Materials and methods for modulating T cell-mediated immunity

Abstract

The present invention describes anti-TRGV9 antibodies or antigen-binding fragments thereof. The present invention also describes nucleic acids encoding the antibodies, compositions comprising the antibodies, methods of producing the antibodies, and methods of using the antibodies to treat or prevent diseases such as cancer.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims the benefit of the following U.S. patent applications: U.S. application serial number 62 / 844,959 filed on May 8, 2019; U.S. application serial number 62 / 844,966 filed on May 8, 2019; U.S. application serial number 62 / 844,970 filed on May 8, 2019; U.S. application serial number 62 / 844,976 filed on May 8, 2019; and U.S. application serial number 62 / 844,995 filed on May 8, 2019, each of which is incorporated herein by reference in its entirety. Technical Field

[0003] The present invention particularly relates to anti-TRGV9 molecules, including anti-TRGV9 antibodies, anti-TRGV9 / anti-cancer-associated antigen bispecific antibodies, as well as nucleic acids and expression vectors encoding the antibodies, recombinant cells containing the vectors, and compositions containing the antibodies. Also provided are methods for preparing the antibodies and methods for using the antibodies to kill cancer cells.

[0004] Reference sequence listing submitted electronically

[0005] This application contains a sequence listing, which is submitted electronically via EFS-Web as an ASCII formatted sequence listing with the file name "14620-021-228_SEQLIST" and a creation date of May 4, 2020, with a size of 349,509 bytes. This sequence listing submitted via EFS-Web is part of this specification and is incorporated herein by reference in its entirety. Summary of the Invention

[0006] In one aspect, provided herein is an antibody that binds to T cell receptor gamma variable region 9 (TRGV9). In some embodiments, the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL).

[0007] In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH complementarity determining region (CDR) 1 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: 31; and (ii) a VL comprising 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 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 some embodiments, the antibody comprises a VH 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 specifically binds to TRGV9. In other 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 antibody. In other embodiments, the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody. In some embodiments, the antibody is a bispecific antibody. In certain embodiments, the antibody is a multivalent 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.

[0008] In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 1, a VH CDR2 having an amino acid sequence of SEQ ID NO: 2, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 32; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 4, a VL CDR2 having an amino acid sequence of SEQ ID NO: 5, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 6. In some embodiments, the antibody comprises a VH having an amino acid sequence of SEQ ID NO: 35. In some embodiments, the antibody comprises a VL having an amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody comprises a VH having an amino acid sequence of SEQ ID NO: 35 and a VL having an 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 some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments, the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody. In some embodiments, the antibody is a bispecific antibody. In certain embodiments, the antibody is a multivalent 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.

[0009] In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 1, a VH CDR2 having an amino acid sequence of SEQ ID NO: 2, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 33; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 4, a VL CDR2 having an amino acid sequence of SEQ ID NO: 5, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 6. In some embodiments, the antibody comprises a VH having an amino acid sequence of SEQ ID NO: 36. In some embodiments, the antibody comprises a VL having an amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody comprises a VH having an amino acid sequence of SEQ ID NO: 36 and a VL having an 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 some embodiments, the antibody is a humanized antibody. In certain embodiments, the antibody is an IgG antibody. In other embodiments, the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody. In some embodiments, the antibody is a bispecific antibody. In certain embodiments, the antibody is a multivalent 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.

[0010] In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 1, a VH CDR2 having an amino acid sequence of SEQ ID NO: 76, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 3; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 77, a VL CDR2 having an amino acid sequence of SEQ ID NO: 5, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 6. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 60, a VHCDR2 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 VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 63, a VL CDR2 having the amino acid sequence of SEQ ID NO: 64, and 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: 65. In some embodiments, the antibody comprises 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: 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 VL having the amino acid sequence of SEQ ID NO: 68. In some embodiments, the antibody specifically binds to TRGV9. In other 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 antibody. In other embodiments, the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody. In some embodiments, the antibody is a bispecific antibody. In certain embodiments, the antibody is a multivalent 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, wherein the antibody comprises: (i) a VH comprising 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, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 100; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 101, a VL CDR2 having the amino acid sequence of SEQ ID NO: 102, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 103. 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 some embodiments, the antibody comprises a VH 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. In other 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 antibody. In other embodiments, the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody. In some embodiments, the antibody is a bispecific antibody. In certain embodiments, the antibody is a multivalent 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, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 107, a VHCDR2 having the amino acid sequence of SEQ ID NO: 108, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 109; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 110, a VL CDR2 having the amino acid sequence of SEQ ID NO: 111, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 112. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 113. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO: 114. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 113 and a VL having the amino acid sequence of SEQ ID NO: 114. In some embodiments, the antibody specifically binds to TRGV9. In other 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 antibody. In other embodiments, the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody. In some embodiments, the antibody is a bispecific antibody. In certain embodiments, the antibody is a multivalent 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] In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 117, a VHCDR2 having the amino acid sequence of SEQ ID NO: 118, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 119; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 120, a VL CDR2 having the amino acid sequence of SEQ ID NO: 121, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 122. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 123. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO: 124. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 123 and a VL having the amino acid sequence of SEQ ID NO: 124. In some embodiments, the antibody specifically binds to TRGV9. In other 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 antibody. In other embodiments, the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody. In some embodiments, the antibody is a bispecific antibody. In certain embodiments, the antibody is a multivalent 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.

[0014] In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising 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: 128, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 129; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 130, a VL CDR2 having the amino acid sequence of SEQ ID NO: 131, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 132. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 133. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO: 134. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 133 and a VL having the amino acid sequence of SEQ ID NO: 134. In some embodiments, the antibody specifically binds to TRGV9. In other 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 antibody. In other embodiments, the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody. In some embodiments, the antibody is a bispecific antibody. In certain embodiments, the antibody is a multivalent 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.

[0015] Also provided are nucleic acids encoding antibodies that bind to TRGV9 as provided herein. Also provided are vectors comprising nucleic acids encoding antibodies that bind to TRGV9 as provided herein. Also provided are host cells comprising vectors comprising nucleic acids encoding antibodies that bind to TRGV9 as provided herein. Also provided are kits comprising vectors and packaging for the vectors comprising nucleic acids encoding antibodies that bind to TRGV9 as provided herein.

[0016] Also provided is a pharmaceutical composition comprising an antibody that binds to TRGV9 provided herein and a pharmaceutically acceptable carrier. Also provided is a method for preparing the pharmaceutical composition, comprising combining the antibody with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition.

[0017] Also provided is a method for activating γδT cells expressing TRGV9, the method comprising contacting the γδT cells with an antibody that binds to TRGV9 provided herein. In some embodiments, the contact results in an increase in CD69, CD25, and / or granzyme B expression compared to control γδT cells expressing TRGV9. Also provided is a method for inactivating γδT cells expressing TRGV9, the method comprising contacting the γδT cells with an antibody that binds to TRGV9 provided herein. Also provided is a method for blocking activation of γδT cells expressing TRGV9, the method comprising contacting the γδT cells with an antibody that binds to TRGV9 provided herein. Also provided is a method for regulating the activity of γδT cells expressing TRGV9, the method comprising contacting the γδT cells with an antibody that binds to TRGV9 provided herein.

[0018] In another aspect, provided herein is a bispecific antibody 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. 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 antibody. In other embodiments, the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody.

[0019] In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising 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: 3; and (ii) a VL comprising 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 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 comprises a VH having the amino acid sequence of SEQ ID NO: 7 and a VL having the amino acid sequence of SEQ ID NO: 8. In 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 antibody. In other embodiments, the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody.

[0020] In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising 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: 31; and (ii) a VL comprising 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 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: 34. 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 comprises a VH having the amino acid sequence of SEQ ID NO: 34 and a VL having the amino acid sequence of SEQ ID NO: 8. 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 antibody. In other embodiments, the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody.

[0021] In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising 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: 32; and (ii) a VL comprising 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 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: 35. 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 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 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 antibody. In other embodiments, the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody.

[0022] In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising 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 comprising 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 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: 36. 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 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 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 antibody. In other embodiments, the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody.

[0023] In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 1, a VH CDR2 having an amino acid sequence of SEQ ID NO: 76, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 3; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 77, a VL CDR2 having an amino acid sequence of SEQ ID NO: 5, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 6. In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 60, a VH CDR2 having an amino acid sequence of SEQ ID NO: 61, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 62; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 63, a VL CDR2 having an amino acid sequence of SEQ ID NO: 64, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 6. In some embodiments, the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 65. In some embodiments, the first binding domain comprises a VL having an amino acid sequence of SEQ ID NO: 66. In some embodiments, the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 65 and a VL having an amino acid sequence of SEQ ID NO: 66. In some embodiments, the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 67. In some embodiments, the first binding domain comprises a VL having an amino acid sequence of SEQ ID NO: 68. In some embodiments, the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 67 and a VL having an amino acid sequence of SEQ ID NO: 68. 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 antibody.In other embodiments, the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody.

[0024] In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 89, a VH CDR2 having an amino acid sequence of SEQ ID NO: 90, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 91; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 92, a VL CDR2 having an amino acid sequence of SEQ ID NO: 93, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 94. In some embodiments, the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 95. In some embodiments, the first binding domain comprises a VL having an amino acid sequence of SEQ ID NO: 96. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of 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 antibody. In other embodiments, the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody.

[0025] In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 98, a VH CDR2 having an amino acid sequence of SEQ ID NO: 99, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 100; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 101, a VL CDR2 having an amino acid sequence of SEQ ID NO: 102, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 103. In some embodiments, the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 104. In some embodiments, the first binding domain comprises a VL having an amino acid sequence of SEQ ID NO: 105. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 104 and a VL having the amino acid sequence of SEQ ID NO: 105. 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 antibody. In other embodiments, the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody.

[0026] In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 107, a VH CDR2 having an amino acid sequence of SEQ ID NO: 108, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 109; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 110, a VL CDR2 having an amino acid sequence of SEQ ID NO: 111, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 112. In some embodiments, the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 113. In some embodiments, the first binding domain comprises a VL having an amino acid sequence of SEQ ID NO: 114. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 113 and a VL having the amino acid sequence of SEQ ID NO: 114. In 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 antibody. In other embodiments, the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody.

[0027] In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 117, a VH CDR2 having an amino acid sequence of SEQ ID NO: 118, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 119; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 120, a VL CDR2 having an amino acid sequence of SEQ ID NO: 121, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 122. In some embodiments, the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 123. In some embodiments, the first binding domain comprises a VL having an amino acid sequence of SEQ ID NO: 124. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 123 and a VL having the amino acid sequence of SEQ ID NO: 124. In 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 antibody. In other embodiments, the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody.

[0028] In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 127, a VH CDR2 having an amino acid sequence of SEQ ID NO: 128, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 129; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 130, a VL CDR2 having an amino acid sequence of SEQ ID NO: 131, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 132. In some embodiments, the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 133. In some embodiments, the first binding domain comprises a VL having an amino acid sequence of SEQ ID NO: 134. In some embodiments, the first binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 133 and a VL having the amino acid sequence of SEQ ID NO: 134. In 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 antibody. In other embodiments, the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody.

[0029] On the other hand, provided herein is a bispecific antibody comprising: (a) a first binding domain that binds to TRGV9, and (b) a second binding domain that binds to a cancer antigen present on the surface of a cancer cell. In some embodiments, the antigen on the surface of the cancer cell is a tumor-specific antigen, a tumor-associated antigen, or a new antigen. 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 γδT cells. In some embodiments, when the bispecific antibody binds to TRGV9 on the surface of γδT cells and an antigen on the surface of a cancer cell, the cancer cell is killed. In some embodiments, the first binding domain is humanized, the second binding domain is humanized, or both the first binding domain and the second binding domain are humanized. In some embodiments, the bispecific antibody is an IgG antibody. In some embodiments, the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody.

[0030] On the other hand, a bispecific antibody is provided herein, comprising: (a) a first binding domain that binds to TRGV9, and (b) a second binding domain that binds to CD123. 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 γδT cells. In some embodiments, CD123 is located on the surface of cells. In certain embodiments, TRGV9 is present on the surface of γδT cells, and CD123 is present on the surface of cells. In some embodiments, when the bispecific antibody binds to TRGV9 on the surface of γδT cells and CD123 on the surface of the cells, cells with CD123 on the surface are killed. In some embodiments, CD123 is located on the surface of cancer cells. In certain embodiments, TRGV9 is present on the surface of γδT cells, and CD123 is present on the surface of cancer cells. In some embodiments, when the bispecific antibody binds to TRGV9 on the surface of γδT cells and CD123 on the surface of cancer cells, the cancer cells are killed. In some embodiments, the first binding domain is humanized, the second binding domain is humanized, or both the first binding domain and the second binding domain are humanized. In some embodiments, the bispecific antibody is an IgG antibody. In some embodiments, the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody.

[0031] In another aspect, provided herein is a bispecific antibody comprising: (a) a first binding domain that binds to TRGV9, and (b) a second binding domain that binds to CD123, wherein the second binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 9, a VH CDR2 having an amino acid sequence of SEQ ID NO: 10, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 11; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 12, a VL CDR2 having an amino acid sequence of SEQ ID NO: 13, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 14. In some embodiments, the second binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 15. In some embodiments, the second binding domain comprises a VL having an amino acid sequence of SEQ ID NO: 16. In some embodiments, the second binding domain comprises a VH having the amino acid sequence of SEQ ID NO: 15 and a VL having the amino acid sequence of SEQ ID NO: 16. In some embodiments, CD123 is located on the surface of a cell. In certain embodiments, TRGV9 is present on the surface of a γδT cell, and CD123 is present on the surface of a cell. In some embodiments, when the bispecific antibody binds to TRGV9 on the surface of a γδT cell and CD123 on the surface of the cell, the cell having CD123 on the surface is killed. In some embodiments, CD123 is located on the surface of a cancer cell. In certain embodiments, TRGV9 is present on the surface of a γδT cell, and CD123 is present on the surface of a cancer cell. In some embodiments, when the bispecific antibody binds to TRGV9 on the surface of a γδT cell and CD123 on the surface of the cancer cell, the cancer cell is killed. In some embodiments, the first binding domain is humanized, the second binding domain is humanized, or both the first binding domain and the second binding domain are humanized. In some embodiments, the bispecific antibody is an IgG antibody. In some embodiments, the IgG antibody is an IgG1, IgG2, IgG3, or IgG4 antibody.

[0032] In some embodiments of the various bispecific antibodies provided herein, the first binding domain that binds to TRGV9 comprises VH CDR1, VH CDR2, VH CDR3, VL CDR1, VLCDR2, and VL CDR3 having an amino acid sequence as provided herein. In some embodiments, the first binding domain that binds to TRGV9 comprises VH CDR1, VH CDR2, and VH CDR3 of a VH domain having an amino acid sequence as provided herein. In some embodiments, the first binding domain that binds to TRGV9 comprises VL CDR1, VLCDR2, and VL CDR3 of a VL domain having an amino acid sequence as provided herein. In some embodiments, the first binding domain that binds to TRGV9 comprises: VH CDR1, VH CDR2, and VH CDR3 of a VH domain having an amino acid sequence as provided herein; and VL CDR1, VL CDR2, and VL CDR3 of a VL domain having an amino acid sequence as provided herein. In some embodiments, the first binding domain that binds to TRGV9 comprises a VH domain having an amino acid sequence as provided herein. In some embodiments, the first binding domain that binds to TRGV9 comprises a VL domain having an amino acid sequence as provided herein. In some embodiments, the first binding domain that binds to TRGV9 comprises: a VH domain having an amino acid sequence as provided herein; and a VL domain having an amino acid sequence as provided herein.

[0033] Also provided is a nucleic acid encoding a bispecific antibody as provided herein, the bispecific antibody 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. Also provided is a vector comprising a nucleic acid encoding a bispecific antibody that binds to TRGV9 as provided herein. Also provided is a host cell comprising a vector comprising a nucleic acid encoding a bispecific antibody that binds to TRGV9 as provided herein. Also provided is a kit comprising a vector and packaging for the vector, the vector comprising a nucleic acid encoding a bispecific antibody that binds to TRGV9 as provided herein.

[0034] In another aspect, provided herein is a pharmaceutical composition 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, and a pharmaceutically acceptable carrier. It is contemplated that any of the bispecific antibodies provided herein may be used in the pharmaceutical composition. In certain embodiments, the second binding domain binds to CD123.

[0035] In another aspect, provided herein is a method of directing a γδ T cell expressing TRGV9 to a cancer cell, the method comprising contacting the γδ T cell with a bispecific antibody provided herein. In some embodiments, the contact directs the γδ T cell to the cancer cell.

[0036] In another aspect, provided herein is a method for inhibiting the growth or proliferation of a cancer cell that expresses a cancer antigen on its surface, the method comprising contacting the cancer cell with a bispecific antibody provided herein. In some embodiments, contacting the cancer cell with the pharmaceutical composition inhibits the growth or proliferation of the cancer cell. In some embodiments, the cancer cell is contacted with the bispecific antibody in the presence of γδ T cells that express TRGV9.

[0037] On the other hand, the present invention provides a method for eliminating cancer cells in a subject, the method comprising administering to the subject an effective amount of a bispecific antibody as provided herein. In some embodiments, the subject is a subject in need. In some embodiments, the subject is a human.

[0038] In another aspect, provided herein is a method of activating a γδ T cell expressing TRGV9, the method comprising contacting the γδ T cell with a bispecific antibody as provided herein.

[0039] Provided herein are isolated TRGV9 bispecific antibodies or antigen-binding fragments thereof, comprising:

[0040] a. First heavy chain (HC1);

[0041] b. Second heavy chain (HC2);

[0042] c. first light chain (LC1); and

[0043] d. Second light chain (LC2),

[0044] wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises a heavy chain complementarity determining region 1 (HCDR1), HCDR2, and HCDR3 having the following amino acid sequence:

[0045] i. SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively,

[0046] ii. SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 31, respectively,

[0047] iii. SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 32, respectively, or

[0048] iv. SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 33, respectively,

[0049] and LC1 comprises a light chain complementary determining region 1 (LCDR1), LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 and LC1: the HC1 comprises an amino acid sequence that is at least 95% identical to an amino acid sequence selected from SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:8. In another embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises HC1 and LC1: the HC1 comprises an amino acid sequence selected from SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36, and the LC1 comprises the amino acid sequence of SEQ ID NO:8.

[0050] Also provided herein is an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HCl; (b) HC2; (c) LC1; and (d) LC2, wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl comprises HCDR1, HCDR2, and HCDR3 having the amino acid sequences of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR3 having the amino acid sequences of SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises the following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 7, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 8. In another embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises the following HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 7, and the LC1 comprises the amino acid sequence of SEQ ID NO: 8.

[0051] Also provided herein is an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HCl; (b) HC2; (c) LC1; and (d) LC2, wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR3 having amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises the following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 34, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 8. In another embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises the following HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 34, and the LC1 comprises the amino acid sequence of SEQ ID NO: 8.

[0052] Also provided herein is an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HCl; (b) HC2; (c) LC1; and (d) LC2, wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl comprises HCDR1, HCDR2, and HCDR3 having the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR3 having the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises the following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 35, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 8. In another embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises the following HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 35, and the LC1 comprises the amino acid sequence of SEQ ID NO: 8.

[0053] Also provided herein is an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HCl; (b) HC2; (c) LC1; and (d) LC2, wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR3 having amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises the following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 36, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 8. In another embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises the following HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 36, and the LC1 comprises the amino acid sequence of SEQ ID NO: 8.

[0054] Also provided herein is an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HCl; (b) HC2; (c) LC1; and (d) LC2, wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl comprises HCDR1, HCDR2, and HCDR3 having the amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 76, and SEQ ID NO: 3, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR3 having the amino acid sequences of SEQ ID NO: 77, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises an HCl comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 65 and an LC1 comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 66. In another embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises an HCl comprising an amino acid sequence of SEQ ID NO: 65 and an LC1 comprising an amino acid sequence of SEQ ID NO: 66. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises an HCl comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 67 and an LC1 comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 68. In another embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises the following HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 67, and the LC1 comprises the amino acid sequence of SEQ ID NO: 68.

[0055] Also provided herein is an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HCl; (b) HC2; (c) LC1; and (d) LC2, wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl comprises HCDR1, HCDR2, and HCDR3 having the amino acid sequences of SEQ ID NO: 60, SEQ ID NO: 61, and SEQ ID NO: 62, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR3 having the amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 64, and SEQ ID NO: 6, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises an HCl comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 65 and an LC1 comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 66. In another embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises an HCl comprising an amino acid sequence of SEQ ID NO: 65 and an LC1 comprising an amino acid sequence of SEQ ID NO: 66. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises an HCl comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 67 and an LC1 comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 68. In another embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises the following HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 67, and the LC1 comprises the amino acid sequence of SEQ ID NO: 68.

[0056] Also provided herein is an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HCl; (b) HC2; (c) LC1; and (d) LC2, wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl comprises HCDR1, HCDR2, and HCDR3 having the amino acid sequences of SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR3 having the amino acid sequences of SEQ ID NO: 92, SEQ ID NO: 93, and SEQ ID NO: 94, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises the following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 95, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 96. In another embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises the following HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 95, and the LC1 comprises the amino acid sequence of SEQ ID NO: 96.

[0057] Also provided herein is an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HCl; (b) HC2; (c) LC1; and (d) LC2, wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl comprises HCDR1, HCDR2, and HCDR3 having the amino acid sequences of SEQ ID NO: 98, SEQ ID NO: 99, and SEQ ID NO: 100, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR3 having the amino acid sequences of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 103, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises the following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 104, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 105. In another embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises the following HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 104, and the LC1 comprises the amino acid sequence of SEQ ID NO: 105.

