Materials and methods for modulating immune responses

Abstract

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

Description

[0001] Cross-reference to related applications

[0002] This application claims the rights of the following applications filed on February 27, 2020: U.S. Serial No. 62 / 982,492; U.S. Serial No. 62 / 982,505; U.S. Serial No. 62 / 982,374; U.S. Serial No. 62 / 982,462; U.S. Serial No. 62 / 982,478; U.S. Serial No. 62 / 982,469; U.S. Serial No. 62 / 982,525; and U.S. Serial No. 62 / 982,535. US serial number 62 / 982,574 submitted on February 27, 2020; US serial number 62 / 982,591 submitted on February 27, 2020; US serial number 62 / 982,664 submitted on February 27, 2020; US serial number 62 / 982,669 submitted on February 27, 2020; US serial number 62 / 982,602 submitted on February 27, 2020; US serial number 62 / 982,548 submitted on February 27, 2020; US serial number 62 / 988,996 submitted on March 13, 2020; US serial number 62 / 989,002 submitted on March 13, 2020; US serial number 62 / ... submitted on March 13, 2020... 989,006; US serial number 62 / 989,010 submitted on March 13, 2020; US serial number 62 / 989,018 submitted on March 13, 2020; US serial number 62 / 989,024 submitted on March 13, 2020; US serial number 62 / 989,027 submitted on March 13, 2020; US serial number 62 / 989,036 submitted on March 13, 2020; US serial number 62 / 989,042 submitted on March 13, 2020; US serial number 62 / 989,045 submitted on March 13, 2020; US serial number 62 / 989,052 submitted on March 13, 2020; US serial number 62 / 989,057 submitted on [date missing]; US serial number 62 / 989,068 submitted on March 13, 2020; US serial number 62 / 989,075 submitted on March 13, 2020; International serial number PCT / US20 / 31749 submitted on May 7, 2020; US serial number 63 / 074,655 submitted on September 4, 2020; US serial number 63 / 074,676 submitted on September 4, 2020; US serial number 63 / 074,854 submitted on September 4, 2020; US serial number 63 / 074,700 submitted on September 4, 2020; US serial number 63 / 074,749 submitted on September 4, 2020.US serial number 63 / 074,735, submitted on September 4, 2020; US serial number 63 / 074,839, submitted on September 4, 2020; US serial number 63 / 074,759, submitted on September 4, 2020; US serial number 63 / 074,903, submitted on September 4, 2020; US serial number 63 / 074,893, submitted on September 4, 2020; US serial number submitted on September 4, 2020. U.S. Serial No. 63 / 074,925; U.S. Serial No. 63 / 074,937 filed on September 4, 2020; U.S. Serial No. 63 / 074,962 filed on September 4, 2020; U.S. Serial No. 63 / 074,946 filed on September 4, 2020; U.S. Serial No. 63 / 112,462 filed on November 11, 2020; and U.S. Serial No. 63 / 112,475 filed on November 11, 2020. Technical Field

[0003] This invention relates to T-cell receptor (TCR) retargeting techniques, such as those targeting the T-cell receptor γ variable region 9 (TRGV9) molecule, including TRGV9 antibodies, bispecific antibodies, nucleic acids encoding the antibodies and expression vectors, recombinant cells containing the vectors, and compositions containing the antibodies. Methods for preparing these antibodies and methods for modulating immune responses against cancer cells using these antibodies are also provided.

[0004] Reference sequence list submitted electronically

[0005] This application includes a sequence list, which is submitted electronically via EFS-Web in ASCII format, file name "14620-381-228_SEQLISTING" and created on February 22, 2021, and is 440,714 bytes in size. This sequence list submitted via EFS-Web is an integral part of this specification and is incorporated herein by reference in its entirety. Summary of the Invention

[0006] T-cell receptor retargeting technologies are provided, including, for example, TRGV9 molecules, such as TRGV9 antibodies and multispecific antibodies, as well as nucleic acids encoding antibodies and expression vectors, recombinant cells containing vectors, and compositions containing antibodies.

[0007] In one aspect, this article provides an antibody that binds to TRGV9. In some embodiments, the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL).

[0008] In one embodiment, the TRGV9 antibody has the VH and VL amino acid sequences of L7A5_2 (TRGV9_2). In one embodiment, the TRGV9 antibody comprises: (i) a VH containing VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences VH CDR1, VH CDR2, and VH CDR3, respectively, which belong to the VH having the amino acid sequence of SEQ ID NO: 34; and (ii) a VL containing VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences VL CDR1, VL CDR2, and VL CDR3, respectively, which belong to the VL having the amino acid sequence of SEQ ID NO: 8.

[0009] In one embodiment, the TRGV9 antibody has the VH and VL amino acid sequences of L7A5_3 (TRGV9_3). In one embodiment, the TRGV9 antibody comprises: (i) a VH containing VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences VH CDR1, VH CDR2, and VH CDR3, respectively, which belong to the VH having the amino acid sequence of SEQ ID NO: 35; and (ii) a VL containing VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences VL CDR1, VL CDR2, and VL CDR3, respectively, which belong to the VL having the amino acid sequence of SEQ ID NO: 8.

[0010] In one embodiment, the TRGV9 antibody has the VH and VL amino acid sequences of L7A5_4 (TRGV9_4). In one embodiment, the TRGV9 antibody comprises: (i) a VH containing VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences VH CDR1, VH CDR2, and VH CDR3, respectively, which belong to the VH having the amino acid sequence of SEQ ID NO: 36; and (ii) a VL containing VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences VL CDR1, VL CDR2, and VL CDR3, respectively, which belong to the VL having the amino acid sequence of SEQ ID NO: 8.

[0011] In one embodiment, the TRGV9 antibody has the VH and VL amino acid sequences of TRGV9Ab_var17. In one embodiment, the TRGV9 antibody comprises: (i) a VH containing VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences VH CDR1, VH CDR2, and VH CDR3, respectively, which belong to the VH having the amino acid sequence of SEQ ID NO: 65; and (ii) a VL containing VL CDR1, VLCDR2, and VL CDR3 having the amino acid sequences VL CDR1, VL CDR2, and VL CDR3, respectively, which belong to the VL having the amino acid sequence of SEQ ID NO: 66.

[0012] In one embodiment, the TRGV9 antibody has the VH and VL amino acid sequences of TRGV9Ab_var29. In one embodiment, the TRGV9 antibody comprises: (i) a VH containing VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, which belong to the VH having the amino acid sequence of SEQ ID NO: 67; and (ii) a VL containing VL CDR1, VLCDR2, and VL CDR3 having amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, which belong to the VL having the amino acid sequence of SEQ ID NO: 68.

[0013] In one embodiment, the TRGV9 antibody has the VH and VL amino acid sequences of VG9B420. In one embodiment, the TRGV9 antibody comprises: (i) a VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences VH CDR1, VH CDR2, and VH CDR3, respectively, which belong to the VH having the amino acid sequence of SEQ ID NO: 104; and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences VL CDR1, VL CDR2, and VL CDR3, respectively, which belong to the VL having the amino acid sequence of SEQ ID NO: 105.

[0014] In one embodiment, the TRGV9 antibody has the VH and VL amino acid sequences of VG9SB10SC1087_P18_D08. In one embodiment, the TRGV9 antibody comprises: (i) a VH containing VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences VH CDR1, VH CDR2, and VHCDR3, respectively, which belong to the VH having the amino acid sequence of SEQ ID NO: 113; and (ii) a VL containing VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences VL CDR1, VL CDR2, and VL CDR3, respectively, which belong to the VL having the amino acid sequence of SEQ ID NO: 114.

[0015] In one embodiment, the TRGV9 antibody has the VH and VL amino acid sequences of VG9SB10SC1087_P18_C12. In one embodiment, the TRGV9 antibody comprises: (i) a VH containing VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences VH CDR1, VH CDR2, and VHCDR3, respectively, which belong to the VH having the amino acid sequence of SEQ ID NO: 123; and (ii) a VL containing VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences VL CDR1, VL CDR2, and VL CDR3, respectively, which belong to the VL having the amino acid sequence of SEQ ID NO: 124.

[0016] In one embodiment, the TRGV9 antibody has the VH and VL amino acid sequences of VG9SB10SC1087_P19_C03. In one embodiment, the TRGV9 antibody comprises: (i) a VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences VH CDR1, VH CDR2, and VHCDR3, respectively, wherein these VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 133; and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences VL CDR1, VL CDR2, and VL CDR3, respectively, wherein these VH CDR1, VH CDR2, and VH CDR3 belong to the VL having the amino acid sequence of SEQ ID NO: 134.

[0017] In some embodiments, the amino acid sequences of the TRGV9 antibody, namely VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, are based on the Kabat numbering system. In some embodiments, the amino acid sequences of the TRGV9 antibody, namely VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, are based on the Chothia numbering system. In some embodiments, the amino acid sequences of the TRGV9 antibody, namely VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, are based on the AbM numbering system. In some embodiments, the amino acid sequences of the TRGV9 antibody, namely VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, are based on the Contact numbering system. In some embodiments, the amino acid sequences of the TRGV9 antibody, namely VHCDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, are based on the IMGT numbering system. In some embodiments, the amino acid sequences of the TRGV9 antibody, namely VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, are based on an exemplary numbering system.

[0018] In some embodiments, the antibody binds to the TRGV9 antigen. In some embodiments, the antibody binds to a TRGV9 epitope. In some embodiments, the antibody specifically binds to TRGV9. In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 form binding sites for the TRGV9 antigen. In some embodiments, VHCDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 form binding sites for the TRGV9 epitope. In some embodiments, TRGV9 is present on the surface of T cells. In some embodiments, the T cells are γδ T cells.

[0019] In some embodiments, the TRGV9 antibody is chimeric. In some embodiments, the TRGV9 antibody is human. In some embodiments, the TRGV9 antibody is humanized. In some embodiments, the TRGV9 antibody is an isolated TRGV9 antibody. In some embodiments, the TRGV9 antibody is a TRGV9 antigen-binding fragment. In some embodiments, the TRGV9 antigen-binding fragment is chimeric. In some embodiments, the TRGV9 antigen-binding fragment is human. In some embodiments, the TRGV9 antigen-binding fragment is humanized. In some embodiments, the TRGV9 antigen-binding fragment is an isolated TRGV9 antigen-binding fragment. In some embodiments, the TRGV9 antibody is an IgG antibody. In some embodiments, the TRGV9 antibody is an IgG1 antibody. In some embodiments, the TRGV9 antibody is an IgG2 antibody. In some embodiments, the TRGV9 antibody is an IgG3 antibody. In some embodiments, the TRGV9 antibody is an IgG4 antibody. In some embodiments, the TRGV9 antibody contains a κ light chain. In some embodiments, the TRGV9 antibody contains a λ light chain. In some embodiments, the TRGV9 antibody is a monoclonal antibody. In some embodiments, the TRGV9 antibody is multivalent. In some embodiments, the TRGV9 antibody is capable of binding to at least three antigens. In some embodiments, the TRGV9 antibody is capable of binding to at least four antigens. In some embodiments, the TRGV9 antibody is capable of binding to at least five antigens. In some embodiments, the TRGV9 antibody is a multispecific antibody. In some embodiments, the TRGV9 antibody is a bispecific antibody. In some embodiments, the TRGV9 antibody is a trispecific antibody. In some embodiments, the TRGV9 antibody is a tetraspecific antibody.

[0020] In one specific implementation, the TRGV9 antibody is a multispecific TRGV9 antibody. In another specific implementation, the multispecific TRGV9 antibody is a bispecific TRGV9 antibody.

[0021] Therefore, in one aspect, a multispecific TRGV9 antibody is provided, which comprises the TRGV9 antibody provided herein. In one embodiment, the multispecific TRGV9 antibody comprises: (a) a first binding domain that binds to TRGV9, and (b) a second binding domain that binds to a second target that is not TRGV9.

[0022] In one embodiment, the first binding domain binding to TRGV9 comprises the VH and VL amino acid sequences of L7A5_1 (TRGV9_1). In one embodiment, the first binding domain binding to TRGV9 comprises: (i) VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, wherein these VHCDRs belong to the VH having the amino acid sequence of SEQ ID NO: 7; and (ii) VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences of VL CDR1, VLCDR2, and VL CDR3, respectively, wherein these VH CDR1, VH CDR2, and VHCDR3 belong to the VL having the amino acid sequence of SEQ ID NO: 8.

[0023] In one embodiment, the first binding domain binding to TRGV9 comprises the VH and VL amino acid sequences of L7A5_2 (TRGV9_2). In one embodiment, the first binding domain binding to TRGV9 comprises: (i) VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, wherein these VHCDRs belong to the VH having the amino acid sequence of SEQ ID NO: 34; and (ii) VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences of VL CDR1, VLCDR2, and VL CDR3, respectively, wherein these VH CDR1, VH CDR2, and VHCDR3 belong to the VL having the amino acid sequence of SEQ ID NO: 8.

[0024] In one embodiment, the first binding domain binding to TRGV9 comprises the VH and VL amino acid sequences of L7A5_3 (TRGV9_3). In one embodiment, the first binding domain binding to TRGV9 comprises: (i) a VH comprising VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, wherein these VHCDRs belong to the VH having the amino acid sequence of SEQ ID NO: 35; and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences of VL CDR1, VLCDR2, and VL CDR3, respectively, wherein these VH CDR1, VH CDR2, and VHCDR3 belong to the VL having the amino acid sequence of SEQ ID NO: 8.

[0025] In one embodiment, the first binding domain binding to TRGV9 comprises the VH and VL amino acid sequences of L7A5_4 (TRGV9_4). In one embodiment, the first binding domain binding to TRGV9 comprises: (i) a VH comprising VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, wherein these VHCDRs belong to the VH having the amino acid sequence of SEQ ID NO: 36; and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences of VL CDR1, VLCDR2, and VL CDR3, respectively, wherein these VH CDR1, VH CDR2, and VHCDR3 belong to the VL having the amino acid sequence of SEQ ID NO: 8.

[0026] In one embodiment, the first binding domain that binds to TRGV9 comprises the VH and VL amino acid sequences of TRGV9Ab_var17. In one embodiment, the first binding domain that binds to TRGV9 comprises: (i) VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, wherein these VHCDRs belong to the VH having the amino acid sequence of SEQ ID NO: 65; and (ii) VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences of VL CDR1, VLCDR2, and VL CDR3, respectively, wherein these VH CDR1, VH CDR2, and VHCDR3 belong to the VL having the amino acid sequence of SEQ ID NO: 66.

[0027] In one embodiment, the first binding domain that binds to TRGV9 comprises the VH and VL amino acid sequences of TRGV9Ab_var29. In one embodiment, the first binding domain that binds to TRGV9 comprises: (i) a VH comprising VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, wherein these VHCDRs belong to the VH having the amino acid sequence of SEQ ID NO: 67; and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences of VL CDR1, VLCDR2, and VL CDR3, respectively, wherein these VH CDR1, VH CDR2, and VHCDR3 belong to the VL having the amino acid sequence of SEQ ID NO: 68.

[0028] In one embodiment, the first binding domain that binds to TRGV9 comprises the VH and VL amino acid sequences of VG9_B3_RN. In one embodiment, the first binding domain that binds to TRGV9 comprises: (i) VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, these VH CDRs belonging to the VH having the amino acid sequence of SEQ ID NO: 95; and (ii) VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, these VH CDR1, VH CDR2, and VH CDR3 belonging to the VL having the amino acid sequence of SEQ ID NO: 96.

[0029] In one embodiment, the first binding domain that binds to TRGV9 comprises the VH and VL amino acid sequences of VG9B420. In one embodiment, the first binding domain that binds to TRGV9 comprises: (i) VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, these VH CDRs belonging to the VH having the amino acid sequence of SEQ ID NO: 104; and (ii) VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, these VH CDR1, VH CDR2, and VH CDR3 belonging to the VL having the amino acid sequence of SEQ ID NO: 105.

[0030] In one embodiment, the first binding domain binding to TRGV9 comprises the VH and VL amino acid sequences of VG9SB10SC1087_P18_D08. In one embodiment, the first binding domain binding to TRGV9 comprises: (i) VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, these VH CDRs belonging to the amino acid sequence of SEQ ID NO: 113; and (ii) VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences of VLCDR1, VL CDR2, and VL CDR3, respectively, these VH CDR1, VHCDR2, and VH CDR3 belonging to the amino acid sequence of SEQ ID NO: 114.

[0031] In one embodiment, the first binding domain binding to TRGV9 comprises the VH and VL amino acid sequences of VG9SB10SC1087_P18_C12. In one embodiment, the first binding domain binding to TRGV9 comprises: (i) VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, these VH CDRs belonging to the amino acid sequence of SEQ ID NO: 123; and (ii) VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences of VLCDR1, VL CDR2, and VL CDR3, respectively, these VH CDR1, VHCDR2, and VH CDR3 belonging to the amino acid sequence of SEQ ID NO: 124.

[0032] In one embodiment, the first binding domain binding to TRGV9 comprises the VH and VL amino acid sequences of VG9SB10SC1087_P19_C03. In one embodiment, the first binding domain binding to TRGV9 comprises: (i) VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, these VH CDRs belonging to the VH having the amino acid sequence of SEQ ID NO: 133; and (ii) VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences of VLCDR1, VL CDR2, and VL CDR3, respectively, these VH CDR1, VHCDR2, and VH CDR3 belonging to the VL having the amino acid sequence of SEQ ID NO: 134.

[0033] In some embodiments, the amino acid sequences of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 binding to the first binding domain of TRGV9 are numbered according to the Kabat numbering system. In some embodiments, the amino acid sequences of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 binding to the first binding domain of TRGV9 are numbered according to the Chothia numbering system. In some embodiments, the amino acid sequences of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 binding to the first binding domain of TRGV9 are numbered according to the AbM numbering system. In some embodiments, the amino acid sequences of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VLCDR3 binding to the first binding domain of TRGV9 are numbered according to the Contact numbering system. In some embodiments, the amino acid sequences of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 binding to the first binding domain of TRGV9 are defined according to the IMGT numbering system. In some embodiments, the amino acid sequences of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 binding to the first binding domain of TRGV9 are defined according to an exemplary numbering system.

[0034] In some embodiments, the first binding domain binds to the TRGV9 antigen. In some embodiments, the first binding domain binds to a TRGV9 epitope. In some embodiments, the first binding domain specifically binds to TRGV9. In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of the first binding domain form binding sites for the TRGV9 antigen. In some embodiments, VH CDR1, VH CDR2, VHCDR3, VL CDR1, VL CDR2, and VL CDR3 of the first binding domain form binding sites for the TRGV9 epitope. In some embodiments, TRGV9 is present on the surface of T cells.

[0035] In some embodiments of the multispecific TRGV9 antibody provided herein, the second target is not the TRGV9 antigen.

[0036] In some embodiments of the multispecific TRGV9 antibody provided herein, the second target is CD123. In one embodiment, the second binding domain binding to CD123 comprises: (i) a VH comprising VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, which belong to the VH having the amino acid sequence of SEQ ID NO: 15; and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, which belong to the VL having the amino acid sequence of SEQ ID NO: 16.

[0037] In some embodiments of the multispecific TRGV9 antibody provided herein, the second target is CD33. In one embodiment, the second target is the C2 domain of CD33. The second target is the V domain of CD33. In one embodiment, the second binding domain binding to CD33 comprises: (i) VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences VH CDR1, VH CDR2, and VH CDR3, respectively, belonging to the VH having the amino acid sequence of SEQ ID NO: 43; and (ii) VL, which comprises VLCDR1, VL CDR2, and VL CDR3 having the amino acid sequences VL CDR1, VL CDR2, and VL CDR3, respectively, belonging to the VL having the amino acid sequence of SEQ ID NO: 44.

[0038] In some embodiments of the multispecific TRGV9 antibody provided herein, the second target is TRBC1. In one embodiment, the second binding domain binding to TRBC1 comprises: (i) a VH comprising VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, wherein these VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 55; and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, wherein these VH CDR1, VH CDR2, and VH CDR3 belong to the VL having the amino acid sequence of SEQ ID NO: 56.

[0039] In some embodiments of the multispecific TRGV9 antibody provided herein, the second target is B cell maturation antigen (BCMA). In one embodiment, the second binding domain binds to BCMA. In one embodiment, the second binding domain binding to BCMA comprises: (i) VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences VH CDR1, VH CDR2, and VH CDR3, respectively, belonging to the amino acid sequence of SEQ ID NO: 143; and (ii) VL, which comprises VL CDR1, VLCDR2, and VL CDR3 having the amino acid sequences VL CDR1, VL CDR2, and VL CDR3, respectively, belonging to the amino acid sequence of SEQ ID NO: 144.

[0040] In some embodiments of the multispecific TRGV9 antibody provided herein, the second target is prostate-specific membrane antigen (PSMA). In one embodiment, the second binding domain binds to PSMA. In one embodiment, the second binding domain binding to PSMA comprises: (i) VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, belonging to the amino acid sequence of VH having SEQ ID NO: 775; and (ii) VL, which comprises VLCDR1, VL CDR2, and VL CDR3 having amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, belonging to the amino acid sequence of VL having SEQ ID NO: 776.

[0041] In some embodiments of the multispecific TRGV9 antibody provided herein, the second target is expressed by the target cell. In some embodiments of the multispecific TRGV9 antibody provided herein, the second target is located on the surface of the target cell. In specific embodiments, the target cell is an undesirable cell.

[0042] In one embodiment, the target cell is a cancer cell. In one embodiment, the target cell is a T cell. In one embodiment, the target cell is a B cell. In one embodiment, the target cell is a dendritic cell. In one embodiment, the target cell is an NK cell. In one embodiment, the target cell is a stem cell. In one embodiment, the target cell is a stem cell precursor. In one embodiment, the target cell is a monocyte. In one embodiment, the target cell is a macrophage. In one embodiment, the target cell is a granulocyte. In one embodiment, the target cell is a platelet. In one embodiment, the target cell is a red blood cell. In one embodiment, the target cell is an endothelial cell. In one embodiment, the target cell is an epithelial cell. In one embodiment, the second target is a pathogen. In one embodiment, the target cell is a cell containing a pathogen. In one embodiment, the target cell is a blood cell. In one embodiment, the target cell is a bone marrow cell.

