of SEQ ID NO:

114. or (G) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

123. and LC1 has an amino acid sequence having at least one amino acid sequence similar to that of SEQ ID NO:

124. or (H) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

133. and LC1 has an amino acid sequence having at least one amino acid sequence similar to that of SEQ ID NO:

134.

120. The isolated TRG of claim 119, comprising an amino acid sequence having at least 95% identity to V9 bispecific antibody or an antigen-binding fragment thereof.

121. (A) HC1 is selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 34, SEQ ID NO: 35, and SEQ ID NO:

36. LC1 comprises the amino acid sequence of SEQ ID NO: 8; or (B) HC1 comprises the amino acid sequence of SEQ ID NO:65 and LC1 comprises the amino acid sequence of SEQ ID NO:

66. Contains a nucleotide sequence, (C) HC1 comprises the amino acid sequence of SEQ ID NO:67 and LC1 comprises the amino acid sequence of SEQ ID NO:

68. Contains a nucleotide sequence, (D) HC1 comprises the amino acid sequence of SEQ ID NO:95 and LC1 comprises the amino acid sequence of SEQ ID NO:

96. Contains a nucleotide sequence, (E) HC1 comprises the amino acid sequence of SEQ ID NO: 104, and LC1 comprises the amino acid sequence of SEQ ID NO:

105. Contains an amino acid sequence, (F) HC1 comprises the amino acid sequence of SEQ ID NO: 113 and LC1 comprises the amino acid sequence of SEQ ID NO:

114. Contains an amino acid sequence, (G) HC1 comprises the amino acid sequence of SEQ ID NO: 123 and LC1 comprises the amino acid sequence of SEQ ID NO:

124. or (H) HC1 comprises the amino acid sequence of SEQ ID NO: 133 and LC1 comprises the amino acid sequence of SEQ ID NO:

134. The isolated TRGV9 bispecific antibody of claim 120 or An antigen-binding fragment of.

122. The binding site for a first antigen binds to TRGV9 on a γδ T cell.

122. An isolated TRGV9 bispecific antibody according to any one of claims 119 to 121 or its antibody. Original binding fragment.

123. wherein the binding site for the second antigen binds to a cancer antigen present on the surface of a cancer cell. The isolated TRGV9 bispecific antibody or its derivative according to any one of claims 119 to 122. An antigen-binding fragment of.

124. Presence of the bispecific antibody against TRGV9 present on the surface of the γδ T cell and said binding of said cancer antigen present on said surface of said cancer cell.

124. The isolated TRGV9 bispecific antibody or antigen-binding molecule of claim 123, Combined fragment.

125. HC1 and LC1 are humanized according to any one of claims 119 to 124. An isolated TRGV9 bispecific antibody or antigen-binding fragment thereof.

126. HC2 and LC2 bind to CD123.

2. An isolated TRGV9 bispecific antibody or antigen-binding fragment thereof as described herein.

127. The bispecific antibody or antigen-binding fragment thereof is selected from the group consisting of IgG1, IgG2, IgG3 or IgG4 isotype. A TRGV9 bispecific antibody or antigen-binding fragment thereof.

128. the bispecific antibody or antigen-binding fragment thereof is of the IgG4 isotype; An isolated TRGV9 bispecific antibody according to any one of claims 119 to 127, or and an antigen-binding fragment thereof.

129. The bispecific antibody or antigen-binding fragment thereof has an EC ５０ in Inducing γδ T cell-dependent cytotoxicity of cancer cells in vitro.

28. The isolated TRGV9 bispecific antibody or its antigen-binding fragment according to any one of claims 27 to 29. segment.

130. The bispecific antibody or antigen-binding fragment thereof has an EC ５０ in The method according to claim 129, which induces γδ T cell-dependent cytotoxicity of cancer cells in vitro. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof.

131. The bispecific antibody or antigen-binding fragment thereof has an EC ５０ in The method according to claim 129, which induces γδ T cell-dependent cytotoxicity of cancer cells in vitro. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof.

132. The EC ５０ However, the mixture of γδ T effector cells and Kasumi3 AML target cells The isolated TRGV9 of any one of claims 129 to 131 is evaluated in a combination A bispecific antibody or an antigen-binding fragment thereof.

133. 10. The method of claim 1, wherein the effector cell to target cell ratio is from about 0.01:1 to about 5:

1.

33. An isolated TRGV9 bispecific antibody or antigen-binding fragment thereof according to claim 32.

134. 13. The effector cell to target cell ratio of about 0.1:1 to about 2:

1.

3. An isolated TRGV9 bispecific antibody or an antigen-binding fragment thereof according to claim 3.

135. 135. The isolated method of claim 134, wherein the effector cell to target cell ratio is about 1:

1. A TRGV9 bispecific antibody or antigen-binding fragment thereof.

136. The bispecific antibody or antigen-binding fragment thereof is multivalent.

35. An isolated TRGV9 bispecific antibody or its antigen-binding fragment according to any one of claims 35 to 37. segment.

137. The bispecific antibody or antigen-binding fragment thereof binds to at least three antigens. The isolated TRGV9 bispecific antibody of claim 136 or its antibody. Original binding fragment.

138. The bispecific antibody or antigen-binding fragment thereof binds to at least five antigens. The isolated TRGV9 bispecific antibody of claim 136 or its antibody. Original binding fragment.

139. An isolated γδ cell bispecific antibody or antigen-binding fragment thereof, comprising: The isolated γδ T cell bispecific antibody or antigen-binding fragment thereof a. HC1; b. HC2; c. LC1; d. LC2; HC1 is associated with LC1, HC2 is associated with LC2, HC1 and LC1 form the binding site for the first antigen on γδ T cells; HC2 and LC2 form a binding site for a second antigen in an isolated γδ T cell. Bispecific antibodies or antigen-binding fragments thereof.