[0058] Also provided herein is an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HCl; (b) HC2; (c) LC1; and (d) LC2, wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 109, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR3 having amino acid sequences of SEQ ID NO: 110, SEQ ID NO: 111, and SEQ ID NO: 112, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises the following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 113, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 114. In another embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises the following HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 113, and the LC1 comprises the amino acid sequence of SEQ ID NO: 114.

[0059] Also provided herein is an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HCl; (b) HC2; (c) LC1; and (d) LC2, wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 119, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR3 having amino acid sequences of SEQ ID NO: 120, SEQ ID NO: 121, and SEQ ID NO: 122, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises the following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 123, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 124. In another embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises the following HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 123, and the LC1 comprises the amino acid sequence of SEQ ID NO: 124.

[0060] Also provided herein is an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HCl; (b) HC2; (c) LC1; and (d) LC2, wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 129, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR3 having amino acid sequences of SEQ ID NO: 130, SEQ ID NO: 131, and SEQ ID NO: 132, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises the following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 133, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 134. In another embodiment, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises the following HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 133, and the LC1 comprises the amino acid sequence of SEQ ID NO: 134.

[0061] In another embodiment, the binding site for the first antigen binds to TRGV9 on γδ T cells.

[0062] In another embodiment, the second antigen binding site binds to a cancer antigen present on the surface of a cancer cell.

[0063] In another embodiment, the bispecific antibody binds to TRGV9 present on the surface of γδ T cells, and binding to the cancer antigen present on the surface of the cancer cell results in killing of the cancer cell.

[0064] In another embodiment, the TRGV9 bispecific antibody comprises humanized HCl and humanized LC1.

[0065] In another embodiment, HC2 and LC2 of the TRGV9 antibody bind to CD123.

[0066] In another embodiment, the bispecific antibody or antigen-binding fragment thereof is of the IgG1, IgG2, IgG3 or IgG4 isotype.

[0067] In a specific embodiment, the bispecific antibody or antigen-binding fragment thereof is of the IgG4 isotype.

[0068] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof is expressed in vitro at an EC of less than about 500 pM. 50 Induces γδ T cell-dependent cytotoxicity of cancer cells.

[0069] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof is expressed in vitro at an EC of less than about 300 pM. 50 Induces γδ T cell-dependent cytotoxicity of cancer cells.

[0070] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof is expressed in vitro at an EC of less than about 160 pM. 50 Induces γδ T cell-dependent cytotoxicity of cancer cells.

[0071] In one embodiment, ECs are assessed using a mixture of γδ T effector cells and Kasumi3 AML target cells. 50 .

[0072] In another embodiment, the ratio of effector cells to target cells is from about 0.01 to 1 to about 5 to 1.

[0073] In yet another embodiment, the ratio of effector cells to target cells is from about 0.1 to 1 to about 2 to 1.

[0074] In a specific embodiment, the ratio of effector cells to target cells is about 1:1.

[0075] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof is multivalent.

[0076] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof is capable of binding to at least three antigens.

[0077] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof is capable of binding to at least five antigens.

[0078] Also provided is an isolated γδ T cell bispecific antibody or an antigen-binding fragment thereof, comprising:

[0079] a.HC1;

[0080] b.HC2;

[0081] c.LC1; and

[0082] d.LC2,

[0083] Where HC1 associates with LC1, and HC2 associates with LC2,

[0084] HC1 and LC1 form the binding site for the first antigen on γδ T cells, and

[0085] HC2 and LC2 form the binding site for the second antigen.

[0086] Also provided herein are bispecific antibodies comprising: a first component capable of specifically binding to a T cell receptor gamma chain; and a second component capable of specifically binding to a target molecule that is not a T cell receptor gamma chain.

[0087] Also provided is a method for preparing a molecule capable of specifically binding to more than one target molecule, the molecule comprising: a step for performing the function of obtaining an oligopeptide or polypeptide capable of binding to a T-cell receptor γ chain; a step for performing the function of obtaining an oligopeptide or polypeptide capable of binding to a target; and a step for performing the function of providing a molecule capable of specifically binding to a T-cell receptor γ chain and a target molecule.

[0088] In one embodiment, the step of performing the function of obtaining an oligopeptide or polypeptide capable of binding to a target in the method is repeated n times, and further comprises n steps of performing the function of providing a molecule capable of specifically binding to the T cell receptor γ chain and n target molecules, wherein n is at least 2.

[0089] Provided herein are isolated anti-TRGV9 / anti-CD123 bispecific antibodies or antigen-binding fragments thereof, comprising:

[0090] a.HC1;

[0091] b.HC2;

[0092] c.LC1; and

[0093] d.LC2,

[0094] wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having the following amino acid sequence:

[0095] i. SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively,

[0096] ii. SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 31, respectively,

[0097] iii. SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 32, respectively, or

[0098] iv. SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 33, respectively,

[0099] And LC1 contains LCDR1, LCDR2 and LCDR3 having amino acid sequences of SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6, respectively, to form a binding site that specifically binds to a first antigen of Vγ9, and wherein HC2 contains HCDR1, HCDR2 and HCDR3 having amino acid sequences of SEQ ID NO:9, SEQ ID NO:10 and SEQ ID NO:11, respectively, and LC2 contains LCDR1, LCDR2 and LCDR3 having amino acid sequences of SEQ ID NO:12, SEQ ID NO:13 and SEQ ID NO:14, respectively, to form a binding site that specifically binds to a second antigen of CD123. In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to an amino acid sequence selected from SEQ ID NO: 7, SEQ ID NO: 34, SEQ ID NO: 35, or SEQ ID NO: 36, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 8. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl has an amino acid sequence selected from SEQ ID NO: 7, SEQ ID NO: 34, SEQ ID NO: 35, or SEQ ID NO: 36, and the LC1 comprises the amino acid sequence of SEQ ID NO: 8. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HC2 and LC2: the HC2 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 15, and the LC2 comprises an amino acid sequence that is at least 95% identical 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 the following HC2 and LC2: the HC2 comprises the amino acid sequence of SEQ ID NO: 15, and the LC2 comprises the amino acid sequence of SEQ ID NO: 16.

[0100] Also provided herein are isolated anti-TRGV9 / anti-CD123 bispecific antibodies or antigen-binding fragments thereof comprising: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR3 having amino acid sequences of SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, respectively, to form a binding site that specifically binds to a first antigen of Vγ9, and wherein HC2 comprises HCDR1, HCDR2, and HCDR3 having 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 having amino acid sequences of SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:14, respectively. NO:14 LCDR1, LCDR2 and LCDR3 to form a binding site for a second antigen that specifically binds to CD123. In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the selected amino acid sequence SEQ ID NO:7, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence SEQ ID NO:8. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises the amino acid sequence SEQ ID NO:7, and the LC1 comprises the amino acid sequence SEQ ID NO:8. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HC2 and LC2: the HC2 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 15, and the LC2 comprises an amino acid sequence that is at least 95% identical 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 the following HC2 and LC2: the HC2 comprises the amino acid sequence of SEQ ID NO: 15, and the LC2 comprises the amino acid sequence of SEQ ID NO: 16.

[0101] Also provided herein are isolated anti-TRGV9 / anti-CD123 bispecific antibodies or antigen-binding fragments thereof comprising: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR3 having amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site that specifically binds to a first antigen of Vγ9, and wherein HC2 comprises HCDR1, HCDR2, and HCDR3 having 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 having amino acid sequences of SEQ ID NO: 12, SEQ ID NO: 13, and SEQ ID NO: 14, respectively. NO:14 LCDR1, LCDR2 and LCDR3 to form a binding site for a second antigen that specifically binds to CD123. In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the selected amino acid sequence SEQ ID NO:34, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence SEQ ID NO:8. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises the amino acid sequence SEQ ID NO:34, and the LC1 comprises the amino acid sequence SEQ ID NO:8. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HC2 and LC2: the HC2 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 15, and the LC2 comprises an amino acid sequence that is at least 95% identical 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 the following HC2 and LC2: the HC2 comprises the amino acid sequence of SEQ ID NO: 15, and the LC2 comprises the amino acid sequence of SEQ ID NO: 16.

[0102] Also provided herein are isolated anti-TRGV9 / anti-CD123 bispecific antibodies or antigen-binding fragments thereof comprising: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR3 having amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site that specifically binds to a first antigen of Vγ9, and wherein HC2 comprises HCDR1, HCDR2, and HCDR3 having 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 having amino acid sequences of SEQ ID NO: 12, SEQ ID NO: 13, and SEQ ID NO: 14, respectively. NO:14 LCDR1, LCDR2 and LCDR3, to form a binding site for a second antigen that specifically binds to CD123. In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the selected amino acid sequence SEQ ID NO:35, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence SEQ ID NO:8. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises the amino acid sequence SEQ ID NO:35, and the LC1 comprises the amino acid sequence SEQ ID NO:8. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HC2 and LC2: the HC2 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 15, and the LC2 comprises an amino acid sequence that is at least 95% identical 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 the following HC2 and LC2: the HC2 comprises the amino acid sequence of SEQ ID NO: 15, and the LC2 comprises the amino acid sequence of SEQ ID NO: 16.

[0103] Also provided herein are isolated anti-TRGV9 / anti-CD123 bispecific antibodies or antigen-binding fragments thereof comprising: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR3 having amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site that specifically binds to a first antigen of Vγ9, and wherein HC2 comprises HCDR1, HCDR2, and HCDR3 having 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 having amino acid sequences of SEQ ID NO: 12, SEQ ID NO: 13, and SEQ ID NO: 14, respectively. NO:14 LCDR1, LCDR2 and LCDR3, to form a binding site for a second antigen that specifically binds to CD123. In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the selected amino acid sequence SEQ ID NO:36, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence SEQ ID NO:8. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises the amino acid sequence SEQ ID NO:36, and the LC1 comprises the amino acid sequence SEQ ID NO:8. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HC2 and LC2: the HC2 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 15, and the LC2 comprises an amino acid sequence that is at least 95% identical 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 the following HC2 and LC2: the HC2 comprises the amino acid sequence of SEQ ID NO: 15, and the LC2 comprises the amino acid sequence of SEQ ID NO: 16.

[0104] Also provided herein are isolated anti-TRGV9 / anti-CD123 bispecific antibodies or antigen-binding fragments thereof comprising: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 76, and SEQ ID NO: 3, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR3 having amino acid sequences of SEQ ID NO: 77, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site that specifically binds to a first antigen of Vγ9, and wherein HC2 comprises HCDR1, HCDR2, and HCDR3 having 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 having amino acid sequences of SEQ ID NO: 12, SEQ ID NO: 13, and SEQ ID NO: 14, respectively. NO:14 LCDR1, LCDR2 and LCDR3, to form a binding site for a second antigen that specifically binds to CD123. In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the selected amino acid sequence SEQ ID NO:65, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence SEQ ID NO:66. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises the amino acid sequence SEQ ID NO:65, and the LC1 comprises the amino acid sequence SEQ ID NO:66. In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the selected amino acid sequence SEQ ID NO: 67, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence SEQ ID NO: 68. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises the amino acid sequence SEQ ID NO: 67, and the LC1 comprises the amino acid sequence SEQ ID NO: 68.In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HC2 and LC2: the HC2 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 15, and the LC2 comprises an amino acid sequence that is at least 95% identical 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 the following HC2 and LC2: the HC2 comprises the amino acid sequence of SEQ ID NO: 15, and the LC2 comprises the amino acid sequence of SEQ ID NO: 16.

[0105] Also provided herein are isolated anti-TRGV9 / anti-CD123 bispecific antibodies or antigen-binding fragments thereof comprising: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 60, SEQ ID NO: 61, and SEQ ID NO: 62, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR3 having amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 64, and SEQ ID NO: 65, respectively, to form a binding site that specifically binds to a first antigen of Vγ9, and wherein HC2 comprises HCDR1, HCDR2, and HCDR3 having 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 having amino acid sequences of SEQ ID NO: 12, SEQ ID NO: 13, and SEQ ID NO: 14, respectively. NO:14 LCDR1, LCDR2 and LCDR3, to form a binding site for a second antigen that specifically binds to CD123. In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the selected amino acid sequence SEQ ID NO:65, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence SEQ ID NO:66. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises the amino acid sequence SEQ ID NO:65, and the LC1 comprises the amino acid sequence SEQ ID NO:66. In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the selected amino acid sequence SEQ ID NO: 67, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence SEQ ID NO: 68. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises the amino acid sequence SEQ ID NO: 67, and the LC1 comprises the amino acid sequence SEQ ID NO: 68.In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HC2 and LC2: the HC2 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 15, and the LC2 comprises an amino acid sequence that is at least 95% identical 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 the following HC2 and LC2: the HC2 comprises the amino acid sequence of SEQ ID NO: 15, and the LC2 comprises the amino acid sequence of SEQ ID NO: 16.

[0106] Also provided herein are isolated anti-TRGV9 / anti-CD123 bispecific antibodies or antigen-binding fragments thereof comprising: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO:89, SEQ ID NO:90, and SEQ ID NO:91, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR3 having amino acid sequences of SEQ ID NO:92, SEQ ID NO:93, and SEQ ID NO:94, respectively, to form a binding site that specifically binds to a first antigen of Vγ9, and wherein HC2 comprises HCDR1, HCDR2, and HCDR3 having 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 having amino acid sequences of SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:14, respectively. NO:14 LCDR1, LCDR2 and LCDR3, to form a binding site for a second antigen that specifically binds to CD123. In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the selected amino acid sequence SEQ ID NO:95, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence SEQ ID NO:96. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises the amino acid sequence SEQ ID NO:95, and the LC1 comprises the amino acid sequence SEQ ID NO:96. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HC2 and LC2: the HC2 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 15, and the LC2 comprises an amino acid sequence that is at least 95% identical 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 the following HC2 and LC2: the HC2 comprises the amino acid sequence of SEQ ID NO: 15, and the LC2 comprises the amino acid sequence of SEQ ID NO: 16.

[0107] Also provided herein are isolated anti-TRGV9 / anti-CD123 bispecific antibodies or antigen-binding fragments thereof comprising: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO:98, SEQ ID NO:99, and SEQ ID NO:100, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR3 having amino acid sequences of SEQ ID NO:101, SEQ ID NO:102, and SEQ ID NO:103, respectively, to form a binding site that specifically binds to a first antigen of Vγ9, and wherein HC2 comprises HCDR1, HCDR2, and HCDR3 having 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 having amino acid sequences of SEQ ID NO:12, SEQ ID NO:13, and SEQ ID NO:14, respectively. NO:14 LCDR1, LCDR2 and LCDR3 to form a binding site for a second antigen that specifically binds to CD123. In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the selected amino acid sequence SEQ ID NO:104, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence SEQ ID NO:105. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises the amino acid sequence SEQ ID NO:104, and the LC1 comprises the amino acid sequence SEQ ID NO:105. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HC2 and LC2: the HC2 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 15, and the LC2 comprises an amino acid sequence that is at least 95% identical 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 the following HC2 and LC2: the HC2 comprises the amino acid sequence of SEQ ID NO: 15, and the LC2 comprises the amino acid sequence of SEQ ID NO: 16.

[0108] Also provided herein are isolated anti-TRGV9 / anti-CD123 bispecific antibodies or antigen-binding fragments thereof comprising: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 109, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR3 having amino acid sequences of SEQ ID NO: 110, SEQ ID NO: 111, and SEQ ID NO: 112, respectively, to form a binding site that specifically binds to a first antigen of Vγ9, and wherein HC2 comprises HCDR1, HCDR2, and HCDR3 having 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 having amino acid sequences of SEQ ID NO: 12, SEQ ID NO: 13, and SEQ ID NO: 14, respectively. NO:14 LCDR1, LCDR2 and LCDR3 to form a binding site for a second antigen that specifically binds to CD123. In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the selected amino acid sequence SEQ ID NO:113, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence SEQ ID NO:114. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises the amino acid sequence SEQ ID NO:113, and the LC1 comprises the amino acid sequence SEQ ID NO:114. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HC2 and LC2: the HC2 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 15, and the LC2 comprises an amino acid sequence that is at least 95% identical 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 the following HC2 and LC2: the HC2 comprises the amino acid sequence of SEQ ID NO: 15, and the LC2 comprises the amino acid sequence of SEQ ID NO: 16.

[0109] Also provided herein are isolated anti-TRGV9 / anti-CD123 bispecific antibodies or antigen-binding fragments thereof comprising: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 119, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR3 having amino acid sequences of SEQ ID NO: 120, SEQ ID NO: 121, and SEQ ID NO: 122, respectively, to form a binding site that specifically binds to a first antigen of Vγ9, and wherein HC2 comprises HCDR1, HCDR2, and HCDR3 having 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 having amino acid sequences of SEQ ID NO: 12, SEQ ID NO: 13, and SEQ ID NO: 14, respectively. NO:14 LCDR1, LCDR2 and LCDR3 to form a binding site for a second antigen that specifically binds to CD123. In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the selected amino acid sequence SEQ ID NO:123, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence SEQ ID NO:124. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises the amino acid sequence SEQ ID NO:123, and the LC1 comprises the amino acid sequence SEQ ID NO:124. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HC2 and LC2: the HC2 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 15, and the LC2 comprises an amino acid sequence that is at least 95% identical 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 the following HC2 and LC2: the HC2 comprises the amino acid sequence of SEQ ID NO: 15, and the LC2 comprises the amino acid sequence of SEQ ID NO: 16.

[0110] Also provided herein are isolated anti-TRGV9 / anti-CD123 bispecific antibodies or antigen-binding fragments thereof comprising: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 129, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR3 having amino acid sequences of SEQ ID NO: 130, SEQ ID NO: 131, and SEQ ID NO: 132, respectively, to form a binding site that specifically binds to a first antigen of Vγ9, and wherein HC2 comprises HCDR1, HCDR2, and HCDR3 having 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 having amino acid sequences of SEQ ID NO: 12, SEQ ID NO: 13, and SEQ ID NO: 14, respectively. NO:14 LCDR1, LCDR2 and LCDR3 to form a binding site for a second antigen that specifically binds to CD123. In one embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the selected amino acid sequence SEQ ID NO:133, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence SEQ ID NO:134. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises the amino acid sequence SEQ ID NO:133, and the LC1 comprises the amino acid sequence SEQ ID NO:134. In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises the following HC2 and LC2: the HC2 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 15, and the LC2 comprises an amino acid sequence that is at least 95% identical 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 the following HC2 and LC2: the HC2 comprises the amino acid sequence of SEQ ID NO: 15, and the LC2 comprises the amino acid sequence of SEQ ID NO: 16.

[0111] In another embodiment, TRGV9 is located on the surface of a γδ T cell.

[0112] In another embodiment, CD123 is located on the surface of a tumor cell or a CD34+ stem cell.

[0113] In another embodiment, the bispecific antibody binds to TRGV9 present on the surface of a γδ T cell and to CD123 on the surface of the cancer cell, resulting in killing of the cancer cell.

[0114] In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof comprises humanized HCl and humanized LC1.

[0115] In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment comprises humanized HC2 and humanized LC2.

[0116] In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or its antigen-binding fragment is an IgG1, IgG2, IgG3 or IgG4 isotype. In a specific embodiment, the bispecific antibody is an IgG4 isotype.

[0117] In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof is expressed in vitro at an EC of less than about 500 pM. 50 Induces γδ T cell-dependent cytotoxicity of cancer cells.

[0118] In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof is expressed in vitro at an EC of less than about 300 pM. 50 Induces γδ T cell-dependent cytotoxicity of cancer cells.

[0119] In another embodiment, the isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof is expressed in vitro at an EC of less than about 160 pM. 50 Induces γδ T cell-dependent cytotoxicity of cancer cells.

[0120] In one embodiment, ECs are assessed using a mixture of γδ T effector cells and Kasumi3 AML target cells. 50 .

[0121] In another embodiment, the ratio of effector cells to target cells is from about 0.01 to 1 to about 5 to 1.

[0122] In yet another embodiment, the ratio of effector cells to target cells is from about 0.1 to 1 to about 2 to 1.

[0123] In a specific embodiment, the ratio of effector cells to target cells is about 1:1.

[0124] Also provided are methods for preparing the isolated anti-TRGV9 / anti-CD123 bispecific antibodies or antigen-binding fragments provided herein, comprising culturing a cell comprising a nucleic acid encoding the anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof under conditions that produce the bispecific antibody or antigen-binding fragment thereof, and recovering the bispecific antibody or antigen-binding fragment thereof.

[0125] In another aspect, provided herein is an isolated TRGV9 bispecific antibody or antigenic epitope-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigenic epitope-binding fragment thereof comprises a binding site for a first antigen and a binding site for a second antigen, wherein the binding site for the first antigen binds a TRGV9 epitope on a γδ T cell and the binding site for the second antigen binds an epitope of the second antigen on the surface of a target cell, and binding to the TRGV9 epitope on the γδ T cell and binding to the second antigen epitope on the target cell results in killing of the target cell.

[0126] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises:

[0127] a.HC1;

[0128] b.HC2;

[0129] c.LC1; and

[0130] d.LC2,

[0131] wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having the following amino acid sequence:

[0132] i. SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively,

[0133] ii. SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 31, respectively,

[0134] iii. SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 32, respectively, or

[0135] iv. SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 33, respectively,

[0136] and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, respectively, to form a binding site for the first antigen, and wherein HC2 and LC2 form a binding site for the second antigen epitope. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 and LC1: the HC1 comprises an amino acid sequence that is at least 95% identical to an amino acid sequence selected from SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:8. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 and LC1: the HC1 comprises an amino acid sequence selected from SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36, and the LC1 comprises the amino acid sequence of SEQ ID NO:8.

[0137] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form the binding site for a second antigen epitope. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 and LC1 such that the HC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 7, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 8. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO:7, and the LC1 comprises the amino acid sequence of SEQ ID NO:8.