[0043] In some embodiments, the amino acid sequences of VH CDR1, VH CDR2, VHCDR3, VL CDR1, VL CDR2, and VL CDR3 binding to the second binding domain of the second target are numbered according to the Kabat numbering system. In some embodiments, the amino acid sequences of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 binding to the second binding domain of the second target are numbered according to the Chothia numbering system. In some embodiments, the amino acid sequences of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 binding to the second binding domain of the second target are numbered according to the AbM numbering system. In some embodiments, the amino acid sequences of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 binding to the second binding domain of the second target are numbered according to the Contact numbering system. In some embodiments, the amino acid sequences of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 binding to the second binding domain of the second target are specified according to the IMGT numbering system. In some embodiments, the amino acid sequences of VH CDR1, VHCDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 binding to the second binding domain of the second target are specified according to an exemplary numbering system.

[0044] In some embodiments, the second binding domain binds to the antigen of the second target. In some embodiments, the second binding domain binds to the epitope of the second target. In some embodiments, the second binding domain specifically binds to the second target. In some embodiments, the second binding domain specifically binds to the antigen of the second target. In some embodiments, the second binding domain specifically binds to the epitope of the second target. In some embodiments, VHCDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of the second binding domain form binding sites for the antigen of the second target. In some embodiments, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VLCDR3 of the second binding domain form binding sites for the epitope of the second target. In some embodiments, the second target is present on the surface of the target cell. In some embodiments, when the multispecific TRGV9 antibody binds to the second target and TRGV9 located on the surface of T cells, the target cells expressing the second target are killed. In the specific implementation plan, the T cells are γδT cells.

[0045] In some embodiments, the first binding domain of a multispecific TRGV9 antibody is multivalent. In some embodiments, the first binding domain of a multispecific TRGV9 antibody is capable of binding to at least three antigens. In some embodiments, the first binding domain of a multispecific TRGV9 antibody is capable of binding to at least four antigens. In some embodiments, the first binding domain of a multispecific TRGV9 antibody is capable of binding to at least five antigens. In some embodiments, the second binding domain of a multispecific TRGV9 antibody is multivalent. In some embodiments, the second binding domain of a multispecific TRGV9 antibody is capable of binding to at least three antigens. In some embodiments, the second binding domain of a multispecific TRGV9 antibody is capable of binding to at least four antigens. In some embodiments, the second binding domain of a multispecific TRGV9 antibody is capable of binding to at least five antigens.

[0046] In some embodiments, the first binding domain is humanized. In some embodiments, the second binding domain is humanized. In some embodiments, both the first and second binding domains are humanized. In some embodiments, the multispecific TRGV9 antibody includes a κ light chain. In some embodiments, the multispecific TRGV9 antibody includes a λ light chain. In some embodiments, the multispecific TRGV9 antibody is an IgG antibody. In some embodiments, the IgG antibody is an IgG1 antibody. In some embodiments, the IgG antibody is an IgG2 antibody. In some embodiments, the IgG antibody is an IgG3 antibody. In some embodiments, the IgG antibody is an IgG4 antibody.

[0047] In some implementations, the multispecific TRGV9 antibody is expressed in vitro at an EC50 concentration of less than about 500 pM. 50 Induces T cell-dependent cytotoxicity in target cells expressing a second target. In some embodiments, the multispecific TRGV9 antibody is expressed in vitro at an EC50 concentration of less than approximately 300 pM. 50 Induces T cell-dependent cytotoxicity in target cells expressing a second target. In some embodiments, the multispecific TRGV9 antibody is expressed in vitro at an EC50 concentration of less than approximately 160 pM. 50 Inducing T cell-dependent cytotoxicity in target cells expressing a second target. In some embodiments, EC is evaluated using a mixture of T cell effector cells and target cells expressing the second target. 50 In some embodiments, the effector cell to target cell ratio is from about 0.01:1 to about 5:1. In some embodiments, the effector cell to target cell ratio is from about 0.1:1 to about 2:1. In some embodiments, the effector cell to target cell ratio is about 1:1. In a specific embodiment, the T cells are γδT cells. In one embodiment, the target cells are Kasumi-3 AML target cells.

[0048] In another aspect, a nucleic acid encoding the TRGV9 antibody provided herein is provided. A vector is also provided containing the nucleic acid encoding the TRGV9 antibody provided herein. A host cell containing the vector, which contains the nucleic acid encoding the TRGV9 antibody provided herein, is also provided. A kit is also provided comprising a vector containing the nucleic acid encoding the TRGV9 antibody provided herein and packaging for the vector. A method for preparing the TRGV9 antibody provided herein is also provided, the method comprising culturing cells containing the nucleic acid encoding the TRGV9 antibody under conditions for preparing the TRGV9 antibody. In another aspect, a kit is provided containing the TRGV9 antibody provided herein and its packaging. In another aspect, a pharmaceutical composition is provided herein comprising the TRGV9 antibody provided herein and a pharmaceutically acceptable vector. In another aspect, a method for preparing a pharmaceutical composition comprising the TRGV9 antibody provided herein is provided, the method comprising combining the TRGV9 antibody with a pharmaceutically acceptable vector to obtain the pharmaceutical composition. In a specific embodiment, the TRGV9 antibody is the multispecific TRGV9 antibody provided herein.

[0049] In another embodiment, a multispecific TRGV9 antibody is provided, comprising: a first component capable of binding TRGV9; and a second component capable of binding a second target. In some embodiments, the second target is not TRGV9. In another embodiment, a multispecific TRGV9 antibody is provided, comprising: a first component binding to TRGV9; and a second component binding to a second target. In some embodiments, the second target is not TRGV9. In some embodiments, TRGV9 is located on the surface of T cells. In some embodiments, the T cells are γδT cells. In some embodiments, the first component is capable of specifically binding TRGV9. In some embodiments, the first component specifically binds TRGV9. In one embodiment, TRGV9 is a TRGV9 antigen. In another embodiment, TRGV9 is a TRGV9 epitope. In one embodiment, the first component is a complementary site. In some embodiments, the complementary site is the complementary site of the TRGV9 antibody provided herein. In one embodiment, the first component is an antibody. In some embodiments, the antibody is the TRGV9 antibody provided herein. In some embodiments, the TRGV9 antibody is an antigen-binding fragment. In some embodiments, the second component is capable of specifically binding to a second target. In some embodiments, the second component specifically binds to a second target. In some embodiments, the second target is an antigen of the second target. In some embodiments, the second target is an epitope of the second target. In some embodiments, the second target is located on the surface of a target cell. In some embodiments, the second target is CD123. In some embodiments, the second target is CD33. In some embodiments, the second target is TRBC1. In some embodiments, the second target is BCMA. In some embodiments, the second target is PSMA. In one embodiment, the second component is a complementary site. In some embodiments, the complementary site is the complementary site of a second binding arm provided herein. In some embodiments, the complementary site is the complementary site of a CD123 antibody provided herein. In some embodiments, the complementary site is the complementary site of a CD33 antibody provided herein. In some embodiments, the complementary site is the complementary site of a TRBC1 antibody provided herein. In some embodiments, the complementary site is the complementary site of a BCMA antibody provided herein. In some embodiments, the complementary site is the complementary site of a PSMA antibody provided herein. In one embodiment, the second component is an antibody that binds to a second target provided herein. In some embodiments, the second component is a CD123 antibody provided herein. In one embodiment, the CD123 antibody is its antigen-binding fragment. In some embodiments, the second component is a CD33 antibody provided herein. In one embodiment, the CD33 antibody is its antigen-binding fragment. In some embodiments, the second component is a TRBC1 antibody provided herein. In one embodiment, the TRBC1 antibody is its antigen-binding fragment.In some embodiments, the second component is the BCMA antibody provided herein. In one embodiment, the BCMA antibody is its antigen-binding fragment. In some embodiments, the second component is the PSMA antibody provided herein. In one embodiment, the PSMA antibody is its antigen-binding fragment.

[0050] On the other hand, a method for preparing an antibody that binds to more than one target is provided, the method comprising: performing a step of acquiring the function of a first binding domain capable of binding to TRGV9; performing a step of acquiring the function of a second binding domain capable of binding to a second target; and performing a step of providing an antibody capable of binding to both TRGV9 and the second target. In some embodiments, the step of acquiring the function of the second binding domain capable of binding to the second target is repeated n times, and further comprises performing n steps of providing the function of the first binding domain capable of binding to TRGV9 and n targets, wherein n is at least 2. In some embodiments, the second target is not TRGV9. In some embodiments, the first binding domain is capable of specifically binding to TRGV9. In one embodiment, TRGV9 is a TRGV9 antigen. In another embodiment, TRGV9 is a TRGV9 epitope. In one embodiment, the first binding domain binds to the TRGV9 antigen. In one embodiment, the first binding domain binds to the TRGV9 epitope. In some embodiments, TRGV9 is located on the surface of T cells. In some embodiments, the T cells are γδT cells. In some embodiments, the second binding domain is capable of specifically binding to a second target. In one embodiment, the second binding domain binds to an antigen of the second target. In one embodiment, the second binding domain binds to an epitope of the second target. In some embodiments, the second target is located on the surface of the target cell. In some embodiments, the second target is CD123. In some embodiments, the second target is CD33. In some embodiments, the second target is TRBC1. In some embodiments, the second target is BCMA. In some embodiments, the second target is PSMA. In one embodiment, the target cell is a cancer cell.

[0051] In another aspect, a method for activating T cells expressing TRGV9 is provided, the method comprising contacting the T cells with an antibody against TRGV9 provided herein. In some embodiments, this contact results in increased expression of CD69, CD25, and / or granzyme B compared to control T cells expressing TRGV9. In another aspect, a method for inactivating T cells expressing TRGV9 is provided, the method comprising contacting the T cells with an antibody binding to TRGV9 provided herein. A method for blocking the activation of T cells expressing TRGV9 is also provided, the method comprising contacting the T cells with an antibody binding to TRGV9 provided herein. A method for modulating the activity of T cells expressing TRGV9 is also provided, the method comprising contacting the T cells with an antibody binding to TRGV9 provided herein. In a specific embodiment, the T cells are γδ T cells. In some embodiments, the TRGV9 antibody is a multispecific TRGV9 antibody provided herein.

[0052] In another aspect, a method is provided for guiding TRGV9-expressing T cells to target cells, the method comprising contacting the T cells with a multispecific TRGV9 antibody provided herein, wherein the contact guides the T cells to the target cells. In another aspect, a method is provided for inhibiting the growth or proliferation of target cells, the method comprising contacting the target cells with a multispecific TRGV9 antibody provided herein, wherein the contact inhibits the growth or proliferation of the target cells. In some embodiments, the target cells are contacted with the multispecific TRGV9 antibody in the presence of TRGV9-expressing T cells. In some embodiments, the target cells express a second target that is not TRGV9. In some embodiments, the T cells are γδT cells. In some embodiments, the second target is an antigen of a second target. In some embodiments, the second target is an epitope of a second target. In some embodiments, the second target is located on the surface of the target cells. In some embodiments, the second target is CD123. In some embodiments, the second target is CD33. In some embodiments, the second target is TRBC1. In some embodiments, the second target is BCMA. In some embodiments, the second target is PSMA. In one implementation, the target cells are cancer cells.

[0053] In another aspect, a method for eliminating target cells in a subject is provided, the method comprising administering to the subject an effective amount of the multispecific TRGV9 antibody provided herein. In another aspect, a method for treating a disease, disorder, or symptom (hereinafter “disease”) wholly or partially caused by target cells in a subject is provided, the method comprising administering to the subject an effective amount of the multispecific TRGV9 antibody provided herein. In another aspect, a method for preventing a disease wholly or partially caused by target cells in a subject is provided, the method comprising administering to the subject an effective amount of the multispecific TRGV9 antibody provided herein. In another aspect, a method for modulating a disease wholly or partially caused by target cells in a subject is provided, the method comprising administering to the subject an effective amount of the multispecific TRGV9 antibody provided herein. In some embodiments, the target cells express a second target that is not a TRGV9 target. In some embodiments, the second target is located on the surface of the target cells. In some embodiments, the second target is CD123. In some embodiments, the second target is CD33. In some embodiments, the second target is TRBC1. In some embodiments, the second target is BCMA. In some embodiments, the second target is PSMA. In one embodiment, the target cells are cancer cells. In one embodiment, the target cell is a T cell. In one embodiment, the target cell is a B cell. In one embodiment, the target cell is a dendritic cell. In one embodiment, the target cell is an NK cell. In one embodiment, the target cell is a stem cell. In one embodiment, the target cell is a stem cell precursor. In one embodiment, the target cell is a monocyte. In one embodiment, the target cell is a macrophage. In one embodiment, the target cell is a granulocyte. In one embodiment, the target cell is a platelet. In one embodiment, the target cell is a red blood cell. In one embodiment, the target cell is an endothelial cell. In one embodiment, the target cell is an epithelial cell. In one embodiment, the second target is a pathogen. In one embodiment, the target cell is a cell containing a pathogen. In one embodiment, the target cell is a blood cell. In one embodiment, the target cell is a bone marrow cell. In some embodiments, the second target is located on a cancer cell. In some embodiments, the target cell is a cancer cell. In a specific embodiment, the second target is located on the surface of a cancer cell. In some embodiments, the second target is an antigen on the surface of a cancer cell. In some embodiments, the antigen on the surface of a cancer cell is a tumor-specific antigen, a tumor-associated antigen, or a neoantigen; in a specific embodiment, the disease is cancer. In some implementations, the subject is a subject who needs it. In some implementations, the subject is a person. In some implementations, the method further includes identifying subjects who need it. Attached Figure Description

[0054] A better understanding of the foregoing invention and the following detailed description of specific embodiments of this patent application can be achieved by reading the accompanying drawings. However, it should be understood that this patent application is not limited to the precise embodiments shown in the drawings.

[0055] Figure 1 A schematic diagram illustrating the binding of an exemplary multispecific TRGV9 antibody is shown. This antibody includes a first binding domain that binds to TRGV9 and a second binding domain that binds to a second target antigen on a target cell to recruit γδT cells to the target cell and induce target cell death. The second target antigen may be a tumor-associated antigen (TAA), and the target cell may be a tumor cell, wherein the anti-TRGV9 / anti-TAA bispecific antibody recruits γδT cells to cancer cells and induces cancer cell death.

[0056] Figure 2 A diagram showing the selective expansion of Vγ9Vδ2 cells from whole peripheral blood mononuclear cells (PBMCs) by zoledronic acid is shown.

[0057] Figures 3A to 3E The phenotypic characteristics of Vγ9+γδT cells are shown. Figure 3A A schematic diagram (left) is shown to describe the phylogenetic hierarchy of γδT cells. A representative FACS dot plot shows Vγ9 from fresh PBMCs (left) and PBMCs cultured in vitro for 14 days with zoledronic acid + IL-2 + IL-15 (right). + Differentiation profile of γδ T cells. The numbers in the quadrants reflect fresh and activated Vγ9 cells. + Frequency of the corresponding population in γδT cells (mean ± SEM). Data represented are the mean (± SEM) of five donors (n=5) from a single experiment. Figure 3B The figures shown in the representative dot plot reflect the positive Vγ9 values ​​for the corresponding activation markers from fresh PBMCs (ascending) or PBMCs cultured for 14 days with zoledronic acid + IL-2 + IL-15 (descending). + Frequency of γδT cells (mean ± SEM). Data presented are the mean (± SEM) of expression data for seven donors (n=7) targeting CD62L, CD69, and CD44 from two independent experiments. Expression data for n=5 donors targeting NKG2D and for two donors targeting CD45RO and CD71 were from individual experiments. Figure 3C The figures above the gates in the dotted plot depict Vγ9 cells from fresh PBMCs (upward) or PBMCs cultured for 14 days with zoledronic acid + IL-2 + IL-15 (downward) that are positive for the corresponding inhibitory receptor surface expression. +Frequency of γδT cells (mean ± SEM). The data shown here are the mean (± SEM) of data from five donors (n=5) for PD1, CTLA4, TIGIT, and LAG3 surface expression in two independent experiments, and from seven donors (n=7) for 2B4 and TIM3 surface expression. Figure 3D A representative FACS dot plot is shown, displaying the expression of intracellular granzyme B (left column) and perforin (right column) Vγ9 from fresh PBMCs (upper row) and PBMCs cultured in vitro for 14 days with zoledronic acid + IL-2 + IL-15 (lower row). + Frequency of γδT cells (mean ± SEM). The data depicted are the mean (± SEM) of data from four (n=4) and seven (n=7) donors of granzyme B and perforin from two independent experiments. Figure 3E Bar graphs representing the mean (±SEM) concentrations (pg / mL) of cytokines in the cell culture supernatant on days 0 and 14 of PBMCs cultured with zoledronic acid + IL-2 + IL-15 are shown. The data presented are the mean (±SEM) values ​​from four wells (n=4) of a single donor.

[0058] Figure 4 A bar chart showing the recruitment of Vγ9+ T cells by VG1 (anti-TRGV9 / anti-CD123 bispecific antibody) is shown, as illustrated by the conjugate formation between γδT cells and Kasumi-3 cells.

[0059] Figures 5A to 5C The diagram illustrates the cytotoxicity of γδT cells to Kasumi-3 cells mediated by VG1 bispecific antibody (anti-TRGV9 / anti-CD123 bispecific antibody) at different effector cell to target cell ratios. Figure 5A The ratio is 1:1; for Figure 5B The ratio is 5:1; and for Figure 5C (The ratio is 10:1).

[0060] Figures 6A to 6C This demonstrates the presence of CD69 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 without bispecific antibodies. Figure 6A CD25 Figure 6B ) or granzyme B ( Figure 6C (The diagram is used to express this idea.)

[0061] Figure 7 This diagram illustrates how binding to an anti-TRGV9 / anti-CD33 bispecific antibody recruits γδT cells to CD33+ cancer cells and induces cancer cell death.

[0062] Figure 8 An SDS-PAGE (non-reducing) gel demonstrating the integrity of the VG4 bispecific antibody is shown.

[0063] Figure 9 A graph showing the binding of anti-CD33 antibody (clone C33B904) to the MOLM-13 tumor cell line is shown, as measured by FACS.

[0064] Figure 10 A graph showing the binding of anti-CD33 antibody (clone C33B904) to the Kasumi-1 tumor cell line is shown, as measured by FACS.

[0065] Figure 11 A graph showing the binding of anti-CD33 antibody (clone C33B904) to the OCI-AML-3 tumor cell line is shown, as measured by FACS.

[0066] Figure 12 A graph illustrating the cytotoxicity of anti-TRGV9 / anti-CD33 bispecific antibody-mediated γδT cells against CD33-expressing Kasumi-3 cells at a 1:1 effector cell to target cell ratio is shown. Effector cells are enriched γδT cells isolated from PBMCs.

[0067] Figure 13 A graph illustrating the cytotoxicity of anti-TRGV9 / anti-CD33 bispecific antibody-mediated γδT cells against CD33-expressing Kasumi-3 cells at an effector cell to target cell ratio of 5:1 is shown. Effector cells are enriched γδT cells isolated from PBMCs.

[0068] Figure 14 A graph illustrating the cytotoxicity of anti-TRGV9 / anti-CD33 bispecific antibody-mediated γδT cells against CD33-expressing Kasumi-3 cells at a 1:1 effector cell to target cell ratio is shown. The effector cells are PBMCs derived from healthy donors.

[0069] Figure 15 A schematic diagram is shown demonstrating the binding of anti-TRGV9 / anti-TRBC1 bispecific antibodies to recruit γδT cells to TRBC1+ cancer cells and induce cancer cell death.

[0070] Figure 16 This demonstrates the selective cell binding of anti-TRBC1 (JOVI-1mIgG2a, TRB1B1) to transfected Jurkat cells. The binding of EC... 50The concentration was approximately 1 nM to 2 nM. TRB1B1 did not show any significant binding with HPB-ALL cell lines that endogenously expressed TRBC2 TCR.

[0071] Figure 17 This study demonstrates selective protein binding of anti-TRBC1 (JOVI-1mIgG2a, TRB1B1) to recombinant TCRs containing the TRBC1 constant domain (TRB1W16). TRB1B1 did not show any significant binding to recombinant TCRs containing the TRBC2 constant domain (TRB2W16).

[0072] Figure 18 The phenotype of Vγ9+ cells used in a cytotoxicity study of the JOVI-1×Vg9 bispecific antibody (TRB1B50) from a healthy donor is shown.

[0073] Figure 19 This study demonstrates the in vitro cytotoxicity of γδT cells against TRBC1-expressing Jurkat cells mediated by the anti-TRGV9 / anti-TRBC1 bispecific antibody. The cytotoxicity values ​​presented here are derived by subtracting the baseline cytotoxicity observed in the absence of the bispecific antibody. EC50 was calculated as described in the methods section. 50 Values. The representative data shown here comes from a single experiment.

[0074] Figure 20 This study demonstrates bispecific antibody-mediated cytotoxicity. Cytotoxicity was induced in the Jurkat cell line (E:T ratio 1:1) using expanded and enriched Vγ9Vδ2 T cells from various donors in the presence of specified concentrations of Vγ9×Jovi. Assays were performed over 16 hours. The percentage of dead target cells under various conditions is shown in the figure.

[0075] Figure 21 The binding of the anti-TRGV9 / anti-BCMA bispecific antibody (BCV9B106(B3)) to γδT cells (left panel) and its mediating in vitro cytotoxicity of γδT cells against BCMA-expressing H929 cells (right panel) are shown. EC50 was calculated as described in the method. 50 Values. The representative data shown here comes from a single experiment.