140. A first means capable of specifically binding to the T cell receptor gamma chain and a T cell receptor γ chain. and a second means capable of specifically binding to a target molecule that is not a nucleic acid chain. Heterogeneous antibodies.

141. A process for producing a molecule capable of specifically binding to two or more target molecules. wherein the molecule is an oligopeptide capable of binding to the T cell receptor gamma chain or A process serving to obtain a polypeptide and an oligopeptide or The present invention relates to a method for obtaining a polypeptide comprising the steps of: and a step which serves to provide a molecule capable of specific binding.

142. To serve the function of obtaining an oligopeptide or polypeptide capable of binding to a target The above steps are repeated n times to specifically bind the T cell receptor gamma chain to the n target molecules. The method further comprises n steps for performing the function of providing a molecule capable of synthesizing a target molecule, n being at least 142. The process of claim 141, wherein the number of ions is at least 2.

143. Isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof And, a. HC1; b. HC2; c. LC1; d. LC2; HC1 is associated with LC1, HC2 is associated with LC2, (A) HC1 is i. SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3, respectively; ii. SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:31, respectively; iii. SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:32, respectively; or iv. the amino acid sequences of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:33, respectively; HCDR1, HCDR2, and HCDR3, LC1 has the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. A nucleic acid sequence that specifically binds to Vγ9, comprising LCDR1, LCDR2, and LCDR3. form a binding site for one antigen, (B) HC1 is the amino acid sequence of SEQ ID NO:1, SEQ ID NO:76, and SEQ ID NO:3, respectively. HCDR1, HCDR2, and HCDR3 comprising the sequences LC1 has the amino acid sequences of SEQ ID NO:77, SEQ ID NO:5, and SEQ ID NO:6, respectively. and specifically binds to Vγ9, comprising LCDR1, LCDR2, and LCDR3 comprising: forming a binding site for a first antigen; (C) HC1 is an amine of SEQ ID NO: 60, SEQ ID NO: 61, or SEQ ID NO: 62, respectively. HCDR1, HCDR2, and HCDR3 each containing the amino acid sequence LC1 has the amino acid sequence of SEQ ID NO:63, SEQ ID NO:64, and SEQ ID NO:6, respectively. and a LCDR1, LCDR2, and LCDR3 that contain the sequence, and specifically bind to Vγ9. forming a binding site for a first antigen, (D) HC1 is an amine of SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, respectively. HCDR1, HCDR2, and HCDR3 each containing the amino acid sequence LC1 is the amino acid sequence of SEQ ID NO:92, SEQ ID NO:93, and SEQ ID NO:94, respectively. and specifically binds to Vγ9, comprising LCDR1, LCDR2, and LCDR3 having the sequence forming a binding site for a first antigen that (E) HC1 is selected from the group consisting of SEQ ID NO: 98, SEQ ID NO: 99, and SEQ ID NO: 100, respectively. HCDR1, HCDR2, and HCDR3 each containing an amino acid sequence; LC1 is the sequence of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 103, respectively. The LCDR1, LCDR2, and LCDR3 contain amino acid sequences specific for Vγ9. or forming a binding site for a first antigen that binds to (F) HC1 is SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 109, respectively. and a HCDR1, a HCDR2, and a HCDR3 comprising the amino acid sequence LC1 is the sequence of SEQ ID NO: 110, SEQ ID NO: 111, and SEQ ID NO: 112, respectively. The LCDR1, LCDR2, and LCDR3 contain amino acid sequences specific for Vγ9. or forming a binding site for a first antigen that binds to (G) HC1 is SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 119, respectively. and a HCDR1, a HCDR2, and a HCDR3 comprising the amino acid sequence LC1 is the sequence of SEQ ID NO: 120, SEQ ID NO: 121, and SEQ ID NO: 122, respectively. The LCDR1, LCDR2, and LCDR3 contain amino acid sequences specific for Vγ9. or forming a binding site for a first antigen that binds to (H) HC1 is SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 129, respectively. and a HCDR1, a HCDR2, and a HCDR3 comprising the amino acid sequence LC1 is the sequence of SEQ ID NO: 130, SEQ ID NO: 131, and SEQ ID NO: 132, respectively. The LCDR1, LCDR2, and LCDR3 contain amino acid sequences specific for Vγ9. forming a binding site for a first antigen that binds to HC2 has the amino acid sequence of SEQ ID NO:9, SEQ ID NO:10, and SEQ ID NO:11, respectively. and LC2 comprises HCDR1, HCDR2, and HCDR3 each having the sequence LCDR1, LCDR2, LCDR3, LCDR4, LCDR5, LCDR6, LCDR7, LCDR8, LCDR9, LCDR10, LCDR11, LCDR12, LCDR13, LCDR14, LCDR15, LCDR16, LCDR17, LCDR18, LCDR19, LCDR20, LCDR21, LCDR22, LCDR23, LCDR24, LCDR25, LCDR26, LCDR27, LCDR28, LCDR30, LCDR31, LCDR32, LCDR40, LCDR51, LCDR62, LCDR73, LCDR84, LCDR95, LCDR116, LCDR125, LCDR13, LCDR14, LCDR15, LCDR16, LCDR17, LCDR18, LCDR19, LCDR21, LCDR22, LCDR33, LCDR44, LCDR55, LCDR66, LCDR 2, and LCDR3, and binding to a second antigen that specifically binds to CD123. An isolated anti-TRGV9 / anti-CD123 bispecific antibody or its antigen binding site Combined fragment.