[0138] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form the binding site for a second antigen epitope. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 and LC1 such that the HC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 34, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 8. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 34, and the LC1 comprises the amino acid sequence of SEQ ID NO: 8.

[0139] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form the binding site for a second antigen epitope. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 and LC1 such that the HC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 35, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 8. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 35, and the LC1 comprises the amino acid sequence of SEQ ID NO: 8.

[0140] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form the binding site for a second antigen epitope. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 and LC1 such that the HC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 36, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 8. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 36, and the LC1 comprises the amino acid sequence of SEQ ID NO: 8.

[0141] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 76, and SEQ ID NO: 3, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 77, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form the binding site for a second antigen epitope. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 and LC1 such that the HC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 65, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 66. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl 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 following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 67, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 68. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 67, and the LC1 comprises the amino acid sequence of SEQ ID NO: 68.

[0142] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 60, SEQ ID NO: 61, and SEQ ID NO: 62, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 64, and SEQ ID NO: 6, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form the binding site for a second antigen epitope. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 and LC1 such that the HC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 65, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 66. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl 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 following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 67, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 68. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 67, and the LC1 comprises the amino acid sequence of SEQ ID NO: 68.

[0143] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 92, SEQ ID NO: 93, and SEQ ID NO: 94, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form the binding site for a second antigen epitope. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises HC1 and LC1 such that the HC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 95, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 96. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO:95, and the LC1 comprises the amino acid sequence of SEQ ID NO:96.

[0144] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 98, SEQ ID NO: 99, and SEQ ID NO: 100, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 103, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form the binding site for an epitope of a second antigen. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 104, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 105. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 104, and the LC1 comprises the amino acid sequence of SEQ ID NO: 105.

[0145] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 109, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 110, SEQ ID NO: 111, and SEQ ID NO: 112, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form the binding site for an epitope of a second antigen. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 113, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 114. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 113, and the LC1 comprises the amino acid sequence of SEQ ID NO: 114.

[0146] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 119, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 120, SEQ ID NO: 121, and SEQ ID NO: 122, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form the binding site for an epitope of a second antigen. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 123, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 124. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 123, and the LC1 comprises the amino acid sequence of SEQ ID NO: 124.

[0147] In one embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 129, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 130, SEQ ID NO: 131, and SEQ ID NO: 132, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form the binding site for an epitope of a second antigen. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 133, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 134. In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises the following HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 133, and the LC1 comprises the amino acid sequence of SEQ ID NO: 134.

[0148] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises humanized HCl and humanized LC.

[0149] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment binds to a CD123 epitope.

[0150] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises the following HC2 and LC2: the HC2 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 15, and the LC2 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 16.

[0151] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment comprises the following HC2 and LC2: the HC2 comprises the amino acid sequence of SEQ ID NO:15, and the LC2 comprises the amino acid sequence of SEQ ID NO:16.

[0152] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof is of IgG1, IgG2, IgG3 or IgG4 isotype. In a specific embodiment, the bispecific antibody or antigen-binding fragment thereof is of IgG4 isotype.

[0153] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof is expressed in vitro at an EC of less than about 500 pM. 50 Induces γδ T cell-dependent cytotoxicity of cancer cells.

[0154] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof is expressed in vitro at an EC of less than about 300 pM. 50 Induces γδ T cell-dependent cytotoxicity of cancer cells.

[0155] In another embodiment, the TRGV9 bispecific antibody or antigen-binding fragment thereof is expressed in vitro at an EC of less than about 160 pM. 50 Induces γδ T cell-dependent cytotoxicity of cancer cells.

[0156] In one embodiment, ECs are assessed using a mixture of γδ T effector cells and Kasumi3 AML target cells. 50 .

[0157] In another embodiment, the ratio of effector cells to target cells is from about 0.01 to 1 to about 5 to 1. In another embodiment, the ratio of effector cells to target cells is from about 0.1 to 1 to about 2 to 1. In a specific embodiment, the ratio of effector cells to target cells is about 1:1.

[0158] Also provided is an isolated γδ T cell bispecific antibody or antigen-binding fragment thereof, wherein the isolated γδ T cell bispecific antibody or antigen-binding fragment thereof comprises a binding site for a first antigenic epitope and a binding site for a second antigenic epitope, wherein the binding site for the first antigenic epitope binds a first antigen on a γδ T cell and the binding site for the second antigenic epitope binds the second antigenic epitope on the surface of a target cell, and binding to the first antigenic epitope on the γδ T cell and binding to the second antigenic epitope on the target cell results in killing the target cell.

[0159] In another aspect, provided herein is an isolated nucleic acid encoding a TRGV9 bispecific antibody or an antigen-binding fragment thereof, the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprising:

[0160] a.HC1;

[0161] b.HC2;

[0162] c.LC1; and

[0163] d.LC2,

[0164] wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having the following amino acid sequence:

[0165] i. SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively,

[0166] ii. SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 31, respectively,

[0167] iii. SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 32, respectively, or

[0168] iv. SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 33, respectively,

[0169] and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 and LC1: the HC1 comprising an amino acid sequence at least 95% identical to an amino acid sequence selected from SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36, and the LC1 comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:8. In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising HC1 and LC1: the HC1 comprising an amino acid sequence selected from SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35, or SEQ ID NO:36, and the LC1 comprising the amino acid sequence of SEQ ID NO:8.

[0170] In another aspect, provided herein is an isolated nucleic acid encoding a TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HCl; (b) HC2; (c) LC1; and (d) LC2; wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising an HCl comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 7 and an LC1 comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 8. In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising an HCl comprising the amino acid sequence of SEQ ID NO: 7 and an LC1 comprising the amino acid sequence of SEQ ID NO: 8.

[0171] In another aspect, provided herein is an isolated nucleic acid encoding a TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HCl; (b) HC2; (c) LC1; and (d) LC2; wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 31, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising an HCl comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 34 and an LC1 comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 8. In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising an HCl comprising the amino acid sequence of SEQ ID NO: 34 and an LC1 comprising the amino acid sequence of SEQ ID NO: 8.

[0172] In another aspect, provided herein is an isolated nucleic acid encoding a TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HCl; (b) HC2; (c) LC1; and (d) LC2; wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 32, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising an HCl comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 35 and an LC1 comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 8. In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising an HCl comprising the amino acid sequence of SEQ ID NO: 35 and an LC1 comprising the amino acid sequence of SEQ ID NO: 8.

[0173] In another aspect, provided herein is an isolated nucleic acid encoding a TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HCl; (b) HC2; (c) LC1; and (d) LC2; wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 33, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising an HCl comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 36 and an LC1 comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 8. In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising an HCl comprising the amino acid sequence of SEQ ID NO: 36 and an LC1 comprising the amino acid sequence of SEQ ID NO: 8.

[0174] In another aspect, provided herein is an isolated nucleic acid encoding a TRGV9 bispecific antibody or antigen-binding fragment thereof, comprising: (a) HCl; (b) HC2; (c) LC1; and (d) LC2; wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 76, and SEQ ID NO: 3, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 77, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising an HCl comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 65 and an LC1 comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 66. In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising an HCl comprising an amino acid sequence of SEQ ID NO: 65 and an LC1 comprising an amino acid sequence of SEQ ID NO: 66. In one embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising an HCl comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 67 and an LC1 comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 68. In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising the following HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 67, and the LC1 comprises the amino acid sequence of SEQ ID NO: 68.

[0175] In another aspect, provided herein is an isolated nucleic acid encoding a TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HCl; (b) HC2; (c) LC1; and (d) LC2; wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 60, SEQ ID NO: 61, and SEQ ID NO: 62, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 64, and SEQ ID NO: 6, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising an HCl comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 65 and an LC1 comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 66. In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising an HCl comprising an amino acid sequence of SEQ ID NO: 65 and an LC1 comprising an amino acid sequence of SEQ ID NO: 66. In one embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising an HCl comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 67 and an LC1 comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 68. In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising the following HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 67, and the LC1 comprises the amino acid sequence of SEQ ID NO: 68.

[0176] In another aspect, provided herein is an isolated nucleic acid encoding a TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HCl; (b) HC2; (c) LC1; and (d) LC2; wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 92, SEQ ID NO: 93, and SEQ ID NO: 94, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising an HCl comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 95 and an LC1 comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 96. In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising an HCl comprising the amino acid sequence of SEQ ID NO: 95 and an LC1 comprising the amino acid sequence of SEQ ID NO: 96.

[0177] In another aspect, provided herein is an isolated nucleic acid encoding a TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HCl; (b) HC2; (c) LC1; and (d) LC2; wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 98, SEQ ID NO: 99, and SEQ ID NO: 100, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 103, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising an HCl comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 104 and an LC1 comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 105. In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising an HCl comprising the amino acid sequence of SEQ ID NO: 104 and an LC1 comprising the amino acid sequence of SEQ ID NO: 105.

[0178] In another aspect, provided herein is an isolated nucleic acid encoding a TRGV9 bispecific antibody or antigen-binding fragment thereof, comprising: (a) HCl; (b) HC2; (c) LC1; and (d) LC2; wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 109, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 110, SEQ ID NO: 111, and SEQ ID NO: 112, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising an HCl comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 113 and an LC1 comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 114. In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising an HCl comprising the amino acid sequence of SEQ ID NO: 113 and an LC1 comprising the amino acid sequence of SEQ ID NO: 114.

[0179] In another aspect, provided herein is an isolated nucleic acid encoding a TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HCl; (b) HC2; (c) LC1; and (d) LC2; wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 119, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 120, SEQ ID NO: 121, and SEQ ID NO: 122, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising an HCl comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 123 and an LC1 comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 124. In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising an HCl comprising the amino acid sequence of SEQ ID NO: 123 and an LC1 comprising the amino acid sequence of SEQ ID NO: 124.

[0180] In another aspect, provided herein is an isolated nucleic acid encoding a TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HCl; (b) HC2; (c) LC1; and (d) LC2; wherein HCl associates with LC1 and HC2 associates with LC2, and wherein HCl comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 129, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 130, SEQ ID NO: 131, and SEQ ID NO: 132, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen. In one embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising an HCl comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 133 and an LC1 comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 134. In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising an HCl comprising the amino acid sequence of SEQ ID NO: 133 and an LC1 comprising the amino acid sequence of SEQ ID NO: 134.

[0181] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising a binding site comprising a first antigen that binds to TRGV9 on a γδ T cell.

[0182] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody comprising a binding site that binds to a second antigen that is a cancer antigen present on the surface of a cancer cell.

[0183] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody, wherein the bispecific antibody binds to TRGV9 present on the surface of a γδ T cell and to the cancer antigen present on the surface of the cancer cell, resulting in killing of the cancer cell.

[0184] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody wherein HCl and LC1 are humanized.

[0185] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody wherein HC2 and LC2 bind to CD123.

[0186] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody, wherein the bispecific antibody or antigen-binding fragment thereof is of the IgG1, IgG2, IgG3, or IgG4 isotype.

[0187] In a specific embodiment, the bispecific antibody or antigen-binding fragment thereof is of the IgG4 isotype.

[0188] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody, wherein the bispecific antibody or antigen-binding fragment thereof is expressed in vitro at an EC of less than about 500 pM. 50 Induces γδ T cell-dependent cytotoxicity of cancer cells.

[0189] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody, wherein the bispecific antibody or antigen-binding fragment thereof is expressed in vitro at an EC of less than about 300 pM. 50 Induces γδ T cell-dependent cytotoxicity of cancer cells.

[0190] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody, wherein the bispecific antibody or antigen-binding fragment thereof is expressed in vitro at an EC of less than about 160 pM. 50 Induces γδ T cell-dependent cytotoxicity of cancer cells.

[0191] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody, wherein EC is assessed using a mixture of γδ T effector cells and Kasumi3 AML target cells. 50 .

[0192] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody, wherein the ratio of effector cells to target cells is about 0.01 to 1 to about 5 to 1. In one embodiment, the ratio of effector cells to target cells is about 0.1 to 1 to about 2 to 1. In yet another embodiment, the ratio of effector cells to target cells is about 1:1.

[0193] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody, wherein the bispecific antibody or antigen-binding fragment thereof is multivalent.

[0194] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody, wherein the bispecific antibody or antigen-binding fragment thereof is capable of binding to at least three antigens.

[0195] In another embodiment, the isolated nucleic acid encodes a TRGV9 bispecific antibody, wherein the bispecific antibody or antigen-binding fragment thereof is capable of binding to at least five antigens.

[0196] Also provided are vectors comprising the isolated nucleic acids provided herein.

[0197] Also provided are host cells comprising the vectors provided herein.

[0198] Also provided are kits comprising the vectors provided herein and packaging for the vectors.

[0199] Provided herein are pharmaceutical compositions comprising: (A) an isolated TRGV9 bispecific antibody or an antigen-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or an antigen-binding fragment thereof comprises:

[0200] a.HC1;

[0201] b.HC2;

[0202] c.LC1; and

[0203] d. LC2, wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having the following amino acid sequence:

[0204] i. SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively,

[0205] ii. SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 31, respectively,

[0206] iii. SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 32, respectively, or

[0207] iv. SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 33, respectively,

[0208] and wherein LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen;

[0209] and (B) a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HCl and LC1: the HCl comprising an amino acid sequence at least 95% identical to an amino acid sequence selected from SEQ ID NO: 7, SEQ ID NO: 34, SEQ ID NO: 35, or SEQ ID NO: 36, and the LC1 comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 8. In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HCl and LC1: the HCl having an amino acid sequence selected from SEQ ID NO: 7, SEQ ID NO: 34, SEQ ID NO: 35, or SEQ ID NO: 36, and the LC1 comprising the amino acid sequence of SEQ ID NO: 8.

[0210] Also provided herein are pharmaceutical compositions comprising: (A) an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3, respectively; and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen; and (B) a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HCl and LC1: the HCl comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 7, and the LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 8. In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 7, and the LC1 comprises the amino acid sequence of SEQ ID NO: 8.

[0211] Also provided herein are pharmaceutical compositions comprising: (A) an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:31, respectively; and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen; and (B) a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HCl and LC1: the HCl comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 34, and the LC1 comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 8. In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 34, and the LC1 comprises the amino acid sequence of SEQ ID NO: 8.

[0212] Also provided herein are pharmaceutical compositions comprising: (A) an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:32, respectively; and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen; and (B) a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HCl and LC1: the HCl comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 35, and the LC1 comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 8. In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 35, and the LC1 comprises the amino acid sequence of SEQ ID NO: 8.

[0213] Also provided herein are pharmaceutical compositions comprising: (A) an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:33, respectively; and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen; and (B) a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HCl and LC1: the HCl comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 36, and the LC1 comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 8. In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 36, and the LC1 comprises the amino acid sequence of SEQ ID NO: 8.

[0214] Also provided herein are pharmaceutical compositions comprising: (A) an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 1, SEQ ID NO: 76, and SEQ ID NO: 3, respectively; and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 77, SEQ ID NO: 5, and SEQ ID NO: 6, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen; and (B) a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HCl and LC1: the HCl comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 65, and the LC1 comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 66. In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 65, and the LC1 comprises the amino acid sequence of SEQ ID NO: 66. In one embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HCl and LC1: the HCl comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 67, and the LC1 comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 68. In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising the following HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 67, and the LC1 comprises the amino acid sequence of SEQ ID NO: 68.

[0215] Also provided herein are pharmaceutical compositions comprising: (A) an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 60, SEQ ID NO: 61, and SEQ ID NO: 62, respectively; and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 63, SEQ ID NO: 64, and SEQ ID NO: 6, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen; and (B) a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HCl and LC1: the HCl comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 65, and the LC1 comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 66. In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 65, and the LC1 comprises the amino acid sequence of SEQ ID NO: 66. In one embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HCl and LC1: the HCl comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 67, and the LC1 comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 68. In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising the following HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 67, and the LC1 comprises the amino acid sequence of SEQ ID NO: 68.

[0216] Also provided herein are pharmaceutical compositions comprising: (A) an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 89, SEQ ID NO: 90, and SEQ ID NO: 91, respectively; and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 92, SEQ ID NO: 93, and SEQ ID NO: 94, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen; and (B) a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HCl and LC1: the HCl comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 95, and the LC1 comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 96. In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 95, and the LC1 comprises the amino acid sequence of SEQ ID NO: 96.

[0217] Also provided herein are pharmaceutical compositions comprising: (A) an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 98, SEQ ID NO: 99, and SEQ ID NO: 100, respectively; and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 101, SEQ ID NO: 102, and SEQ ID NO: 103, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen; and (B) a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HCl and LC1: the HCl comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 104, and the LC1 comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 105. In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 104, and the LC1 comprises the amino acid sequence of SEQ ID NO: 105.

[0218] Also provided herein are pharmaceutical compositions comprising: (A) an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 107, SEQ ID NO: 108, and SEQ ID NO: 109, respectively; and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 110, SEQ ID NO: 111, and SEQ ID NO: 112, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen; and (B) a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HCl and LC1: the HCl comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 113, and the LC1 comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 114. In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 113, and the LC1 comprises the amino acid sequence of SEQ ID NO: 114.

[0219] Also provided herein are pharmaceutical compositions comprising: (A) an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 117, SEQ ID NO: 118, and SEQ ID NO: 119, respectively; and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 120, SEQ ID NO: 121, and SEQ ID NO: 122, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen; and (B) a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HCl and LC1: the HCl comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 123, and the LC1 comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 124. In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 123, and the LC1 comprises the amino acid sequence of SEQ ID NO: 124.

[0220] Also provided herein are pharmaceutical compositions comprising: (A) an isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprising: (a) HC1; (b) HC2; (c) LC1; and (d) LC2; wherein HC1 associates with LC1 and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2, and HCDR3 having amino acid sequences of SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 129, respectively; and LC1 comprises LCDR1, LCDR2, and LCDR2 having amino acid sequences of SEQ ID NO: 130, SEQ ID NO: 131, and SEQ ID NO: 132, respectively, to form a binding site for a first antigen, and wherein HC2 and LC2 form a binding site for a second antigen; and (B) a pharmaceutically acceptable carrier. In one embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HCl and LC1: the HCl comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 133, and the LC1 comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 134. In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising HCl and LC1: the HCl comprises the amino acid sequence of SEQ ID NO: 133, and the LC1 comprises the amino acid sequence of SEQ ID NO: 134.

[0221] In another embodiment, the pharmaceutical composition comprises a bispecific antibody comprising a binding site that binds to a first antigen of TRGV9 on γδ T cells.

[0222] In another embodiment, the pharmaceutical composition comprises a bispecific antibody, wherein the second antigen binding site binds to a cancer antigen present on the surface of a cancer cell.

[0223] In another embodiment, the pharmaceutical composition comprises a bispecific antibody, wherein the bispecific antibody binds to TRGV9 present on the surface of γδ T cells and to the cancer antigen present on the surface of the cancer cell, resulting in killing of the cancer cell.

[0224] In another embodiment, the pharmaceutical composition comprises a bispecific antibody wherein HCl and LC1 are humanized.

[0225] In another embodiment, the pharmaceutical composition comprises a bispecific antibody wherein HC2 and LC2 bind to CD123.

[0226] In another embodiment, the pharmaceutical composition comprises a bispecific antibody, wherein the bispecific antibody or antigen-binding fragment thereof is of IgG1, IgG2, IgG3 or IgG4 isotype.

[0227] Also provided is a method for directing Vγ9-expressing γδT cells to cancer cells, the method comprising contacting Vγ9-expressing γδT cells with a pharmaceutical composition provided herein, wherein contacting the Vγ9-expressing γδT cells with the pharmaceutical composition directs the Vγ9-expressing γδT cells to cancer cells.

[0228] Also provided are methods of inhibiting the growth or proliferation of a cancer cell that expresses a cancer antigen on its cell surface, the method comprising contacting the cancer cell with a pharmaceutical composition provided herein, wherein contacting the cancer cell with the pharmaceutical composition inhibits the growth or proliferation of the cancer cell.

[0229] In one embodiment, the cancer cell is contacted with an anti-TRGV9 bispecific antibody or antigen-binding fragment thereof in the presence of γδ T cells expressing Vγ9.

[0230] Also provided is a method for treating cancer in a subject in need thereof, the method comprising:

[0231] a. Identifying subjects in need of cancer treatment; and

[0232] b. administering a pharmaceutical composition provided herein to a subject in need thereof, wherein administering the pharmaceutical composition to a subject in need thereof treats the cancer in the subject.

[0233] Also provided is a method for activating Vγ9-expressing γδT cells, the method comprising contacting the Vγ9-expressing γδT cells with a pharmaceutical composition provided herein, wherein contacting the Vγ9-expressing γδT cells with the pharmaceutical composition results in increased expression of CD69, CD25 and / or granzyme B compared to control Vγ9-expressing γδT cells.

[0234] Also provided is a method of preparing the pharmaceutical composition provided herein, comprising combining the bispecific antibody or antigen-binding fragment thereof with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition. BRIEF DESCRIPTION OF THE DRAWINGS

[0235] The foregoing summary, as well as the following detailed description of certain embodiments of the present application, will be better understood when read in conjunction with the accompanying drawings. However, it should be understood that this patent application is not limited to the precise embodiments shown in the drawings.

[0236] Figure 1Schematic diagram showing binding of anti-TRGV9 / anti-tumor-associated antigen (TAA) bispecific antibodies to recruit γδ T cells to cancer cells and induce cancer cell death.

[0237] Figure 2 Shown are graphs demonstrating that zoledronic acid selectively expands Vγ9Vδ2 T cells from whole peripheral blood mononuclear cells (PBMCs).