[0076] Figure 22 The binding of the anti-TRGV9 / anti-BCMA bispecific antibody (HC1: VG9B420-LH-scFv; HC2: BCMA-Fab (BCMB519-Fab) (BCV9B71.001)) to γδT cells (left panel) and its mediating in vitro cytotoxicity of γδT cells against BCMA-expressing H929 cells (right panel) is shown. EC50 was calculated as described in the method. 50 Values. The representative data shown here comes from a single experiment.

[0077] Figure 23 The binding of the anti-TRGV9 / anti-BCMA bispecific antibody (VG9SB10SC1087_P18_D08-Fab RF, BCMA-scFv (BCMB519-scFv (BCV9B100.001)) to γδT cells (left panel) and its mediating in vitro cytotoxicity of γδT cells against BCMA-expressing H929 cells (right panel) are shown. EC50 was calculated as described in the method. 50 Values. The representative data shown here comes from a single experiment.

[0078] Figure 24 The binding of the anti-TRGV9 / anti-BCMA bispecific antibody (VG9SB10SC1087_P18_C12-Fab RF, BCMA-scFv (BCMB519-scFv) (BCV9B101.001)) to γδT cells (left panel) and its mediating in vitro cytotoxicity of γδT cells against BCMA-expressing H929 cells (right panel) are shown. EC50 was calculated as described in the method. 50 Values. The representative data shown here comes from a single experiment.

[0079] Figure 25 The binding of the anti-TRGV9 / anti-BCMA bispecific antibody (VG9SB10SC1087_P19_C03-Fab RF, BCMA-scFv (BCMB519-scFv)(BCV9B103.001)) to γδT cells (left panel) and its mediating in vitro cytotoxicity of γδT cells against BCMA-expressing H929 cells (right panel) are shown. EC50 was calculated as described in the method. 50 Values. The representative data shown here comes from a single experiment.

[0080] Figure 26 Humanization of the mouse anti-Vγ9 antibody is illustrated. Humanization of mouse clone 7A5 was performed according to the method outlined by Singh et al. (Mabs, 2015, Vol. 7: 778-791). Germ lines IGHV1-8*01 and IGKV4-1*01 were selected for frame fitting based on sequence homology. Potential Iso-Asp isomerization sites (DG motifs) were also included in the design.

[0081] Figures 27A to 27B The positions of the epitope and complementary bit are shown. Figure 27AHX-MS epitope localization of mouse anti-human TCRVγ9 [clone 7A5] mAb and Vγ9 / Vδ2 fused with human Fc is shown. The sequences of VG9 (SEQ ID NO: 789 (amino acids 20-261 of SEQ ID NO: 156)) and VD2 (SEQ ID NO: 790 (amino acids 20-248 of SEQ ID NO: 157)) are shown at the bottom. Containing SEQ ID NO: 789 (L... 49 VSISYDGTVRKESGIPSGK 68 The peptide region of amino acids 49-68 of (SEQ ID NO: 774)(italic) is protected by mAb 7A5. The molecular model of TCR Vγ9-Vδ2 (using crystal structure PBD: 1HXM, see Allison et al., Nature, 2001, Vol. 411: pp. 820-824) and residues in the epitopes are highlighted in the sphere representation. Figure 27B The location of the HDX complementary site on mouse clone 7A5 (Vg9_7A5_VH SEQ ID NO: 7; Vg9_7A5_VL SEQ ID NO: 8) is shown. The molecular model of Fab with residues in the complementary site is highlighted.

[0082] Figures 28A to 28B This shows that healthy individuals have a wide range of Vγ9 throughout the entire PBMC. + γδT cells. Figure 28A Vγ9 in the whole PBMC is shown + γδT cells (TCRVγ9) + CD3 + Cell frequency. The numbers in the quadrants represent the frequencies of the corresponding populations. Figure 28B Vγ9 in the whole PBMCs of healthy individuals is shown. + A scatter plot summarizing the frequencies of γδT cells (mean ± SEM). Each point represents data from a healthy individual.

[0083] Figures 29A to 29C Vγ9 was shown + Characteristics of γδT cells. Figure 29A The left and middle figures show a summary of the frequencies of Vγ9+γδT cells in whole PBMCs on days 0 and 14 of zoledronic acid cultures containing selectively activated and expanded Vγ9+γδT cells. Figure 29A The right-hand figure shows representative data from n=15 donors across 6 independent experiments, as shown in the figure. The percentage of Vγ9+γδT cells in total CD3+ T cells at day 0 and day 14 of activation, with each point representing data from a donor. Figure 29BThe two figures on the left show the numbers in a representative FACS plot, depicting the differentiation profile of Vγ9+γδT cells on day 0 and day 14 of a culture containing zoledronic acid. Figure 29B The two plots on the right show scatter plots summarizing the frequencies of Vγ9+γδT cells positive for naive cells (CD27+CD45RA+), central memory cells (CD27+CD45RA-), effector memory cells (CD27-CD45RA-), and effector memory cells re-expressing the CD45RA phenotype (EMRA, CD27-CD45RA+) on days 0 and 14 of cultures containing zoledronic acid. Each point represents data from healthy donors. The plots show representative data from n=13 donors across four independent experiments. Figure 29C The figures shown in the representative FACS plot depict the frequency (mean ± SEM) of intracellular expression of granzyme B and perforin in Vγ9+γδT cells on day 0 (top row) and day 14 (bottom row). The plot presents data on intracellular expression of granzyme B and perforin from n=12 and n=7 donors from fresh Vγ9+γδT cells (day 0) and n=14 and n=9 donors from activated Vγ9+γδT cells (day 14), respectively.

[0084] Figures 30A to 30D The binding of the anti-TRGV9 / anti-CD123 bispecific antibody to Vγ9+γδT cells and CD123-expressing tumor cells was demonstrated. Target cells expressing CD123 and PBMCs activated and expanded with zoledronic acid on day 14 were incubated with or without the specified Vγ9 bispecific antibody and a Null-arm control bispecific antibody. Binding bispecific antibody staining was assessed by flow cytometry. Figure 30A The frequency of Vγ9 bispecific antibody binding in Kasumi-3 cells is shown in three independent experiments. ECs are also shown in the figure. 50 The value refers to the average of three independent experiments. Figure 30B This image shows Vγ9+γδT cells at various concentrations in two independent experiments with eight healthy donors. EC2 cells are also shown in the figure. 50 The value refers to two healthy donors. The right and left lines represent the specified Vγ9 bispecific antibody and its corresponding Vγ9 Null arm bispecific control antibody, respectively. The EC shown in the figure... 50 The values ​​are derived using a 4-parameter dose-response curve, where the concentration of the specified bispecific antibody is located on the x-axis (logarithmic scale) and the specific binding is located on the y-axis (linear scale). Figure 30CThe image shows FACS sorting of depleted Vγ9+γδT cells from Pan-T cells in whole PBMCs. Total Pan-T cells and Pan-T cells depleted of Vγ9+γδT cells were incubated with various concentrations of specified bispecific antibodies in both the presence and absence of these antibodies. Representative FACS plots illustrate the depletion efficiency of Vγ9+γδT cells in Pan-T cells. The numbers in the quadrants represent the frequency of the corresponding population. The binding of Vγ9 / CD123 and Vγ9 / Null bispecific antibodies to Pan-T cells (Pan-T cells not depleted of Vγ9) and Pan-T cells depleted of Vγ9+γδT cells (Pan-T cells depleted of Vγ9) at specified concentrations is also shown. Figure 30D The image shows staining of Kasumi-3 cell lines expressing CD123 and 22Rv1 cell lines not expressing CD123 with an anti-CD123 monoclonal antibody. A representative overlay histogram shows staining of CD123, an allotype control, and an FMO control on Kasumi-3 (left) and 22Rv1 (right) cell lines (top). At the bottom, a representative diagram shows the binding of Vγ9 / CD123 and Vγ9 / Null bispecific antibodies to the Kasumi-3 (left) cell line at specified concentrations. ECs are shown in the figure. 50 The values ​​are derived using a 4-parameter dose-response curve, where the concentration of the specified bispecific antibody is located on the x-axis (logarithmic scale) and the specific binding is located on the y-axis (linear scale).

[0085] Figures 31A to 31F The study demonstrated that the Vγ9 / CD123 bispecific antibody selectively recruits, activates, and induces cytotoxicity mediated by Vγ9+γδT cells. Figure 31A Cell trace-labeled enriched γδT cells are shown, co-cultured at 37°C for 1 hour with Cell trace yellow-labeled Kasumi-3 cells at a 1:1 ET ratio in the presence of 1 μg / mL of the specified bispecific antibody. Cell-cell associations and quantification were determined by flow cytometry, with cells located in the upper right quadrant of the FACS plot. The numbers in the quadrants indicate the frequency of the corresponding population. Figure 31B and Figure 31C Pan T cells (effective cells) from fresh PBMCs, co-cultured with Kasumi-3 cells (target) at a 1:1 ET ratio for 72 hours at 37°C with or without the specified bispecific antibody, are shown. Vγ9+γδT cells, Vγ9-γδT cells, and non-γδT cells are shown that are positive for CD69 (left), CD25 (right) surface expression and intracellular granzyme B expression. Figure 31DThis study illustrates the cytotoxicity of Vγ9 / CD123 bispecific antibody-mediated γδT cells against CD123 cells. PBMCs (effector cells) cultured with zoledronic acid for 14 days in the presence of a specified concentration of Vγ9 bispecific antibody and a Vγ9 Null arm control antibody were co-cultured with CFSE-labeled target (Kasumi-3) cells at a 1:1 ET ratio for 16 hours (by normalizing the ET ratio in the amplified PBMCs to the Vγ9+γδT cell frequency). Target cell lysis was determined by 7-AAD staining and flow cytometry. The figure shows the frequency of specific target cell lysis at specified concentrations of Vγ9 bispecific antibody and their corresponding Vγ9 / Null arm controls. Representative ECs are shown in the figure. 50 The value is the average of Vγ9 / CD123 from eight healthy donors in three independent experiments. Figure 31E This demonstrates how the Vγ9 / CD123 bispecific antibody effectively mediates the cytotoxicity of AML γδ T cells against Kasumi-3 cells. The upper and lower lines in the representative figure indicate the frequencies (7-AAD) of target (kasumi-3) cell lysis mediated by the Vγ9 / CD123 and vγ9 / Null bispecific antibodies, respectively, after 16 hours of co-culturing AML patient PBMCs with target cells on day 14 of Zol culture. + cell%). Figure 31F Vγ9 was shown in pan-T cells. + γδT cell depletion efficiency. The numbers in the quadrants represent the frequency of the corresponding population. The figure shows the depletion efficiency of pan-T cells (without Vγ9 depletion) and depleted Vγ9. + The frequency of target cell lysis mediated by Vγ9 / CD123 and Vγ9 / Null bispecific antibodies at specified concentrations when pan-T cells (Vγ9 depleted) were co-cultured with target (Kasumi-3) cells (7-AAD). + (Cells %) (middle figure). The figure below shows target cell lysis mediated by CD3 / CD123 and CD3 / Null bispecific antibodies at specified concentrations.

[0086] Figures 32A to 32C This demonstrates that the Vγ9 / CD123 bispecific antibody effectively mediates Vγ9 in all PBMCs. + Activation, proliferation, and effector function of γδT cells. CFSE-labeled whole PBMCs were cultured in the presence or absence of kasumi-3 cells in the presence of a specified bispecific antibody at a concentration of 3 ng / mL. Figure 32A Vγ9 was shown to be positive for surface expression of CD69 and CD25. + Cell frequency. Figure 32B The CFSE dilution (proliferation curve) is shown. Figure 32CThe ability to eliminate exogenously added Kasumi-3 cells is shown. Each point represents data from a single donor. Representative data from n=5 donors in two independent experiments are shown here.

[0087] Figure 33 This demonstrates that selective retargeting of Vγ9+γδT cells, compared to Pan-T cell retargeting, does not induce a cytokine storm. As shown in Figure 30, whole PBMCs were cultured with or without the specified bispecific antibody (3 ng / mL) in or without incorporated Kasumi-3 cells. Starting from day 3 of culture, 100 μL of culture medium was removed from the wells daily without disturbing the cells, and fresh medium was added until day 8. Cytokines were assessed in the cell culture supernatant from day 3 to day 8. Figure 33 The concentrations of various cytokines or effector molecules in the culture supernatant of whole PBMCs stimulated with the specified bispecific antibody are shown. Circles and squares represent PBMCs from four individual donors stimulated with either the specified bispecific antibody or a null-arm control bispecific antibody. Representative data from n=4 donors from a single independent experiment are shown here.

[0088] Figure 34 The mean tumor growth kinetics of NOD SCID mice with subcutaneous KG-1 tumor xenografts are shown. Subcutaneous seeding of 1.5 × 10⁻⁶ cells weekly with PBS or Vγ9Vδ2γδT cells is presented. 6 Female NOD SCID mice with 1 KG-1 cells were subcutaneously treated. All mice received 15 μg / kg IL-2 and, as indicated, 1.5 mg / kg (vβ17×DLL3). Tumor volume (left) of each mouse was measured every three days during the experiment. Values ​​are expressed as mean ± SEM of 6 animals per group. Statistical analysis was performed using Graph Pad Prism (version 8.3.0) via two-way ANOVA followed by Bonferroni post-test. *p < 0.05 & ****p < 0.0001 when the corresponding test group was compared with Group 1 - tumor + PBS (control group).

[0089] Figure 35 The binding kinetics of mouse anti-human TCRVγ9 [clone 7A5] and recombinant Vγ9-Vδ2-Fc antigens studied by SPR at 25 °C are shown. Different concentrations of antigen (100 nM, from top to bottom in the figure) were passed over anti-Vγ9 mAb trapped on the surface. Experimental data (black dashed lines) and a 1:1 Langmuir binding fit (smooth line) are shown. A dissociation phase follows the first association phase of approximately 250 seconds. A global fit to the 1:1 simple Langmuir binding model results in k... on =1.3±0.2×105 M -1 S -1 and k off =2.43±0.3×10 -4 S -1 , obtain K D =1.9nM.

[0090] Figures 36A to 36D The study demonstrated that the Vγ9+ subset of γδT cells is suitable for redirection to eliminate tumors. Figure 36A The results show positive results for the activation marker on day 0 (top row) and day 14 (bottom row). Frequency of T cells (mean ± SEM). Figure 36B The characteristics of antigen-presenting cells are shown. Figure 36C The exhaustion marker is shown. Figure 36D NK markers / characteristics are shown. On day 0, in Vγ9+γδT cells, n = representative data for 7 donors expressing CD62L, CD69, and CD44, 2 donors expressing CD45RO and CD71, 3 donors expressing CD86, HLA-DR, and CD16, 5 donors expressing NKG2D, and 3 donors expressing CD95(Fas). On activated Vγ9+γδT cells, n = representative data for 8 donors expressing CD62L, 9 donors expressing CD69 and CD44, 5 donors expressing CD45RO and CD71, 3 donors expressing CD86, HLA-DR, and CD16, 14 donors expressing NKG2D, and 6 donors expressing CD95(Fas) (day 14). On fresh Vγ9+γδT cells, n = representative data from 13 donors for PD1 and Lag3 surface expression, 5 donors for CTLA4 and 2B4 surface expression, and 4 and 7 donors for TIGIT and Tim3 surface expression, respectively (day 0). On activated Vγ9+γδT cells, n = representative data from 16 donors for PD1 surface expression, 5 donors for CTLA4 and 2B4 surface expression, 13 donors for Lag3 surface expression, and 14 donors for TIGIT surface expression (day 14). >5 separate experiments were performed.

[0091] Figures 37A to 37B This demonstrates the interaction between the Vγ9 bispecific antibody and Vγ9. +Binding of γδT cells to TAA-expressing tumor cells. Target cells expressing tumor-associated antigens (TAA) and Zol-expanded PBMCs on day 14 were incubated with or without specified Vγ9 bispecific antibodies (Vγ9 / CD123 or Vγ9 / PSMA) and Null arm control bispecific antibodies. Binding bispecific antibody staining was assessed by flow cytometry. Representative figures show the frequency of cell binding to Vγ9 bispecific antibodies at various concentrations. Vγ9 bispecific antibodies and their corresponding Vγ9 Null arm bispecific control antibodies are specified. ECs are shown in the figures. 50 The values ​​are derived using a 4-parameter dose-response curve, where the concentration of the specified bispecific antibody is located on the x-axis (logarithmic scale) and the specific binding is located on the y-axis (linear scale). Figure 37A Representative data from n=3 independent experiments of the Kasumi-3 and 22Rv1 cell lines are presented, and Figure 37B Representative data from two independent experiments with n=8 and 2 healthy donors are shown, respectively, for the Vγ9 / CD123 and Vγ9 / PSMA bispecific antibodies. EC is shown in the figure. 50 The value refers to 3 independent experiments (for Figure 37A ) and 9 and 2 healthy donors (for Figure 37B The average value of ).

[0092] Figures 38A to 38B This demonstrates the selectivity of the Vγ9 / CD123 bispecific antibody compared to Vγ9. + γδT cells bind to cell lines expressing CD123. Vγ9 + γδT cells were depleted by FACS sorting from enriched Pan-T cells from whole PBMCs of healthy individuals. Total Pan-T cells and depleted Vγ9 were incubated with various concentrations of specified bispecific antibodies in both the presence and absence of these cells. + Pan-T cells with γδT cells. Figure 38A The image depicts Vγ9 in pan-T cells. + A representative FACS plot of γδT cell depletion efficiency. The numbers in the quadrants represent the frequencies of the corresponding populations. Figure 38A This reflects the effectiveness of Vγ9 / CD123 and Vγ9 / Null bispecific antibodies at specified concentrations against pan-T cells (Pan-T cells with undepleted Vγ9) and depleted Vγ9. + Binding of γδT cells to pan-T cells (Vγ9-depleted Pan-T cells). Kasumi-3 cell line expressing CD123 TAA and 22Rv1 cell line not expressing CD123 TAA were stained with anti-CD123 monoclonal antibody. Figure 38BThe image above shows staining of CD123, isotype control, and FMO control in Kasumi-3 (left) and 22Rv1 (right) cell lines, respectively. Figure 38B The figure below shows the binding of Vγ9 / CD123 and Vγ9 / Null bispecific antibodies to Kasumi-3 (left) and 22Rv1 (right) cell lines at specified concentrations. EC20 cells are shown in the figure. 50 The values ​​are derived using a 4-parameter dose-response curve, where the concentration of the specified bispecific antibody is located on the x-axis (logarithmic scale) and the specific binding is located on the y-axis (linear scale).

[0093] Figures 39A to 39B The study demonstrated that Vγ9 bispecific antibody-mediated retargeting of γδT cells effectively eliminated both liquid tumors and solid tumors. Whole PBMCs were cultured for 14 days in the presence of Zol + IL-2 + I1-15. Vγ9 levels in whole PBMCs were assessed by flow cytometry. + γδT cell frequency. In the presence of specified concentrations of Vγ9 bispecific antibody and Vγ9 Null arm control antibody, Zol-cultured PBMCs (effector cells) on day 14 were co-cultured with CFSE-labeled target (Kasumi-3) cells at an ET ratio of 1:1 (for Kasumi-3 cells) and 5:1 (for 22Rv1) (ET ratios normalized to Vγ9 frequency in Zol-amplified PBMCs) in a humidified CO2 incubator for 16 h (for Kasumi-3 target cells) and 72 h (for 22Rv1) at 37°C. Target cell lysis was determined by 7-AAD staining and flow cytometry. Figure 39A and Figure 39B The graph shown represents the frequency of specific target cell lysis at specified concentrations of Vγ9 bispecific antibodies and their corresponding Vγ9 / Null arm controls. A representative graph shows EC... 50 The values ​​are from 3 independent experiments (for Figure 39A ) and an independent experiment (for Figure 39B ) respectively targeting Vγ9 / CD123 ( Figure 39A ) and Vγ9 / PSMA ( Figure 39B The average value of 8 and 2 healthy donors for bispecific antibodies.

[0094] Figures 40A to 40E This demonstrates that the Vγ9 / CD123 bispecific antibody effectively mediates Vγ9 in all PBMCs. + Activation, proliferation, and effector functions of γδT cells. Figure 40AThis demonstrates how to culture CFSE-labeled whole PBMCs at a concentration of 3 ng / mL in the presence or absence of incorporated Kasumi-3 cells. As a control, CFSE-labeled whole PBMCs (with or without incorporated Kasumi-3 cells) were cultured in the absence of any bispecific antibody. Figure 40B The text describes Vγ9, indicating positive surface expression for CD69, CD25, and CD71 (activation markers). + A graph of the mean (±SEM) frequency of cells. Figure 40C The CFSE dilution (proliferation curve) is shown and Figure 40D This demonstrates the elimination of exogenously added Kasumi-3 cells or endogenous CD123 in the entire PBMC (effector profile) after culture with or without the specified bispecific antibody. + Cells (e.g.) Figure 40E (as shown) ability ( Figures 40C to 40E Each point represents data from a single healthy donor. Representative data from n=5 donors across two independent experiments are shown here.

[0095] Figures 41A to 41C This demonstrates that selective retargeting of Vγ9+γδT cells, compared to Pan-T cell retargeting, does not induce a cytokine storm. As shown in Figure 40, whole PBMCs were cultured with or without the specified bispecific antibody (3 ng / mL) in or without incorporated Kasumi-3 cells. Starting from day 3 of culture, 100 μL of culture medium was removed from the wells daily without disturbing the cells, and fresh medium was added until day 8. Cytokines were assessed in the cell culture supernatant from day 3 to day 8. Figure 41A , Figure 41B and Figure 41C The concentrations of various cytokines or effector molecules in the culture supernatant of whole PBMCs stimulated with the specified bispecific antibody are shown. Circles and squares represent PBMCs from four individual donors stimulated with either the specified bispecific antibody or a null-arm control bispecific antibody. Representative data from n=4 donors from a single independent experiment are shown here.