144. (A) HC1 is selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 34, SEQ ID NO: 35, and SEQ ID NO:

36. an amino acid sequence having at least 95% identity to the amino acid sequence of , an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8 Contains or (B) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

65. and LC1 has an amino acid sequence which is at least 9 times the amino acid sequence of SEQ ID NO:

66. Contains an amino acid sequence with 5% identity (C) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

67. and LC1 has an amino acid sequence which is at least 9 times the amino acid sequence of SEQ ID NO:

68. Contains an amino acid sequence with 5% identity (D) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

95. and LC1 has an amino acid sequence which is at least 90% identical to the amino acid sequence of SEQ ID NO:

96. Contains an amino acid sequence with 5% identity (E) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

104. and LC1 has at least one amino acid sequence having the amino acid sequence of SEQ ID NO:

105. or (F) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

113. and LC1 has an amino acid sequence having at least one amino acid sequence similar to that of SEQ ID NO:

114. or (G) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

123. and LC1 has an amino acid sequence having at least one amino acid sequence similar to that of SEQ ID NO:

124. or (H) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

133. and LC1 has an amino acid sequence having at least one amino acid sequence similar to that of SEQ ID NO:

134. The isolated anti-TR peptide according to claim 143, comprising an amino acid sequence having at least 95% identity with said peptide. GV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof.

145. (A) HC1 is selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 34, SEQ ID NO: 35, and SEQ ID NO:

36. LC1 comprises the amino acid sequence of SEQ ID NO: 8; or (B) HC1 comprises the amino acid sequence of SEQ ID NO:65 and LC1 comprises the amino acid sequence of SEQ ID NO:

66. Contains a nucleotide sequence, (C) HC1 comprises the amino acid sequence of SEQ ID NO:67 and LC1 comprises the amino acid sequence of SEQ ID NO:

68. Contains a nucleotide sequence, (D) HC1 comprises the amino acid sequence of SEQ ID NO:95 and LC1 comprises the amino acid sequence of SEQ ID NO:

96. Contains a nucleotide sequence, (E) HC1 comprises the amino acid sequence of SEQ ID NO: 104, and LC1 comprises the amino acid sequence of SEQ ID NO:

105. Contains an amino acid sequence, (F) HC1 comprises the amino acid sequence of SEQ ID NO: 113 and LC1 comprises the amino acid sequence of SEQ ID NO:

114. Contains an amino acid sequence, (G) HC1 comprises the amino acid sequence of SEQ ID NO: 123 and LC1 comprises the amino acid sequence of SEQ ID NO:

124. or (H) HC1 comprises the amino acid sequence of SEQ ID NO: 133 and LC1 comprises the amino acid sequence of SEQ ID NO:

134.

145. The isolated anti-TRGV9 / anti-CD123 dual antibody of claim 144, comprising the amino acid sequence Specific antibodies or antigen-binding fragments thereof.

146. HC2 has at least 95% identity to the amino acid sequence of SEQ ID NO:

15. LC2 has at least 95% identity to the amino acid sequence of SEQ ID NO:

16. The isolated polypeptide according to any one of claims 143 to 145, comprising an amino acid sequence having identity thereto. A bispecific anti-TRGV9 / anti-CD123 antibody or antigen-binding fragment thereof.

147. HC2 comprises the amino acid sequence of SEQ ID NO:15 and LC2 comprises the amino acid sequence of SEQ ID NO:

16.

147. The isolated anti-TRGV9 / anti-CD123 bispecific antibody of claim 146, comprising a sequence or an antigen-binding fragment thereof.

148. Any one of claims 143 to 147, wherein the TRGV9 is on the surface of a γδ T cell. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or its antigen-binding fragment according to any one of claims 1 to 5, segment.

149. The CD123 is on the surface of a tumor cell or a CD34+ stem cell.

48. An isolated anti-TRGV9 / anti-CD123 bispecific antibody according to any one of claims 47 to 49, and an antigen-binding fragment thereof.

150. Presence of the bispecific antibody against TRGV9 present on the surface of the γδ T cell The binding, and the binding of the CD123 on the surface of the cancer cell, results in the killing of the cancer cell. The isolated anti-TRGV9 / anti- CD123 bispecific antibodies or antigen-binding fragments thereof.

151. The method according to any one of claims 143 to 150, wherein HC1 and LC1 are humanized. Isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof .

152. The method according to any one of claims 143 to 151, wherein HC2 and LC2 are humanized. Isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof .

153. The bispecific antibody or antigen-binding fragment thereof is selected from the group consisting of IgG1, IgG2, IgG3 or IgG4 isotype. A bispecific anti-TRGV9 / anti-CD123 antibody or antigen-binding fragment thereof.

154. the bispecific antibody or antigen-binding fragment thereof is of the IgG4 isotype; The isolated anti-TRGV9 / anti-CD123 antibody of any one of claims 143 to 153. A polyspecific antibody or antigen-binding fragment thereof.

155. The bispecific antibody or antigen-binding fragment thereof has an EC ５０ in Inducing γδ T cell-dependent cytotoxicity of cancer cells in vitro.

54. An isolated anti-TRGV9 / anti-CD123 bispecific antibody according to any one of claims 54 to 54. and an antigen-binding fragment thereof.

156. The bispecific antibody or antigen-binding fragment thereof has an EC ５０ in The method according to claim 155, which induces γδ T cell-dependent cytotoxicity of cancer cells in vitro. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof to.

157. The bispecific antibody or antigen-binding fragment thereof has an EC ５０ in The method according to claim 155, which induces γδ T cell-dependent cytotoxicity of cancer cells in vitro. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof to.

158. The EC ５０ However, the mixture of γδ T effector cells and Kasumi3 AML target cells The isolated anti-TRGV antibody of any one of claims 155 to 157 is evaluated in a combination. 9 / Anti-CD123 bispecific antibody or antigen-binding fragment thereof.

159. 10. The method of claim 1, wherein the effector cell to target cell ratio is from about 0.01:1 to about 5:

1.

58. An isolated anti-TRGV9 / anti-CD123 bispecific antibody or its antigen-binding fragment according to claim 58. Fragment.