[0238] Figures 3A to 3E Phenotypic characterization of Vγ9+γδ T cells is shown. Figure 3A Schematic diagram of the gate used to describe γδ T cell differentiation is shown (left panel). Representative FACS dot plots show Vγ9 from fresh PBMC (left panel) and PBMC cultured ex vivo with zoledronic acid + IL-2 + IL-15 for 14 days (right panel). + Differentiation map of γδ T cells. The numbers in the quadrants reflect fresh Vγ9 + Frequency of the respective populations of γδ T cells and activated these cells (mean ± SEM). The data represented are means (± SEM) of five donors (n=5) from a single experiment. Figure 3B In representative dot plots, numbers are shown reflecting the expression of Vγ9 positive for the corresponding activation markers from fresh PBMC (upper row) or PBMC cultured with zoledronic acid + IL-2 + IL-15 for 14 days (lower row). + Frequency of γδδ T cells (mean ± SEM). Data presented are the mean (± SEM) of CD62L, CD69, and CD44 expression data from seven donors (n=7) from two independent experiments. n=5 donors were used for NKG2D expression data, and 2 donors were used for CD45RO and CD71 expression data, each from a single experiment. Figure 3C Numbers are shown above the gates in the dot plots depicting Vγ9 positive for the corresponding inhibitory receptor surface expression from fresh PBMC (upper row) or PBMC cultured with zoledronic acid + IL-2 + IL-15 for 14 days (lower row). + Frequency of γδ T cells (mean ± SEM). Data shown here are the mean (± SEM) of PD1, CTLA4, TIGIT and LAG3 surface expression from two independent experiments for five donors (n=5), and the mean (± SEM) of 2B4 and TIM3 surface expression data from two independent experiments for seven donors (n=7). Figure 3D Representative FACS dot plots showing Vγ9 expressing intracellular granzyme B (left column) and perforin (right column) from fresh PBMC (upper row) and PBMC cultured ex vivo for 14 days with zoledronic acid + IL-2 + IL-15 (lower row) are shown. +Frequency of γδ T cells (mean ± SEM). The data depicted are the mean (± SEM) of granzyme B data and perforin data from two independent experiments for four (n=4) and seven (n=7) donors, respectively. Figure 3E The bars shown represent the mean (±SEM) concentrations (pg / mL) of cytokines in cell culture supernatants when PBMCs were cultured with zoledronic acid + IL-2 + IL-15 on day 0 and day 14. The data presented are the mean (±SEM) of four wells (n=4) from a single donor.

[0239] Figure 4 The histogram shown demonstrates that VG1 (anti-TRGV9 / anti-CD123 bispecific antibody) recruits Vγ9+ T cells, as confirmed by the formation of conjugates between γδ T cells and Kasumi-3 cells.

[0240] Figures 5A to 5C The graphs shown show the effect of VG1 (anti-TRGV9 / anti-CD123 bispecific antibody) bispecific antibody-mediated γδ T cell activation at different effector cell to target cell ratios ( Figure 5A is 1:1; for Figure 5B is 5:1; for Figure 5C The cytotoxicity of the cells was 10:1) against Kasumi-3 cells.

[0241] Figures 6A to 6C The graph shows CD69 expression on Vγ9+γδT cells, non-Vγ9+γδT cells and Pan-T cells (non-γδT cells) co-cultured with Kasumi-3 cells and VG1, VG3 or not co-cultured with bispecific antibodies ( Figure 6A ), CD25 expression ( Figure 6B ) or granzyme B expression ( Figure 6C ).

[0242] Figure 7 Selective cell binding of anti-TAA1 (TAA mIgG2a, TAA1B1) to transfected Jurkat cells is shown. 50 TAA1B1 did not show any significant binding to a control ALL cell line that endogenously expresses an irrelevant protein (TAA1-NULL) but does not express TAA1.

[0243] Figure 8 Selective protein binding of anti-TAA1 (TAA1 mIgG2a, TAA1B1) to recombinant TAA1 protein (TAA1W16) was shown. TAA1B1 did not show any significant binding to an unrelated protein (TAA1-NULL-W16).

[0244] Figure 9 Shown are phenotyping of Vg9+ cells from a healthy donor used for cytotoxicity studies of the TAA1 x Vγ9 bispecific (TAA1B50).

[0245] Figure 10 The anti-TRGV9 / anti-TAA1 bispecific antibody is shown to mediate γδ T cell cytotoxicity against TAA1-expressing Jurkat cells in vitro. The cytotoxicity values ​​presented here were subtracted from the basal cytotoxicity values ​​observed in the absence of the bispecific antibody. EC 50 Values ​​were calculated as described in Methods. Representative data shown here are from a single experiment.

[0246] Figure 11 Figure 2 shows the cytotoxicity mediated by bispecific antibodies. In the presence of Vγ9xTAA1 at a specified concentration, the Vγ9Vδ2 T cells from various donors' amplification and enrichment were used to induce cytotoxicity (E:T ratio 1:1) to Jurkat cell lines. The assay was carried out for 16 hours. The percentage of dead target cells under various conditions is provided in the accompanying drawings.

[0247] Figure 12 The anti-TRGV9 / anti-TAA2 bispecific antibody (TAA2V9B106(B3)) is shown to bind to γδ T cells (left panel) and mediate γδ T cell cytotoxicity against TAA2-expressing H929 cells in vitro (right panel). 50 Values ​​were calculated as described in Methods. Representative data shown here are from a single experiment.

[0248] Figure 13 Anti-TRGV9 / anti-TAA2 bispecific antibody (HC1: VG9B420-LH-scFv; HC2: TAA2-Fab (TAA2V9B71.001)) is shown to bind to γδ T cells (left panel) and mediate γδ T cell cytotoxicity against TAA2-expressing H929 cells in vitro (right panel). 50 Values ​​were calculated as described in Methods. Representative data shown here are from a single experiment.

[0249] Figure 14 The anti-TRGV9 / anti-TAA2 bispecific antibody (VG9SB10SC1087_P18_D08-Fab RF, TAA2-scFv (TAA2V9B100.001)) is shown to bind to γδ T cells (left panel) and mediate γδ T cell cytotoxicity against TAA2-expressing H929 cells in vitro (right panel). 50 Values ​​were calculated as described in Methods. Representative data shown here are from a single experiment.

[0250] Figure 15 The anti-TRGV9 / anti-TAA2 bispecific antibody (VG9SB10SC1087_P18_C12-Fab RF, TAA2-scFv (TAA2V9B101.001)) is shown to bind to γδ T cells (left panel) and mediate γδ T cell cytotoxicity against TAA2-expressing H929 cells in vitro (right panel). 50 Values ​​were calculated as described in Methods. Representative data shown here are from a single experiment.

[0251] Figure 16 The anti-TRGV9 / anti-TAA2 bispecific antibody (VG9SB10SC1087_P19_C03-Fab RF, TAA2-scFv (TAA2V9B103.001)) is shown to bind to γδ T cells (left panel) and mediate γδ T cell cytotoxicity against TAA2-expressing H929 cells in vitro (right panel). 50 Values ​​were calculated as described in Methods. Representative data shown here are from a single experiment. DETAILED DESCRIPTION

[0252] Various publications, articles, and patents are cited or described in the Background and throughout the specification; each of these references is incorporated herein by reference in its entirety. The discussion of documents, acts, materials, devices, articles, and the like included in this specification is intended to provide a context for the present invention. Such discussion is not an admission that any or all of these matters form part of the prior art with respect to any invention disclosed or claimed.

[0253] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. Otherwise, certain terms used herein have the meanings described in this specification.

[0254] It must be noted that as used herein and in the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0255] Unless otherwise indicated, any numerical value, such as a concentration or concentration range described herein, is understood to be modified by the term "about" in all cases. Therefore, numerical values ​​generally include the value ± 10%. For example, a concentration of 1 mg / mL includes 0.9 mg / mL to 1.1 mg / mL. Similarly, a concentration range of 1% to 10% (w / v) includes 0.9% (w / v) to 11% (w / v). Unless the context clearly indicates otherwise, as used herein, the numerical range used explicitly includes all possible subranges, all individual values ​​within the range, including integers within such ranges and fractions within the range.

[0256] Unless otherwise indicated, the term "at least" preceding a series of elements should be understood to refer to every element in the series. Those skilled in the art will recognize, or be able to ascertain using only routine experimentation, multiple equivalents to the specific embodiments described herein. Such equivalents are intended to be encompassed by the present invention.

[0257] As used herein, the terms "comprises," "including," "having," or "containing," or any other variations thereof, should be understood to mean the inclusion of the stated integer or groups of integers but not the exclusion of any other integer or groups of integers, and are intended to be non-exclusive or open-ended. For example, a composition, mixture, process, method, article, or apparatus that comprises a list of elements is not necessarily limited to only those elements but may include other elements not expressly listed or inherent to such composition, mixture, process, method, article, or apparatus. Furthermore, unless expressly indicated to the contrary, "or" refers to an inclusive or and not to an exclusive or. For example, condition A or B is satisfied by any of: A being true (or present) and B being false (or absent), A being false (or absent) and B being true (or present), and both A and B being true (or present).

[0258] As used herein, the connection term "and / or" between multiple listed elements is understood to include both individual options and combined options. For example, where two elements are connected by "and / or", the first option refers to the application of the first element without the second element. The second option refers to the application of the second element without the first element. The third option refers to the application of the first element and the second element together. Any of these options is understood to fall within the meaning and therefore meets the requirements of the term "and / or" as used herein. The parallel applicability of more than one option is also understood to fall within the meaning and therefore meets the requirements of the term "and / or".

[0259] As used herein, the term "consisting of" used throughout the specification and claims is intended to include any recited integer or group of integers, but does not imply that additional integers or groups of integers may be added to a specified method, structure, or composition.

[0260] As used herein, the term "consisting essentially of" as used throughout the specification and claims means including any recited integer or group of integers, and optionally including any recited integer or group of integers that does not materially change the basic or novel characteristics of the specified method, structure, or composition. See MPEP §2111.03.

[0261] As used herein, "subject" means any animal, such as a mammal, such as a human. As used herein, the term "mammal" encompasses any mammal. Examples of mammals include, but are not limited to, cows, horses, sheep, pigs, cats, dogs, mice, rats, rabbits, guinea pigs, monkeys, humans, etc., or such as humans.

[0262] It should also be understood that the terms "about," "approximately," "substantially," and similar terms used herein when referring to a dimension or characteristic of a component indicate that the dimension / characteristic being described is not a strict boundary or parameter and does not preclude minor variations that are functionally identical or similar, as understood by those of ordinary skill in the art. At a minimum, such references, including numerical parameters, will include variations using mathematical and industrial principles accepted in the art (e.g., rounding, measurement or other systematic errors, manufacturing tolerances, etc.) and will not change the least significant digit.

[0263] The terms "identical" or "percentage identity" in the context of two or more nucleic acid or polypeptide sequences (e.g., anti-TRGV9 / anti-cancer associated antigen bispecific antibodies and polynucleotides encoding these antibodies, anti-TRGV9 / anti-CD123 bispecific antibodies and polynucleotides encoding these antibodies, TRGV9 polypeptides and TRGV9 polynucleotides encoding these polypeptides, CD123 polypeptides and CD123 polynucleotides encoding these polypeptides) refer to two or more sequences or subsequences that are identical or have a specified percentage of amino acid residues or nucleotides that are the same when compared and aligned for maximum correspondence, as measured using one of the following sequence comparison algorithms or by visual inspection.

[0264] For sequence comparison, one sequence is typically used as a reference sequence to which a test sequence is compared. When using a sequence comparison algorithm, the test and reference sequences are input into a computer, subsequence coordinates are specified (if necessary), and program parameters for the sequence algorithm are specified. The sequence comparison algorithm then calculates the percent sequence identity for the test sequence relative to the reference sequence based on the specified program parameters.

[0265] Optimal alignment of sequences for comparison can be performed, for example, by the local homology algorithm of Smith and Waterman, Adv. Appl. Math. 2:482 (1981); by the homology alignment algorithm of Needleman and Wunsch, J. Mol. Biol. 48:443 (1970); by searching the similarity method of Pearson and Lipman, Proc. Nat'l. Acad. Sci. USA 85:2444 (1988); by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package (Genetics Computer Group, 575 Science Dr., Madison, WI)), or by visual inspection (see generally, Current Protocols in Molecular Biology, FM Ausubel et al., eds., Current Protocols, Greene Publishing Associates, Inc. and John A joint venture of Wiley & Sons, Inc. (1995 Supplement) (Ausubel)).

[0266] The example of an algorithm suitable for determining percentage sequence identity and sequence similarity is BLAST and BLAST 2.0 algorithm, which are described in Altschul et al. (1990) J. Mol. Biol. 215: 403-410 and Altschul et al. (1997) Nucleic Acids Res. 25: 3389-3402, respectively. Software for performing BLAST analysis is publicly available through the National Center for Biotechnology Information. The algorithm involves first identifying high-scoring sequence pairs (HSPs) by identifying short words of length W in the query sequence that match or satisfy some positive threshold score T when aligned with words of the same length in the database sequence. T is referred to as the neighborhood word score threshold (Altschul et al., supra). These initial neighborhood word hits serve as seeds for initiating searches to find longer HSPs containing them. The word hits are then extended in both directions along each sequence as far as the cumulative alignment score can be increased.

[0267] For nucleotide sequences, the cumulative score is calculated using the parameters M (reward score for a pair of matching residues; 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. Extension of the word hit in each direction stops when: the cumulative alignment score drops by the amount X from its maximum achieved value; the cumulative score becomes zero or lower due to the accumulation of one or more negative-scoring residue alignments; or the end of either sequence is reached. The BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment. The BLASTN program (for nucleotide sequences) uses a word length (W) of 11, an expectation (E) of 10, M=5, N=-4, and a comparison of both chains by default. For amino acid sequences, the BLASTP program uses a word length (W) of 3, an expectation (E) of 10, and the BLOSUM62 scoring matrix (see Henikoff and Henikoff, Proc. Natl. Acad. Sci. USA 89:10915 (1989)).

[0268] In addition to calculating percent sequence identity, the BLAST algorithm also performs a statistical analysis of the similarity between two sequences (see, e.g., Karlin and Altschul, Proc. Nat'l. Acad. Sci. USA 90:5873-5787 (1993)). One measure of similarity provided by the BLAST algorithm is the smallest sum probability (P(N)), which provides an indication of the probability that a match between two nucleotide or amino acid sequences would occur by chance. For example, a nucleic acid is considered similar to a reference sequence if the smallest sum probability in a comparison of the test nucleic acid to the reference nucleic acid is less than about 0.1, less than about 0.01, or less than about 0.001.

[0269] Another indication that two nucleic acid sequences or polypeptides are substantially identical is that the polypeptide encoded by the first nucleic acid immunologically cross-reacts with the polypeptide encoded by the second nucleic acid, as described below. Thus, a polypeptide is typically substantially identical to a second polypeptide, for example, where the two peptides differ only by conservative substitutions. Another indication that two nucleic acid sequences are substantially identical is that the two molecules hybridize to each other under stringent conditions.

[0270] As used herein, the term "polynucleotide," also referred to as "nucleic acid molecule," "nucleotide," or "nucleic acid," refers to any polyribonucleotide or polydeoxyribonucleotide, which may be unmodified RNA or DNA or modified RNA or DNA. "Polynucleotide" includes, but is not limited to, single-stranded and double-stranded DNA, DNA that is a mixture of single-stranded and double-stranded regions, single-stranded and double-stranded RNA, and RNA that is a mixture of single-stranded and double-stranded regions, hybrid molecules comprising DNA and RNA that may be single-stranded or, more typically, double-stranded or a mixture of single-stranded and double-stranded regions. In addition, "polynucleotide" refers to a triple-stranded region comprising RNA or DNA or both RNA and DNA. The term polynucleotide also includes DNA or RNA containing one or more modified bases, as well as DNA or RNA having a backbone modified for stability or other reasons. "Modified" bases include, for example, tritylated bases and rare bases such as inosine. A variety of modifications can be made to DNA and RNA; thus, "polynucleotide" includes chemically, enzymatically, or metabolically modified forms of polynucleotides that commonly occur in nature, as well as chemical forms of DNA and RNA that are unique to viruses and cells. "Polynucleotide" also includes relatively short nucleic acid chains, commonly referred to as oligonucleotides.

[0271] As used herein, the term "vector" is a replicon into which another nucleic acid segment may be operably inserted so as to bring about the replication or expression of that segment.

[0272] As used herein, the term "host cell" refers to a cell that comprises a nucleic acid molecule that this paper provides. A "host cell" can be any type of cell, for example, a primary cell, a cell in culture, or a cell from a cell line. In one embodiment, a "host cell" is a cell transfected with the nucleic acid molecule that this paper provides. In another embodiment, a "host cell" is an offspring or potential offspring of this type of transfected cell. The offspring of a cell can be identical or different from the parental cell, for example, due to mutations or environmental influences that may occur in subsequent generations or during the integration of nucleic acid molecules into the host cell genome.

[0273] As used herein, the term "expression" refers to the biosynthesis of a gene product. The term encompasses the transcription of a gene into RNA. The term also encompasses the translation of RNA into one or more polypeptides, and also encompasses all naturally occurring post-transcriptional and post-translational modifications. The expressed bispecific antibody may be in the cytoplasm of the host cell, in the extracellular environment (such as the growth medium of a cell culture), or anchored to the cell membrane.

[0274] As used herein, the terms "peptide," "polypeptide," or "protein" may refer to molecules composed of amino acids and may be recognized as proteins by one skilled in the art. Conventional single-letter or three-letter codes for amino acid residues are used herein. The terms "peptide," "polypeptide," and "protein" are used interchangeably herein to refer to polymers of amino acids of any length. The polymer may be linear or branched, it may contain modified amino acids, and it may be interspersed with non-amino acids. The term also encompasses amino acid polymers that have been modified naturally or by intervention; natural modification or intervention modification being, for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation or modification, such as conjugation to a labeling component. The definition also includes, for example, polypeptides containing one or more amino acid analogs (including, for example, non-natural amino acids, etc.), as well as other modifications known in the art.

[0275] The peptide sequences described herein are written according to common convention, wherein the N-terminal region of the peptide is on the left and the C-terminal region is on the right. Although isomeric forms of amino acids are known, unless otherwise specifically indicated, it is the L form of the amino acid represented.

[0276] Antibody

[0277] Provided herein are anti-TRGV9 antibodies or their antigen-binding fragments, nucleic acids and expression vectors encoding the antibodies, recombinant cells containing the vectors, and compositions comprising the antibodies. Also provided herein are anti-TRGV9 bispecific antibodies or their antigen-binding fragments, nucleic acids and expression vectors encoding the bispecific antibodies, recombinant cells containing the vectors, and compositions comprising the bispecific antibodies. Also provided herein are anti-TRGV9 / anti-CD123 bispecific antibodies or their antigen-binding fragments, nucleic acids and expression vectors encoding the bispecific antibodies, recombinant cells containing the vectors, and compositions comprising the bispecific antibodies. Also provided herein are methods for preparing the antibodies, and methods for treating diseases (including cancer) using the antibodies. The antibodies disclosed herein have one or more desired functional properties, including but not limited to high-affinity binding to TRGV9 and / or high-affinity binding to CD123, high specificity to TRGV9 and / or high specificity to CD123, and the ability to treat or prevent cancer when administered alone or in combination with other anticancer therapies.

[0278] As used herein, the term "antibody" is used broadly and includes immunoglobulins or antibody molecules, including human antibodies, humanized antibodies, composite antibodies and chimeric antibodies, as well as monoclonal or polyclonal antibody fragments. Generally speaking, an antibody is a protein or peptide chain that exhibits binding specificity for a specific antigen. Antibody structure is well known. Based on the amino acid sequence of the heavy chain constant domain, immunoglobulins can be designated as five major classes (i.e., IgA, IgD, IgE, IgG, and IgM). IgA and IgG are further subclassified into isotypes IgA1, IgA2, IgG1, IgG2, IgG3, and IgG4. Therefore, the antibodies provided herein can be any of the five major classes or corresponding subclasses. In certain embodiments, the antibodies provided herein are IgG1. In some embodiments, the antibodies provided herein are IgG2. In some embodiments, the antibodies provided herein are IgG3. In some embodiments, the antibodies provided herein are IgG4. Based on the amino acid sequence of their constant domains, the light chains of antibodies of vertebrate species can be designated as one of two completely different types, i.e., κ and λ. Thus, the antibodies provided herein can contain a kappa or lambda light chain constant domain.According to specific embodiments, the antibodies provided herein include a heavy chain constant region and / or a light chain constant region from a rat antibody or a human antibody.

[0279] In addition to the heavy chain constant domain and the light chain constant domain, the antibody also includes an antigen binding region consisting of a light chain variable region and a heavy chain variable region, each of which includes three domains (i.e., complementary determining regions 1 to 3; CDR1, CDR2, and CDR3). "CDR" refers to one of the three hypervariable regions (HCDR1, HCDR2, or HCDR3) within the non-framework region of the immunoglobulin (Ig or antibody) VH β sheet framework, or one of the three hypervariable regions (LCDR1, LCDR2, or LCDR3) within the non-framework region of the antibody VL β sheet framework. Therefore, CDRs are variable region sequences interspersed within the framework region sequence. CDR regions are well known to those skilled in the art and have been defined, for example, by Kabat as regions with the greatest hypervariability within the antibody variable (V) domain (Kabat et al., J. Biol. Chem. 252: 6609-6616 (1977); Kabat, Adv. Prot. Chem. 32: 1-75 (1978)). CDR region sequences have also been structurally defined by Chothia as those residues that are not part of the conserved β-sheet framework and are therefore able to adapt to different conformations (Chothia and Lesk, J. Mol. Biol. 196:901-917 (1987)). Both terms are well known in the art. CDR region sequences have also been defined by AbM, Contact, and IMGT. Exemplary CDR region sequences are shown herein, for example, in the sequence listing and in the tables provided in the examples below. The positions of CDRs within typical antibody variable regions have been determined by comparing multiple structures (Al-Lazikani et al., J. Mol. Biol. 273:927-948 (1997); Morea et al., Methods 20:267-279 (2000)). Because the number of residues within the hypervariable regions varies among different antibodies, additional residues relative to typical positions are conventionally numbered with a, b, c, etc. next to the residue number in the typical variable region numbering scheme (Al-Lazikani et al., supra, (1997)). Similarly, this nomenclature is well known to those skilled in the art.