[0096] Figures 42A to 42D This study demonstrates Vγ9 / CD123 bispecific antibody-mediated γδT cell retargeting in PBMCs of AML patients. Figure 42A TCR Vγ9 from AML patients was shown. + γδT cells can expand via ZoL. The figures in the representative FACS figures show Vγ9 in PBMCs of AML patients on day 0 (left) and day 14 (right) after culture with ZoL + IL-2 + IL-15. +and Vγ9 - Frequency of γδT cells. Figure 42B TCRVγ9 from PBMCs of four AML patients is shown. + The expansion fold of γδT cells. Figure 42C TCR Vγ9 from PBMCs of LC patients is shown. + γδT cells exhibited a more activated phenotype. The scatter plot shows the effect of fresh PBMCs on immature cells (CD27). + CD45RA + ), central memory cells (T) CM CD27 + CD45RA - ), effector memory cells (T) EM CD27 - CD45RA - ) and effector memory cells that re-express the CD45RA phenotype (EMRA: CD27) - CD45RA + ) Positive Vγ9 + Frequency of γδT cells. Each point represents data from a lung cancer patient sample. Figure 42D This demonstrates the effectiveness of the Vγ9 / CD123 bispecific antibody in mediating AML γδ T cell cytotoxicity against Kasumi-3 cells. It shows the frequency (7-AAD+ cells%) of target (kasumi-3) cell lysis mediated by the Vγ9 / CD123 and Vγ9 / Null bispecific antibodies after 16 hours of co-culturing healthy (left) or AML patient PBMCs (middle and right) with target cells on day 14 of Zol culture. Values ​​from control wells without bispecific antibodies were subtracted from values ​​from those with bispecific antibodies. Detailed Implementation

[0097] The background and description throughout this specification reference or describe various publications, articles, and patents; the full text of each of these references is incorporated herein by reference. Discussions of documents, actions, materials, devices, articles, etc., included in this specification are intended to provide context for the invention. Such discussions are not intended to acknowledge that any or all of these matters constitute prior art with respect to any disclosed or claimed invention.

[0098] 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 this invention pertains. Otherwise, certain terms used herein have the meanings set forth in this specification.

[0099] It should be noted that, unless the context clearly indicates otherwise, the singular forms “a” and “the” as used herein and in the appended claims include plural references.

[0100] Unless otherwise stated, any numerical value, such as concentrations or concentration ranges described herein, should be understood to be modified by the term "about" in all cases. Therefore, numerical values ​​typically include ±10% of the stated value. For example, a concentration of 1 mg / mL includes 0.9 mg / mL to 1.1 mg / mL. Similarly, a concentration range of 1% to 10% (w / v) includes 0.9% (w / v) to 11% (w / v). Unless the context clearly indicates otherwise, as used herein, numerical ranges explicitly include all possible subranges, all individual numerical values ​​within that range, including integers and fractions within such ranges.

[0101] Unless otherwise stated, the term "at least" preceding a series of elements should be understood to refer to each element in the series. Those skilled in the art will recognize, or be able to determine, various equivalents of specific embodiments of the invention described herein using only conventional experiments. Such equivalents are intended to be covered by this invention.

[0102] As used herein, the terms “comprising,” “including,” “having,” or “containing,” or any other variation thereof, should be understood to mean including the specified integers or groups of integers, but not excluding any other integers 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 includes a list of elements is not necessarily limited to those elements, but may include other elements not expressly listed or inherent in such compositions, mixtures, processes, methods, articles, or apparatus. Furthermore, unless expressly indicated otherwise, “or” means inclusive or not exclusive or. For example, condition A or B is satisfied by any of the following: A is true (or exists) and B is false (or does not exist), A is false (or does not exist) and B is true (or exists), and both A and B are true (or exist).

[0103] As used herein, the connecting term "and / or" between multiple listed elements is understood to include both single options and combined options. For example, in the case where two elements are connected by "and / or", the first option means that the first element applies even without the second element. The second option means that the second element applies even without the first element. The third option means that it is appropriate to use the first and second elements together. Any of these options is understood to fall within the meaning and therefore satisfies the requirement of the term "and / or" as used herein. The concurrent applicability of more than one option is also understood to fall within the meaning and therefore satisfies the requirement of the term "and / or".

[0104] As used herein, the term "composed of" as used throughout the specification and claims means that any of the listed integers or groups of integers may be included, but additional integers or groups of integers may not be added to the specified method, structure, or composition.

[0105] As used herein, the term "substantially composed of" as used throughout the specification and claims means to include any enumerated integers or groups of integers, and optionally includes any enumerated integers or groups of integers that do not substantially alter the basic or novel characteristics of the specified method, structure, or composition. See MPEP §2111.03.

[0106] As used herein, “subject” means any animal, preferably a mammal, and most preferably a human. As used herein, the term “mammal” covers 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., and more preferably, humans.

[0107] It should also be understood that when referring to the dimensions or characteristics of components of the preferred invention, the terms “about,” “approximately,” “generally,” “substantially,” and similar terms used herein indicate that the described dimensions / characteristics are not strict boundaries or parameters, and do not exclude minor variations that are functionally identical or similar, as understood by one 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.) without altering the least significant figures.

[0108] In the context of two or more nucleic acid or polypeptide sequences (e.g., anti-TRGV9 / anti-cancer-associated antigen bispecific antibody and the polynucleotide encoding them, anti-TRGV9 / anti-CD123 bispecific antibody and the polynucleotide encoding them, TRGV9 polypeptide and the TRGV9 polynucleotide encoding them, CD123 polypeptide and the CD123 polynucleotide encoding them), the term "identical" or percentage "identity" refers to two or more sequences or subsequences that are identical or have a specified percentage of the same amino acid residues or nucleotides when compared and aligned to obtain the maximum correspondence, as measured by one of the following sequence comparison algorithms or by visual inspection.

[0109] For sequence alignment, a reference sequence is typically used, and the test sequence is compared to it. When using a sequence alignment algorithm, the test and reference sequences are input into the computer, the coordinates of the subsequences are specified (if necessary), and the program parameters of the sequence alignment algorithm are specified. The sequence alignment algorithm then calculates the percentage of sequence identity between the test sequence and the reference sequence based on the specified program parameters.

[0110] The optimal alignment of sequences for comparison can be performed, for example, by Smith & Waterman’s local homology algorithm (Adv. Appl. Math. Vol. 2: p. 482, 1981), by Needleman & Wunsch’s homology alignment algorithm (J Mol. Biol. Vol. 48: p. 443, 1970), by searching Pearson & Lipman’s similarity method (Proc. Nat'l. Acad. Sci. USA 85: 2444 (1988)), by computerization of these algorithms (GAP, BESTFIT, FASTA, and TFASTA, Genetics Package, Computational Genetics Group, 575 Science Dr., Madison, WI, Wisconsin), or by visual inspection (see, Current Protocols in Molecular Biology Laboratory Guide). Biology), edited by FMAusubel et al., Laboratory Guide, a joint venture between Greenney Publishing Association and John Willie & Sons (1995 supplement) (Ausubel).

[0111] Examples of algorithms suitable for determining sequence identity percentages and sequence similarity are the BLAST and BLAST 2.0 algorithms, described in Altschul et al., (1990) J. Mol. Biol. Vol. 215, pp. 403-410 and Altschul et al., (1997) Nucleic Acids Res. 25: 3389-3402, respectively. Software for performing BLAST analyses is publicly available from the National Center for Biotechnology Information. The algorithm involves first identifying high-scoring sequence pairs (HSPs) in the query sequence by recognizing short words of length W that match or satisfy a positive threshold score T when compared to words of the same length in a database sequence. T is called the neighboring word score threshold (Altschul et al., ibid.). These initial neighboring word hits act as seeds for initiating searches to find longer HSPs containing them. The word hits are then extended in both directions along each sequence, as long as the accumulated alignment score can be increased.

[0112] For nucleotide sequences, cumulative scores are calculated using 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. Word hits in each direction cease when the cumulative alignment score decreases by an amount X from its maximum realized value; the cumulative score becomes zero or lower due to the accumulation of one or more negative score 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) defaults to a word length (W) of 11, an expected value (E) of 10, M = 5, N = -4, and a comparison of two strands. For amino acid sequences, the BLASTP program defaults to a word length (W) of 3, an expected value (E) of 10, and a BLOSUM62 scoring matrix (see Henikoff and Henikoff, Proc. Natl. Acad. Sci. USA 89: 10915 (1989)).

[0113] In addition to calculating the percentage of sequence identity, the BLAST algorithm also performs a statistical analysis of the similarity between two sequences (see, for example, Karlin and Altschul, Proc. Nat'l. Acad. Sci. USA 90: 5873-5787 (1993)). One similarity measure provided by the BLAST algorithm is the minimum sum probability (P(N)), which provides an indication of the probability that a match will occur by chance between two nucleotide or amino acid sequences. For example, if the minimum sum probability in a comparison of the test nucleic acid with a reference nucleic acid is less than about 0.1, more preferably less than about 0.01, and most preferably less than about 0.001, the nucleic acid is considered similar to the reference sequence.

[0114] Another indication that two nucleic acid sequences or polypeptides are substantially identical is that the polypeptide encoded by the first nucleic acid cross-reacts with the polypeptide encoded by the second nucleic acid, as described below. Therefore, the polypeptide is usually substantially identical to the second polypeptide, for example, where the two peptides differ only by conserved substitutions. Another indication that two nucleic acid sequences are substantially identical is that the two molecules hybridize with each other under stringent conditions.

[0115] As used herein, the term "polynucleotide," synonymously referred to as "nucleic acid molecule," "nucleotide," or "nucleic acid," means any polynucleotide or polydeoxynucleotide that 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 consisting of a mixture of single-stranded and double-stranded regions, single-stranded and double-stranded RNA, and RNA consisting of a mixture of single-stranded and double-stranded regions, and 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. Furthermore, "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, and DNA or RNA having a backbone modified for stability or other reasons. "Modified" bases include, for example, triphenylmethylated bases and rare bases such as inosine. DNA and RNA can be modified in various ways; therefore, "polynucleotides" include chemically modified, enzymatically modified, or metabolically modified forms of polynucleotides that are normally found naturally, as well as chemical forms of DNA and RNA specific to viruses and cells. "Polynucleotides" also include relatively short nucleic acid chains, often referred to as oligonucleotides.

[0116] As used herein, the term "vector" is a replicon in which another nucleic acid segment can be operatively inserted to induce replication or expression of that segment.

[0117] As used herein, the term "host cell" refers to a cell containing the nucleic acid molecules of the present invention. A "host cell" can be any type of cell, such as a primary cell, a cultured cell, or a cell derived from a cell line. In one embodiment, a "host cell" is a cell transfected with the nucleic acid molecules of the present invention. In another embodiment, a "host cell" is a descendant or potential descendant of such transfected cells. The descendant of a cell may or may not be identical to the parent cell, for example, due to mutations or environmental influences that may occur in the descendant or due to the integration of the nucleic acid molecules into the host cell genome.

[0118] As used herein, the term "expression" refers to the biosynthesis of a gene product. This term encompasses transcription from a gene to RNA. It also encompasses translation from RNA to one or more polypeptides, and all naturally occurring post-transcriptional and post-translational modifications. Expressed bispecific antibodies may reside in the cytoplasm of the host cell, in an extracellular environment such as a growth medium for cell cultures, or anchored to the cell membrane.

[0119] As used herein, the terms “peptide,” “polypeptide,” or “protein” can refer to a molecule composed of amino acids and can be recognized by those skilled in the art as a protein. 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 a polymer of amino acids of any length. This polymer can be linear or branched, may contain modified amino acids, and may be intercalated with non-amino acids. The term also covers amino acid polymers that have been naturally modified or modified by intervention; natural or interventional modifications include, for example, disulfide bond formation, glycosylation, esterification, acetylation, phosphorylation, or any other operation or modification, such as conjugation with a labeled component. This definition also includes, for example, polypeptides containing one or more amino acid analogs (including, for example, non-natural amino acids) and other modifications known in the art.

[0120] The peptide sequences described herein are written according to usual convention, with the N-terminal region of the peptide on the left and the C-terminal region on the right. Although isomers of amino acids are known, they are the L-forms of the amino acids represented unless otherwise explicitly stated.

[0121] Antibody

[0122] This document provides TRGV9 antibodies, nucleic acids encoding the antibodies and expression vectors, recombinant cells containing the vectors, and compositions containing the antibodies. In some embodiments, isolated TRGV9 antibodies, nucleic acids encoding the antibodies and expression vectors, recombinant cells containing the vectors, and compositions containing the antibodies are provided. Methods for preparing these antibodies and methods for treating diseases using these antibodies are also provided. The antibodies disclosed herein have one or more desired functional properties, including but not limited to high affinity binding to TRGV9 or high specificity for TRGV9. In some embodiments, the antibodies disclosed herein have the ability to treat or prevent a disease or condition when administered to a subject alone or in combination with other therapies. In some embodiments, the TRGV9 antibody comprises a TRGV9 antigen-binding fragment. In some embodiments, the TRGV9 antibody consists of a TRGV9 antigen-binding fragment. In other embodiments, the TRGV9 antibody is a multispecific TRGV9 antibody. In other embodiments, the multispecific TRGV9 antibody is a bispecific TRGV9 antibody. While TRGV9 antibodies are illustrated herein, it should be understood that other molecules that bind to TRGV9 are also contemplated. Such molecules include other alternative binding agents, including the antibody and other antibody-binding fragments provided herein.

[0123] This document also provides TRGV9 multispecific antibodies, nucleic acids encoding multispecific antibodies and expression vectors, recombinant cells containing the vectors, and compositions comprising multispecific antibodies. Methods for preparing these antibodies and methods for treating diseases, including cancer, using these multispecific antibodies are also provided. The antibodies disclosed herein have one or more desired functional properties. In some embodiments, the multispecific antibodies provided herein bind with high affinity to TRGV9. In some embodiments, the multispecific antibodies provided herein bind with high affinity to a second target antigen. In some embodiments, the multispecific antibodies provided herein exhibit high specificity for TRGV9. In some embodiments, the multispecific antibodies provided herein exhibit high specificity to a second target antigen. In some embodiments, the multispecific antibodies provided herein, when administered alone, have the ability to treat or prevent a disease or condition. In some embodiments, the multispecific antibodies provided herein, when administered in combination with other therapies, have the ability to treat or prevent a disease or condition. In a specific embodiment, the multispecific antibody is a bispecific antibody. In some embodiments, the TRGV9 antibody comprises its antigen-binding fragment.

[0124] As used herein, the term "antibody" is used broadly and includes immunoglobulins or antibody molecules, including human antibodies, humanized antibodies, complex antibodies, chimeric antibodies, and monoclonal or polyclonal antibody fragments. Generally, an antibody is a protein or peptide chain that exhibits binding specificity to a particular antigen. Antibody structures are well known. Immunoglobulins can be designated into five major classes (i.e., IgA, IgD, IgE, IgG, and IgM) based on the amino acid sequence of their heavy chain constant domain. IgA and IgG are further subclassed into isotypes IgA1, IgA2, IgG1, IgG2, IgG3, and IgG4. Therefore, the antibodies of the present invention can be any of these five major classes or their corresponding subclasses. In specific embodiments, the antibodies provided herein are IgG1, IgG2, IgG3, or IgG4. Based on the amino acid sequence of their constant domain, the light chains of vertebrate antibodies can be designated into two distinct types, namely κ and λ. Therefore, the antibodies provided herein can contain either the κ or λ light chain constant domain. According to a specific implementation, the antibody of the present invention includes a constant region of the heavy chain and / or light chain derived from rat or human antibodies.

[0125] In addition to the constant heavy and light chain domains, antibodies also contain antigen-binding regions consisting of a light chain variable region (VL) and a heavy chain variable region (VH), each of which contains three domains (i.e., complementarity-determining regions 1 (CDR1), 2, and 3). "CDR" refers to one of the three hypervariable regions (HCDR1, HCDR2, or HCDR3) within the non-framework region of the immunoglobulin (Ig or antibody) VHβ-sheet framework, or one of the three hypervariable regions (LCDR1, LCDR2, or LCDR3) within the non-framework region of the antibody VLβ-sheet framework. Therefore, CDRs are variable region sequences scattered within the framework sequence. The CDR region is well known to those skilled in the art and has been defined, for example, by Kabat as the most hypervariable region within the antibody variable (V) domain (Kabat et al., J. Biol. Chem. Vol. 252: pp. 6609-6616, 1977; Kabat, Adv. Protein Chem. Vol. 32: pp. 1-75, 1978). Chothia also structurally defines CDR region sequences as those residues that do not belong to the conserved β-sheet framework and are therefore adaptable to different conformations (Chothia and Lesk, J. Mol. Biol. Vol. 196: pp. 901-917, 1987). Both terms are recognized in the art. CDR region sequences are also defined by AbM, Contact, and IMGT. Exemplary CDR region sequences are shown herein, for example, in the sequence listing and the tables provided in the following examples. The location of the CDR within the canonical antibody variable region has been determined by comparing numerous structures (Al-Lazikani et al., J. Mol. Biol. Vol. 273: pp. 927-948, 1997; Morea et al., Methods, Vol. 20: pp. 267-279, 2000). Because the number of residues in the hypervariable region varies among different antibodies, the additional residues relative to the canonical position are usually numbered a, b, c, etc., next to the residue number in the canonical variable region numbering scheme (Al-Lazikani et al., ibid., 1997). This nomenclature is also well known to those skilled in the art.

[0126] The CDR1 domain of the light chain variable region is interchangeably referred to as LCDR1 or VL CDR1 in this paper. The CDR2 domain of the light chain variable region is interchangeably referred to as LCDR2 or VL CDR2 in this paper. The CDR3 domain of the light chain variable region is interchangeably referred to as LCDR3 or VL CDR3 in this paper. The CDR1 domain of the heavy chain variable region is interchangeably referred to as HCDR1 or VH CDR1 in this paper. The CDR2 domain of the heavy chain variable region is interchangeably referred to as HCDR2 or VH CDR2 in this paper. The CDR1 domain of the heavy chain variable region is interchangeably referred to as HCDR3 or VH CDR3 in this paper.

[0127] When used herein, the term “hypervariant region” (such as VH or VL) refers to a region within the antibody variable region that is sequence-hypervariant and / or forms a structurally defined loop. Typically, an antibody contains six hypervariant regions; three in VH (HCDR1, HCDR2, HCDR3) and three in VL (LCDR1, LCDR2, LCDR3). Many hypervariant region descriptions are in use and are included herein. “Kabat” CDR is based on sequence variability and is the most commonly used (see, for example, Kabat et al., Sequences of Proteins of Immunological Interest, 5th ed., Public Health Service, National Institutes of Health, Bethesda, MD., 1991). “Chothia”, conversely, refers to the location of a structural loop (see, for example, Chothia and Lesk, J. Mol. Biol., Vol. 196: pp. 901–917, 1987). When using the Kabat numbering convention, the end of the Chothia CDR-HCDR1 loop varies between H32 and H34, depending on the loop length (this is because the Kabat numbering scheme places insertions at H35A and H35B; if neither 35A nor 35B exists, the loop ends at 32; if only 35A exists, the loop ends at 33; if both 35A and 35B exist, the loop ends at 34). The "AbM" hypervariable region represents a compromise between the Kabat CDR and Chothia structural loops and is used by the AbM antibody modeling software from Oxford Molecular (see, for example, Martin, "Antibody Engineering", Vol. 2, Chapter 3, Springer Verlag). The "Contact" hypervariable region is based on the analysis of the available complex crystal structures.

[0128] Recently, a universal numbering system has been developed and widely adopted, namely ImMunoGeneTics (IMGT) Information. (Lafranc et al., Dev. Comp. Immunol. Vol. 27, No. 1: pp. 55-77, 2003). IMGT is an integrated information system specifically for the study of immunoglobulins (IG), T cell receptors (TR), and major histocompatibility complex (MHC) in humans and other vertebrates. In this paper, CDRs are referenced based on both their amino acid sequence and their position within either the light or heavy chain. Since the “position” of CDRs within the variable domain structure of immunoglobulins is conserved across species and exists in structures called loops, CDRs and framework residues are readily identified 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 receptor frameworks typically derived from human antibodies. Honegger and Plückthun developed an additional numbering system (AHon), J. Mol. Biol. Vol. 309: pp. 657-670, 2001. The correspondence between numbering systems, including, for example, the Kabat numbering and the IMGT unique numbering system, is well known to those skilled in the art (see, for example, Kabat, ibid.; Chothia and Lesk, ibid.; Martin, ibid.; Lefranc et al., ibid.). The exemplary system shown herein combines Kabat and Chothia.

[0129] Example IMGT Kabat AbM Chothia Contact <![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

[0130] High-variable regions may include the following "extended high-variable regions": 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. This document provides CDR sequences reflecting each of the above numbering schemes, included in the sequence table.

[0131] The terms "constant region" or "constant domain" refer to the carboxyl-terminal portions of the light and heavy chains that do not directly participate in antibody-antigen binding but exhibit various effector functions, such as interaction with Fc receptors. These terms refer to portions of the immunoglobulin molecule that have a more conserved amino acid sequence compared to other parts of the immunoglobulin (including the variable region containing 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.

[0132] The term "framework" or "FR" residues refers to those variable domain residues that flank a CDR. FR residues are found in, for example, chimeric, humanized, human domain antibodies, bivalent antibodies, linear antibodies, and bispecific antibodies. FR residues are variable domain residues other than hypervariable region residues or CDR residues.

[0133] As used herein, the term "isolated antibody" refers to an antibody that is substantially free of other antibodies with different antigen 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 a second target (e.g., CD123) is substantially free of antibodies that do not bind to the second target (e.g., CD123)). Additionally, isolated antibodies may be substantially free of other cellular material and / or chemicals.

[0134] As used herein, the term "monoclonal antibody" refers to an antibody obtained from a substantially homogeneous group of antibodies, that is, the individual antibodies constituting the group are identical except for the possibility of a small number of naturally occurring mutations. The monoclonal antibodies of this invention 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 from hybridomas comprising B cells derived from transgenic nonhuman animals such as transgenic mice or rats, the transgenic nonhuman animals having a genome containing human heavy chain transgenes and light chain transgenes.