160. 16. The method of claim 15, wherein the effector cell to target cell ratio is about 0.1:1 to about 2:

1.

9. An isolated anti-TRGV9 / anti-CD123 bispecific antibody or its antigen-binding fragment according to claim 9. segment.

161. 161. The isolated method of claim 160, wherein the effector cell to target cell ratio is about 1:

1. A bispecific anti-TRGV9 / anti-CD123 antibody or antigen-binding fragment thereof.

162. The isolated anti-TRGV9 / anti-CD123 antibody of any one of claims 143 to 161. A method for making a bispecific antibody or antigen-binding fragment thereof, comprising: under conditions to produce an antibody or antigen-binding fragment thereof, 3. Culturing Cells Containing Nucleic Acids Encoding Bispecific Antibodies or Antigen-Binding Fragments Thereof and recovering the bispecific antibody or antigen-binding fragment thereof. method.

163. An isolated TRGV9 bispecific antibody or an antigen epitope-binding fragment thereof. The isolated TRGV9 bispecific antibody or antigen epitope-binding fragment thereof comprises a binding site for a first antigen and a binding site for a second antigen, the binding site for an antigen binds to a TRGV9 epitope on a γδ T cell; The binding site for the second antigen binds to an epitope of the second antigen on the surface of a target cell. and combining said binding of said TRGV9 epitope on said γδ T cell and said and an isolated T cell, wherein the binding of the second antigenic epitope results in the killing of the target cell. RGV9 bispecific antibody or antigen epitope-binding fragment thereof.

164. An isolated TRGV9 bispecific antibody or antigen-binding fragment thereof, comprising: The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises: a. HC1; b. HC2; c. LC1; d. LC2; HC1 is associated with LC1, HC2 is associated with LC2, (A) HC1 is i. SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3, respectively; ii. SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:31, respectively; iii. SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:32, respectively; or iv. the amino acid sequences of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:33, respectively; HCDR1, HCDR2, and HCDR3, LC1 has the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. a binding site for a first antigen comprising LCDR1, LCDR2, and LCDR3; or (B) HC1 is the amino acid sequence of SEQ ID NO:1, SEQ ID NO:76, and SEQ ID NO:3, respectively. HCDR1, HCDR2, and HCDR3 comprising the sequences LC1 has the amino acid sequences of SEQ ID NO:77, SEQ ID NO:5, and SEQ ID NO:6, respectively. A binding site for a first antigen comprising LCDR1, LCDR2, and LCDR3 comprising: Form a position or (C) HC1 is an amine of SEQ ID NO: 60, SEQ ID NO: 61, or SEQ ID NO: 62, respectively. HCDR1, HCDR2, and HCDR3 each containing the amino acid sequence LC1 has the amino acid sequence of SEQ ID NO:63, SEQ ID NO:64, and SEQ ID NO:6, respectively. and a LCDR1, LCDR2, and LCDR3 that comprise a sequence that binds to a first antigen. Form a part or (D) HC1 is an amine of SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, respectively. HCDR1, HCDR2, and HCDR3 each containing the amino acid sequence LC1 is the amino acid sequence of SEQ ID NO:92, SEQ ID NO:93, and SEQ ID NO:94, respectively. The LCDR1, LCDR2, and LCDR3 have the sequence Form a binding site or (E) HC1 is selected from the group consisting of SEQ ID NO: 98, SEQ ID NO: 99, and SEQ ID NO: 100, respectively. HCDR1, HCDR2, and HCDR3 each containing an amino acid sequence; LC1 is the sequence of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 103, respectively. and an LCDR1, LCDR2, and LCDR3 each including an amino acid sequence, or form a binding site for (F) HC1 is SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 109, respectively. and a HCDR1, a HCDR2, and a HCDR3 comprising the amino acid sequence LC1 is the sequence of SEQ ID NO: 110, SEQ ID NO: 111, and SEQ ID NO: 112, respectively. and an LCDR1, LCDR2, and LCDR3 each including an amino acid sequence, or form a binding site for (G) HC1 is SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 119, respectively. and a HCDR1, a HCDR2, and a HCDR3 comprising the amino acid sequence LC1 is the sequence of SEQ ID NO: 120, SEQ ID NO: 121, and SEQ ID NO: 122, respectively. and an LCDR1, LCDR2, and LCDR3 each including an amino acid sequence, or (H) HC1 is SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 129, respectively. and a HCDR1, a HCDR2, and a HCDR3 comprising the amino acid sequence LC1 is the sequence of SEQ ID NO: 130, SEQ ID NO: 131, and SEQ ID NO: 132, respectively. and an LCDR1, LCDR2, and LCDR3 each including an amino acid sequence, forms a binding site for An isolated antibody in which HC2 and LC2 form a binding site for a second antigen epitope. TRGV9 bispecific antibody or antigen-binding fragment thereof.

165. (A) HC1 is selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 34, SEQ ID NO: 35, and SEQ ID NO:

36. an amino acid sequence having at least 95% identity to the amino acid sequence of , an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8 Contains or (B) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

65. and LC1 has an amino acid sequence which is at least 9 times the amino acid sequence of SEQ ID NO:

66. Contains an amino acid sequence with 5% identity (C) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

67. and LC1 has an amino acid sequence which is at least 9 times the amino acid sequence of SEQ ID NO:

68. Contains an amino acid sequence with 5% identity (D) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

95. and LC1 has an amino acid sequence which is at least 90% identical to the amino acid sequence of SEQ ID NO:

96. Contains an amino acid sequence with 5% identity (E) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

104. and LC1 has at least one amino acid sequence having the amino acid sequence of SEQ ID NO:

105. or (F) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

113. and LC1 has an amino acid sequence having at least one amino acid sequence similar to that of SEQ ID NO:

114. or (G) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

123. and LC1 has an amino acid sequence having at least one amino acid sequence similar to that of SEQ ID NO:

124. or (H) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

133. and LC1 has an amino acid sequence having at least one amino acid sequence similar to that of SEQ ID NO:

134.