[0280] The light chain variable region CDR1 domain is interchangeably referred to herein as LCDR1 or VL CDR1. The light chain variable region CDR2 domain is interchangeably referred to herein as LCDR2 or VL CDR2. The light chain variable region CDR3 domain is interchangeably referred to herein as LCDR3 or VL CDR3. The heavy chain variable region CDR1 domain is interchangeably referred to herein as HCDR1 or VH CDR1. The heavy chain variable region CDR2 domain is interchangeably referred to herein as HCDR2 or VH CDR2. The heavy chain variable region CDR1 domain is interchangeably referred to herein as HCDR3 or VH CDR3.

[0281] As used herein, the term "hypervariable region" (such as VH or VL) refers to a region of an antibody variable region that is highly variable in sequence and / or forms a structurally defined loop. Generally, an antibody comprises six hypervariable regions; three in VH (HCDR1, HCDR2, HCDR3) and three in VL (LCDR1, LCDR2, LCDR3). Various hypervariable region division methods are in use and are encompassed herein. "Kabat" CDRs are based on sequence variability and are the most commonly used (see, e.g., Kabat et al., Sequences of Proteins of Immunological Interest, 5th ed., Public Health Service, National Institutes of Health, Bethesda, MD. (1991)). In contrast, "Chothia" refers to the position of the structural loops (see, e.g., Chothia and Lesk, J. Mol. Biol. 196:901-917 (1987)). When numbered using the Kabat numbering convention, the ends of the Chothia CDR-HCDR1 loop vary between H32 and H34, depending on the length of the loop (this is because the Kabat numbering scheme places the insertion at H35A and H35B; if neither 35A or 35B is present, the loop ends at 32; if only 35A is present, the loop ends at 33; if both 35A and 35B are present, the loop ends at 34). The "AbM" hypervariable regions represent a compromise between the Kabat CDR and Chothia structural loops and are used by Oxford Molecular's AbM antibody modeling software (see, e.g., Martin, Antibody Engineering, Vol. 2, Chapter 3, Springer-Verlag). The "Contact" hypervariable regions are based on analysis of available complex crystal structures.

[0282] Recently, a universal numbering system has been developed and widely adopted, the ImMunoGeneTics (IMGT) Information (Lafranc et al., Dev. Comp. Immunol. 27(1):55-77(2003)). IMGT is an integrated information system specifically for immunoglobulins (IG), T cell receptors (TRs) and major histocompatibility complexes (MHCs) of humans and other vertebrates. In this article, CDRs are referred to both by amino acid sequence and by position within the light or heavy chain. Since the "position" of CDRs within the structure of the immunoglobulin variable domain is conserved between species and is present in structures called loops, CDRs and framework residues are easily identified by using a numbering system that aligns variable domain sequences based on structural features. This information can be used to transplant and replace CDR residues from immunoglobulins of one species into an acceptor framework, typically from a human antibody. An additional numbering system (AHon) has been developed by Honegger and Plückthun, J. Mol. Biol. 309:657-670(2001). The correspondence between numbering systems, including, for example, the Kabat numbering system and the IMGT unique numbering system, is well known to those skilled in the art (see, e.g., Kabat, supra; Chothia and Lesk, supra; Martin, supra; Lefranc et al., supra). The exemplary system shown herein combines Kabat and Chothia.

[0283] Exemplary IMGT Kabat AbM Chothia touch <![CDATA[V H CDR1]]> 26-35 27-38 31-35 26-35 26-32 30-35 <![CDATA[V H CDR2]]> 50-65 56-65 50-65 50-58 53-55 47-58 <![CDATA[V H CDR3]]> 95-102 105-117 95-102 95-102 96-101 93-101 <![CDATA[V L CDR1]]> 24-34 27-38 24-34 24-34 26-32 30-36 <![CDATA[V L CDR2]]> 50-56 56-65 50-56 50-56 50-52 46-55 <![CDATA[V L CDR3]]> 89-97 105-117 89-97 89-97 91-96 89-96

[0284] The hypervariable region can include the following "extended hypervariable region": 24-36 or 24-34 (LCDR1), 46-56 or 50-56 (LCDR2) and 89-97 or 89-96 (LCDR3) in VL, and 26-35 or 26-35A (HCDR1), 50-65 or 49-65 (HCDR2) and 93-102, 94-102 or 95-102 (HCDR3) in VH. CDR sequences reflecting each of the above numbering schemes are provided herein, including those provided in the sequence listing.

[0285] The term "constant region" or "constant domain" refers to the carboxyl terminal portion of the light and heavy chains that is not directly involved in the binding of the antibody to the antigen, but rather exhibits various effector functions, such as interactions with Fc receptors. The term refers to the portion of the immunoglobulin molecule that has a more conserved amino acid sequence relative to the other part of the immunoglobulin (the variable region), which contains the antigen binding site. The constant region may include the CH1, CH2, and CH3 regions of the heavy chain, and the CL region of the light chain.

[0286] The term "framework" or "FR" residues are those variable region residues that flank the CDRs. FR residues are found, for example, in chimeric antibodies, humanized antibodies, human antibodies, domain antibodies, diabodies, linear antibodies, and bispecific antibodies. FR residues are those variable domain residues other than the hypervariable region residues or CDR residues.

[0287] As used herein, the term "isolated antibody" refers to an antibody that is substantially free of other antibodies with different antigenic specificities (e.g., an isolated antibody that specifically binds to TRGV9 is substantially free of antibodies that do not bind to Vγ9; an isolated antibody that specifically binds to CD123 is substantially free of antibodies that do not bind to CD123). In addition, the isolated antibody may be substantially free of other cellular material and / or chemicals.

[0288] As used herein, the term "monoclonal antibody" refers to an antibody obtained from a population of substantially homogeneous antibodies (i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that may be present in trace amounts). The monoclonal antibodies provided herein can be prepared by hybridoma methods, phage display technology, single lymphocyte gene cloning technology, or by recombinant DNA methods. For example, monoclonal antibodies can be produced by hybridomas comprising B cells obtained from transgenic non-human animals such as transgenic mice or rats, which have a genome comprising a human heavy chain transgene and a light chain transgene.

[0289] As used herein, the term "antigen binding fragment" refers to an antibody fragment, such as a diabody, Fab, Fab', F(ab')2, an Fv fragment, a disulfide-stabilized Fv fragment (dsFv), (dsFv)2, a bispecific dsFv (dsFv-dsFv'), a disulfide-stabilized diabody (dsdiabody), a single-chain antibody molecule (scFv), a single domain antibody (sdAb), a scFv dimer (bivalent diabody), a multispecific antibody formed by a portion of an antibody comprising one or more CDRs, a camel-humped single domain antibody, a nanobody, a domain antibody, a bivalent domain antibody, or any other antibody fragment that binds to an antigen but does not have the structure of a complete antibody. The antigen binding fragment is capable of binding to the same antigen as the antigen to which the parent antibody or parent antibody fragment binds. According to specific embodiments, the antigen binding fragment comprises a light chain variable region, a light chain constant region, and the Fd segment of the heavy chain. According to other specific embodiments, the antigen binding fragment comprises Fab and F(ab').

[0290] As used herein, the term "single-chain antibody" refers to a conventional single-chain antibody in the art, which comprises a heavy chain variable region and a light chain variable region connected by a short peptide of about 15 to about 20 amino acids. As used herein, the term "single-domain antibody" refers to a conventional single-domain antibody in the art, which comprises a heavy chain variable region and a heavy chain constant region or only a heavy chain variable region.

[0291] As used herein, the term "human antibody" refers to an antibody produced by a human or an antibody having an amino acid sequence corresponding to an antibody produced by a human prepared using any technique known in the art. This definition of a human antibody includes intact or full-length antibodies, fragments thereof, and / or antibodies comprising at least one human heavy chain polypeptide and / or light chain polypeptide.

[0292] As used herein, the term "humanized antibody" refers to a non-human antibody that has been modified to increase sequence homology with a human antibody, such that the antigen-binding properties of the antibody are retained but its antigenicity in the human body is reduced.

[0293] As used herein, the term "chimeric antibody" refers to an antibody whose amino acid sequence of an immunoglobulin molecule is derived from two or more species. The variable regions of both the light and heavy chains generally correspond to those of an antibody with desired specificity, affinity, and capacity derived from one mammalian species (e.g., mouse, rat, rabbit, etc.), while the constant regions correspond to sequences of antibodies derived from another mammalian species (e.g., human) to avoid eliciting an immune response in that species.

[0294] As used herein, the term "multispecific antibody" refers to an antibody comprising multiple immunoglobulin variable domain sequences, wherein the first immunoglobulin variable domain sequence in the multiple immunoglobulin variable domain sequences has binding specificity to the first epitope, and the second immunoglobulin variable domain sequence in the multiple immunoglobulin variable domain sequences has binding specificity to the second epitope. In one embodiment, the first epitope and the second epitope do not overlap or do not substantially overlap. In one embodiment, the first epitope and the second epitope are on different antigens, such as different proteins (or different subunits of multimeric proteins). In one embodiment, the multispecific antibody comprises a third, fourth or fifth immunoglobulin variable domain. In one embodiment, the multispecific antibody is a bispecific antibody molecule, a trispecific antibody molecule or a tetraspecific antibody molecule.

[0295] As used herein, the term "bispecific antibody" refers to a multispecific antibody that is bound to no more than two epitopes or two antigens. Bispecific antibodies are characterized in that there is a first immunoglobulin variable domain sequence with binding specificity to a first epitope (e.g., an epitope on a TRGV9 antigen), and a second immunoglobulin variable domain sequence with binding specificity to a second epitope (e.g., an epitope on a tumor-associated antigen (e.g., CD123 antigen)). In one embodiment, the first epitope and the second epitope are in different antigens, such as different proteins (or different subunits of a multimeric protein). In one embodiment, the bispecific antibody comprises a heavy chain variable domain sequence and a light chain variable domain sequence with binding specificity to the first epitope and a heavy chain variable domain sequence and a light chain variable domain sequence with binding specificity to the second epitope. In one embodiment, the bispecific antibody comprises a half antibody or a fragment thereof with binding specificity to the first epitope and a half antibody or a fragment thereof with binding specificity to the second epitope. In one embodiment, the bispecific antibody comprises an scFv or a fragment thereof with binding specificity to the first epitope and an scFv or a fragment thereof with binding specificity to the second epitope. In one embodiment, the first epitope is located on TRGV9 and the second epitope is located on CD 123. In one embodiment, the first epitope is located on TRGV9 and the second epitope is located on PD-1, PD-L1, CTLA-4, EGFR, HER-2, CD19, CD20, CD3 and / or other cancer-associated immunosuppressive factors or surface antigens.

[0296] As used herein, the term "half antibody" refers to an immunoglobulin heavy chain associated with an immunoglobulin light chain. An exemplary half antibody is shown in SEQ ID NO: 17. Those skilled in the art will readily appreciate that a half antibody may encompass fragments thereof and may also have an antigen binding domain consisting of a single variable domain, such as from Camelidae.

[0297] As used herein, the term "TRGV9" refers to a polypeptide that can form a T cell receptor when expressed on the surface of γδT cells. γδT cells expressing TRGV9 belong to the first T cells developed in the human fetus and are the main γδT cell subsets in the peripheral blood cells of healthy adults. The term "TRGV9" includes any TRGV9 variants, isoforms, and species homologs that are naturally expressed by cells (including T cells) or can be expressed on cells transfected with genes or cDNAs encoding the polypeptide. Unless otherwise indicated, in specific embodiments, the TRGV9 is human TRGV9. The human TRGV9 amino acid sequence is provided by GenBank accession number NG_001336.2.

[0298] The term "CD123" refers to a molecule present on a cell that helps transmit the signal of interleukin-3 (a soluble cytokine that is very important in the immune system). CD123 may also be referred to as "interleukin-3 receptor". The receptor belongs to the type I cytokine receptor family and is a heterodimer with a unique α chain paired with a common β subunit (βc or CD131). The CD123 receptor may be present on multipotent progenitor cells and may induce tyrosine phosphorylation within the cell and promote proliferation and differentiation within the hematopoietic cell line. CD123 may also be expressed in acute myeloid leukemia (AML) subtypes. Unless otherwise indicated, the term "CD123" includes any CD123 variants, isoforms, and species homologs that are naturally expressed by cells (including T cells) or can be expressed on cells transfected with genes or cDNA encoding those polypeptides, and in a specific embodiment, "CD123" is human CD123. Human CD123 amino acid sequence is provided by GenBank accession number AY789109.1.

[0299] As used herein, an antibody that "specifically binds to TRGV9" refers to an antibody that binds to TRGV9 at a concentration of 1×10 -7 M or smaller, such as 1×10 - 8 M or smaller, 5×10 -9 M or smaller, 1×10 -9 M or smaller, 5×10 -10 M or smaller or 1×10 -10 An antibody that binds to TRGV9 (such as human TRGV9) with a KD of M or less. The term "KD" refers to the dissociation constant obtained from the ratio of Kd to Ka (i.e., Kd / Ka) and expressed as a molar concentration (M). According to the present disclosure, the KD value of an antibody can be determined using methods in the art. For example, the KD of an antibody can be determined using surface plasmon resonance, such as by using a biosensor system (e.g., system), or by using bio-layer interferometry techniques (such as the Octet RED96 system).

[0300] As used herein, an antigen-binding domain or antigen-binding fragment that "specifically binds to a tumor-associated antigen" refers to a -7 M or smaller, such as 1×10 -8 M or smaller, 5×10 -9 M or smaller, 1×10 -9 M or smaller, 5×10 -10 M or smaller or 1×10 -10 An antigen-binding domain or antigen-binding fragment that binds to a tumor-associated antigen with a KD of M or less.

[0301] The term "KD" refers to the dissociation constant obtained from the ratio of Kd to Ka (i.e., Kd / Ka) and expressed as a molar concentration (M). According to the present disclosure, the KD value of an antibody can be determined using methods in the art. For example, the KD of an antigen-binding domain or antigen-binding fragment can be determined using surface plasmon resonance, such as by using a biosensor system (e.g., system), or by using bio-layer interferometry techniques (such as the Octet RED96 system).

[0302] As used herein, an antibody that "specifically binds to CD123" refers to an antibody that binds to CD123 at a concentration of 1×10 -7 M or smaller, such as 1×10 - 8 M or smaller, 5×10 -9 M or smaller, 1×10 -9 M or smaller, 5×10 -10 M or smaller or 1×10 -10 An antibody that binds to CD123 (such as human CD123) with a KD of M or less. The term "KD" refers to the dissociation constant obtained from the ratio of Kd to Ka (i.e., Kd / Ka) and expressed as a molar concentration (M). According to the present disclosure, the KD value of an antibody can be determined using methods in the art. For example, the KD of an antibody can be determined using surface plasmon resonance, such as by using a biosensor system (e.g., system), or by using bio-layer interferometry techniques (such as the Octet RED96 system).

[0303] The smaller the KD value of an antibody, the higher the affinity of the antibody for binding to the target antigen.

[0304] In one aspect, provided herein is an antibody that binds to TRGV9. In some embodiments, the antibody 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. In some embodiments, the TRGV1 antibody is a humanized antibody.

[0305] In certain embodiments, provided herein is an anti-TRGV9 antibody comprising the VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and / or VL CDR3 of any one of the antibodies described herein. In some embodiments, provided herein is an anti-TRGV9 antibody comprising the VH region of any one of the antibodies described herein. In some embodiments, provided herein is an anti-TRGV9 antibody comprising the VL region of any one of the antibodies described herein. In some embodiments, provided herein is an anti-TRGV9 antibody comprising the VH region of any one of the antibodies described herein and the VL region of any one of the antibodies described herein. In some embodiments, provided herein is an anti-TRGV9 antibody comprising the VH region of any one of the antibodies described herein and the VL region of any one of the antibodies described herein. In some embodiments, provided herein is an anti-TRGV9 antibody comprising the VH CDR1, VH CDR2 and VH CDR3 of any one of the antibodies described herein. In some embodiments, provided herein is an anti-TRGV9 antibody comprising the VLCDR1, VL CDR2 and VL CDR3 of any one of the antibodies described herein. In some embodiments, provided herein is an anti-TRGV9 antibody comprising the VH CDR1, VH CDR2, and VH CDR3 of any one of the antibodies described herein; and the VL CDR1, VL CDR2, and VL CDR3 of any one of the antibodies described herein. Representative VH amino acid sequences and VL amino acid sequences of the TRGV9 antibodies provided herein (including VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences) are provided in the sequence listing and in Tables 1 to 31.

[0306] In certain embodiments, provided herein is an anti-TRGV9 bispecific antibody comprising a binding domain that binds to TRGV9, the binding domain having the VH region, VL region, VH CDR1, VHCDR2, VH CDR3, VL CDR1, VL CDR2 and / or VL CDR3 of any one of the antibodies described herein. In some embodiments, provided herein is an anti-TRGV9 bispecific antibody comprising a binding domain that binds to TRGV9, the binding domain having the VH region of any one of the antibodies described herein. In some embodiments, provided herein is an anti-TRGV9 bispecific antibody comprising a binding domain that binds to TRGV9, the binding domain having the VL region of any one of the antibodies described herein. In some embodiments, provided herein is an anti-TRGV9 bispecific antibody comprising a binding domain that binds to TRGV9, the binding domain having the VH region of any one of the antibodies described herein and the VL region of any one of the antibodies described herein. In some embodiments, provided herein is an anti-TRGV9 bispecific antibody comprising a binding domain that binds to TRGV9, the binding domain having the VH CDR1, VH CDR2, and VHCDR3 of any one of the antibodies described herein. In some embodiments, provided herein is an anti-TRGV9 bispecific antibody comprising a binding domain that binds to TRGV9, the binding domain having the VL CDR1, VL CDR2, and VLCDR3 of any one of the antibodies described herein. In some embodiments, provided herein is an anti-TRGV9 bispecific antibody comprising a binding domain that binds to TRGV9, the binding domain having the VH CDR1, VH CDR2, and VHCDR3 of any one of the antibodies described herein. And the VL CDR1, VL CDR2, and VL CDR3 of any one of the antibodies described herein.

[0307] In certain embodiments, the anti-TRGV9 antibody is a bispecific antibody. In some embodiments, the anti-TRGV9 bispecific antibody further includes a second binding domain that is bonded to CD123, and the second binding domain has the VH district, VL district, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and / or VLCDR3 of the anti-CD123 antibodies provided herein. In some embodiments, the anti-TRGV9 bispecific antibody further includes a second binding domain that is bonded to CD123, and the second binding domain has the VH district of the anti-CD123 antibodies provided herein. In some embodiments, the anti-TRGV9 bispecific antibody further includes a second binding domain that is bonded to CD123, and the second binding domain has the VL district of the anti-CD123 antibodies provided herein. In some embodiments, the anti-TRGV9 bispecific antibody further comprises a second binding domain that is bound to CD123, and the second binding domain has the VH district of the anti-CD123 antibody provided herein and the VL district of the anti-CD123 antibody provided herein. In some embodiments, the anti-TRGV9 bispecific antibody further comprises a second binding domain that is bound to CD123, and the second binding domain has VH CDR1, VH CDR2 and VH CDR3 of the anti-CD123 antibody provided herein. In some embodiments, the anti-TRGV9 bispecific antibody further comprises a second binding domain that is bound to CD123, and the second binding domain has VL CDR1, VL CDR2 and VL CDR3 of the anti-CD123 antibody provided herein. In some embodiments, the anti-TRGV9 bispecific antibody further comprises a second binding domain that binds to CD123, the second binding domain having VH CDR1, VH CDR2, and VH CDR3 of an anti-CD123 antibody provided herein, and VL CDR1, VL CDR2, and VL CDR3 of an anti-CD123 antibody provided herein.

[0308] In certain embodiments, an anti-TRGV9 antibody is provided that is a complete antibody. In other embodiments, an anti-TRGV9 antibody is provided that is an antigen-binding fragment of the anti-TRGV9 antibody. In some embodiments, the antigen-binding fragment of the anti-TRGV9 antibody is a functional fragment. In some embodiments, the antigen-binding fragment is a diabody. 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')2. In some embodiments, the antigen-binding fragment is an Fv fragment. In some embodiments, the antigen-binding fragment is a disulfide-stabilized Fv fragment (dsFv). In some embodiments, the antigen-binding fragment is (dsFv)2. In some embodiments, the antigen-binding fragment is a bispecific dsFv (dsFv-dsFv'). In some embodiments, the antigen-binding fragment is a disulfide-stabilized diabody (dsdiabody). In some embodiments, the antigen-binding fragment is a single-chain antibody molecule (scFv). In some embodiments, the antigen binding fragment is a single domain antibody (sdAb). In some embodiments, the antigen binding fragment is a scFv dimer (bivalent diabody). In some embodiments, the antigen binding fragment is a multispecific antibody formed by a portion of an antibody comprising one or more CDRs. In some embodiments, the antigen binding fragment is a humped single domain antibody. In some embodiments, the antigen binding fragment is a nanobody. In some embodiments, the antigen binding fragment is a domain antibody. In some embodiments, the antigen binding fragment is a bivalent domain antibody. In some embodiments, the antigen binding fragment is an antibody fragment that binds to an antigen but does not have the structure of a complete antibody.