[0135] As used herein, the term "antigen-binding fragment" refers to an antibody fragment such as, biantibody, Fab, Fab', F(ab')2, Fv fragment, disulfide-stabilized Fv fragment (dsFv), (dsFv)2, bispecific dsFv (dsFv-dsFv'), disulfide-stabilized biantibody (ds biantibody), single-chain antibody molecule (scFv), single-domain antibody (sdAb), scFv dimer (bivalent bivalent antibody), multispecific antibody formed from a portion of an antibody containing one or more CDRs, camelified single-domain antibody, nanobody, domain antibody, bivalent domain antibody, or any other antibody fragment that binds to an antigen but does not contain the complete antibody structure. The antigen-binding fragment is capable of binding to the same antigen as the parent antibody or the antigen bound to the parent antibody fragment. According to a specific embodiment, the antigen-binding fragment comprises a light chain variable region, a light chain constant region, and an Fd segment of the heavy chain. According to other specific embodiments, the antigen-binding fragment comprises Fab and F(ab').

[0136] As used herein, the term "single-chain antibody" refers to a conventional single-chain antibody in the art that comprises a heavy chain variable region and a light chain variable region linked by a short peptide of about 15 to about 20 amino acids. As used herein, the term "single-domain antibody" refers to a conventional single-domain antibody in the art that comprises a heavy chain variable region and a heavy chain constant region or comprises only a heavy chain variable region.

[0137] As used herein, the term "human antibody" refers to an antibody produced by a human being or an antibody having an amino acid sequence corresponding to that of a human-produced antibody prepared using any technique known in the art. This definition of human antibody includes full-length or complete antibodies, fragments thereof, and / or antibodies containing at least one human heavy-chain polypeptide and / or light-chain polypeptide.

[0138] As used in this article, the term "humanized antibody" refers to a non-human antibody that has been modified to increase sequence homology with human antibodies, so that the antigen-binding properties of the antibody are retained, but its antigenicity in the human body is reduced.

[0139] 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 often correspond to the variable regions of antibodies derived from one mammalian species (e.g., mouse, rat, rabbit, etc.) with the desired specificity, affinity, and capability, while the constant regions correspond to sequences in antibodies derived from another mammalian species (e.g., human) in order to avoid eliciting an immune response in that species.

[0140] As used herein, the term "multispecific antibody" refers to an antibody comprising a plurality of immunoglobulin variable domain sequences, wherein a first immunoglobulin variable domain sequence of the plurality of immunoglobulin variable domain sequences has binding specificity for a first epitope, and a second immunoglobulin variable domain sequence of the plurality of immunoglobulin variable domain sequences has binding specificity for a second epitope. In one embodiment, the first and second epitopes do not overlap or substantially do not overlap. In one embodiment, the first and second epitopes are located 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.

[0141] As used herein, the term "bispecific antibody" refers to a multispecific antibody that binds to no more than two epitopes or two antigens. A bispecific antibody is characterized by a first immunoglobulin variable domain sequence having binding specificity to a first epitope (e.g., an epitope on the TRGV9 antigen) and a second immunoglobulin variable domain sequence having binding specificity to a second epitope. In one embodiment, the first and second epitopes are located on different antigens, such as different proteins (or different subunits of a multimeric protein). In one embodiment, the bispecific antibody comprises heavy chain variable domain sequences and light chain variable domain sequences having binding specificity to the first epitope, and heavy chain variable domain sequences and light chain variable domain sequences having binding specificity to the second epitope. In one embodiment, the bispecific antibody comprises a hapten or fragment thereof having binding specificity to the first epitope and a hapten or fragment thereof having binding specificity to the second epitope. In one embodiment, the bispecific antibody comprises an scFv or fragment thereof having binding specificity to the first epitope and an scFv or fragment thereof having binding specificity to the second epitope. In one embodiment, the first epitope is located on TRGV9, and the second epitope is located on CD123. In one embodiment, the first epitope is located on TRGV9 and the second epitope is located on CD33. In one embodiment, the first epitope is located on TRGV9 and the second epitope is located on TRBC1. In one embodiment, the first epitope is located on TRGV9 and the second epitope is located on BCMA. In one embodiment, the first epitope is located on TRGV9 and the second epitope is located on PSMA. 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-related immunosuppressive factors or surface antigens.

[0142] As used herein, the term "hapten" refers to an immunoglobulin heavy chain associated with an immunoglobulin light chain. An exemplary hapten is shown in SEQ ID NO: 17. Those skilled in the art will readily understand that haptens can encompass fragments thereof and can also have an antigen-binding domain consisting of a single variable domain, for example, derived from camelids.

[0143] As used herein, the term "TRGV9" refers to a polypeptide that, when expressed on the surface of γδT cells, can form a T cell receptor. γδT cells expressing TRGV9 are among the earliest T cells to develop in human fetuses and are the major γδT cell subset in the peripheral blood of healthy adults. The term "TRGV9" includes any TRGV9 variant, isotype, and species homolog that is naturally expressed by cells (including T cells) or that can be expressed on cells transfected with a gene or cDNA encoding the polypeptide. In a specific embodiment, TRGV9 is human TRGV9. An exemplary human TRGV9 amino acid sequence is provided by GenBank accession number NG_001336.2. Figure 27A The exemplary human TRGV9 is also provided with SEQ ID NO: 789.

[0144] The term "CD123" refers to a cellular molecule that facilitates the transmission of interleukin-3 (a soluble cytokine important in the immune system). CD123 may also be referred to as the "interleukin-3 receptor." This receptor belongs to the type I cytokine receptor family and is a heterodimer with a unique α chain that pairs with a common β subunit (βc or CD131). The CD123 receptor can be present on pluripotent progenitor cells and can induce tyrosine phosphorylation intracellularly, promoting proliferation and differentiation within hematopoietic cell lines. CD123 can also be expressed in subtypes of acute myeloid leukemia (AML). Unless otherwise specified, the term "CD123" includes any CD123 variant, isotype, and species homolog that is naturally expressed by cells (including T cells) or can be expressed on cells transfected with genes or cDNA encoding those polypeptides; in a specific embodiment, "CD123" is human CD123. The amino acid sequence of human CD123 is provided by GenBank accession number AY789109.1.

[0145] The term "CD33" refers to a 67 kDa single-pass transmembrane glycoprotein and a member of the sialic acid-binding immunoglobulin-like lectins (Siglecs) family. While its exact biological function is not fully understood, in normal individuals it is primarily considered a myeloid differentiation antigen, expressed at low levels in myeloid progenitor cells, neutrophils, and macrophages, and highly expressed in circulating monocytes and dendritic cells. CD33 has been detected in blast cells and leukemia stem cells in 85% to 90% of patients with acute myeloid leukemia (AML). Unless otherwise specified, the term "CD33" includes any CD33 variant, isotype, and species homolog that is naturally expressed by cells or capable of being expressed on cells transfected with genes or cDNA encoding those polypeptides; "CD33" refers to human CD33. The amino acid sequence of human CD33 is provided by GenBank accession number BC028152.1.

[0146] As used in this article, antibodies that "specifically bind" to a target refer to antibodies with a concentration of 1 × 10⁻⁶. -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 with a molecular weight (M) or smaller (KD) that binds to a target. In a specific implementation, the target is a human target. The target can be, for example, TRGV9, CD123, CD33, TRBC1, BCMA, or PSMA.

[0147] 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 this 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 by using surface plasmon resonance, such as by using a biosensor system (e.g., The KD value of an antibody can be determined either by a system or by using biolayer interferometry techniques such as the Octet RED96 system. A lower KD value indicates a higher affinity between the antibody and the target antigen.

[0148] In one aspect, this document provides antibodies that bind to TRGV9. In some embodiments, the antibody comprises a heavy chain variable (VH) region and a light chain variable (VL) region. In some embodiments, the TRGV9 antibody is not a single-domain antibody or nanobody. In some embodiments, the TRGV9 antibody is a humanized antibody.

[0149] In some embodiments, this document provides a TRGV9 antibody comprising the VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 of any of the antibodies described herein. In some embodiments, this document provides a TRGV9 antibody comprising the VH region of any of the antibodies described herein. In some embodiments, this document provides a TRGV9 antibody comprising the VL region of any of the antibodies described herein. In some embodiments, this document provides a TRGV9 antibody comprising both the VH region and the VL region of any of the antibodies described herein. In some embodiments, this document provides a TRGV9 antibody comprising VH CDR1, VH CDR2, and VH CDR3 of any of the antibodies described herein. In some embodiments, this document provides a TRGV9 antibody comprising VL CDR1, VL CDR2, and VL CDR3 of any of the antibodies described herein. In some embodiments, this document provides a TRGV9 antibody comprising VH CDR1, VHCDR2, and VH CDR3 of any of the antibodies described herein; and VL CDR1, VL CDR2, and VL CDR3 of any of the antibodies described herein. Representative VH and VL amino acid sequences of the TRGV9 antibodies provided herein, including the VH CDR1, VHCDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences, are provided in the sequence listing and in Tables 1 through 39.

[0150] In some embodiments, the TRGV9 antibody is the multispecific TRGV9 antibody provided herein. In some embodiments, the multispecific TRGV9 antibody is a bispecific TRGV9 antibody. In one embodiment, the multispecific TRGV9 antibody comprises: (a) a first binding domain that binds to TRGV9, and (b) a second binding domain that binds to a second target that is not TRGV9.

[0151] In some embodiments, the first binding domain for TRGV9 includes the VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 of any of the TRGV9 antibodies described herein. In some embodiments, the first binding domain for TRGV9 includes the VH region of any of the TRGV9 antibodies described herein. In some embodiments, the first binding domain for TRGV9 includes the VL region of any of the TRGV9 antibodies described herein. In some embodiments, the first binding domain for TRGV9 includes both the VH and VL regions of any of the TRGV9 antibodies described herein. In some embodiments, the first binding domain for TRGV9 includes VH CDR1, VH CDR2, and VH CDR3 of any of the TRGV9 antibodies described herein. In some embodiments, the first binding domain for TRGV9 comprises VL CDR1, VL CDR2, and VLCDR3 of any of the TRGV9 antibodies described herein. In some embodiments, the first binding domain for TRGV9 comprises VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of any of the TRGV9 antibodies described herein. Representative VH and VL amino acid sequences of the TRGV9 antibodies described herein, including the amino acid sequences of VH CDR1, VH CDR2, VHCDR3, VL CDR1, VL CDR2, and VL CDR3, are provided in the sequence listing and in Tables 1 through 39.

[0152] In some embodiments, the second target is CD123. In some embodiments, the second binding domain for CD123 has the VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VLCDR2, and / or VL CDR3 of the CD123 antibody provided herein. In some embodiments, the second binding domain for CD123 has the VH region of the CD123 antibody provided herein. In some embodiments, the second binding domain for CD123 has the VL region of the CD123 antibody provided herein. In some embodiments, the second binding domain for CD123 has both the VH and VL regions of the CD123 antibody provided herein. In some embodiments, the second binding domain for CD123 has VH CDR1, VH CDR2, and VH CDR3 of the CD123 antibody provided herein. In some embodiments, the second binding domain for CD123 has VL CDR1, VL CDR2, and VL CDR3 of the CD123 antibody provided herein. In some implementations, the second binding domain of CD123 has VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the CD123 antibody provided herein.

[0153] In some embodiments, the second target is CD33. In some embodiments, the second binding domain for CD33 has the VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 of the CD33 antibody provided herein. In some embodiments, the second binding domain for CD33 has the VH region of the CD33 antibody provided herein. In some embodiments, the second binding domain for CD33 has the VL region of the CD33 antibody provided herein. In some embodiments, the second binding domain for CD33 has both the VH region and VL region of the CD33 antibody provided herein. In some embodiments, the second binding domain for CD33 has VH CDR1, VHCDR2, and VH CDR3 of the CD33 antibody provided herein. In some embodiments, the second binding domain for CD33 has VL CDR1, VL CDR2, and VL CDR3 of the CD33 antibody provided herein. In some implementations, the second binding domain of CD33 has VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the CD33 antibody provided herein.

[0154] In some embodiments, the second target is TRBC1. In some embodiments, the second binding domain for TRBC1 has the VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VLCDR2, and / or VL CDR3 of the TRBC1 antibody provided herein. In some embodiments, the second binding domain for TRBC1 has the VH region of the TRBC1 antibody provided herein. In some embodiments, the second binding domain for TRBC1 has the VL region of the TRBC1 antibody provided herein. In some embodiments, the second binding domain for TRBC1 has both the VH and VL regions of the TRBC1 antibody provided herein. In some embodiments, the second binding domain for TRBC1 has VH CDR1, VH CDR2, and VH CDR3 of the TRBC1 antibody provided herein. In some embodiments, the second binding domain for TRBC1 has VL CDR1, VL CDR2, and VL CDR3 of the TRBC1 antibody provided herein. In some implementations, the second binding domain of TRBC1 has VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of the TRBC1 antibody provided herein.

[0155] In some embodiments, the second target is BCMA. In some embodiments, the second binding domain for BCMA has the VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, V CDR2, and / or VL CDR3 of the BCMA antibody provided herein. In some embodiments, the second binding domain for BCMA has the VH region of the BCMA antibody provided herein. In some embodiments, the second binding domain for BCMA has the VL region of the BCMA antibody provided herein. In some embodiments, the second binding domain for BCMA has both the VH and VL regions of the BCMA antibody provided herein. In some embodiments, the second binding domain for BCMA has VH CDR1, VHCDR2, and VH CDR3 of the BCMA antibody provided herein. In some embodiments, the second binding domain for BCMA has VL CDR1, VL CDR2, and VL CDR3 of the BCMA antibody provided herein. In some implementations, the second binding domain of BCMA has VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of the BCMA antibody provided herein.

[0156] In some embodiments, the second target is PSMA. In some embodiments, the second binding domain for PSMA has the VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and / or VL CDR3 of the PSMA antibody provided herein. In some embodiments, the second binding domain for PSMA has the VH region of the PSMA antibody provided herein. In some embodiments, the second binding domain for PSMA has the VL region of the PSMA antibody provided herein. In some embodiments, the second binding domain for PSMA has both the VH region and VL region of the PSMA antibody provided herein. In some embodiments, the second binding domain for PSMA has VH CDR1, VHCDR2, and VH CDR3 of the PSMA antibody provided herein. In some embodiments, the second binding domain for PSMA has VL CDR1, VL CDR2, and VL CDR3 of the PSMA antibody provided herein. In some implementations, the second binding domain of PSMA has VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of the PSMA antibody provided herein.

[0157] In some embodiments, the antibody specifically binds to TRGV9. In other embodiments, TRGV9 is present on the surface of T cells.

[0158] In some embodiments, the TRGV9 antibody is chimeric. In some embodiments, the TRGV9 antibody is human. In some embodiments, the TRGV9 antibody is humanized. In some embodiments, the TRGV9 is an isolated TRGV9 antibody. In some embodiments, a complete TRGV9 antibody is provided.

[0159] In some embodiments, the TRGV9 antibody is an IgG antibody. In some embodiments, the TRGV9 antibody is an IgG1 antibody. In some embodiments, the TRGV9 antibody is an IgG2 antibody. In some embodiments, the TRGV9 antibody is an IgG3 antibody. In some embodiments, the TRGV9 antibody is an IgG4 antibody. In some embodiments, the TRGV9 antibody contains a κ light chain. In some embodiments, the TRGV9 antibody contains a λ light chain. In some embodiments, the TRGV9 antibody is a monoclonal antibody. In some embodiments, the TRGV9 antibody is multivalent. In some embodiments, the TRGV9 antibody is capable of binding to at least three antigens. In some embodiments, the TRGV9 antibody is capable of binding to at least four antigens. In some embodiments, the TRGV9 antibody is capable of binding to at least five antigens. In some embodiments, the TRGV9 antibody is a multispecific antibody. In some embodiments, the TRGV9 antibody is a bispecific antibody. In some embodiments, the TRGV9 antibody is a trispecific antibody. In some embodiments, the TRGV9 antibody is a tetraspecific antibody.

[0160] In other embodiments, the provided TRGV9 antibody is an antigen-binding fragment of a TRGV9 antibody. In some embodiments, the antigen-binding fragment of the TRGV9 antibody is a functional fragment. In some embodiments, the TRGV9 antigen-binding fragment is chimeric. In some embodiments, the TRGV9 antigen-binding fragment is human. In some embodiments, the TRGV9 antigen-binding fragment is humanized. In some embodiments, the TRGV9 antigen-binding fragment is an isolated TRGV9 antigen-binding fragment.

[0161] In some embodiments, the antigen-binding fragment is a bivalent antibody. In some embodiments, the antigen-binding fragment is Fab. In some embodiments, the antigen-binding fragment is Fab'. In some embodiments, the antigen-binding fragment is F(ab')2. In some embodiments, the antigen-binding fragment is an Fv fragment. In some embodiments, the antigen-binding fragment is a disulfide-stabilized Fv fragment (dsFv). In some embodiments, the antigen-binding fragment is (dsFv)2. In some embodiments, the antigen-binding fragment is a bispecific dsFv (dsFv-dsFv'). In some embodiments, the antigen-binding fragment is a disulfide-stabilized bivalent antibody (ds bivalent antibody). In some embodiments, the antigen-binding fragment is a single-chain antibody molecule (scFv). In some embodiments, the antigen-binding fragment is a single-domain antibody (sdAb). In some embodiments, the antigen-binding fragment is an scFv dimer (bivalent bivalent antibody). In some embodiments, the antigen-binding fragment is a multispecific antibody formed from a portion of an antibody containing one or more CDRs. In some embodiments, the antigen-binding fragment is a camelified single-domain antibody. In some embodiments, the antigen-binding fragment is a nanobody. In some embodiments, the antigen-binding fragment is a domain antibody. In some embodiments, the antigen-binding fragment is a bivalent domain antibody. In some embodiments, the antigen-binding fragment is an antibody fragment that binds to an antigen but does not contain a complete antibody structure.

[0162] In some embodiments, the TRGV9 antibody is a multispecific antibody. In other embodiments, the TRGV9 antibody is a bispecific antibody. In some embodiments, the multispecific antibody comprises an antigen-binding fragment of the TRGV9 antibody provided herein. In other embodiments, the bispecific antibody comprises an antigen-binding fragment of the TRGV9 antibody provided herein. In some embodiments, the TRGV9 antibody is an agonist antibody. In some embodiments, the TRGV9 antibody activates T cells. In other embodiments, the TRGV9 antibody is an antagonist antibody. In some embodiments, the TRGV9 antibody inactivates T cells. In some embodiments, the TRGV9 antibody blocks T cell activation. In some embodiments, the TRGV9 antibody modulates T cell activity. In some embodiments, the TRGV9 antibody neither activates nor inactivates γδT cell activity. In a specific embodiment, the T cell is a γδT cell.

[0163] In specific embodiments, the γδT cells are human γδT cells. In specific embodiments, a bispecific antibody is provided comprising the TRGV9 antibody provided herein, in a club-and-mortar configuration. In some embodiments, the TRGV9 antibody provided herein may be included in a bispecific antibody. In some embodiments, the TRGV9 bispecific antibody provided herein may be included in a multispecific antibody. In some embodiments, the bispecific antibody provided herein comprises: a first binding domain comprising the TRGV9 antibody provided herein binding to a first TRGV9 epitope; and a second binding domain comprising the TRGV9 antibody provided herein binding to a second TRGV9 epitope, wherein the first TRGV9 epitope and the second TRGV9 epitope are different. In specific embodiments, the TRGV9 antibody provided herein or its antigen-binding fragment specifically binds to TRGV9. In some embodiments, the TRGV9 antibody provided herein or its antigen-binding fragment does not bind to the Vδ2 epitope.

[0164] In some embodiments, the sequences VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 are based on the Kabat numbering system. In some embodiments, the sequences VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 are based on the Chothia numbering system. In some embodiments, the sequences VH CDR1, VH CDR2, VH CDR3, VLCDR1, VL CDR2, and VL CDR3 are based on an exemplary numbering system. In some embodiments, the sequences VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 are based on the Contact numbering system. In some embodiments, the sequences VHCDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 are based on the IMGT numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences are numbered according to the AbM numbering system. This document provides exemplary groups of six CDRs (VH CDR1-3 and VL CDR1-3) for certain antibody embodiments. Other CDR groups are envisioned and are within the scope of the antibody embodiments provided herein.