165. The isolated TRG of claim 164, comprising an amino acid sequence having at least 95% identity to V9 bispecific antibody or an antigen-binding fragment thereof.

166. (A) HC1 is selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 34, SEQ ID NO: 35, and SEQ ID NO:

36. LC1 comprises the amino acid sequence of SEQ ID NO: 8; or (B) HC1 comprises the amino acid sequence of SEQ ID NO:65 and LC1 comprises the amino acid sequence of SEQ ID NO:

66. Contains a nucleotide sequence, (C) HC1 comprises the amino acid sequence of SEQ ID NO:67 and LC1 comprises the amino acid sequence of SEQ ID NO:

68. Contains a nucleotide sequence, (D) HC1 comprises the amino acid sequence of SEQ ID NO:95 and LC1 comprises the amino acid sequence of SEQ ID NO:

96. Contains a nucleotide sequence, (E) HC1 comprises the amino acid sequence of SEQ ID NO: 104, and LC1 comprises the amino acid sequence of SEQ ID NO:

105. Contains an amino acid sequence, (F) HC1 comprises the amino acid sequence of SEQ ID NO: 113 and LC1 comprises the amino acid sequence of SEQ ID NO:

114. Contains an amino acid sequence, (G) HC1 comprises the amino acid sequence of SEQ ID NO: 123 and LC1 comprises the amino acid sequence of SEQ ID NO:

124. or (H) HC1 comprises the amino acid sequence of SEQ ID NO: 133 and LC1 comprises the amino acid sequence of SEQ ID NO:

134. The isolated TRGV9 bispecific antibody of claim 165, comprising the amino acid sequence An antigen-binding fragment of.

167. HC1 and LC1 are humanized according to any one of claims 164 to 166. An isolated TRGV9 bispecific antibody or antigen-binding fragment thereof.

168. Any of claims 164 to 167, wherein HC2 and LC2 bind to a CD123 epitope. An isolated TRGV9 bispecific antibody or antigen-binding fragment thereof described in any one of claims 1 to 4.

169. HC2 has at least 95% identity to the amino acid sequence of SEQ ID NO:

15. LC2 has at least 95% identity to the amino acid sequence of SEQ ID NO:

16. The isolated TRGV9 bispecific antibody of claim 168, comprising an amino acid sequence having identity. Heterologous antibodies or antigen-binding fragments thereof.

170. HC2 comprises the amino acid sequence of SEQ ID NO:15 and LC2 comprises the amino acid sequence of SEQ ID NO:

16.

170. The isolated TRGV9 bispecific antibody or antigen binding thereof of claim 169, comprising an array Fragment.

171. The bispecific antibody or antigen-binding fragment thereof is selected from the group consisting of IgG1, IgG2, IgG3 or IgG4 isotype. A TRGV9 bispecific antibody or antigen-binding fragment thereof.

172. the bispecific antibody or antigen-binding fragment thereof is of the IgG4 isotype; An isolated TRGV9 bispecific antibody according to any one of claims 163 to 171, or and an antigen-binding fragment thereof.

173. The bispecific antibody or antigen-binding fragment thereof has an EC ５０ in Inducing γδ T cell-dependent cytotoxicity of cancer cells in vitro.

72. An isolated TRGV9 bispecific antibody or its antigen-binding fragment according to any one of claims 72 to 74. segment.

174. The bispecific antibody or antigen-binding fragment thereof has an EC ５０ in The method according to claim 173, which induces γδ T cell-dependent cytotoxicity of cancer cells in vitro. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof.

175. The bispecific antibody or antigen-binding fragment thereof has an EC ５０ in The method according to claim 174, which induces γδ T cell-dependent cytotoxicity of cancer cells in vitro. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof.

176. The EC ５０ However, the mixture of γδ T effector cells and Kasumi3 AML target cells The isolated TRGV9 of any one of claims 173 to 175, A bispecific antibody or an antigen-binding fragment thereof.

177. 10. The method of claim 1, wherein the effector cell to target cell ratio is from about 0.01:1 to about 5:

1.

77. An isolated TRGV9 bispecific antibody or antigen-binding fragment thereof according to claim 76.

178. 18. The method of claim 17, wherein the effector cell to target cell ratio is from about 0.1:1 to about 2:

1.

8. An isolated TRGV9 bispecific antibody or an antigen-binding fragment thereof according to claim 7.

179. 179. The isolated method of claim 178, wherein the ratio of effector cells to target cells is about 1:

1. A TRGV9 bispecific antibody or antigen-binding fragment thereof.

180. An isolated γδ T cell bispecific antibody or antigen-binding fragment thereof, comprising: The isolated γδ T cell bispecific antibody or antigen-binding fragment thereof is a binding site for a first antigenic epitope and a binding site for a second antigenic epitope, The binding site for one antigen epitope binds to a first antigen on a γδ T cell and The binding site for the second antigen epitope is located on the surface of the second antigen. epitope, and said binding and pre-regulation of said first antigen epitope on said γδ T cell. The binding of the second antigenic epitope on the target cell results in the killing of the target cell. , an isolated γδ T cell bispecific antibody or antigen-binding fragment thereof.