[0309] In specific embodiments, the anti-TRGV9 antibody comprises a VH region and a VL region. 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. In some embodiments, the anti-TRGV9 antibody is not a nanobody. 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 some embodiments, the anti-TRGV9 bispecific antibody does not include a single-domain antibody. In certain embodiments, the anti-TRGV9 bispecific antibody does not include a nanobody. In certain embodiments, the anti-TRGV9 bispecific antibody does not include a VHH antibody. In certain embodiments, the anti-TRGV9 bispecific antibody does not include a llama antibody. In some embodiments, the anti-TRGV9 antibody is a multispecific antibody. In other embodiments, the anti-TRGV9 antibody is a bispecific antibody. In certain embodiments, the multispecific antibody includes an antigen-binding fragment of an anti-TRGV9 antibody provided herein. In other embodiments, the bispecific antibody comprises an antigen-binding fragment of an anti-TRGV9 antibody provided herein. In some embodiments, the anti-TRGV9 antibody is an agonist antibody. In certain embodiments, the anti-TRGV9 antibody activates γδT cells. In other embodiments, the anti-TRGV9 antibody is an antagonist antibody. In certain embodiments, the anti-TRGV9 antibody inactivates γδT cells. In some embodiments, the anti-TRGV9 antibody blocks activation of γδT cells. In some embodiments, the anti-TRGV9 antibody modulates the activity of γδT cells. In some embodiments, the anti-TRGV9 antibody neither activates nor inactivates the activity of γδT cells. In specific embodiments, the γδT cells are human γδT cells. In specific embodiments, a bispecific antibody is provided, comprising a TRGV9 antibody provided herein in a knob-in-hole configuration. In some embodiments, the anti-TRGV9 antibody provided herein may be included in a bispecific antibody. In some embodiments, the anti-TRGV9 bispecific antibody provided herein may be included in a multispecific antibody. In certain embodiments, the bispecific antibodies provided herein comprise a first binding domain comprising an anti-TRGV9 antibody that binds to a first TRGV9 epitope as provided herein and a second binding domain comprising an anti-TRGV9 antibody that binds to a second TRGV9 epitope as provided herein, wherein the first TRGV9 epitope and the second TRGV9 epitope are not the same. In a specific embodiment, the TRGV9 antibody or antigen-binding fragment thereof provided herein specifically binds to TRGV9.In certain embodiments, the TRGV9 antibodies or antigen-binding fragments thereof provided herein do not bind to an epitope of Vδ2.

[0310] In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 34; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 8. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising 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: 31; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 4, a VLCDR2 having the amino acid sequence of SEQ ID NO: 5, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 6. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 196, a VH CDR2 having an amino acid sequence of SEQ ID NO: 197, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 198; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 199, a VL CDR2 having an amino acid sequence of SEQ ID NO: 200, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 201. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 202, a VH CDR2 having an amino acid sequence of SEQ ID NO: 203, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 204; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 205, a VL CDR2 having an amino acid sequence of SEQ ID NO: 206, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 207.In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 208, a VH CDR2 having an amino acid sequence of SEQ ID NO: 209, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 210; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 211, a VL CDR2 having an amino acid sequence of SEQ ID NO: 212, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 213. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 214, a VHCDR2 having an amino acid sequence of SEQ ID NO: 215, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 216; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 217, a VL CDR2 having an amino acid sequence of SEQ ID NO: 218, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 219. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 214, a VH CDR2 having an amino acid sequence of SEQ ID NO: 702, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 703; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 217, a VL CDR2 having an amino acid sequence of SEQ ID NO: 218, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 219. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 220, a VH CDR2 having the amino acid sequence of SEQ ID NO: 221, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 222; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 223, a VL CDR2 having the amino acid sequence of SEQ ID NO: 224, 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, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 226, a VH CDR2 having 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 comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 229, a VL CDR2 having the amino acid sequence of SEQ ID NO: 230, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 231. 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 some embodiments, the antibody comprises a VH 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 comprises a VH comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 34. In some embodiments, the antibody comprises a VL comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody comprises a VH and a VL comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 34, and a VL comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 8.

[0311] In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1, a VHCDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 35; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 8. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising 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: 32; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 4, a VLCDR2 having the amino acid sequence of SEQ ID NO: 5, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 6. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 232, a VH CDR2 having an amino acid sequence of SEQ ID NO: 233, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 234; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 235, a VL CDR2 having an amino acid sequence of SEQ ID NO: 236, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 237. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 238, a VH CDR2 having an amino acid sequence of SEQ ID NO: 239, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 240; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 241, a VL CDR2 having an amino acid sequence of SEQ ID NO: 242, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 243.In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 244, a VH CDR2 having an amino acid sequence of SEQ ID NO: 245, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 246; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 247, a VL CDR2 having an amino acid sequence of SEQ ID NO: 248, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 249. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 250, a VHCDR2 having an amino acid sequence of SEQ ID NO: 251, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 252; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 253, a VL CDR2 having an amino acid sequence of SEQ ID NO: 254, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 255. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 250, a VH CDR2 having an amino acid sequence of SEQ ID NO: 704, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 705; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 253, a VL CDR2 having an amino acid sequence of SEQ ID NO: 254, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 255. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 256, a VH CDR2 having an amino acid sequence of SEQ ID NO: 257, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 258; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 259, a VL CDR2 having an amino acid sequence of SEQ ID NO: 260, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 261.In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 262, a VH CDR2 having 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 comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 265, a VL CDR2 having the amino acid sequence of SEQ ID NO: 266, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 267. 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: 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 comprises a VH comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 35. In some embodiments, the antibody comprises a VL comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody comprises a VH and a VL comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 35, and a VL comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 8.

[0312] In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1, a VHCDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 36; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 8. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising 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 comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 4, a VLCDR2 having the amino acid sequence of SEQ ID NO: 5, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 6. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VHCDR1 having an amino acid sequence of SEQ ID NO: 268, a VH CDR2 having an amino acid sequence of SEQ ID NO: 269, and a VHCDR3 having an amino acid sequence of SEQ ID NO: 270; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 271, a VL CDR2 having an amino acid sequence of SEQ ID NO: 272, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 273. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 274, a VH CDR2 having an amino acid sequence of SEQ ID NO: 275, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 276; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 277, a VL CDR2 having an amino acid sequence of SEQ ID NO: 278, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 279.In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 280, a VH CDR2 having an amino acid sequence of SEQ ID NO: 281, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 282; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 283, a VL CDR2 having an amino acid sequence of SEQ ID NO: 284, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 285. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 286, a VHCDR2 having an amino acid sequence of SEQ ID NO: 287, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 288; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 289, a VL CDR2 having an amino acid sequence of SEQ ID NO: 290, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 291. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 286, a VH CDR2 having an amino acid sequence of SEQ ID NO: 706, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 707; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 289, a VL CDR2 having an amino acid sequence of SEQ ID NO: 290, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 291. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 292, a VH CDR2 having the amino acid sequence of SEQ ID NO: 293, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 294; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 295, a VL CDR2 having the amino acid sequence of SEQ ID NO: 296, 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, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 298, a VH CDR2 having 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 comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 301, a VL CDR2 having the amino acid sequence of SEQ ID NO: 302, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 303. 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: 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 comprises a VH comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 36. In some embodiments, the antibody comprises a VL comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody comprises a VH and a VL comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 36, and a VL comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 8.

[0313] In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 65; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 66. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VHCDR3, respectively, of SEQ ID NO: 67; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 68. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising 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 a VH CDR3 having the amino acid sequence of SEQ ID NO: 3; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 77, a VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 6. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 60, 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 VL comprising a VLCDR1 having the amino acid sequence of SEQ ID NO: 63, a VL CDR2 having the amino acid sequence of SEQ ID NO: 64, and a VLCDR3 having the amino acid sequence of SEQ ID NO: 6.In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 304, a VH CDR2 having an amino acid sequence of SEQ ID NO: 305, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 306; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 307, a VL CDR2 having an amino acid sequence of SEQ ID NO: 308, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 309. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 310, a VH CDR2 having an amino acid sequence of SEQ ID NO: 311, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 312; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 313, a VL CDR2 having an amino acid sequence of SEQ ID NO: 314, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 315. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 316, a VH CDR2 having the amino acid sequence of SEQ ID NO: 317, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 318; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 319, a VLCDR2 having 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, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 322, a VH CDR2 having an amino acid sequence of SEQ ID NO: 323, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 324; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 325, a VL CDR2 having an amino acid sequence of SEQ ID NO: 326, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 327.In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 322, a VH CDR2 having an amino acid sequence of SEQ ID NO: 708, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 709; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 325, a VL CDR2 having an amino acid sequence of SEQ ID NO: 326, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 327. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 328, a VH CDR2 having the amino acid sequence of SEQ ID NO: 329, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 330; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 331, a VL CDR2 having the amino acid sequence of SEQ ID NO: 332, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 333. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 334, a VHCDR2 having an amino acid sequence of SEQ ID NO: 335, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 336; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 337, a VL CDR2 having an amino acid sequence of SEQ ID NO: 338, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 339. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 340, a VH CDR2 having an amino acid sequence of SEQ ID NO: 341, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 342; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 343, a VL CDR2 having an amino acid sequence of SEQ ID NO: 344, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 345.In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 346, a VH CDR2 having an amino acid sequence of SEQ ID NO: 347, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 348; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 349, a VL CDR2 having an amino acid sequence of SEQ ID NO: 350, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 351. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 352, a VH CDR2 having an amino acid sequence of SEQ ID NO: 353, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 354; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 355, a VL CDR2 having an amino acid sequence of SEQ ID NO: 356, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 357. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 358, a VH CDR2 having the amino acid sequence of SEQ ID NO: 359, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 360; and (ii) a VL comprising a VLCDR1 having the amino acid sequence of SEQ ID NO: 361, a VL CDR2 having the amino acid sequence of SEQ ID NO: 362, and a VLCDR3 having the amino acid sequence of SEQ ID NO: 363. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 358, a VH CDR2 having an amino acid sequence of SEQ ID NO: 710, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 711; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 361, a VL CDR2 having an amino acid sequence of SEQ ID NO: 362, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 363.In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 364, a VH CDR2 having an amino acid sequence of SEQ ID NO: 365, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 366; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 367, a VL CDR2 having an amino acid sequence of SEQ ID NO: 368, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 369. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 370, a VH CDR2 having the amino acid sequence of SEQ ID NO: 371, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 372; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 373, a VLCDR2 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 VH having the amino acid sequence of SEQ ID NO: 65. In some embodiments, the antibody comprises 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: 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 VL 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 has the amino acid sequence of SEQ ID NO: 70. In some embodiments, the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 74. In some embodiments, the antibody comprises a light chain having the amino acid sequence of SEQ ID NO: 75.In some embodiments, the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 74 and a light chain having the amino acid sequence of SEQ ID NO: 75. In some embodiments, the antibody has the amino acid sequence of SEQ ID NO: 73. In some embodiments, the antibody comprises a VH comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 65. In some embodiments, the antibody comprises a VL comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 66. In some embodiments, the antibody comprises a VH and a VL comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 65, and a VL comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 66. In some embodiments, the antibody comprises a VH comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 67. In some embodiments, the antibody comprises a VL comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 68. In some embodiments, the antibody comprises a VH and VL comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 67, and the VL comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 68. In some embodiments, the antibody comprises a heavy chain comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 71. In some embodiments, the antibody comprises a light chain comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 72. In some embodiments, the antibody comprises a heavy chain and a light chain comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 71, and the light chain comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 72. In some embodiments, the antibody has the amino acid sequence of SEQ ID NO: 70. In some embodiments, the antibody comprises a heavy chain comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 74. In some embodiments, the antibody comprises a light chain comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 75.In some embodiments, the antibody comprises a heavy chain comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 74 and a light chain comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 75. In some embodiments, the antibody has the amino acid sequence of SEQ ID NO: 73.

[0314] In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 104; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 105. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:98, a VH CDR2 having an amino acid sequence of SEQ ID NO:99, and a VH CDR3 having an amino acid sequence of SEQ ID NO:100; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:101, a VL CDR2 having an amino acid sequence of SEQ ID NO:102, and a VL CDR3 having an amino acid sequence of SEQ ID NO:103. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 412, a VH CDR2 having an amino acid sequence of SEQ ID NO: 413, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 414; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 415, a VL CDR2 having an amino acid sequence of SEQ ID NO: 416, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 417. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 418, a VH CDR2 having the amino acid sequence of SEQ ID NO: 419, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 420; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 421, a VL CDR2 having the amino acid sequence of SEQ ID NO: 422, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 423.In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 424, a VHCDR2 having an amino acid sequence of SEQ ID NO: 425, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 426; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 427, a VL CDR2 having an amino acid sequence of SEQ ID NO: 428, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 429. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 430, a VH CDR2 having an amino acid sequence of SEQ ID NO: 431, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 432; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 433, a VL CDR2 having an amino acid sequence of SEQ ID NO: 434, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 435. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 430, a VH CDR2 having an amino acid sequence of SEQ ID NO: 714, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 715; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 433, a VL CDR2 having an amino acid sequence of SEQ ID NO: 434, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 435. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 436, a VH CDR2 having an amino acid sequence of SEQ ID NO: 437, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 438; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 439, a VL CDR2 having an amino acid sequence of SEQ ID NO: 440, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 441.In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 442, a VH CDR2 having the amino acid sequence of SEQ ID NO: 443, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 444; and (ii) a VL comprising a VLCDR1 having the amino acid sequence of SEQ ID NO: 445, a VL CDR2 having the amino acid sequence of SEQ ID NO: 446, and a VLCDR3 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 some embodiments, the antibody comprises a VH 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 has the amino acid sequence of SEQ ID NO: 106. In some embodiments, the antibody comprises a VH comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 104. In some embodiments, the antibody comprises a VL comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 105. In some embodiments, the antibody comprises a VH and a VL comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 104 and a VL comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 105. In some embodiments, the antibody has the amino acid sequence of SEQ ID NO: 106.

[0315] In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 113; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 114. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 107, a VH CDR2 having an amino acid sequence of SEQ ID NO: 108, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 109; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 110, a VL CDR2 having an amino acid sequence of SEQ ID NO: 111, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 112. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 448, a VH CDR2 having an amino acid sequence of SEQ ID NO: 449, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 450; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 451, a VL CDR2 having an amino acid sequence of SEQ ID NO: 452, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 453. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 454, a VH CDR2 having an amino acid sequence of SEQ ID NO: 455, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 456; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 457, a VL CDR2 having an amino acid sequence of SEQ ID NO: 458, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 459.In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 460, a VHCDR2 having an amino acid sequence of SEQ ID NO: 461, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 462; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 463, a VL CDR2 having an amino acid sequence of SEQ ID NO: 464, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 465. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 466, a VH CDR2 having an amino acid sequence of SEQ ID NO: 467, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 468; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 469, a VL CDR2 having an amino acid sequence of SEQ ID NO: 470, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 471. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 466, a VH CDR2 having an amino acid sequence of SEQ ID NO: 716, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 717; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 469, a VL CDR2 having an amino acid sequence of SEQ ID NO: 470, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 471. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 472, a VH CDR2 having an amino acid sequence of SEQ ID NO: 473, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 474; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 475, a VL CDR2 having an amino acid sequence of SEQ ID NO: 476, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 477.In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 478, a VH CDR2 having the amino acid sequence of SEQ ID NO: 479, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 480; and (ii) a VL comprising a VLCDR1 having the amino acid sequence of SEQ ID NO: 481, a VL CDR2 having the amino acid sequence of SEQ ID NO: 482, and a VLCDR3 having the amino acid sequence of SEQ ID NO: 483. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 113. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO: 114. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 113 and a VL having the amino acid sequence of SEQ ID NO: 114. In some embodiments, the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 115. In some embodiments, the antibody comprises a light chain having the amino acid sequence of SEQ ID NO: 116. In some embodiments, the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 115 and a light chain having the amino acid sequence of SEQ ID NO: 116. In some embodiments, the antibody comprises a VH comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 113. In some embodiments, the antibody comprises a VL comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 114. In some embodiments, the antibody comprises a VH and a VL comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 113, and a VL comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 114. In some embodiments, the antibody comprises a heavy chain comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 115. In some embodiments, the antibody comprises a light chain comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 116. In some embodiments, the antibody comprises a heavy chain comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 115, and a light chain comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 116.

[0316] In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 123; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 124. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VHCDR1 having an amino acid sequence of SEQ ID NO: 117, a VH CDR2 having an amino acid sequence of SEQ ID NO: 118, and a VHCDR3 having an amino acid sequence of SEQ ID NO: 119; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 120, a VL CDR2 having an amino acid sequence of SEQ ID NO: 121, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 122. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 484, a VH CDR2 having an amino acid sequence of SEQ ID NO: 485, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 486; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 487, a VL CDR2 having an amino acid sequence of SEQ ID NO: 488, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 489. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 490, a VH CDR2 having an amino acid sequence of SEQ ID NO: 491, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 492; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 493, a VL CDR2 having an amino acid sequence of SEQ ID NO: 494, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 495.In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 496, a VHCDR2 having an amino acid sequence of SEQ ID NO: 497, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 498; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 499, a VL CDR2 having an amino acid sequence of SEQ ID NO: 500, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 501. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 502, a VH CDR2 having an amino acid sequence of SEQ ID NO: 503, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 504; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 505, a VL CDR2 having an amino acid sequence of SEQ ID NO: 506, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 507. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 502, a VH CDR2 having an amino acid sequence of SEQ ID NO: 718, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 719; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 505, a VL CDR2 having an amino acid sequence of SEQ ID NO: 506, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 507. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 508, a VH CDR2 having an amino acid sequence of SEQ ID NO: 509, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 510; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 511, a VL CDR2 having an amino acid sequence of SEQ ID NO: 512, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 513.In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 514, a VH CDR2 having the amino acid sequence of SEQ ID NO: 515, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 516; and (ii) a VL comprising a VLCDR1 having the amino acid sequence of SEQ ID NO: 517, a VL CDR2 having the amino acid sequence of SEQ ID NO: 518, and a VLCDR3 having the amino acid sequence of SEQ ID NO: 519. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 123. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO: 124. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 123 and a VL having the amino acid sequence of SEQ ID NO: 124. In some embodiments, the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 125. In some embodiments, the antibody comprises a light chain having the amino acid sequence of SEQ ID NO: 126. In some embodiments, the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 125 and a light chain having the amino acid sequence of SEQ ID NO: 126. In some embodiments, the antibody comprises a VH comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 123. In some embodiments, the antibody comprises a VL comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 124. In some embodiments, the antibody comprises a VH and a VL comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 123, and a VL comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 124. In some embodiments, the antibody comprises a heavy chain comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 125. In some embodiments, the antibody comprises a light chain comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 126. In some embodiments, the antibody comprises a heavy chain comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 125, and a light chain comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 126.

[0317] In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 133; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 134. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 127, a VH CDR2 having an amino acid sequence of SEQ ID NO: 128, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 129; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 130, a VL CDR2 having an amino acid sequence of SEQ ID NO: 131, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 132. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 520, a VH CDR2 having an amino acid sequence of SEQ ID NO: 521, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 522; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 523, a VL CDR2 having an amino acid sequence of SEQ ID NO: 524, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 525. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 526, a VH CDR2 having an amino acid sequence of SEQ ID NO: 527, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 528; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 529, a VL CDR2 having an amino acid sequence of SEQ ID NO: 530, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 531.In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 532, a VHCDR2 having an amino acid sequence of SEQ ID NO: 533, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 534; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 535, a VL CDR2 having an amino acid sequence of SEQ ID NO: 536, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 537. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 538, a VH CDR2 having an amino acid sequence of SEQ ID NO: 539, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 540; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 541, a VL CDR2 having an amino acid sequence of SEQ ID NO: 542, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 543. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 538, a VH CDR2 having an amino acid sequence of SEQ ID NO: 720, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 721; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 541, a VL CDR2 having an amino acid sequence of SEQ ID NO: 542, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 543. In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 544, a VH CDR2 having an amino acid sequence of SEQ ID NO: 545, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 546; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 547, a VL CDR2 having an amino acid sequence of SEQ ID NO: 548, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 549.In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 550, a VH CDR2 having the amino acid sequence of SEQ ID NO: 551, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 552; and (ii) a VL comprising a VLCDR1 having the amino acid sequence of SEQ ID NO: 553, a VL CDR2 having the amino acid sequence of SEQ ID NO: 554, and a VLCDR3 having the amino acid sequence of SEQ ID NO: 555. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 133. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO: 134. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 133 and a VL having the amino acid sequence of SEQ ID NO: 134. In some embodiments, the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 135. In some embodiments, the antibody comprises a light chain having the amino acid sequence of SEQ ID NO: 136. In some embodiments, the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 135 and a light chain having the amino acid sequence of SEQ ID NO: 136. In some embodiments, the antibody comprises a VH comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 133. In some embodiments, the antibody comprises a VL comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 134. In some embodiments, the antibody comprises a VH and a VL comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 133, and a VL comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 134. In some embodiments, the antibody comprises a heavy chain comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 135. In some embodiments, the antibody comprises a light chain comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 136. In some embodiments, the antibody comprises a heavy chain and a light chain comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 135, and the light chain comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 136.

[0318] 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. In some embodiments, the anti-TRGV9 antibody is not a nanobody. In certain embodiments, the anti-TRGV9 antibody is not a VHH antibody. In certain embodiments, the anti-TRGV9 antibody is not a llama antibody.