[0165] In one aspect, the TRGV9 antibody provided herein has the VH and VL amino acid sequences of L7A5_1 (TRGV9_1). In another aspect, the TRGV9 antibody provided herein comprises: VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 respectively, these VH CDRs belonging to the VH having the amino acid sequence of SEQ ID NO: 7. In another aspect, the TRGV9 antibody provided herein comprises: VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 respectively, these VH CDR1, VH CDR2, and VH CDR3 belonging to the VL having the amino acid sequence of SEQ ID NO: 8. In one aspect, this document provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, which belong to the VH having the amino acid sequence of SEQ ID NO: 7; and (ii) a VL comprising VLCDR1, VL CDR2, and VL CDR3 having amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, which belong to the VL having the amino acid sequence of SEQ ID NO: 8. On the other hand, this article provides a TRGV9 antibody comprising: (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 VLCDR1 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 VLCDR3 having the amino acid sequence of SEQ ID NO: 6.On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising VHCDR1 having the amino acid sequence of SEQ ID NO: 160, VH CDR2 having the amino acid sequence of SEQ ID NO: 161, and VH CDR3 having the amino acid sequence of SEQ ID NO: 162; and (ii) a VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 163, VL CDR2 having the amino acid sequence of SEQ ID NO: 164, and VL CDR3 having the amino acid sequence of SEQ ID NO: 165. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 166, a VH CDR2 having the amino acid sequence of SEQ ID NO: 167, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 168; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 169, a VL CDR2 having the amino acid sequence of SEQ ID NO: 170, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 171. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 172, a VH CDR2 having the amino acid sequence of SEQ ID NO: 173, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 174; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 175, a VL CDR2 having the amino acid sequence of SEQ ID NO: 176, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 177. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 178, a VH CDR2 having the amino acid sequence of SEQ ID NO: 179, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 180; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 181, a VL CDR2 having the amino acid sequence of SEQ ID NO: 182, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 183.On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 178, a VH CDR2 having the amino acid sequence of SEQ ID NO: 700, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 701; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 181, a VL CDR2 having the amino acid sequence of SEQ ID NO: 182, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 183. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 184, VH CDR2 having the amino acid sequence of SEQ ID NO: 185, and VH CDR3 having the amino acid sequence of SEQ ID NO: 186; and (ii) a VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 187, VLCDR2 having the amino acid sequence of SEQ ID NO: 188, and VL CDR3 having the amino acid sequence of SEQ ID NO: 189. On the other hand, this document provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 190, VH CDR2 having the amino acid sequence of SEQ ID NO: 191, and VH CDR3 having the amino acid sequence of SEQ ID NO: 192; and (ii) a VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 193, VL CDR2 having the amino acid sequence of SEQ ID NO: 194, and VL CDR3 having the amino acid sequence of SEQ ID NO: 195. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 7. 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: 7 and a VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 23. In some embodiments, the antibody comprises a light chain having the amino acid sequence of SEQ ID NO: 24. In some embodiments, the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 23 and a light chain having the amino acid sequence of SEQ ID NO: 24. In some embodiments, the antibody comprises the amino acid sequence of SEQ ID NO: 17.In some embodiments, the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 69. In some embodiments, the antibody comprises a light chain having the amino acid sequence of SEQ ID NO: 24. In some embodiments, the antibody comprises a heavy chain having the amino acid sequence of SEQ ID NO: 69 and a light chain having the amino acid sequence of SEQ ID NO: 24. In some embodiments, the antibody comprises VH, which comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 7. In some embodiments, the antibody comprises VL, which comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody comprises: VH, which comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 7; and VL, which comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody comprises a heavy chain, which comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 23. In some embodiments, the antibody comprises a light chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 24. In some embodiments, the antibody comprises: a heavy chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 23; and a light chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 24. In some embodiments, the antibody comprises the amino acid sequence of SEQ ID NO: 17. In some embodiments, the antibody comprises a heavy chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 69. In some embodiments, the antibody comprises a light chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 24. In some embodiments, the antibody comprises: a heavy chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 69; and a light chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 24.

[0166] In one aspect, the TRGV9 antibody provided herein has the VH and VL amino acid sequences of TRGV9Ab_2(L7A5_2). In another aspect, the TRGV9 antibody provided herein comprises: VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 respectively, as specified in SEQ ID NO: 34. In another aspect, the TRGV9 antibody provided herein comprises: VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VLCDR1, VL CDR2, and VL CDR3 respectively, as specified in SEQ ID NO: 8. In one aspect, this article provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 34, respectively; and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 8, respectively. On the other hand, this article provides a TRGV9 antibody comprising: (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. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 196, VH CDR2 having the amino acid sequence of SEQ ID NO: 197, and VH CDR3 having the amino acid sequence of SEQ ID NO: 198; and (ii) a VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 199, VL CDR2 having the amino acid sequence of SEQ ID NO: 200, and VLCDR3 having the amino acid sequence of SEQ ID NO: 201.On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 202, a VH CDR2 having the amino acid sequence of SEQ ID NO: 203, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 204; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 205, a VL CDR2 having the amino acid sequence of SEQ ID NO: 206, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 207. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 208, a VH CDR2 having the amino acid sequence of SEQ ID NO: 209, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 210; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 211, a VL CDR2 having the amino acid sequence of SEQ ID NO: 212, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 213. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 214, VH CDR2 having the amino acid sequence of SEQ ID NO: 215, and VH CDR3 having the amino acid sequence of SEQ ID NO: 216; and (ii) a VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 217, VL CDR2 having the amino acid sequence of SEQ ID NO: 218, and VL CDR3 having the amino acid sequence of SEQ ID NO: 219. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 214, a VH CDR2 having the amino acid sequence of SEQ ID NO: 702, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 703; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 217, a VL CDR2 having the amino acid sequence of SEQ ID NO: 218, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 219.On the other hand, this article provides a TRGV9 antibody comprising: (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. On the other hand, this document provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 226, VH CDR2 having the amino acid sequence of SEQ ID NO: 227, and VH CDR3 having the amino acid sequence of SEQ ID NO: 228; and (ii) a VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 229, VLCDR2 having the amino acid sequence of SEQ ID NO: 230, and VL CDR3 having the amino acid sequence of SEQ ID NO: 231. In some embodiments, the antibody comprises a 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 VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 34. In some embodiments, the antibody comprises VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody comprises: VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 34; and VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 8.

[0167] In one aspect, the TRGV9 antibody provided herein has the VH and VL amino acid sequences of TRGV9Ab_3(L7A5_3). In another aspect, the TRGV9 antibody provided herein comprises a VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 as specified in SEQ ID NO: 35, respectively. In another aspect, the TRGV9 antibody provided herein comprises a VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VLCDR1, VL CDR2, and VL CDR3 as specified in SEQ ID NO: 8, respectively. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 35, respectively; and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 8, respectively. On the other hand, this article provides a TRGV9 antibody comprising: (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. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 232, VH CDR2 having the amino acid sequence of SEQ ID NO: 233, and VH CDR3 having the amino acid sequence of SEQ ID NO: 234; and (ii) a VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 235, VL CDR2 having the amino acid sequence of SEQ ID NO: 236, and VLCDR3 having the amino acid sequence of SEQ ID NO: 237.On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 238, a VH CDR2 having the amino acid sequence of SEQ ID NO: 239, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 240; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 241, a VL CDR2 having the amino acid sequence of SEQ ID NO: 242, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 243. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 244, a VH CDR2 having the amino acid sequence of SEQ ID NO: 245, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 246; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 247, a VL CDR2 having the amino acid sequence of SEQ ID NO: 248, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 249. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 250, a VHCDR2 having the amino acid sequence of SEQ ID NO: 251, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 252; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 253, a VL CDR2 having the amino acid sequence of SEQ ID NO: 254, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 255. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 250, a VH CDR2 having the amino acid sequence of SEQ ID NO: 704, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 705; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 253, a VL CDR2 having the amino acid sequence of SEQ ID NO: 254, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 255.On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 256, a VH CDR2 having the amino acid sequence of SEQ ID NO: 257, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 258; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 259, a VL CDR2 having the amino acid sequence of SEQ ID NO: 260, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 261. On the other hand, this document provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 262, VH CDR2 having the amino acid sequence of SEQ ID NO: 263, and VH CDR3 having the amino acid sequence of SEQ ID NO: 264; and (ii) a VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 265, VL CDR2 having the amino acid sequence of SEQ ID NO: 266, and VL CDR3 having the amino acid sequence of SEQ ID NO: 267. In some embodiments, the 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 VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 35. In some embodiments, the antibody comprises VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody comprises: VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 35; and VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 8.

[0168] In one aspect, the TRGV9 antibody provided herein has the VH and VL amino acid sequences of TRGV9Ab_4(L7A5_4). In another aspect, the TRGV9 antibody provided herein comprises a VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 respectively, as specified in SEQ ID NO: 36. In another aspect, the TRGV9 antibody provided herein comprises a VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VLCDR1, VL CDR2, and VL CDR3 respectively, as specified in SEQ ID NO: 8. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 36, respectively; and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 8, respectively. On the other hand, this article provides a TRGV9 antibody comprising: (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. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 268, VH CDR2 having the amino acid sequence of SEQ ID NO: 269, and VH CDR3 having the amino acid sequence of SEQ ID NO: 270; and (ii) a VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 271, VL CDR2 having the amino acid sequence of SEQ ID NO: 272, and VLCDR3 having the amino acid sequence of SEQ ID NO: 273.On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 274, a VH CDR2 having the amino acid sequence of SEQ ID NO: 275, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 276; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 277, a VL CDR2 having the amino acid sequence of SEQ ID NO: 278, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 279. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 280, a VH CDR2 having the amino acid sequence of SEQ ID NO: 281, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 282; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 283, a VL CDR2 having the amino acid sequence of SEQ ID NO: 284, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 285. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 286, a VHCDR2 having the amino acid sequence of SEQ ID NO: 287, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 288; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 289, a VL CDR2 having the amino acid sequence of SEQ ID NO: 290, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 291. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 286, a VH CDR2 having the amino acid sequence of SEQ ID NO: 706, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 707; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 289, a VL CDR2 having the amino acid sequence of SEQ ID NO: 290, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 291.On the other hand, this article provides a TRGV9 antibody comprising: (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. On the other hand, this document provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 298, VH CDR2 having the amino acid sequence of SEQ ID NO: 299, and VH CDR3 having the amino acid sequence of SEQ ID NO: 300; and (ii) a VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 301, VL CDR2 having the amino acid sequence of SEQ ID NO: 302, and VL CDR3 having the amino acid sequence of SEQ ID NO: 303. In some embodiments, the 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 VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 36. In some embodiments, the antibody comprises VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody comprises: VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 36; and VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 8.

[0169] In one aspect, the TRGV9 antibody provided herein has the VH and VL amino acid sequences of TRGV9Ab_var17. In another aspect, the TRGV9 antibody provided herein has the VH and VL amino acid sequences of TRGV9Ab_var29. In one aspect, the TRGV9 antibody provided herein comprises a VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VHCDR2, and VH CDR3 respectively, as specified in SEQ ID NO: 65. In one aspect, the TRGV9 antibody provided herein comprises a VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VLCDR3 respectively, as specified in SEQ ID NO: 66. In another aspect, this document provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 as specified in SEQ ID NO: 65, respectively; and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VLCDR1, VL CDR2, and VL CDR3 as specified in SEQ ID NO: 66, respectively. In another aspect, this document provides a TRGV9 antibody comprising a VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 as specified in SEQ ID NO: 67, respectively. In another aspect, this document provides a TRGV9 antibody comprising: a VL containing VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 as specified in SEQ ID NO: 68, respectively. In another aspect, this document provides a TRGV9 antibody comprising: (i) a VH containing VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 as specified in SEQ ID NO: 67, respectively; and (ii) a VL containing VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 as specified in SEQ ID NO: 68, respectively.On the other hand, this article provides a TRGV9 antibody comprising: (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. On the other hand, this article provides a TRGV9 antibody comprising: (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 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. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising VHCDR1 having the amino acid sequence of SEQ ID NO: 304, VH CDR2 having the amino acid sequence of SEQ ID NO: 305, and VH CDR3 having the amino acid sequence of SEQ ID NO: 306; and (ii) a VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 307, VL CDR2 having the amino acid sequence of SEQ ID NO: 308, and VL CDR3 having the amino acid sequence of SEQ ID NO: 309. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 310, a VH CDR2 having the amino acid sequence of SEQ ID NO: 311, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 312; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 313, a VL CDR2 having the amino acid sequence of SEQ ID NO: 314, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 315.On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 316, VH CDR2 having the amino acid sequence of SEQ ID NO: 317, and VH CDR3 having the amino acid sequence of SEQ ID NO: 318; and (ii) a VL comprising VLCDR1 having the amino acid sequence of SEQ ID NO: 319, VL CDR2 having the amino acid sequence of SEQ ID NO: 320, and VL CDR3 having the amino acid sequence of SEQ ID NO: 321. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 322, a VH CDR2 having the amino acid sequence of SEQ ID NO: 323, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 324; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 325, a VL CDR2 having the amino acid sequence of SEQ ID NO: 326, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 327. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 322, a VH CDR2 having the amino acid sequence of SEQ ID NO: 708, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 709; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 325, a VL CDR2 having the amino acid sequence of SEQ ID NO: 326, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 327. On the other hand, this article provides a TRGV9 antibody comprising: (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.On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 334, VH CDR2 having the amino acid sequence of SEQ ID NO: 335, and VH CDR3 having the amino acid sequence of SEQ ID NO: 336; and (ii) a VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 337, VL CDR2 having the amino acid sequence of SEQ ID NO: 338, and VL CDR3 having the amino acid sequence of SEQ ID NO: 339. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 340, VH CDR2 having the amino acid sequence of SEQ ID NO: 341, and VH CDR3 having the amino acid sequence of SEQ ID NO: 342; and (ii) a VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 343, VLCDR2 having the amino acid sequence of SEQ ID NO: 344, and VL CDR3 having the amino acid sequence of SEQ ID NO: 345. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 346, a VH CDR2 having the amino acid sequence of SEQ ID NO: 347, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 348; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 349, a VL CDR2 having the amino acid sequence of SEQ ID NO: 350, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 351. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising VHCDR1 having the amino acid sequence of SEQ ID NO: 352, VH CDR2 having the amino acid sequence of SEQ ID NO: 353, and VH CDR3 having the amino acid sequence of SEQ ID NO: 354; and (ii) a VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 355, VL CDR2 having the amino acid sequence of SEQ ID NO: 356, and VL CDR3 having the amino acid sequence of SEQ ID NO: 357.On the other hand, this article provides a TRGV9 antibody comprising: (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 VL CDR1 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 VL CDR3 having the amino acid sequence of SEQ ID NO: 363. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 358, VH CDR2 having the amino acid sequence of SEQ ID NO: 710, and VH CDR3 having the amino acid sequence of SEQ ID NO: 711; and (ii) a VL comprising VLCDR1 having the amino acid sequence of SEQ ID NO: 361, VL CDR2 having the amino acid sequence of SEQ ID NO: 362, and VL CDR3 having the amino acid sequence of SEQ ID NO: 363. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 364, a VH CDR2 having the amino acid sequence of SEQ ID NO: 365, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 366; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 367, a VL CDR2 having the amino acid sequence of SEQ ID NO: 368, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 369. On the other hand, this document provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 370, VHCDR2 having the amino acid sequence of SEQ ID NO: 371, and VH CDR3 having the amino acid sequence of SEQ ID NO: 372; and (ii) a VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 373, VL CDR2 having the amino acid sequence of SEQ ID NO: 374, and VL CDR3 having the amino acid sequence of SEQ ID NO: 375. In some embodiments, the antibody comprises 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 comprises 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 comprises the amino acid sequence of SEQ ID NO: 73. In some embodiments, the antibody comprises VH, which comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 65. In some embodiments, the antibody comprises VL, which comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 66. In some embodiments, the antibody comprises: VH, which comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 65; and VL, which comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 66. In some embodiments, the antibody comprises VH, which comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 67. In some embodiments, the antibody comprises VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 68. In some embodiments, the antibody comprises: VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 67; and VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 68.In some embodiments, the antibody comprises a heavy chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 71. In some embodiments, the antibody comprises a light chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 72. In some embodiments, the antibody comprises: a heavy chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 71; and a light chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 72. In some embodiments, the antibody comprises the amino acid sequence of SEQ ID NO: 70. In some embodiments, the antibody comprises a heavy chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 74. In some embodiments, the antibody comprises a light chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 75. In some embodiments, the antibody comprises: a heavy chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 74; and a light chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 75. In some embodiments, the antibody comprises the amino acid sequence of SEQ ID NO: 73.

[0170] In one aspect, the TRGV9 antibody provided herein has the VH and VL amino acid sequences of VG3_B3_RN. In another aspect, the TRGV9 antibody provided herein comprises a VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VHCDR1, VH CDR2, and VH CDR3 respectively, as specified in SEQ ID NO: 95. In another aspect, the TRGV9 antibody provided herein comprises a VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 respectively, as specified in SEQ ID NO: 96. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VHCDR3 as specified in SEQ ID NO: 95; and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 as specified in SEQ ID NO: 96. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 89, a VH CDR2 having the amino acid sequence of SEQ ID NO: 90, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 91; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 92, a VL CDR2 having the amino acid sequence of SEQ ID NO: 93, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 94. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 376, VH CDR2 having the amino acid sequence of SEQ ID NO: 377, and VH CDR3 having the amino acid sequence of SEQ ID NO: 378; and (ii) a VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 379, VL CDR2 having the amino acid sequence of SEQ ID NO: 380, and VLCDR3 having the amino acid sequence of SEQ ID NO: 381.On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 382, ​​a VH CDR2 having the amino acid sequence of SEQ ID NO: 383, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 384; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 385, a VL CDR2 having the amino acid sequence of SEQ ID NO: 386, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 387. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 388, a VH CDR2 having the amino acid sequence of SEQ ID NO: 389, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 390; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 391, a VL CDR2 having the amino acid sequence of SEQ ID NO: 392, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 393. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 394, VHCDR2 having the amino acid sequence of SEQ ID NO: 395, and VH CDR3 having the amino acid sequence of SEQ ID NO: 396; and (ii) a VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 397, VL CDR2 having the amino acid sequence of SEQ ID NO: 398, and VL CDR3 having the amino acid sequence of SEQ ID NO: 399. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 394, a VH CDR2 having the amino acid sequence of SEQ ID NO: 712, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 713; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 397, a VL CDR2 having the amino acid sequence of SEQ ID NO: 398, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 399.On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 400, a VH CDR2 having the amino acid sequence of SEQ ID NO: 401, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 402; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 403, a VL CDR2 having the amino acid sequence of SEQ ID NO: 404, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 405. On the other hand, this document provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 406, VH CDR2 having the amino acid sequence of SEQ ID NO: 407, and VH CDR3 having the amino acid sequence of SEQ ID NO: 408; and (ii) a VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 409, VL CDR2 having the amino acid sequence of SEQ ID NO: 410, and VL CDR3 having the amino acid sequence of SEQ ID NO: 411. In some embodiments, the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 95. In some embodiments, the antibody comprises a VL having the amino acid sequence of SEQ ID NO: 96. In some embodiments, the antibody 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 some embodiments, the antibody comprises the amino acid sequence of SEQ ID NO: 97. In some embodiments, the antibody comprises VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 95. In some embodiments, the antibody comprises VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 96. In some embodiments, the antibody comprises: VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 95; and VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 96. In some embodiments, the antibody comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 97.

[0171] In one aspect, the TRGV9 antibody provided herein has the VH and VL amino acid sequences of VG9B420. In another aspect, the TRGV9 antibody provided herein comprises a VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VHCDR1, VH CDR2, and VH CDR3 as specified in SEQ ID NO: 104, respectively. In another aspect, the TRGV9 antibody provided herein comprises a VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VLCDR2, and VL CDR3 as specified in SEQ ID NO: 105, respectively. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of SEQ ID NO: 104, respectively; and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 105, respectively. On the other hand, this article provides a TRGV9 antibody comprising: (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 VLCDR1 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. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 412, a VH CDR2 having the amino acid sequence of SEQ ID NO: 413, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 414; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 415, a VL CDR2 having the amino acid sequence of SEQ ID NO: 416, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 417.On the other hand, this article provides a TRGV9 antibody comprising: (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. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 424, a VH CDR2 having the amino acid sequence of SEQ ID NO: 425, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 426; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 427, a VL CDR2 having the amino acid sequence of SEQ ID NO: 428, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 429. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 430, a VH CDR2 having the amino acid sequence of SEQ ID NO: 431, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 432; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 433, a VL CDR2 having the amino acid sequence of SEQ ID NO: 434, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 435. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 430, VH CDR2 having the amino acid sequence of SEQ ID NO: 714, and VH CDR3 having the amino acid sequence of SEQ ID NO: 715; and (ii) a VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 433, VLCDR2 having the amino acid sequence of SEQ ID NO: 434, and VL CDR3 having the amino acid sequence of SEQ ID NO: 435.On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 436, a VH CDR2 having the amino acid sequence of SEQ ID NO: 437, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 438; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 439, a VL CDR2 having the amino acid sequence of SEQ ID NO: 440, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 441. On the other hand, this document provides a TRGV9 antibody comprising: (i) a VH comprising VHCDR1 having the amino acid sequence of SEQ ID NO: 442, VH CDR2 having the amino acid sequence of SEQ ID NO: 443, and VH CDR3 having the amino acid sequence of SEQ ID NO: 444; and (ii) a VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 445, VL CDR2 having the amino acid sequence of SEQ ID NO: 446, and VL CDR3 having the amino acid sequence of SEQ ID NO: 447. In some embodiments, the antibody comprises 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 comprises the amino acid sequence of SEQ ID NO: 106. In some embodiments, the antibody comprises VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 104. In some embodiments, the antibody comprises VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 105. In some embodiments, the antibody comprises: VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 104; and VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 105. In some embodiments, the antibody comprises the amino acid sequence of SEQ ID NO: 106.

[0172] In one aspect, the TRGV9 antibody provided herein has the VH and VL amino acid sequences of VG9SB10SC1087_P18_D08. In another aspect, the TRGV9 antibody provided herein comprises a VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 respectively, as specified in SEQ ID NO: 113. In another aspect, the TRGV9 antibody provided herein comprises a VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VLCDR1, VL CDR2, and VL CDR3 respectively, as specified in SEQ ID NO: 114. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VHCDR2, and VH CDR3 of SEQ ID NO: 113, respectively; and (ii) a VL comprising VL CDR1, VL CDR2, and VLCDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 114, respectively. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 107, a VH CDR2 having the amino acid sequence of SEQ ID NO: 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. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 448, a VH CDR2 having the amino acid sequence of SEQ ID NO: 449, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 450; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 451, a VL CDR2 having the amino acid sequence of SEQ ID NO: 452, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 453.On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 454, a VHCDR2 having the amino acid sequence of SEQ ID NO: 455, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 456; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 457, a VL CDR2 having the amino acid sequence of SEQ ID NO: 458, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 459. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 460, a VH CDR2 having the amino acid sequence of SEQ ID NO: 461, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 462; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 463, a VL CDR2 having the amino acid sequence of SEQ ID NO: 464, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 465. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 466, a VH CDR2 having the amino acid sequence of SEQ ID NO: 467, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 468; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 469, a VL CDR2 having the amino acid sequence of SEQ ID NO: 470, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 471. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 466, a VH CDR2 having the amino acid sequence of SEQ ID NO: 716, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 717; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 469, a VL CDR2 having the amino acid sequence of SEQ ID NO: 470, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 471.On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 472, a VH CDR2 having the amino acid sequence of SEQ ID NO: 473, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 474; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 475, a VL CDR2 having the amino acid sequence of SEQ ID NO: 476, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 477. On the other hand, this document provides a TRGV9 antibody comprising: (i) a VH comprising VHCDR1 having the amino acid sequence of SEQ ID NO: 478, VH CDR2 having the amino acid sequence of SEQ ID NO: 479, and VH CDR3 having the amino acid sequence of SEQ ID NO: 480; and (ii) a VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 481, VL CDR2 having the amino acid sequence of SEQ ID NO: 482, and VL CDR3 having the amino acid sequence of SEQ ID NO: 483. In some embodiments, the antibody 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 VH, which comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 113. In some embodiments, the antibody comprises VL, which comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 114. In some embodiments, the antibody comprises: VH, which comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 113; and VL, which comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 114.In some embodiments, the antibody comprises a heavy chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 115. In some embodiments, the antibody comprises a light chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 116. In some embodiments, the antibody comprises: a heavy chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 115; and a light chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 116.