181. An isolated nucleic acid encoding a TRGV9 bispecific antibody or an antigen-binding fragment thereof. wherein the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof is a. HC1; b. HC2; c. LC1; d. LC2; HC1 is associated with LC1, HC2 is associated with LC2, (A) HC1 is i. SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3, respectively; ii. SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:31, respectively; iii. SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:32, respectively; or iv. the amino acid sequences of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:33, respectively; HCDR1, HCDR2, and HCDR3, LC1 has the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. a binding site for a first antigen comprising LCDR1, LCDR2, and LCDR3; or (B) HC1 is the amino acid sequence of SEQ ID NO:1, SEQ ID NO:76, and SEQ ID NO:3, respectively. HCDR1, HCDR2, and HCDR3 comprising the sequences LC1 has the amino acid sequences of SEQ ID NO:77, SEQ ID NO:5, and SEQ ID NO:6, respectively. A binding site for a first antigen comprising LCDR1, LCDR2, and LCDR3 comprising: Form a position or (C) HC1 is an amine of SEQ ID NO: 60, SEQ ID NO: 61, or SEQ ID NO: 62, respectively. HCDR1, HCDR2, and HCDR3 each containing the amino acid sequence LC1 has the amino acid sequence of SEQ ID NO:63, SEQ ID NO:64, and SEQ ID NO:6, respectively. and a LCDR1, LCDR2, and LCDR3 that comprise a sequence that binds to a first antigen. Form a part or (D) HC1 is an amine of SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, respectively. HCDR1, HCDR2, and HCDR3 each containing the amino acid sequence LC1 is the amino acid sequence of SEQ ID NO:92, SEQ ID NO:93, and SEQ ID NO:94, respectively. The LCDR1, LCDR2, and LCDR3 have the sequence Form a binding site or (E) HC1 is selected from the group consisting of SEQ ID NO: 98, SEQ ID NO: 99, and SEQ ID NO: 100, respectively. HCDR1, HCDR2, and HCDR3 each containing an amino acid sequence; LC1 is the sequence of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 103, respectively. and an LCDR1, LCDR2, and LCDR3 each including an amino acid sequence, or form a binding site for (F) HC1 is SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 109, respectively. and a HCDR1, a HCDR2, and a HCDR3 comprising the amino acid sequence LC1 is the sequence of SEQ ID NO: 110, SEQ ID NO: 111, and SEQ ID NO: 112, respectively. and an LCDR1, LCDR2, and LCDR3 each including an amino acid sequence, or form a binding site for (G) HC1 is SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 119, respectively. and a HCDR1, a HCDR2, and a HCDR3 comprising the amino acid sequence LC1 is the sequence of SEQ ID NO: 120, SEQ ID NO: 121, and SEQ ID NO: 122, respectively. and an LCDR1, LCDR2, and LCDR3 each including an amino acid sequence, or (H) HC1 is SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 129, respectively. and a HCDR1, a HCDR2, and a HCDR3 comprising the amino acid sequence LC1 is the sequence of SEQ ID NO: 130, SEQ ID NO: 131, and SEQ ID NO: 132, respectively. and an LCDR1, LCDR2, and LCDR3 each including an amino acid sequence, forms a binding site for An isolated nucleic acid, wherein HC2 and LC2 form a binding site for a second antigen.

182. (A) HC1 is selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 34, SEQ ID NO: 35, and SEQ ID NO:

36. an amino acid sequence having at least 95% identity to the amino acid sequence of , an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8 Includes or (B) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

65. and LC1 has an amino acid sequence which is at least 9 times the amino acid sequence of SEQ ID NO:

66. Contains an amino acid sequence with 5% identity (C) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

67. and LC1 has an amino acid sequence which is at least 9 times the amino acid sequence of SEQ ID NO:

68. Contains an amino acid sequence with 5% identity (D) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

95. and LC1 has an amino acid sequence which is at least 90% identical to the amino acid sequence of SEQ ID NO:

96. Contains an amino acid sequence with 5% identity (E) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

104. and LC1 has at least one amino acid sequence having the amino acid sequence of SEQ ID NO:

105. or (F) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

113. and LC1 has an amino acid sequence having at least one amino acid sequence similar to that of SEQ ID NO:

114. or (G) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

123. and LC1 has an amino acid sequence having at least one amino acid sequence similar to that of SEQ ID NO:

124. or (H) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

133. and LC1 has an amino acid sequence having at least one amino acid sequence similar to that of SEQ ID NO:

134.

182. The isolated nucleic acid of claim 181, comprising an amino acid sequence having at least 95% identity to said nucleic acid.

183. (A) HC1 is selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 34, SEQ ID NO: 35, and SEQ ID NO:

36. LC1 comprises the amino acid sequence of SEQ ID NO: 8; or (B) HC1 comprises the amino acid sequence of SEQ ID NO:65 and LC1 comprises the amino acid sequence of SEQ ID NO:

66. Contains a nucleotide sequence, (C) HC1 comprises the amino acid sequence of SEQ ID NO:67 and LC1 comprises the amino acid sequence of SEQ ID NO:

68. Contains a nucleotide sequence, (D) HC1 comprises the amino acid sequence of SEQ ID NO:95 and LC1 comprises the amino acid sequence of SEQ ID NO:

96. Contains a nucleotide sequence, (E) HC1 comprises the amino acid sequence of SEQ ID NO: 104, and LC1 comprises the amino acid sequence of SEQ ID NO:

105. Contains an amino acid sequence, (F) HC1 comprises the amino acid sequence of SEQ ID NO: 113 and LC1 comprises the amino acid sequence of SEQ ID NO:

114. Contains an amino acid sequence, (G) HC1 comprises the amino acid sequence of SEQ ID NO: 123 and LC1 comprises the amino acid sequence of SEQ ID NO:

124. or (H) HC1 comprises the amino acid sequence of SEQ ID NO: 133 and LC1 comprises the amino acid sequence of SEQ ID NO:

134.

183. The isolated nucleic acid of claim 182, comprising an amino acid sequence.

184. The binding site for a first antigen binds to TRGV9 on a γδ T cell.

184. The isolated nucleic acid of any one of claims 181 to 183.

185. wherein the binding site for the second antigen binds to a cancer antigen present on the surface of a cancer cell. The isolated nucleic acid of any one of claims 181 to 184.