[0319] In some embodiments, the anti-TRGV9 antibodies provided herein do not comprise VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NO: 730, SEQ ID NO: 731, and SEQ ID NO: 732, respectively. In some embodiments, the anti-TRGV9 antibodies provided herein do not comprise VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NO: 733, SEQ ID NO: 734, and SEQ ID NO: 735, respectively. In some embodiments, the anti-TRGV9 antibodies provided herein do not comprise VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NO: 736, SEQ ID NO: 737, and SEQ ID NO: 738, respectively. In some embodiments, the anti-TRGV9 antibodies provided herein do not comprise VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NO: 739, SEQ ID NO: 740, and SEQ ID NO: 741, respectively. In some embodiments, the anti-TRGV9 antibodies provided herein do not comprise a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NO: 742, SEQ ID NO: 743, and SEQ ID NO: 744, respectively. In some embodiments, the anti-TRGV9 antibodies provided herein do not comprise a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NO: 745, SEQ ID NO: 746, and SEQ ID NO: 747, respectively. In some embodiments, the anti-TRGV9 antibodies provided herein do not comprise a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NO: 748, SEQ ID NO: 749, and SEQ ID NO: 750, respectively. In some embodiments, the anti-TRGV9 antibodies provided herein do not comprise a VH domain having the amino acid sequence of SEQ ID NO: 751. In some embodiments, the anti-TRGV9 antibodies provided herein do not comprise a VH domain having the amino acid sequence of SEQ ID NO: 752. In some embodiments, the anti-TRGV9 antibodies provided herein do not comprise a VH domain having the amino acid sequence of SEQ ID NO: 753. In some embodiments, the anti-TRGV9 antibodies provided herein do not comprise a VH domain having the amino acid sequence of SEQ ID NO: 754. In some embodiments, the anti-TRGV9 antibodies provided herein do not comprise a VH domain having the amino acid sequence of SEQ ID NO: 755.In some embodiments, the anti-TRGV9 antibodies provided herein do not comprise a VH domain having the amino acid sequence of SEQ ID NO: 756. In some embodiments, the anti-TRGV9 antibodies provided herein do not comprise a VH domain having the amino acid sequence of SEQ ID NO: 757.

[0320] In another aspect, provided herein is an anti-TRGV9 antibody comprising a VH domain comprising a VH CDR3 having the amino acid sequence APNxGzYTbDF (SEQ ID NO: 758), wherein x is Y or M, z is M or D, and b is I or L. In another aspect, provided herein is an anti-TRGV9 antibody comprising a VH domain having the amino acid sequence SEQ ID NO: 758. In another aspect, provided herein is an anti-TRGV9 antibody comprising a VH domain comprising a VH CDR1 having the amino acid sequence GxTFzz (SEQ ID NO: 761), wherein x is F, D, or G, and z is S or N. In another aspect, provided herein is an anti-TRGV9 antibody comprising a VH domain having the amino acid sequence SEQ ID NO: 761. In another aspect, provided herein is an anti-TRGV9 antibody comprising a VL domain comprising a VL CDR1 having the amino acid sequence RxSQSz (SEQ ID NO: 762), wherein x is A or S, and z is V or L. In another aspect, provided herein is an anti-TRGV9 antibody comprising a VL domain having the amino acid sequence SEQ ID NO: 761.

[0321] In another aspect, provided herein is an antibody that binds to TRGV9, wherein the antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3. In some embodiments, the VH CDR1 comprises a first polar amino acid. In some embodiments, the VH CDR1 comprises a last polar uncharged amino acid. In some embodiments, the VH CDR1 comprises at least one tyrosine. In some embodiments, the VH CDR1 comprises at least 20% hydrophobic amino acids. In some embodiments, the VH CDR1 comprises at least two hydrophobic amino acids. In some embodiments, the VH CDR1 comprises at least about 40% hydrophobic amino acids. In some embodiments, the VH CDR1 comprises the first polar amino acid, the last polar uncharged amino acid, at least one tyrosine, at least 20% hydrophobic amino acids, at least two hydrophobic amino acids, and at least about 40% hydrophobic amino acids. Any combination of two or more of the aforementioned VH CDR1 structural 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 position 15. In some embodiments, the VH CDR2 comprises a 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 comprises a lysine (K) or serine (S) at position 14. In some embodiments, the VH CDR2 comprises a hydrophobic amino acid at position 2. In some embodiments, the VH CDR2 comprises a hydrophobic amino acid at position 3. In some embodiments, the VH CDR2 comprises the penultimate polar amino acid. In some embodiments, the VH CDR2 comprises a polar amino acid at residue 13, a hydrophobic amino acid at position 15, a phenylalanine (F) or leucine (L) at position 15, a polar amino acid at position 14, a lysine (K) or serine (S) at position 14, a hydrophobic amino acid at position 2 or 3, and the penultimate polar amino acid. Any combination of two or more of the aforementioned VH CDR2 structural features is also contemplated. In some embodiments, the VH CDR3 does not comprise a polar charged amino acid at position 3. In some embodiments, the VH CDR3 comprises a hydrophobic amino acid or a polar charged amino acid at position 7. In some embodiments, the VH CDR3 comprises a polar uncharged amino acid or a hydrophobic amino acid at position 6.In some embodiments, the VH CDR3 does not contain a polar charged amino acid at position 3, contains a hydrophobic amino acid or a polar charged amino acid at position 7, and a polar uncharged amino acid or a hydrophobic amino acid at position 6. Any combination of two or more of the aforementioned VH CDR3 structural features is also contemplated. In some embodiments, the VL CDR1 contains a polar amino acid at position 4. In some embodiments, the VL CDR1 contains a polar charged first amino acid. In some embodiments, the VL CDR1 contains a polar uncharged amino acid or a hydrophobic amino acid at position 2. In some embodiments, the VL CDR1 contains a serine at position 3. In some embodiments, the VL CDR1 contains a polar amino acid at position 5. In some embodiments, the VL CDR1 contains a hydrophobic amino acid at position 6. In some embodiments, the VL CDR1 comprises a polar amino acid at position 4, a polar charged first amino acid, a polar uncharged amino acid or a hydrophobic amino acid at position 2, a serine at position 3, a polar amino acid at position 5, and a hydrophobic amino acid at position 6. Any combination of two or more of the aforementioned VL CDR1 structural features is also contemplated. In some embodiments, the VL CDR2 comprises a polar amino acid at position 7. In some embodiments, the VL CDR2 comprises a polar charged amino acid or a hydrophobic amino acid at position 6. 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 comprises a polar amino acid at position 7, a polar charged amino acid or a hydrophobic amino acid at position 6, a polar charged amino acid at position 3, a polar uncharged amino acid at position 4, and a hydrophobic amino acid at position 2. Any combination of two or more of the aforementioned VL CDR2 structural features is also contemplated. In some embodiments, the VL CDR3 comprises a hydrophobic terminal amino acid. 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 comprises a polar, uncharged amino acid or a hydrophobic amino acid at position 1. In some embodiments, the VL CDR3 comprises a hydrophobic amino acid at position 3. In some embodiments, the VL CDR3 comprises a hydrophilic amino acid or a polar, uncharged amino acid at position 6. In some embodiments, the VL CDR3 does not comprise a polar or hydrophobic amino acid at position 7.In some embodiments, the VL CDR3 comprises a hydrophobic terminal amino acid, a terminal tyrosine, a polar uncharged amino acid at position 5, a polar amino acid at position 2, a polar uncharged amino acid or a hydrophobic amino acid at position 1, a hydrophobic amino acid at position 3, a hydrophilic amino acid or a polar uncharged amino acid at position 6, and no polar amino acid or hydrophobic amino acid at position 7. Any combination of two or more of the aforementioned VL CDR3 structural features is also contemplated. In specific embodiments, residue position numbering is according to exemplary numbering.

[0322] In some embodiments, the anti-TRGV9 antibody is a multispecific antibody. In other embodiments, the anti-TRGV9 antibody is a bispecific antibody. In certain embodiments, the multispecific antibody includes an antigen-binding fragment of an anti-TRGV9 antibody provided herein. In some embodiments, the multispecific antibody comprises a first binding domain that binds to a first TRGV9 epitope and a second domain that binds to a second TRGV9 epitope, wherein the first TRGV9 epitope and the second TRGV9 epitope are different. In certain embodiments, the multispecific antibody further comprises a third binding domain that binds to a target that is not TRGV9.

[0323] In another aspect, provided herein is a bispecific antibody 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.

[0324] 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.

[0325] In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 7; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 8. In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 1, a VHCDR2 having an amino acid sequence of SEQ ID NO: 2, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 3; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 4, a VL CDR2 having an amino acid sequence of SEQ ID NO: 5, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 6. In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 160, a VH CDR2 having an amino acid sequence of SEQ ID NO: 161, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 162; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 163, a VL CDR2 having an amino acid sequence of SEQ ID NO: 164, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 165.In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 166, a VH CDR2 having an amino acid sequence of SEQ ID NO: 167, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 168; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 169, a VL CDR2 having an amino acid sequence of SEQ ID NO: 170, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 171. In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 172, a VH CDR2 having an amino acid sequence of SEQ ID NO: 173, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 174; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 175, a VL CDR2 having an amino acid sequence of SEQ ID NO: 176, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 177. In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 178, a VHCDR2 having an amino acid sequence of SEQ ID NO: 179, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 180; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 181, a VL CDR2 having an amino acid sequence of SEQ ID NO: 182, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 183.In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 178, a VH CDR2 having an amino acid sequence of SEQ ID NO: 700, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 701; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 181, a VL CDR2 having an amino acid sequence of SEQ ID NO: 182, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 183. In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 184, a VHCDR2 having an amino acid sequence of SEQ ID NO: 185, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 186; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 187, a VL CDR2 having an amino acid sequence of SEQ ID NO: 188, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 189. In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 190, a VH CDR2 having an amino acid sequence of SEQ ID NO: 191, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 192; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 193, a VL CDR2 having an amino acid sequence of SEQ ID NO: 194, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 195. In some embodiments, the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 7. In some embodiments, the first binding domain comprises a VL having an amino acid sequence of SEQ ID NO: 8.In some embodiments, the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 7 and a VL having an amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises a heavy chain having an amino acid sequence of SEQ ID NO: 23. In some embodiments, the first binding domain comprises a light chain having an amino acid sequence of SEQ ID NO: 24. In some embodiments, the first binding domain comprises a heavy chain having an amino acid sequence of SEQ ID NO: 23 and a light chain having an amino acid sequence of SEQ ID NO: 24. In some embodiments, the first binding domain has an amino acid sequence of SEQ ID NO: 17. In some embodiments, the first binding domain comprises a heavy chain having an amino acid sequence of SEQ ID NO: 69. In some embodiments, the first binding domain comprises a light chain having an amino acid sequence of SEQ ID NO: 24. In some embodiments, the first binding domain comprises a heavy chain having an amino acid sequence of SEQ ID NO: 69 and a light chain having an amino acid sequence of SEQ ID NO: 24. In some embodiments, the first binding domain comprises a VH comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 7. In some embodiments, the first binding domain comprises a VL comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises a VH and a VL comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 7, and the VL comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises a heavy chain comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 23. In some embodiments, the first binding domain comprises a light chain comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the first binding domain comprises a heavy chain comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 23, and a light chain comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the first binding domain has the amino acid sequence of SEQ ID NO: 17. In some embodiments, the first binding domain comprises a heavy chain comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 69.In some embodiments, the first binding domain comprises a light chain comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the first binding domain comprises a heavy chain and a light chain comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 69, and the light chain comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 24.

[0326] In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 34; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 8. In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 1, a VHCDR2 having an amino acid sequence of SEQ ID NO: 2, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 31; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 4, a VL CDR2 having an amino acid sequence of SEQ ID NO: 5, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 6. In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 196, a VH CDR2 having an amino acid sequence of SEQ ID NO: 197, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 198; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 199, a VL CDR2 having an amino acid sequence of SEQ ID NO: 200, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 201.In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 202, a VH CDR2 having an amino acid sequence of SEQ ID NO: 203, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 204; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 205, a VL CDR2 having an amino acid sequence of SEQ ID NO: 206, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 207. In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 208, a VH CDR2 having an amino acid sequence of SEQ ID NO: 209, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 210; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 211, a VL CDR2 having an amino acid sequence of SEQ ID NO: 212, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 213. In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 214, a VHCDR2 having an amino acid sequence of SEQ ID NO: 215, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 216; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 217, a VL CDR2 having an amino acid sequence of SEQ ID NO: 218, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 219.In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 214, a VH CDR2 having an amino acid sequence of SEQ ID NO: 702, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 703; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 217, a VL CDR2 having an amino acid sequence of SEQ ID NO: 218, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 219. In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 220, a VHCDR2 having an amino acid sequence of SEQ ID NO: 221, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 222; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 223, a VL CDR2 having an amino acid sequence of SEQ ID NO: 224, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 225. In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 226, a VH CDR2 having an amino acid sequence of SEQ ID NO: 227, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 228; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 229, a VL CDR2 having an amino acid sequence of SEQ ID NO: 230, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 231. In some embodiments, the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 34. In some embodiments, the first binding domain comprises a VL having an amino acid sequence of SEQ ID NO: 8.In some embodiments, the first binding domain comprises a VH 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 first binding domain comprises a VH comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 34. In some embodiments, the first binding domain comprises a VL comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises a VH and a VL comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 34, and the VL comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 8.

[0327] In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 35; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 8. In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 1, a VHCDR2 having an amino acid sequence of SEQ ID NO: 2, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 32; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 4, a VL CDR2 having an amino acid sequence of SEQ ID NO: 5, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 6. In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 232, a VH CDR2 having an amino acid sequence of SEQ ID NO: 233, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 234; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 235, a VL CDR2 having an amino acid sequence of SEQ ID NO: 236, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 237.In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 238, a VH CDR2 having an amino acid sequence of SEQ ID NO: 239, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 240; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 241, a VL CDR2 having an amino acid sequence of SEQ ID NO: 242, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 243. In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 244, a VH CDR2 having an amino acid sequence of SEQ ID NO: 245, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 246; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 247, a VL CDR2 having an amino acid sequence of SEQ ID NO: 248, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 249. In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 250, a VHCDR2 having an amino acid sequence of SEQ ID NO: 251, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 252; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 253, a VL CDR2 having an amino acid sequence of SEQ ID NO: 254, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 255.In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 250, a VH CDR2 having an amino acid sequence of SEQ ID NO: 704, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 705; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 253, a VL CDR2 having an amino acid sequence of SEQ ID NO: 254, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 255. In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 256, a VHCDR2 having an amino acid sequence of SEQ ID NO: 257, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 258; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 259, a VL CDR2 having an amino acid sequence of SEQ ID NO: 260, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 261. In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 262, a VH CDR2 having an amino acid sequence of SEQ ID NO: 263, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 264; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 265, a VL CDR2 having an amino acid sequence of SEQ ID NO: 266, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 267. In some embodiments, the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 35. In some embodiments, the first binding domain comprises a VL having an amino acid sequence of SEQ ID NO: 8.In some embodiments, the first binding domain 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 first binding domain comprises a VH comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 35. In some embodiments, the first binding domain comprises a VL comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises a VH and a VL comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 35, and the VL comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 8.

[0328] In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 36; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 8. In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 1, a VHCDR2 having an amino acid sequence of SEQ ID NO: 2, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 33; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 4, a VL CDR2 having an amino acid sequence of SEQ ID NO: 5, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 6. In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 268, a VH CDR2 having an amino acid sequence of SEQ ID NO: 269, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 270; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 271, a VL CDR2 having an amino acid sequence of SEQ ID NO: 272, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 273.In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 274, a VH CDR2 having an amino acid sequence of SEQ ID NO: 275, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 276; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 277, a VL CDR2 having an amino acid sequence of SEQ ID NO: 278, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 279. In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 280, a VH CDR2 having an amino acid sequence of SEQ ID NO: 281, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 282; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 283, a VL CDR2 having an amino acid sequence of SEQ ID NO: 284, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 285. In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 286, a VHCDR2 having an amino acid sequence of SEQ ID NO: 287, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 288; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 289, a VL CDR2 having an amino acid sequence of SEQ ID NO: 290, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 291.In another aspect, provided herein is a bispecific antibody 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, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 286, a VH CDR2 having an amino acid sequence of SEQ ID NO: 706, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 707; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 289, a VL CDR2 having an amino acid sequence of SEQ ID NO: 290, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 291. In another aspect, provided herein is a bispecific antibody comprising: (a) a first binding domain that binds to TRGV9, and (b) a second binding domain that binds to a second target that...

Claims

1. An antibody that binds to T cell receptor gamma variable region 9 (TRGV9), wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the antibody comprises: (i) a VH comprising a VH complementarity determining region (CDR) 1 having an amino acid sequence of SEQ ID NO: 1, a VH CDR2 having an amino acid sequence of SEQ ID NO: 2, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 31; and (ii) VL, wherein the VL comprises a VL CDR1 having an amino acid sequence of SEQ ID NO: 4, a VL CDR2 having an amino acid sequence of SEQ ID NO: 5, and a VL CDR3 having an amino acid sequence of SEQ ID NO:

6.

2. The antibody according to claim 1, wherein the antibody comprises a VH having an amino acid sequence of SEQ ID NO:

34.

3. The antibody of claim 1, wherein the antibody comprises a VL having an amino acid sequence of SEQ ID NO:

8. 4 . The antibody according to claim 1 , wherein the antibody comprises a VH having an amino acid sequence of SEQ ID NO: 34 and a VL having an amino acid sequence of SEQ ID NO:

8.

5. An antibody that binds to T cell receptor gamma variable region 9 (TRGV9), wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 1, a VH CDR2 having an amino acid sequence of SEQ ID NO: 2, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 32; and (ii) VL, wherein the VL comprises a VL CDR1 having an amino acid sequence of SEQ ID NO: 4, a VL CDR2 having an amino acid sequence of SEQ ID NO: 5, and a VL CDR3 having an amino acid sequence of SEQ ID NO:

6.

6. The antibody according to claim 5, wherein the antibody comprises a VH having an amino acid sequence of SEQ ID NO:

35.

7. The antibody of claim 5, wherein the antibody comprises a VL having an amino acid sequence of SEQ ID NO:

8.

8. The antibody according to claim 5, wherein the antibody comprises a VH having an amino acid sequence of SEQ ID NO: 35 and a VL having an amino acid sequence of SEQ ID NO:

8.

9. An antibody that binds to T cell receptor gamma variable region 9 (TRGV9), wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 1, a VH CDR2 having an amino acid sequence of SEQ ID NO: 2, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 33; and (ii) VL, wherein the VL comprises a VL CDR1 having an amino acid sequence of SEQ ID NO: 4, a VL CDR2 having an amino acid sequence of SEQ ID NO: 5, and a VL CDR3 having an amino acid sequence of SEQ ID NO:

6.

10. The antibody according to claim 9, wherein the antibody comprises a VH having an amino acid sequence of SEQ ID NO:

36.

11. The antibody of claim 9, wherein the antibody comprises a VL having an amino acid sequence of SEQ ID NO:

8.

12. The antibody according to claim 9, wherein the antibody comprises a VH having an amino acid sequence of SEQ ID NO: 36 and a VL having an amino acid sequence of SEQ ID NO:

8.

13. The antibody according to any one of claims 1 to 12, wherein the TRGV9 is present on the surface of γδ T cells.

14. The antibody according to any one of claims 1 to 12, wherein the antibody is a humanized antibody.

15. The antibody according to any one of claims 1 to 12, wherein the antibody is an IgG antibody. The antibody according to claim 15 , wherein the IgG antibody is an IgG1, IgG2, IgG3 or IgG4 antibody.

17. A nucleic acid encoding the antibody according to any one of claims 1 to 16. A vector comprising the nucleic acid according to claim 17 .

19. A host cell comprising the vector according to claim 18.

20. A kit comprising the vector according to claim 18 and packaging for the vector.

21. A pharmaceutical composition comprising the antibody according to any one of claims 1 to 16, and a pharmaceutically acceptable carrier.

22. A method for preparing the pharmaceutical composition according to claim 21, comprising combining the antibody with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition.

23. A method of activating a γδ T cell expressing TRGV9, the method comprising contacting the γδ T cell with the antibody according to any one of claims 1 to 16.

24. The method of claim 23, wherein the contacting results in an increase in CD69, CD25 and / or granzyme B expression compared to control γδ T cells expressing TRGV9.

25. A bispecific antibody, comprising: (a) binds to the first binding domain of TRGV9, and (b) a second binding domain that binds to CD123, wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 1, a VH CDR2 having an amino acid sequence of SEQ ID NO: 2, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 3; and (ii) VL, wherein the VL comprises a VL CDR1 having an amino acid sequence of SEQ ID NO: 4, a VL CDR2 having an amino acid sequence of SEQ ID NO: 5, and a VL CDR3 having an amino acid sequence of SEQ ID NO:

6.

26. The bispecific antibody of claim 25, wherein the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO:

7.

27. The bispecific antibody of claim 25, wherein the first binding domain comprises a VL having an amino acid sequence of SEQ ID NO:

8.

28. The bispecific antibody of claim 25, wherein the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 7 and a VL having an amino acid sequence of SEQ ID NO:

8.

29. A bispecific antibody, comprising: (a) binds to the first binding domain of TRGV9, and (b) a second binding domain that binds to CD123, Wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 1, a VH CDR2 having an amino acid sequence of SEQ ID NO: 2, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 31; and (ii) VL, wherein the VL comprises a VL CDR1 having an amino acid sequence of SEQ ID NO: 4, a VL CDR2 having an amino acid sequence of SEQ ID NO: 5, and a VL CDR3 having an amino acid sequence of SEQ ID NO:

6.

30. The bispecific antibody of claim 29, wherein the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO:

34.

31. The bispecific antibody of claim 29, wherein the first binding domain comprises a VL having an amino acid sequence of SEQ ID NO:

8.

32. The bispecific antibody of claim 29, wherein the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 34 and a VL having an amino acid sequence of SEQ ID NO:

8.

33. A bispecific antibody, comprising: (a) binds to the first binding domain of TRGV9, and (b) a second binding domain that binds to CD123, Wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 1, a VH CDR2 having an amino acid sequence of SEQ ID NO: 2, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 32; and (ii) VL, wherein the VL comprises a VL CDR1 having an amino acid sequence of SEQ ID NO: 4, a VL CDR2 having an amino acid sequence of SEQ ID NO: 5, and a VL CDR3 having an amino acid sequence of SEQ ID NO:

6.