[0173] In one aspect, the TRGV9 antibody provided herein has the VH and VL amino acid sequences of VG9SB10SC1087_P18_C12. In another aspect, the TRGV9 antibody provided herein comprises a VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 respectively, as specified in SEQ ID NO: 123. In another aspect, the TRGV9 antibody provided herein comprises a VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VLCDR1, VL CDR2, and VL CDR3 respectively, as specified in SEQ ID NO: 124. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VHCDR2, and VH CDR3 of SEQ ID NO: 123, respectively; and (ii) a VL comprising VL CDR1, VL CDR2, and VLCDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 124, respectively. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 117, a VH CDR2 having the amino acid sequence of SEQ ID NO: 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. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 484, a VH CDR2 having the amino acid sequence of SEQ ID NO: 485, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 486; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 487, a VL CDR2 having the amino acid sequence of SEQ ID NO: 488, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 489.On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1 having the amino acid sequence of SEQ ID NO: 490, VHCDR2 having the amino acid sequence of SEQ ID NO: 491, and VH CDR3 having the amino acid sequence of SEQ ID NO: 492; and (ii) a VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 493, VL CDR2 having the amino acid sequence of SEQ ID NO: 494, and VL CDR3 having the amino acid sequence of SEQ ID NO: 495. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 496, a VH CDR2 having the amino acid sequence of SEQ ID NO: 497, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 498; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 499, a VL CDR2 having the amino acid sequence of SEQ ID NO: 500, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 501. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 502, a VH CDR2 having the amino acid sequence of SEQ ID NO: 503, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 504; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 505, a VL CDR2 having the amino acid sequence of SEQ ID NO: 506, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 507. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 502, a VH CDR2 having the amino acid sequence of SEQ ID NO: 718, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 719; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 505, a VL CDR2 having the amino acid sequence of SEQ ID NO: 506, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 507.On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 508, a VH CDR2 having the amino acid sequence of SEQ ID NO: 509, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 510; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 511, a VL CDR2 having the amino acid sequence of SEQ ID NO: 512, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 513. On the other hand, this document provides a TRGV9 antibody comprising: (i) a VH comprising VHCDR1 having the amino acid sequence of SEQ ID NO: 514, VH CDR2 having the amino acid sequence of SEQ ID NO: 515, and VH CDR3 having the amino acid sequence of SEQ ID NO: 516; and (ii) a VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 517, VL CDR2 having the amino acid sequence of SEQ ID NO: 518, and VL CDR3 having the amino acid sequence of SEQ ID NO: 519. In some embodiments, the antibody 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 VH, which comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 123. In some embodiments, the antibody comprises VL, which comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 124. In some embodiments, the antibody comprises: VH, which comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 123; and VL, which comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 124.In some embodiments, the antibody comprises a heavy chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 125. In some embodiments, the antibody comprises a light chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 126. In some embodiments, the antibody comprises: a heavy chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 125; and a light chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 126.

[0174] In one aspect, the TRGV9 antibody provided herein has the VH and VL amino acid sequences of VG9SB10SC1087_P19_C03. In another aspect, the TRGV9 antibody provided herein comprises a VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 respectively, as specified in SEQ ID NO: 133. In another aspect, the TRGV9 antibody provided herein comprises a VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of VLCDR1, VL CDR2, and VL CDR3 respectively, as specified in SEQ ID NO: 134. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of VH CDR1, VHCDR2, and VH CDR3 of SEQ ID NO: 133, respectively; and (ii) a VL comprising VL CDR1, VL CDR2, and VLCDR3 having the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of SEQ ID NO: 134, respectively. On the other hand, this article provides a TRGV9 antibody comprising: (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. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 520, a VH CDR2 having the amino acid sequence of SEQ ID NO: 521, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 522; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 523, a VL CDR2 having the amino acid sequence of SEQ ID NO: 524, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 525.On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 526, a VHCDR2 having the amino acid sequence of SEQ ID NO: 527, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 528; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 529, a VL CDR2 having the amino acid sequence of SEQ ID NO: 530, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 531. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 532, a VH CDR2 having the amino acid sequence of SEQ ID NO: 533, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 534; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 535, a VL CDR2 having the amino acid sequence of SEQ ID NO: 536, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 537. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 538, a VH CDR2 having the amino acid sequence of SEQ ID NO: 539, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 540; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 541, a VL CDR2 having the amino acid sequence of SEQ ID NO: 542, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 543. On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 538, a VH CDR2 having the amino acid sequence of SEQ ID NO: 720, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 721; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 541, a VL CDR2 having the amino acid sequence of SEQ ID NO: 542, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 543.On the other hand, this article provides a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having the amino acid sequence of SEQ ID NO: 544, a VH CDR2 having the amino acid sequence of SEQ ID NO: 545, and a VH CDR3 having the amino acid sequence of SEQ ID NO: 546; and (ii) a VL comprising a VL CDR1 having the amino acid sequence of SEQ ID NO: 547, a VL CDR2 having the amino acid sequence of SEQ ID NO: 548, and a VL CDR3 having the amino acid sequence of SEQ ID NO: 549. On the other hand, this document provides a TRGV9 antibody comprising: (i) a VH comprising VHCDR1 having the amino acid sequence of SEQ ID NO: 550, VH CDR2 having the amino acid sequence of SEQ ID NO: 551, and VH CDR3 having the amino acid sequence of SEQ ID NO: 552; and (ii) a VL comprising VL CDR1 having the amino acid sequence of SEQ ID NO: 553, VL CDR2 having the amino acid sequence of SEQ ID NO: 554, and VL CDR3 having the amino acid sequence of SEQ ID NO: 555. In some embodiments, the antibody 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 VH, which comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 133. In some embodiments, the antibody comprises VL, which comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 134. In some embodiments, the antibody comprises: VH, which comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 133; and VL, which comprises an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 134.In some embodiments, the antibody comprises a heavy chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 135. In some embodiments, the antibody comprises a light chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 136. In some embodiments, the antibody comprises: a heavy chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 135; and a light chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 136.

[0175] In some embodiments, the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of the TRGV9 antibody are based on the Kabat numbering system. In some embodiments, the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of the TRGV9 antibody are based on the Chothia numbering system. In some embodiments, the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of the TRGV9 antibody are based on the AbM numbering system. In some embodiments, the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of the TRGV9 antibody are based on the Contact numbering system. In some embodiments, the amino acid sequences of VH CDR1, VH CDR2, and VHCDR3 of the TRGV9 antibody are based on the IMGT numbering system. In some embodiments, the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 of the TRGV9 antibody are based on an exemplary numbering system. In some embodiments, the amino acid sequences of VL CDR1, VLCDR2, and VL CDR3 of the TRGV9 antibody are based on the Kabat numbering system. In some embodiments, the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of the TRGV9 antibody are based on the Chothia numbering system. In some embodiments, the amino acid sequences of VLCDR1, VL CDR2, and VL CDR3 of the TRGV9 antibody are based on the AbM numbering system. In some embodiments, the amino acid sequences of VLCDR1, VL CDR2, and VL CDR3 of the TRGV9 antibody are based on the Contact numbering system. In some embodiments, the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of the TRGV9 antibody are based on the IMGT numbering system. In some embodiments, the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 of the TRGV9 antibody are based on an exemplary numbering system.

[0176] In some embodiments, the TRGV9 antibody is a multispecific antibody. In other embodiments, the TRGV9 antibody is a bispecific antibody. In some embodiments, the multispecific antibody comprises an antigen-binding fragment of the TRGV9 antibody provided herein. In some embodiments, the multispecific antibody comprises a first binding domain that binds to a first TRGV9 epitope and a second binding domain that binds to a second TRGV9 epitope, wherein the first TRGV9 epitope and the second TRGV9 epitope are different. In some embodiments, the multispecific antibody further comprises a third binding domain that binds to a target that is not TRGV9. In some embodiments, the multispecific antibody comprises a heavy chain variable region and a light chain variable region. In some embodiments, the first binding domain comprises a heavy chain variable region and a light chain variable region. In some embodiments, the second binding domain comprises a heavy chain variable region and a light chain variable region. In some embodiments, the first binding domain of the TRGV9 antibody is not a single-domain antibody or nanobody. In some implementations, the second binding domain of the TRGV9 antibody is not a single-domain antibody or nanobody.

[0177] In specific embodiments, the TRGV9 antibody includes a VH region and a VL region. In some embodiments, the TRGV9 antibody is not a single-chain antibody. In some embodiments, the TRGV9 antibody is not a single-domain antibody. In some embodiments, the TRGV9 antibody is not a nanobody. In some embodiments, the TRGV9 antibody is not a VHH antibody. In some embodiments, the TRGV9 antibody is not a llama antibody. In some embodiments, the TRGV9 bispecific antibody does not include a single-chain antibody. In some embodiments, the TRGV9 bispecific antibody does not include a single-domain antibody. In some embodiments, the TRGV9 bispecific antibody does not include a nanobody. In some embodiments, the TRGV9 bispecific antibody does not include a VHH antibody. In some embodiments, the TRGV9 bispecific antibody does not include a llama antibody.

[0178] In some embodiments, the TRGV9 antibody provided herein does not contain VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NO: 730, 731, and 732, respectively. In some embodiments, the TRGV9 antibody provided herein does not contain VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NO: 733, 734, and 735, respectively. In some embodiments, the TRGV9 antibody provided herein does not contain VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NO: 736, 737, and 738, respectively. In some embodiments, the TRGV9 antibody provided herein does not contain VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NO: 739, 740, and 741, respectively. In some embodiments, the TRGV9 antibody provided herein does not contain VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NO: 742, 743, and 744, respectively. In some embodiments, the TRGV9 antibody provided herein does not contain VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NO: 745, 746, and 747, respectively. In some embodiments, the TRGV9 antibody provided herein does not contain VHCDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NO: 748, 749, and 750, respectively. In some embodiments, the TRGV9 antibody provided herein does not contain a VH domain having the amino acid sequence of SEQ ID NO: 751. In some embodiments, the TRGV9 antibody provided herein does not contain a VH domain having the amino acid sequence of SEQ ID NO: 752. In some embodiments, the TRGV9 antibody provided herein does not contain a VH domain having the amino acid sequence of SEQ ID NO: 753. In some embodiments, the TRGV9 antibody provided herein does not contain a VH domain having the amino acid sequence of SEQ ID NO: 754. In some embodiments, the TRGV9 antibody provided herein does not contain a VH domain having the amino acid sequence of SEQ ID NO: 755. In some embodiments, the TRGV9 antibody provided herein does not contain a VH domain having the amino acid sequence of SEQ ID NO: 756. In some embodiments, the TRGV9 antibody provided herein does not contain a VH domain having the amino acid sequence of SEQ ID NO: 757.

[0179] In another aspect, this document provides a TRGV9 antibody comprising a VH domain having an amino acid sequence of APNxGzYTbDF (SEQ ID NO: 758) as VH CDR3, where x is Y or M, z is M or D, and b is I or L. In another aspect, this document provides a TRGV9 antibody comprising a VH domain having an amino acid sequence of SEQ ID NO: 758. In another aspect, this document provides a TRGV9 antibody comprising a VH domain having an amino acid sequence of GxTFzz (SEQ ID NO: 761) as VH CDR1, where x is F, D, or G, and z is S or N. In another aspect, this document provides a TRGV9 antibody comprising a VH domain having an amino acid sequence of SEQ ID NO: 761. On the other hand, this article provides a TRGV9 antibody comprising a VL domain having an amino acid sequence of RxSQSz (SEQ ID NO: 762) as VL CDR1, where x is A or S and z is V or L. On the other hand, this article provides a TRGV9 antibody comprising a VH domain having an amino acid sequence of SEQ ID NO: 761.

[0180] On the other hand, this document provides antibodies that bind to TRGV9, wherein the antibody comprises: (i) a VH comprising VH CDR1, VH CDR2, and VH CDR3; and (ii) a VL comprising VL CDR1, VL CDR2, and VL CDR3. In some embodiments, VH CDR1 comprises a first polar amino acid. In some embodiments, VH CDR1 comprises a last polar, uncharged amino acid. In some embodiments, VH CDR1 comprises at least one tyrosine. In some embodiments, VH CDR1 comprises at least 20% hydrophobic amino acids. In some embodiments, VH CDR1 comprises at least two hydrophobic amino acids. In some embodiments, VH CDR1 comprises at least about 40% hydrophobic amino acids. In some embodiments, VH CDR1 comprises a first polar amino acid, a last polar, uncharged amino acid, at least one tyrosine, at least 20% hydrophobic amino acids, at least two hydrophobic amino acids, and at least about 40% hydrophobic amino acids. Any combination of two or more of the above-described structural features of VH CDR1 is also considered. In some embodiments, VH CDR2 contains a polar amino acid at residue 13. In some embodiments, VH CDR2 contains a hydrophobic amino acid at amino acid position 15. In some embodiments, VH CDR2 contains phenylalanine (F) or leucine (L) at position 15. In some embodiments, VH CDR2 contains a polar amino acid at position 14. In some embodiments, VH CDR2 contains lysine (K) or serine (S) at position 14. In some embodiments, VH CDR2 contains a hydrophobic amino acid at position 2. In some embodiments, VH CDR2 contains a hydrophobic amino acid at position 3. In some embodiments, VH CDR2 contains the penultimate polar amino acid. In some embodiments, VHCDR2 contains a polar amino acid at residue 13, a hydrophobic amino acid at amino acid position 15, phenylalanine (F) or leucine (L) at position 15, a polar amino acid at position 14, lysine (K) or serine (S) at position 14, a hydrophobic amino acid at position 2 or 3, and the penultimate polar amino acid. Any combination of two or more of the above-described VH CDR2 structural features is also considered. In some embodiments, VH CDR3 does not contain a polar charged amino acid at position 3. In some embodiments, VH CDR3 contains a hydrophobic or polar charged amino acid at position 7. In some embodiments, VH CDR3 contains a polar uncharged or hydrophobic amino acid at position 6. In some embodiments, VH CDR3 does not contain a polar charged amino acid at position 3, does not contain a hydrophobic or polar charged amino acid at position 7, and does not contain a polar uncharged or hydrophobic amino acid at position 6.Any combination of two or more of the above-described VH CDR3 structural features is also considered. In some embodiments, VL CDR1 contains a polar amino acid at position 4. In some embodiments, VL CDR1 contains a first polarly charged amino acid. In some embodiments, VL CDR1 contains a polarly uncharged or hydrophobic amino acid at position 2. In some embodiments, VL CDR1 contains serine at position 3. In some embodiments, VL CDR1 contains a polar amino acid at position 5. In some embodiments, VL CDR1 contains a hydrophobic amino acid at position 6. In some embodiments, VL CDR1 contains a polar amino acid at position 4, a polarly charged first amino acid, a polarly uncharged or hydrophobic amino acid at position 2, serine at position 3, a polar amino acid at position 5, and a hydrophobic amino acid at position 6. Any combination of two or more of the above-described VL CDR1 structural features is also considered. In some embodiments, VL CDR2 contains a polar amino acid at position 7. In some embodiments, VL CDR2 contains a polar charged or hydrophobic amino acid at position 6. In some embodiments, VLCDR2 contains a polar charged amino acid at position 3. In some embodiments, VL CDR2 contains a polar uncharged amino acid at position 4. In some embodiments, VL CDR2 contains a hydrophobic amino acid at position 2. In some embodiments, VL CDR2 contains a polar amino acid at position 7, a polar charged or hydrophobic amino acid at position 6, a polar charged amino acid at position 3, a polar uncharged amino acid at position 4, and a hydrophobic amino acid at position 2. Any combination of two or more of the above-described VL CDR2 structural features is also considered. In some embodiments, VLCDR3 contains a hydrophobic terminal amino acid. In some embodiments, VL CDR3 contains a terminal tyrosine residue. In some embodiments, VL CDR3 contains a polar uncharged amino acid at position 5. In some embodiments, VL CDR3 contains a polar amino acid at position 2. In some embodiments, VL CDR3 contains a polar, uncharged, or hydrophobic amino acid at position 1. In some embodiments, VL CDR3 contains a hydrophobic amino acid at position 3. In some embodiments, VL CDR3 contains a hydrophilic or polar, uncharged amino acid at position 6. In some embodiments, VL CDR3 does not contain a polar or hydrophobic amino acid at position 7.In some embodiments, VL CDR3 comprises a hydrophobic terminal amino acid, a terminal tyrosine residue, a polar, uncharged amino acid at position 5, a polar amino acid at position 2, a polar, uncharged, or hydrophobic amino acid at position 1, a hydrophobic amino acid at position 3, a hydrophilic or polar, uncharged amino acid at position 6, and no polar or hydrophobic amino acid at position 7. Any combination of two or more of the above-described VL CDR3 structural features is also considered. In specific embodiments, residue position numbering follows exemplary numbering.

[0181] On the other hand, this article provides an antibody that binds to TRGV9, wherein the antibody comprises: (i) VH comprising VH CDR1, VH CDR2 and VH CDR3; and (ii) VL comprising VL CDR1, VL CDR2 and VL CDR3.

[0182] In some embodiments of the TRGV9 antibody provided herein, VH CDR1 contains at least three polar amino acids. In some embodiments, VH CDR1 contains at least 40% polar amino acids. In some embodiments, VH CDR1 contains glycine (G) at position 1. In some embodiments, VH CDR1 does not contain a polar, uncharged amino acid at position 2. In some embodiments, VH CDR1 contains a polar, uncharged amino acid at position 3. In some embodiments, VH CDR1 contains threonine (T) or serine (S) at position 3. In some embodiments, VH CDR1 contains a hydrophobic amino acid at position 4. In some embodiments, VH CDR1 contains phenylalanine (F) or isoleucine (I) at position 4. In some embodiments, VH CDR1 contains a polar, uncharged amino acid at position 5. In some embodiments, VH CDR1 contains threonine (T), serine (S), or asparagine (N) at position 5. In some embodiments, VH CDR1 contains a polar amino acid at position 6. In some embodiments, VH CDR1 contains an acidic amino acid or a polar, uncharged amino acid at position 6. In some embodiments, VH CDR1 does not contain a polar, uncharged amino acid at position 7. Any combination of two or more of the above-described structural features of VH CDR1 is also considered. In some embodiments, the amino acid residues are numbered according to Chothia.

[0183] In some embodiments of the TRGV9 antibody provided herein, VH CDR2 does not contain a charged amino acid at position 1. In some embodiments, VH CDR2 does not contain a charged amino acid at position 2. In some embodiments, VH CDR2 contains glycine (G), a hydrophobic or polar uncharged amino acid at position 2. In some embodiments, VH CDR2 does not contain a hydrophobic or polar charged amino acid at position 4. In some embodiments, VH CDR2 does not contain a hydrophobic or polar uncharged amino acid at the last position. In some embodiments, VH CDR2 contains glycine (G) or a polar uncharged amino acid at the last position. Any combination of two or more of the above-described VH CDR2 structural features is also considered. In some embodiments, the amino acid residue numbering is based on Chothia.

[0184] In some embodiments of the TRGV9 antibody provided herein, VH CDR3 does not contain a polar charged amino acid at position 1. In some embodiments, VH CDR3 does not contain a polar charged amino acid at position 2. In some embodiments, VH CDR3 contains glycine (G), tyrosine (Y), or a polar uncharged amino acid at position 2. In some embodiments, VH CDR3 does not contain a polar uncharged amino acid at position 3. In some embodiments, VH CDR3 contains glycine (G), aspartic acid (D), or a hydrophobic amino acid at position 3. In some embodiments, VH CDR3 does not contain a polar charged amino acid at position 5. In some embodiments, VH CDR3 does not contain a polar uncharged amino acid at position 6. In some embodiments, VH CDR3 contains aspartic acid (D) or a hydrophobic amino acid at position 6. In some embodiments, VH CDR3 contains the penultimate hydrophobic amino acid. In some embodiments, VH CDR3 does not contain a polar uncharged amino acid at position 7. In some embodiments, VH CDR3 comprises a terminal aspartic acid (D) or a terminal alanine (A). Any combination of two or more of the above-described VH CDR3 structural features is also considered. In some embodiments, the amino acid residues are numbered according to Chothia.

[0185] In some embodiments of the TRGV9 antibody provided herein, VL CDR1 contains serine (S) at position 1. In some embodiments, VL CDR1 contains glutamine (G) or glutamate (E) at position 2. In some embodiments, VL CDR1 contains a polar, uncharged amino acid at position 3. In some embodiments, VL CDR1 contains serine (S) or asparagine (N) at position 3. In some embodiments, VL CDR1 contains a hydrophobic amino acid at position 4. In some embodiments, VL CDR1 contains leucine (L), valine (V), or isoleucine (I) at position 4. In some embodiments, VL CDR1 contains serine (S) or tyrosine (Y) at position 7. In some embodiments, VL CDR1 contains the penultimate polar, uncharged amino acid. In some embodiments, VL CDR1 contains a terminal tyrosine (Y) or a terminal lysine (K). Any combination of two or more of the above-described VL CDR1 structural features is also considered. In some implementations, the amino acid residues are numbered according to Chothia.