186. Presence of the bispecific antibody against TRGV9 present on the surface of the γδ T cell and said binding of said cancer antigen present on said surface of said cancer cell.

186. The isolated nucleic acid of claim 185, which causes death.

187. The method according to any one of claims 181 to 186, wherein HC1 and LC1 are humanized. Isolated nucleic acid.

188. HC2 and LC2 bind to CD123. The isolated nucleic acid described.

189. The bispecific antibody or antigen-binding fragment thereof is selected from the group consisting of IgG1, IgG2, IgG3 or IgG4 isotype. Nucleic acid.

190. the bispecific antibody or antigen-binding fragment thereof is of the IgG4 isotype; 190. The isolated nucleic acid of any one of claims 181 to 189.

191. The bispecific antibody or antigen-binding fragment thereof has an EC ５０ in Inducing γδ T cell-dependent cytotoxicity of cancer cells in vitro, 90. An isolated nucleic acid according to any one of claims 90.

192. The bispecific antibody or antigen-binding fragment thereof has an EC ５０ in The method according to claim 191, which induces γδ T cell-dependent cytotoxicity of cancer cells in vitro. The isolated nucleic acid described above.

193. The bispecific antibody or antigen-binding fragment thereof has an EC ５０ in The method according to claim 191, which induces γδ T cell-dependent cytotoxicity of cancer cells in vitro. The isolated nucleic acid described above.

194. The EC ５０ However, the mixture of γδ T effector cells and Kasumi3 AML target cells 194. The isolated nucleic acid of any one of claims 191 to 193, wherein the nucleic acid is evaluated in a combination of

195. 10. The method of claim 1, wherein the effector cell to target cell ratio is from about 0.01:1 to about 5:

1.

94. An isolated nucleic acid according to claim 94.

196. 20. The method of claim 19, wherein the effector cell to target cell ratio is about 0.1:1 to about 2:

1.

6. The isolated nucleic acid according to claim 5.

197. 200. The isolated method of claim 196, wherein the effector cell to target cell ratio is about 1:

1. Nucleic acid.

198. The bispecific antibody or antigen-binding fragment thereof is multivalent.

97. An isolated nucleic acid according to any one of claims 97.

199. The bispecific antibody or antigen-binding fragment thereof binds to at least three antigens. The isolated nucleic acid of claim 198,

200. The bispecific antibody or antigen-binding fragment thereof binds to at least five antigens. The isolated nucleic acid of claim 198,

201. A vector comprising the isolated nucleic acid of any one of claims 181 to 200.

202. A host cell comprising the vector described in claim 201.

203. A kit comprising the vector of claim 201 and a package therefor.

204. 1. An isolated TRGV9 bispecific antibody or antigen-binding fragment thereof, comprising: a. HC1; b. HC2; c. LC1; d. LC2; HC1 is associated with LC1, HC2 is associated with LC2, (A) HC1 is i. SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3, respectively; ii. SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:31, respectively; iii. SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:32, respectively; or iv. the amino acid sequences of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:33, respectively; HCDR1, HCDR2, and HCDR3, LC1 has the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively. a binding site for a first antigen comprising LCDR1, LCDR2, and LCDR3; or (B) HC1 is the amino acid sequence of SEQ ID NO:1, SEQ ID NO:76, and SEQ ID NO:3, respectively. HCDR1, HCDR2, and HCDR3 comprising the sequences LC1 has the amino acid sequences of SEQ ID NO:77, SEQ ID NO:5, and SEQ ID NO:6, respectively. A binding site for a first antigen comprising LCDR1, LCDR2, and LCDR3 comprising: Form a position or (C) HC1 is an amine of SEQ ID NO: 60, SEQ ID NO: 61, or SEQ ID NO: 62, respectively. HCDR1, HCDR2, and HCDR3 each containing the amino acid sequence LC1 has the amino acid sequence of SEQ ID NO:63, SEQ ID NO:64, and SEQ ID NO:6, respectively. and a LCDR1, LCDR2, and LCDR3 that comprise a sequence that binds to a first antigen. Form a part or (D) HC1 is an amine of SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, respectively. HCDR1, HCDR2, and HCDR3 each containing the amino acid sequence LC1 is the amino acid sequence of SEQ ID NO:92, SEQ ID NO:93, and SEQ ID NO:94, respectively. The LCDR1, LCDR2, and LCDR3 have the sequence Form a binding site or (E) HC1 is selected from the group consisting of SEQ ID NO: 98, SEQ ID NO: 99, and SEQ ID NO: 100, respectively. HCDR1, HCDR2, and HCDR3 each containing an amino acid sequence; LC1 is the sequence of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 103, respectively. and an LCDR1, LCDR2, and LCDR3 each including an amino acid sequence, or form a binding site for (F) HC1 is SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 109, respectively. and a HCDR1, a HCDR2, and a HCDR3 comprising the amino acid sequence LC1 is the sequence of SEQ ID NO: 110, SEQ ID NO: 111, and SEQ ID NO: 112, respectively. and an LCDR1, LCDR2, and LCDR3 each including an amino acid sequence, or form a binding site for (G) HC1 is SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 119, respectively. and a HCDR1, a HCDR2, and a HCDR3 comprising the amino acid sequence LC1 is the sequence of SEQ ID NO: 120, SEQ ID NO: 121, and SEQ ID NO: 122, respectively. and an LCDR1, LCDR2, and LCDR3 each including an amino acid sequence, or (H) HC1 is SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 129, respectively. and a HCDR1, a HCDR2, and a HCDR3 comprising the amino acid sequence LC1 is the sequence of SEQ ID NO: 130, SEQ ID NO: 131, and SEQ ID NO: 132, respectively. and an LCDR1, LCDR2, and LCDR3 each including an amino acid sequence, forms a binding site for An isolated TRGV9 in which HC2 and LC2 form a binding site for a second antigen. A bispecific antibody or an antigen-binding fragment thereof; and a pharma- ceutically acceptable carrier.