34. The bispecific antibody of claim 33, wherein the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO:

35.

35. The bispecific antibody of claim 33, wherein the first binding domain comprises a VL having an amino acid sequence of SEQ ID NO:

8.

36. The bispecific antibody of claim 33, wherein the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 35 and a VL having an amino acid sequence of SEQ ID NO:

8.

37. A bispecific antibody, comprising: (a) binds to the first binding domain of TRGV9, and (b) a second binding domain that binds to CD123, Wherein the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 1, a VH CDR2 having an amino acid sequence of SEQ ID NO: 2, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 33; and (ii) VL, wherein the VL comprises a VL CDR1 having an amino acid sequence of SEQ ID NO: 4, a VL CDR2 having an amino acid sequence of SEQ ID NO: 5, and a VL CDR3 having an amino acid sequence of SEQ ID NO:

6.

38. The bispecific antibody of claim 37, wherein the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO:

36.

39. The bispecific antibody of claim 37, wherein the first binding domain comprises a VL having an amino acid sequence of SEQ ID NO:

8.

40. The bispecific antibody of claim 37, wherein the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 36 and a VL having an amino acid sequence of SEQ ID NO:

8.

41. The bispecific antibody of any one of claims 25-40, wherein the second binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 9, a VH CDR2 having an amino acid sequence of SEQ ID NO: 10, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 11; and (ii) VL, wherein the VL comprises a VL CDR1 having an amino acid sequence of SEQ ID NO: 12, a VL CDR2 having an amino acid sequence of SEQ ID NO: 13, and a VL CDR3 having an amino acid sequence of SEQ ID NO:

14.

42. The bispecific antibody of claim 41, wherein the second binding domain comprises a VH having an amino acid sequence of SEQ ID NO:

15.

43. The bispecific antibody of claim 41, wherein the second binding domain comprises a VL having an amino acid sequence of SEQ ID NO:

16.

44. The bispecific antibody of claim 41, wherein the second binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 15 and a VL having an amino acid sequence of SEQ ID NO:

16.

45. The bispecific antibody of any one of claims 25 to 40, wherein the TRGV9 is present on the surface of γδ T cells.

46. ​​The bispecific antibody according to any one of claims 25 to 40, wherein the TRGV9 is present on the surface of γδ T cells and the CD123 is a cancer antigen expressed on the surface of cancer cells.

47. The bispecific antibody of claim 46, wherein when the bispecific antibody binds to the TRGV9 on the surface of the γδ T cell and an antigen on the surface of the cancer cell, the cancer cell is killed.

48. The bispecific antibody of any one of claims 25 to 40, wherein the first binding domain is humanized, the second binding domain is humanized, or both the first binding domain and the second binding domain are humanized.

49. The bispecific antibody according to any one of claims 25 to 40, wherein the bispecific antibody is an IgG antibody.

50. The bispecific antibody of claim 49, wherein the IgG antibody is an IgG1, IgG2, IgG3 or IgG4 antibody.

51. A pharmaceutical composition comprising the bispecific antibody according to any one of claims 25 to 50, and a pharmaceutically acceptable carrier.

52. Use of the bispecific antibody according to any one of claims 25 to 50 in the preparation of a medicament for guiding γδT cells expressing TRGV9 to cancer cells expressing CD123, comprising contacting the γδT cells with the medicament, wherein the contacting guides the γδT cells to the cancer cells.

53. Use of the bispecific antibody according to any one of claims 25 to 50 in the preparation of a medicament for inhibiting the growth or proliferation of cancer cells expressing CD123 on the cell surface, comprising contacting the γδ T cells with the medicament, wherein contacting the cancer cells with the medicament inhibits the growth or proliferation of the cancer cells.

54. The use according to claim 53, wherein the cancer cell is contacted with the bispecific antibody in the presence of γδ T cells expressing TRGV9.

55. Use of the bispecific antibody according to any one of claims 25 to 50 in the preparation of a medicament for eliminating cancer cells in a subject, wherein the cancer cells express CD123.

56. The use according to claim 55, wherein the subject is a subject in need thereof.

57. The use according to claim 55 or 56, wherein the subject is a human.

58. A method of activating a γδ T cell expressing TRGV9, the method comprising contacting the γδ T cell with the bispecific antibody according to any one of claims 25 to 50.

59. An isolated TRGV9 bispecific antibody or antigen-binding fragment thereof, comprising: a. First heavy chain (HC1); b. Second heavy chain (HC2); c. the first light chain (LC1); and d. Second light chain (LC2), wherein HC1 associates with LC1, and HC2 associates with LC2, and wherein HC1 comprises a heavy chain complementarity determining region 1 (HCDR1), HCDR2 and HCDR3 having the following amino acid sequence: 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. SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 33, respectively, And LC1 comprises light chain complementary determining region 1 (LCDR1), LCDR2 and LCDR3 with amino acid sequences of SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6, respectively, to form a binding site for the first antigen, and wherein HC2 and LC2 bind to CD123.

60. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 59, wherein HC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35 or SEQ ID NO:36, and LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:

8.

61. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 60, wherein HC1 comprises the amino acid sequence of SEQ ID NO: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.

62. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof according to any one of claims 59 to 61, wherein the binding site for the first antigen binds to TRGV9 on γδ T cells.

63. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof according to any one of claims 59 to 61, wherein the HC and LC bind to a cancer antigen present on the surface of a cancer cell.

64. The isolated TRGV9 bispecific antibody or antigen-binding fragment of claim 63, wherein the bispecific antibody binds to TRGV9 present on the surface of the γδ T cells and to the cancer antigen present on the surface of the cancer cells resulting in killing of the cancer cells.

65. The isolated TRGV9 bispecific antibody or antigen-binding fragment of any one of claims 59 to 61, wherein HC1 and LC1 are humanized.

66. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof according to any one of claims 59 to 61, wherein the bispecific antibody or antigen-binding fragment thereof is of IgG1, IgG2, IgG3 or IgG4 isotype.

67. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof according to any one of claims 59 to 61, wherein the bispecific antibody or antigen-binding fragment thereof is of the IgG4 isotype.

68. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof according to any one of claims 59 to 61, wherein the bispecific antibody or antigen-binding fragment thereof has an EC of less than 500 pM in vitro. 50 Induces γδ T cell-dependent cytotoxicity of cancer cells.

69. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 68, wherein the bispecific antibody or antigen-binding fragment thereof has an EC of less than 300 pM in vitro. 50 Induces γδ T cell-dependent cytotoxicity of cancer cells.

70. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 68, wherein the bispecific antibody or antigen-binding fragment thereof has an EC of less than 160 pM in vitro. 50 Induces γδ T cell-dependent cytotoxicity of cancer cells.

71. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 68, wherein the EC is assessed using a mixture of γδ T effector cells and Kasumi3 AML target cells. 50 .

72. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 71, wherein the ratio of the effector cells to the target cells is between 0.01 to 1 and 5 to 1.

73. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 72, wherein the ratio of the effector cells to the target cells is between 0.1 to 1 and 2 to 1.

74. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 73, wherein the ratio of the effector cells to the target cells is 1:

1.

75. An isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof, comprising: a.HC1; b.HC2 c.LC1; and d.LC2, wherein HC1 associates with LC1, and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2 and HCDR3 with the following amino acid sequence: 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. SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 33, respectively, And LC1 comprises LCDR1, LCDR2 and LCDR3 whose amino acid sequences are SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6, respectively, to form a binding site for the first antigen that specifically binds to Vγ9.

76. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof according to claim 75, wherein The amino acid sequence of HC1 is at least 95% identical to the amino acid sequence of SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35 or SEQ ID NO:36, and the amino acid sequence of LC1 is at least 95% identical to the amino acid sequence of SEQ ID NO:

8.

77. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof according to claim 76, in The amino acid sequence of HC1 is SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35 or SEQ ID NO:36, and the amino acid sequence of LC1 is SEQ ID NO:

8.

78. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof according to claim 77, wherein the amino acid sequence of HC2 is SEQ ID NO: 15 and the amino acid sequence of LC2 is SEQ ID NO:

16.

79. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof according to any one of claims 75 to 78, wherein the TRGV9 is located on the surface of γδ T cells.

80. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof according to any one of claims 76 to 78, wherein the CD123 is located on the surface of a tumor cell or a CD34+ stem cell.

81. An isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof according to any one of claims 75 to 78, wherein the bispecific antibody binds to TRGV9 present on the surface of the γδ T cells and to the CD123 on the surface of tumor cells resulting in killing of the tumor cells.

82. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof according to any one of claims 75 to 78, wherein HC1 and LC1 are humanized.

83. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof according to any one of claims 75 to 78, wherein HC2 and LC2 are humanized.

84. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof according to any one of claims 75 to 78, wherein the bispecific antibody or antigen-binding fragment thereof is of IgG1, IgG2, IgG3 or IgG4 isotype.

85. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof according to any one of claims 75 to 78, wherein the bispecific antibody or antigen-binding fragment thereof is of the IgG4 isotype.

86. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof according to any one of claims 75 to 78, wherein the bispecific antibody or antigen-binding fragment thereof has an EC of less than 500 pM in vitro. 50 Induces γδ T cell-dependent cytotoxicity of cancer cells.

87. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof according to claim 86, wherein the bispecific antibody or antigen-binding fragment thereof has an EC of less than 300 pM in vitro. 50 Induces γδ T cell-dependent cytotoxicity of cancer cells.

88. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof according to claim 86, wherein the bispecific antibody or antigen-binding fragment thereof has an EC of less than 160 pM in vitro. 50 Induces γδ T cell-dependent cytotoxicity of cancer cells.

89. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof according to claim 86, wherein the EC is evaluated using a mixture of γδ T effector cells and Kasumi3 AML target cells. 50 .

90. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof according to claim 89, wherein the ratio of the effector cells to the target cells is 0.01 to 1 to 5 to 1.

91. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof of claim 90, wherein the ratio of the effector cells to the target cells is between 0.1 to 1 and 2 to 1.

92. The isolated anti-TRGV9 / anti-CD123 bispecific antibody or antigen-binding fragment thereof according to claim 91, wherein the ratio of the effector cells to the target cells is 1:

1.

93. A method for preparing an isolated anti-TRGV9 / anti-CD123 bispecific antibody or an antigen-binding fragment thereof according to any one of claims 75 to 92, the method comprising culturing a cell comprising a nucleic acid encoding the anti-TRGV9 / anti-CD123 bispecific antibody or an antigen-binding fragment thereof under conditions that produce the bispecific antibody or the antigen-binding fragment thereof, and recovering the bispecific antibody or the antigen-binding fragment thereof.

94. An isolated TRGV9 bispecific antibody or an antigenic epitope binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or an antigenic epitope binding fragment thereof comprises a binding site for a first antigen and a binding site for a second antigen, wherein the binding site for the first antigen binds a TRGV9 epitope on a γδT cell, and the binding site for the second antigen binds an epitope of the second antigen on the surface of a target cell, and binding to the TRGV9 epitope on the γδT cell and binding to the second antigen epitope on the target cell results in killing the target cell, wherein the second antigen epitope is a CD123 epitope, wherein the isolated TRGV9 bispecific antibody or an antigenic epitope binding fragment thereof comprises: a.HC1; b.HC2; c.LC1; and d.LC2, wherein HC1 associates with LC1, and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2 and HCDR3 having the following amino acid sequence: 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. SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 33, respectively, and LC1 comprises LCDR1, LCDR2 and LCDR3 having amino acid sequences of SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6, respectively, to form a binding site for a first antigen; and And wherein HC2 and LC2 form a binding site for a second antigen epitope.

95. An isolated TRGV9 bispecific antibody or antigen-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or antigen-binding fragment thereof comprises: a.HC1; b.HC2; c.LC1; and d.LC2, wherein HC1 associates with LC1, and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2 and HCDR3 having the following amino acid sequence: 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. SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 33, respectively, and LC1 comprises LCDR1, LCDR2 and LCDR3 having amino acid sequences of SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6, respectively, to form a binding site for a first antigen; and And wherein HC2 and LC2 form a binding site for a second antigen epitope.

96. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 95, wherein HC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35 or SEQ ID NO:36, and LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:

8.

97. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 96, wherein HC1 comprises the amino acid sequence of SEQ ID NO: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.

98. The isolated TRGV9 bispecific antibody or antigen-binding fragment of any one of claims 95 to 97, wherein HC1 and LC1 are humanized.

99. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof according to any one of claims 95 to 97, wherein HC2 and LC2 bind to the CD123 epitope.

100. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 99, wherein HC2 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 15, and LC2 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:

16.

101. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 100, wherein HC2 comprises the amino acid sequence of SEQ ID NO:15 and LC2 comprises the amino acid sequence of SEQ ID NO:

16.

102. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof according to any one of claims 94 to 97, wherein the bispecific antibody or antigen-binding fragment thereof is of IgG1, IgG2, IgG3 or IgG4 isotype.

103. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof according to any one of claims 94 to 97, wherein the bispecific antibody or antigen-binding fragment thereof is of the IgG4 isotype.

104. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof according to any one of claims 94 to 97, wherein the bispecific antibody or antigen-binding fragment thereof has an EC of less than 500 pM in vitro. 50 Induces γδ T cell-dependent cytotoxicity of cancer cells.

105. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 104, wherein the bispecific antibody or antigen-binding fragment thereof has an EC of less than 300 pM in vitro. 50 Induces γδ T cell-dependent cytotoxicity of cancer cells.

106. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 105, wherein the bispecific antibody or antigen-binding fragment thereof has an EC of less than 160 pM in vitro. 50 Induces γδ T cell-dependent cytotoxicity of cancer cells.

107. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 104, wherein the EC is assessed using a mixture of γδ T effector cells and Kasumi3 AML target cells. 50 .

108. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 107, wherein the ratio of the effector cells to the target cells is between 0.01 to 1 and 5 to 1.

109. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 108, wherein the ratio of effector cells to target cells is between 0.1 to 1 and 2 to 1.

110. The isolated TRGV9 bispecific antibody or antigen-binding fragment thereof of claim 109, wherein the ratio of the effector cells to the target cells is 1:

1.

111. An isolated γδT cell bispecific antibody or an antigen-binding fragment thereof, wherein the isolated γδT cell bispecific antibody or an antigen-binding fragment thereof comprises a binding site for a first antigenic epitope and a binding site for a second antigenic epitope, wherein the binding site for the first antigenic epitope binds to a first antigen on a γδT cell, and the binding site for the second antigenic epitope binds to the second antigenic epitope on the surface of a target cell, and binding to the first antigenic epitope on the γδT cell and binding to the second antigenic epitope on the target cell results in killing the target cell, wherein the second antigenic epitope is a CD123 epitope, wherein the isolated TRGV9 bispecific antibody or an antigen-binding fragment thereof comprises: a.HC1; b.HC2; c.LC1; and d.LC2, wherein HC1 associates with LC1, and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2 and HCDR3 having the following amino acid sequence: 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. SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 33, respectively, and LC1 comprises LCDR1, LCDR2 and LCDR3 having amino acid sequences of SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6, respectively, to form a binding site for a first antigen; and And wherein HC2 and LC2 form a binding site for a second antigen epitope.

112. An isolated nucleic acid encoding a TRGV9 bispecific antibody or an antigen-binding fragment thereof, the isolated TRGV9 bispecific antibody or an antigen-binding fragment thereof comprising: a.HC1; b.HC2; c.LC1; and d.LC2, wherein HC1 associates with LC1, and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2 and HCDR3 having the following amino acid sequence: 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. SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 33, respectively, and LC1 comprises LCDR1, LCDR2, and LCDR3 having amino acid sequences of SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, respectively, to form a binding site for a first antigen; HC2 and LC2 form the binding site for the second antigen.

113. The isolated nucleic acid of claim 112, wherein HCl comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35 or SEQ ID NO:36, and LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:

8.

114. The isolated nucleic acid of claim 113, wherein HC1 comprises the amino acid sequence of SEQ ID NO: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.

115. The isolated nucleic acid of any one of claims 112 to 114, wherein the binding site for the first antigen binds to TRGV9 on γδ T cells.

116. The isolated nucleic acid of any one of claims 112 to 114, wherein the binding site for the second antigen binds to a cancer antigen present on the surface of a cancer cell.

117. The isolated nucleic acid of claim 116, wherein the bispecific antibody binds to TRGV9 present on the surface of the γδ T cell and to the cancer antigen present on the surface of the cancer cell resulting in killing of the cancer cell.

118. The isolated nucleic acid of any one of claims 112 to 114, wherein HCl and LC1 are humanized.

119. The isolated nucleic acid of any one of claims 112 to 114, wherein HC2 and LC2 bind to CD123.

120. The isolated nucleic acid of any one of claims 112 to 114, wherein the bispecific antibody or antigen-binding fragment thereof is of the IgG1, IgG2, IgG3 or IgG4 isotype.

121. The isolated nucleic acid of any one of claims 112 to 114, wherein the bispecific antibody or antigen-binding fragment thereof is of the IgG4 isotype.

122. The isolated nucleic acid of any one of claims 112 to 114, wherein the bispecific antibody or antigen-binding fragment thereof has an EC of less than 500 pM in vitro. 50 Induces γδ T cell-dependent cytotoxicity of cancer cells.

123. The isolated nucleic acid of claim 122, wherein the bispecific antibody or antigen-binding fragment thereof is expressed in vitro at an EC of less than 300 pM. 50 Induces γδ T cell-dependent cytotoxicity of cancer cells.

124. The isolated nucleic acid of claim 122, wherein the bispecific antibody or antigen-binding fragment thereof is expressed in vitro at an EC of less than 160 pM. 50 Induces γδ T cell-dependent cytotoxicity of cancer cells.

125. The isolated nucleic acid of claim 122, wherein the EC is assessed using a mixture of γδ T effector cells and Kasumi3 AML target cells. 50 .

126. The isolated nucleic acid of claim 125, wherein the ratio of effector cells to target cells is between 0.01 to 1 and 5 to 1.

127. The isolated nucleic acid of claim 126, wherein the ratio of effector cells to target cells is between 0.1 to 1 and 2 to 1.

128. The isolated nucleic acid of claim 127, wherein the ratio of effector cells to target cells is 1:

1.

129. A vector comprising the isolated nucleic acid of any one of claims 112 to 128.

130. A host cell comprising the vector of claim 129.

131. A kit comprising the vector of claim 129 and packaging for the vector.

132. A pharmaceutical composition comprising an isolated TRGV9 bispecific antibody or an antigen-binding fragment thereof, wherein the isolated TRGV9 bispecific antibody or an antigen-binding fragment thereof comprises: a.HC1; b.HC2; c.LC1; and d.LC2, wherein HC1 associates with LC1, and HC2 associates with LC2, and wherein HC1 comprises HCDR1, HCDR2 and HCDR3 having the following amino acid sequence: 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. SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 33, respectively, and LC1 comprises LCDR1, LCDR2 and LCDR3 having amino acid sequences of SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6, respectively, to form a binding site for a first antigen; and HC2 and LC2 form the binding site for the second antigen. and a pharmaceutically acceptable carrier.

133. The pharmaceutical composition according to claim 132, wherein HC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:7, SEQ ID NO:34, SEQ ID NO:35 or SEQ ID NO:36, and LC1 comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:

8.

134. The pharmaceutical composition according to claim 133, wherein HC1 comprises the amino acid sequence of SEQ ID NO: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.

135. The pharmaceutical composition of any one of claims 132 to 134, wherein the binding site of the first antigen binds to TRGV9 on γδ T cells.

136. A pharmaceutical composition according to any one of claims 132 to 134, wherein the binding site of the second antigen binds to a cancer antigen present on the surface of a cancer cell.

137. The pharmaceutical composition of claim 136, wherein the bispecific antibody binds to TRGV9 present on the surface of the γδ T cells and to the cancer antigen present on the surface of the cancer cells resulting in killing of the cancer cells.

138. A pharmaceutical composition according to any one of claims 132 to 134, wherein HCl and LC1 are humanized.

139. A pharmaceutical composition according to any one of claims 132 to 134, wherein HC2 and LC2 bind to CD123.

140. The pharmaceutical composition of any one of claims 132 to 134, wherein the bispecific antibody or antigen-binding fragment thereof is of IgG1, IgG2, IgG3 or IgG4 isotype.

141. Use of the pharmaceutical composition according to any one of claims 132 to 134 in the preparation of a medicament for guiding γδT cells expressing Vγ9 to cancer cells, wherein the γδT cells expressing Vγ9 are contacted with the medicament to guide the γδT cells expressing Vγ9 to cancer cells.

142. The use of a pharmaceutical composition according to any one of claims 132 to 134 in the preparation of a medicament for inhibiting the growth or proliferation of cancer cells that express cancer antigens on the cell surface, wherein contacting the cancer cells with the medicament inhibits the growth or proliferation of the cancer cells.

143. The use according to claim 142, wherein the cancer cells are contacted with an anti-TRGV9 bispecific antibody or an antigen-binding fragment thereof in the presence of γδ T cells expressing Vγ9.

144. Use of a pharmaceutical composition according to any one of claims 132 to 140 in the preparation of a medicament for treating cancer in a subject in need thereof, comprising: a. Identify subjects in need of cancer treatment; as well as b. administering the drug to a subject in need thereof, wherein administering the medicament to a subject in need thereof treats the cancer in the subject, wherein the cancer involves CD123.

145. A method for activating γδT cells expressing Vγ9, the method comprising contacting the γδT cells expressing Vγ9 with a pharmaceutical composition according to any one of claims 132 to 140, wherein contacting the γδT cells expressing Vγ9 with the pharmaceutical composition results in an increase in CD69, CD25 and / or granzyme B expression compared to control γδT cells expressing Vγ9.

146. A method for preparing a pharmaceutical composition according to any one of claims 132 to 140, the method comprising combining the bispecific antibody or antigen-binding fragment thereof with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition.

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