205. (A) HC1 is selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 34, SEQ ID NO: 35, and SEQ ID NO:

36. an amino acid sequence having at least 95% identity to the amino acid sequence of , an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8 Contains or (B) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

65. and LC1 has an amino acid sequence which is at least 9 times the amino acid sequence of SEQ ID NO:

66. Contains an amino acid sequence with 5% identity (C) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

67. and LC1 has an amino acid sequence which is at least 9 times the amino acid sequence of SEQ ID NO:

68. Contains an amino acid sequence with 5% identity (D) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

95. and LC1 has an amino acid sequence which is at least 90% identical to the amino acid sequence of SEQ ID NO:

96. Contains an amino acid sequence with 5% identity (E) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

104. and LC1 has at least one amino acid sequence having the amino acid sequence of SEQ ID NO:

105. or (F) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

113. and LC1 has an amino acid sequence having at least one amino acid sequence similar to that of SEQ ID NO:

114. or (G) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

123. and LC1 has an amino acid sequence having at least one amino acid sequence similar to that of SEQ ID NO:

124. or (H) HC1 has at least 95% identity to the amino acid sequence of SEQ ID NO:

133. and LC1 has an amino acid sequence having at least one amino acid sequence similar to that of SEQ ID NO:

134. The pharmaceutical composition of claim 204, comprising an amino acid sequence having at least 95% identity to the amino acid sequence of claim 206.

206. (A) HC1 is selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 34, SEQ ID NO: 35, and SEQ ID NO:

36. LC1 comprises the amino acid sequence of SEQ ID NO: 8; or (B) HC1 comprises the amino acid sequence of SEQ ID NO:65 and LC1 comprises the amino acid sequence of SEQ ID NO:

66. Contains a nucleotide sequence, (C) HC1 comprises the amino acid sequence of SEQ ID NO:67 and LC1 comprises the amino acid sequence of SEQ ID NO:

68. Contains a nucleotide sequence, (D) HC1 comprises the amino acid sequence of SEQ ID NO:95 and LC1 comprises the amino acid sequence of SEQ ID NO:

96. Contains a nucleotide sequence, (E) HC1 comprises the amino acid sequence of SEQ ID NO: 104, and LC1 comprises the amino acid sequence of SEQ ID NO:

105. Contains an amino acid sequence, (F) HC1 comprises the amino acid sequence of SEQ ID NO: 113 and LC1 comprises the amino acid sequence of SEQ ID NO:

114. Contains an amino acid sequence, (G) HC1 comprises the amino acid sequence of SEQ ID NO: 123 and LC1 comprises the amino acid sequence of SEQ ID NO:

124. or (H) HC1 comprises the amino acid sequence of SEQ ID NO: 133 and LC1 comprises the amino acid sequence of SEQ ID NO:

134. The pharmaceutical composition of claim 205, comprising an amino acid sequence.

207. The binding site for a first antigen binds to TRGV9 on a γδ T cell.

207. The pharmaceutical composition according to any one of claims 204 to 206.

208. The binding site for a second antigen binds to a cancer antigen present on the surface of a cancer cell.

208. The pharmaceutical composition according to any one of claims 204 to 207.

209. Presence of the bispecific antibody against TRGV9 present on the surface of the γδ T cell and said binding of said cancer antigen present on said surface of said cancer cell. The pharmaceutical composition of claim 208, which causes death.

210. According to any one of claims 204 to 209, HC1 and LC1 are humanized. A pharmaceutical composition comprising:

211. HC2 and LC2 bind to CD123. The pharmaceutical composition described.

212. The bispecific antibody or antigen-binding fragment thereof is selected from the group consisting of IgG1, IgG2, IgG3 or IgG4 isotype, composition.

213. 1. A method for directing Vγ9-expressing γδ T cells to cancer cells, the method comprising: The γδ T cells are contacted with a pharmaceutical composition according to any one of claims 204 to 212. wherein contacting the Vγ9-expressing γδ T cells with the pharmaceutical composition comprises A method for directing γ9-expressing γδ T cells to cancer cells.

214. 1. A method for inhibiting the growth or proliferation of a cancer cell that expresses a cancer antigen on its cell surface, comprising: The method comprises contacting a cell with a pharmaceutical composition according to any one of claims 204 to 212. and contacting the cancer cells with the pharmaceutical composition inhibits the growth or proliferation of the cancer cells. How to do it.

215. contacting the cancer cells with an anti-TRGV9 bispecific antibody or antigen-binding fragment thereof; The method of claim 214, wherein the antibody is in the presence of Vγ9-expressing γδ T cells during the administration of the antibody.

216. 1. A method for treating cancer in a subject in need thereof, said method comprising: a. identifying a subject in need of cancer treatment; b. administering the pharmaceutical composition according to any one of claims 204 to 212 before it is needed; and administering to the subject, Administering the pharmaceutical composition to the subject in need thereof provides a method of treating atherosclerosis in the subject. A method for treating cancer.

217. 20. A method for activating a Vγ9-expressing γδ T cell, the method comprising: Contacting T cells with a pharmaceutical composition according to any one of claims 204 to 212 and contacting the Vγ9-expressing γδ T cell with the pharmaceutical composition comprises contacting the Vγ9-expressing γδ T cell with a control Vγ9 Increased expression of CD69, CD25, and / or granzyme B compared to γδ expressing T cells A method to bring about

218. A method for producing a pharmaceutical composition according to any one of claims 204 to 212, comprising the steps of The bispecific antibody or antigen-binding fragment thereof is combined with a pharma- ceutically acceptable carrier. to obtain the pharmaceutical composition.

Images