[0186] In some embodiments of the TRGV9 antibody provided herein, VL CDR2 contains a hydrophobic amino acid at position 2. In some embodiments, VL CDR2 contains either alanine (A) or isoleucine (I) at position 2. In some embodiments, VL CDR2 contains a polar terminal amino acid. In some embodiments, VL CDR2 contains either a terminal serine (S) or a terminal lysine (K). Any combination of two or more of the above-described VL CDR2 structural features is also considered. In some embodiments, the amino acid residues are numbered according to Chothia.

[0187] In some embodiments of the TRGV9 antibody provided herein, VL CDR3 does not contain a polar, uncharged amino acid at position 1. In some embodiments, VL CDR3 contains arginine (R) or a hydrophobic amino acid at position 1. In some embodiments, VL CDR3 does not contain a hydrophobic amino acid at position 3. In some embodiments, VL CDR3 contains arginine (R) or a polar, uncharged amino acid at position 3. In some embodiments, VL CDR3 does not contain a polar, charged amino acid at position 4. In some embodiments, VL CDR3 contains serine (S) or a hydrophobic amino acid at position 4. In some embodiments, VL CDR3 contains tyrosine (Y) or proline (P) as the penultimate amino acid. In some embodiments, VL CDR3 contains histidine (H) or proline (P) at position 5. In some embodiments, VL CDR3 contains terminal histidine (H), terminal lysine (L), or terminal tyrosine (Y). Any combination of two or more of the above-described VL CDR3 structural features has also been considered. In some embodiments, the amino acid residues are numbered according to Chothia.

[0188] In another aspect, this document provides a TRGV9 antibody comprising a VH containing a VH CDR1 having the amino acid sequence GX1TFX2X3X4 (SEQ ID NO: 777), wherein X1 is F, D, or G; X2 is T, S, or N; X3 is D, S, or N; and X4 is H, N, or Y. In another aspect, this document provides a TRGV9 antibody comprising a VH having the amino acid sequence SEQ ID NO: 777. In another aspect, this document provides a TRGV9 antibody comprising a VH containing a VH CDR2 having the amino acid sequence PGX1G (SEQ ID NO: 778), wherein X1 is D or S. In another aspect, this document provides a TRGV9 antibody comprising a VH having the amino acid sequence SEQ ID NO: 778. In another aspect, this document provides a TRGV9 antibody comprising a VH containing a VH CDR3 having the amino acid sequence X1GX2YTX3D (SEQ ID NO: 779), wherein X1 is Y or M, X2 is D or M, and X3 is I or L. In another aspect, this document provides a TRGV9 antibody comprising a VH having the amino acid sequence SEQ ID NO: 779. In another aspect, this document provides a TRGV9 antibody comprising a VL containing a VL CDR1 having the amino acid sequence SQSX1LYSSNX2X3 (SEQ ID NO: 780), wherein X1 is L or V, X2 is Q or N, and X3 is K or KNY. In another aspect, this document provides a TRGV9 antibody comprising a VL having the amino acid sequence SEQ ID NO: 780.

[0189] On the other hand, this document provides a TRGV9 antibody comprising VH, which includes VH CDR1, VH CDR2, and VH CDR3. In some embodiments, VH CDR1 comprises the amino acid sequence GX1TFX2X3X4 (SEQ ID NO: 777), wherein X1 is F, D, or G; X2 is T, S, or N; X3 is D, S, or N; and X4 is H, N, or Y. In some embodiments, VH CDR1 comprises the amino acid sequence SEQ ID NO: 178. In some embodiments, VH CDR1 comprises the amino acid sequence SEQ ID NO: 394. In some embodiments, VH CDR1 comprises the amino acid sequence SEQ ID NO: 430. In some embodiments, VH CDR1 comprises the amino acid sequence SEQ ID NO: 466. In some embodiments, VH CDR1 comprises the amino acid sequence SEQ ID NO: 502. In some embodiments, VH CDR1 comprises the amino acid sequence SEQ ID NO: 538. In some embodiments, VH CDR2 comprises the amino acid sequence PGX1G (SEQ ID NO: 778), wherein X1 is D or S. In some embodiments, VH CDR3 comprises the amino acid sequence X1GX2YTX3D (SEQ ID NO: 779), wherein X1 is Y or M, X2 is D or M, and X3 is I or L. On the other hand, this document provides a TRGV9 antibody comprising VL having VL CDR1, VL CDR2, and VLCDR3. In one embodiment, VL CDR1 comprises the amino acid sequence SQSX1LYSSNX2X3 (SEQ ID NO: 780), wherein X1 is L or V, X2 is Q or N, and X3 is K or KNY. In some embodiments, VL CDR2 comprises the amino acid sequence SEQ ID NO: 182. In some embodiments, VL CDR2 comprises the amino acid sequence SEQ ID NO: 398. In some embodiments, VL CDR2 comprises the amino acid sequence SEQ ID NO: 434. In some embodiments, VL CDR2 comprises the amino acid sequence of SEQ ID NO: 470. In some embodiments, VL CDR3 comprises the amino acid sequence of SEQ ID NO: 542. In some embodiments, VL CDR3 comprises the amino acid sequence of SEQ ID NO: 399. In some embodiments, VLCDR3 comprises the amino acid sequence of SEQ ID NO: 435. In some embodiments, VL CDR3 comprises the amino acid sequence of SEQ ID NO: 471. In some embodiments, VL CDR3 comprises the amino acid sequence of SEQ ID NO: 507.In some implementations, VL CDR3 contains the amino acid sequence of SEQ ID NO: 543.

[0190] In another aspect, a multispecific TRGV9 antibody is provided, comprising the TRGV9 antibody provided herein. In some embodiments, the multispecific TRGV9 antibody is a bispecific antibody. In one aspect, a multispecific TRGV9 antibody is provided herein, wherein the antibody comprises VH CDR1, VH CDR2, and VH CDR3 of the TRGV9 antibody provided herein. In one aspect, a multispecific TRGV9 antibody is provided herein, wherein the antibody comprises VL CDR1, VL CDR2, and VL CDR3 of the TRGV9 antibody provided herein. In one aspect, a multispecific TRGV9 antibody is provided herein, wherein the antibody comprises VH, VH, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of the TRGV9 antibody provided herein. In one aspect, a multispecific TRGV9 antibody is provided herein, wherein the antibody comprises VH of the TRGV9 antibody provided herein. In one aspect, a multispecific TRGV9 antibody is provided herein, wherein the antibody comprises VL of the TRGV9 antibody provided herein. In one respect, this article provides a multispecific TRGV9 antibody, wherein the antibody comprises the VH and VL of the TRGV9 antibody provided herein.

[0191] In one aspect, this document provides a multispecific TRGV9 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 some embodiments of the multispecific TRGV9 antibody provided herein, the second target is not a TRGV9 antigen. In some embodiments of the multispecific TRGV9 antibody provided herein, the second target is not a TRGV9 epitope.

[0192] In one embodiment of the multispecific TRGV9 antibody provided herein, the first binding domain for binding to TRGV9 comprises the VH and VL amino acid sequences of L7A5_1 (TRGV9_1). In one embodiment, the first binding domain comprises VH, which includes VH CDR1, VH CDR2, and VHCDR3 having the amino acid sequences VH CDR1, VH CDR2, and VH CDR3, respectively, belonging to the VH having the amino acid sequence of SEQ ID NO: 7. In one embodiment, the first binding domain comprises VL, which includes VL CDR1, VLCDR2, and VL CDR3 having the amino acid sequences VL CDR1, VL CDR2, and VL CDR3, respectively, belonging to the VL having the amino acid sequence of SEQ ID NO: 8. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, the VH CDRs belonging to the VH having the amino acid sequence of SEQ ID NO: 7; and (ii) VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, the VH CDR1, VH CDR2, and VH CDR3 belonging to the VL having the amino acid sequence of SEQ ID NO: 8. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 3; and (ii) VL, which comprises VLCDR1 having the amino acid sequence of SEQ ID NO: 4, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VLCDR3 having the amino acid sequence of SEQ ID NO: 6. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 160, VH CDR2 having the amino acid sequence of SEQ ID NO: 161, and VH CDR3 having the amino acid sequence of SEQ ID NO: 162; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 163, VL CDR2 having the amino acid sequence of SEQ ID NO: 164, and VLCDR3 having the amino acid sequence of SEQ ID NO: 165.In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 166, VH CDR2 having the amino acid sequence of SEQ ID NO: 167, and VH CDR3 having the amino acid sequence of SEQ ID NO: 168; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 169, VL CDR2 having the amino acid sequence of SEQ ID NO: 170, and VLCDR3 having the amino acid sequence of SEQ ID NO: 171. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 172, VH CDR2 having the amino acid sequence of SEQ ID NO: 173, and VH CDR3 having the amino acid sequence of SEQ ID NO: 174; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 175, VL CDR2 having the amino acid sequence of SEQ ID NO: 176, and VLCDR3 having the amino acid sequence of SEQ ID NO: 177. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 178, VH CDR2 having the amino acid sequence of SEQ ID NO: 179, and VH CDR3 having the amino acid sequence of SEQ ID NO: 180; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 181, VL CDR2 having the amino acid sequence of SEQ ID NO: 182, and VLCDR3 having the amino acid sequence of SEQ ID NO: 183. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 178, VH CDR2 having the amino acid sequence of SEQ ID NO: 700, and VH CDR3 having the amino acid sequence of SEQ ID NO: 701; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 181, VL CDR2 having the amino acid sequence of SEQ ID NO: 182, and VLCDR3 having the amino acid sequence of SEQ ID NO: 183.In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 184, VH CDR2 having the amino acid sequence of SEQ ID NO: 185, and VH CDR3 having the amino acid sequence of SEQ ID NO: 186; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 187, VL CDR2 having the amino acid sequence of SEQ ID NO: 188, and VLCDR3 having the amino acid sequence of SEQ ID NO: 189. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 190, VH CDR2 having the amino acid sequence of SEQ ID NO: 191, and VH CDR3 having the amino acid sequence of SEQ ID NO: 192; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 193, VL CDR2 having the amino acid sequence of SEQ ID NO: 194, and VLCDR3 having the amino acid sequence of SEQ ID NO: 195. In some embodiments, the first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 7. In some embodiments, the first binding domain comprises VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 7 and VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises a heavy chain having the amino acid sequence of SEQ ID NO: 23. In some embodiments, the first binding domain comprises a light chain having the amino acid sequence of SEQ ID NO: 24. In some embodiments, the first binding domain comprises a heavy chain having the amino acid sequence of SEQ ID NO: 23 and a light chain having the amino acid sequence of SEQ ID NO: 24. In some embodiments, the first binding domain comprises the amino acid sequence of SEQ ID NO: 17. In some embodiments, the first binding domain comprises a heavy chain having the amino acid sequence of SEQ ID NO: 69. In some embodiments, the first binding domain comprises a light chain having the amino acid sequence of SEQ ID NO: 24. In some embodiments, the first binding domain comprises a heavy chain having the amino acid sequence of SEQ ID NO: 69 and a light chain having the amino acid sequence of SEQ ID NO: 24. In some embodiments, the first binding domain comprises a VH containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 7.In some embodiments, the first binding domain comprises VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises: VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 7; and VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises a heavy chain, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 23. In some embodiments, the first binding domain comprises a light chain, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 24. In some embodiments, the first binding domain comprises: a heavy chain, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 23; and a light chain, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 24. In some embodiments, the first binding domain comprises the amino acid sequence of SEQ ID NO: 17. In some embodiments, the first binding domain comprises a heavy chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 69. In some embodiments, the first binding domain comprises a light chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 24. In some embodiments, the first binding domain comprises: a heavy chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 69; and a light chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 24.

[0193] In one embodiment of the multispecific TRGV9 antibody provided herein, the first binding domain that binds to TRGV9 comprises the VH and VL amino acid sequences of L7A5_2 (TRGV9_2). In one embodiment, the first binding domain comprises VH, which contains VH CDR1, VH CDR2, and VHCDR3 having the amino acid sequences VH CDR1, VH CDR2, and VH CDR3, respectively, belonging to the VH having the amino acid sequence of SEQ ID NO: 34. In one embodiment, the first binding domain comprises VL, which contains VL CDR1, VLCDR2, and VL CDR3 having the amino acid sequences VL CDR1, VL CDR2, and VL CDR3, respectively, belonging to the VL having the amino acid sequence of SEQ ID NO: 8. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, the VH CDRs belonging to the amino acid sequence of SEQ ID NO: 34; and (ii) VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, the VH CDR1, VH CDR2, and VH CDR3 belonging to the amino acid sequence of SEQ ID NO: 8. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 31; and (ii) VL, which comprises VLCDR1 having the amino acid sequence of SEQ ID NO: 4, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VLCDR3 having the amino acid sequence of SEQ ID NO: 6. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 196, VH CDR2 having the amino acid sequence of SEQ ID NO: 197, and VH CDR3 having the amino acid sequence of SEQ ID NO: 198; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 199, VL CDR2 having the amino acid sequence of SEQ ID NO: 200, and VLCDR3 having the amino acid sequence of SEQ ID NO: 201.In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 202, VH CDR2 having the amino acid sequence of SEQ ID NO: 203, and VH CDR3 having the amino acid sequence of SEQ ID NO: 204; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 205, VL CDR2 having the amino acid sequence of SEQ ID NO: 206, and VLCDR3 having the amino acid sequence of SEQ ID NO: 207. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 208, VH CDR2 having the amino acid sequence of SEQ ID NO: 209, and VH CDR3 having the amino acid sequence of SEQ ID NO: 210; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 211, VL CDR2 having the amino acid sequence of SEQ ID NO: 212, and VLCDR3 having the amino acid sequence of SEQ ID NO: 213. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 214, VH CDR2 having the amino acid sequence of SEQ ID NO: 215, and VH CDR3 having the amino acid sequence of SEQ ID NO: 216; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 217, VL CDR2 having the amino acid sequence of SEQ ID NO: 218, and VLCDR3 having the amino acid sequence of SEQ ID NO: 219. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 214, VH CDR2 having the amino acid sequence of SEQ ID NO: 702, and VH CDR3 having the amino acid sequence of SEQ ID NO: 703; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 217, VL CDR2 having the amino acid sequence of SEQ ID NO: 218, and VLCDR3 having the amino acid sequence of SEQ ID NO: 219.In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 220, VH CDR2 having the amino acid sequence of SEQ ID NO: 221, and VH CDR3 having the amino acid sequence of SEQ ID NO: 222; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 223, VL CDR2 having the amino acid sequence of SEQ ID NO: 224, and VLCDR3 having the amino acid sequence of SEQ ID NO: 225. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 226, VH CDR2 having the amino acid sequence of SEQ ID NO: 227, and VH CDR3 having the amino acid sequence of SEQ ID NO: 228; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 229, VL CDR2 having the amino acid sequence of SEQ ID NO: 230, and VLCDR3 having the amino acid sequence of SEQ ID NO: 231. In some embodiments, the first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 34. In some embodiments, the first binding domain comprises VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 34 and VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 34. In some embodiments, the first binding domain comprises VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises: VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 34; and VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 8.

[0194] In one embodiment of the multispecific TRGV9 antibody provided herein, the first binding domain for binding to TRGV9 comprises the VH and VL amino acid sequences of L7A5_3 (TRGV9_3). In one embodiment, the first binding domain comprises VH, which contains VH CDR1, VH CDR2, and VHCDR3 having the amino acid sequences VH CDR1, VH CDR2, and VH CDR3, respectively, belonging to the VH having the amino acid sequence of SEQ ID NO: 35. In one embodiment, the first binding domain comprises VL, which contains VL CDR1, VLCDR2, and VL CDR3 having the amino acid sequences VL CDR1, VL CDR2, and VL CDR3, respectively, belonging to the VL having the amino acid sequence of SEQ ID NO: 8. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, the VH CDRs belonging to the VH having the amino acid sequence of SEQ ID NO: 35; and (ii) VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, the VH CDR1, VH CDR2, and VH CDR3 belonging to the VL having the amino acid sequence of SEQ ID NO: 8. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 32; and (ii) VL, which comprises VLCDR1 having the amino acid sequence of SEQ ID NO: 4, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VLCDR3 having the amino acid sequence of SEQ ID NO: 6. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 232, VH CDR2 having the amino acid sequence of SEQ ID NO: 233, and VH CDR3 having the amino acid sequence of SEQ ID NO: 234; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 235, VL CDR2 having the amino acid sequence of SEQ ID NO: 236, and VLCDR3 having the amino acid sequence of SEQ ID NO: 237.In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 238, VH CDR2 having the amino acid sequence of SEQ ID NO: 239, and VH CDR3 having the amino acid sequence of SEQ ID NO: 240; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 241, VL CDR2 having the amino acid sequence of SEQ ID NO: 242, and VLCDR3 having the amino acid sequence of SEQ ID NO: 243. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 244, VH CDR2 having the amino acid sequence of SEQ ID NO: 245, and VH CDR3 having the amino acid sequence of SEQ ID NO: 246; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 247, VL CDR2 having the amino acid sequence of SEQ ID NO: 248, and VLCDR3 having the amino acid sequence of SEQ ID NO: 249. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 250, VH CDR2 having the amino acid sequence of SEQ ID NO: 251, and VH CDR3 having the amino acid sequence of SEQ ID NO: 252; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 253, VL CDR2 having the amino acid sequence of SEQ ID NO: 254, and VLCDR3 having the amino acid sequence of SEQ ID NO: 255. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 250, VH CDR2 having the amino acid sequence of SEQ ID NO: 704, and VH CDR3 having the amino acid sequence of SEQ ID NO: 705; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 253, VL CDR2 having the amino acid sequence of SEQ ID NO: 254, and VLCDR3 having the amino acid sequence of SEQ ID NO: 255.In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 256, VH CDR2 having the amino acid sequence of SEQ ID NO: 257, and VH CDR3 having the amino acid sequence of SEQ ID NO: 258; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 259, VL CDR2 having the amino acid sequence of SEQ ID NO: 260, and VLCDR3 having the amino acid sequence of SEQ ID NO: 261. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 262, VH CDR2 having the amino acid sequence of SEQ ID NO: 263, and VH CDR3 having the amino acid sequence of SEQ ID NO: 264; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 265, VL CDR2 having the amino acid sequence of SEQ ID NO: 266, and VLCDR3 having the amino acid sequence of SEQ ID NO: 267. In some embodiments, the first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 35. In some embodiments, the first binding domain comprises VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 35 and VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 35. In some embodiments, the first binding domain comprises VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises: VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 35; and VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 8.

[0195] In one embodiment of the multispecific TRGV9 antibody provided herein, the first binding domain that binds to TRGV9 comprises the VH and VL amino acid sequences of L7A5_4 (TRGV9_4). In one embodiment, the first binding domain comprises VH, which contains VH CDR1, VH CDR2, and VHCDR3 having the amino acid sequences VH CDR1, VH CDR2, and VH CDR3, respectively, belonging to the VH having the amino acid sequence of SEQ ID NO: 36. In one embodiment, the first binding domain comprises VL, which contains VL CDR1, VLCDR2, and VL CDR3 having the amino acid sequences VL CDR1, VL CDR2, and VL CDR3, respectively, belonging to the VL having the amino acid sequence of SEQ ID NO: 8. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, the VH CDRs belonging to the VH having the amino acid sequence of SEQ ID NO: 36; and (ii) VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, the VH CDR1, VH CDR2, and VH CDR3 belonging to the VL having the amino acid sequence of SEQ ID NO: 8. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 2, and VH CDR3 having the amino acid sequence of SEQ ID NO: 33; and (ii) VL, which comprises VLCDR1 having the amino acid sequence of SEQ ID NO: 4, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VLCDR3 having the amino acid sequence of SEQ ID NO: 6. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 268, VH CDR2 having the amino acid sequence of SEQ ID NO: 269, and VH CDR3 having the amino acid sequence of SEQ ID NO: 270; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 271, VL CDR2 having the amino acid sequence of SEQ ID NO: 272, and VLCDR3 having the amino acid sequence of SEQ ID NO: 273.In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 274, VH CDR2 having the amino acid sequence of SEQ ID NO: 275, and VH CDR3 having the amino acid sequence of SEQ ID NO: 276; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 277, VL CDR2 having the amino acid sequence of SEQ ID NO: 278, and VLCDR3 having the amino acid sequence of SEQ ID NO: 279. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 280, VH CDR2 having the amino acid sequence of SEQ ID NO: 281, and VH CDR3 having the amino acid sequence of SEQ ID NO: 282; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 283, VL CDR2 having the amino acid sequence of SEQ ID NO: 284, and VLCDR3 having the amino acid sequence of SEQ ID NO: 285. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 286, VH CDR2 having the amino acid sequence of SEQ ID NO: 287, and VH CDR3 having the amino acid sequence of SEQ ID NO: 288; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 289, VL CDR2 having the amino acid sequence of SEQ ID NO: 290, and VLCDR3 having the amino acid sequence of SEQ ID NO: 291. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 286, VH CDR2 having the amino acid sequence of SEQ ID NO: 706, and VH CDR3 having the amino acid sequence of SEQ ID NO: 707; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 289, VL CDR2 having the amino acid sequence of SEQ ID NO: 290, and VLCDR3 having the amino acid sequence of SEQ ID NO: 291.In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 292, VH CDR2 having the amino acid sequence of SEQ ID NO: 293, and VH CDR3 having the amino acid sequence of SEQ ID NO: 294; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 295, VL CDR2 having the amino acid sequence of SEQ ID NO: 296, and VLCDR3 having the amino acid sequence of SEQ ID NO: 297. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 298, VH CDR2 having the amino acid sequence of SEQ ID NO: 299, and VH CDR3 having the amino acid sequence of SEQ ID NO: 300; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 301, VL CDR2 having the amino acid sequence of SEQ ID NO: 302, and VLCDR3 having the amino acid sequence of SEQ ID NO: 303. In some embodiments, the first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 36. In some embodiments, the first binding domain comprises VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 36 and VL having the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 36. In some embodiments, the first binding domain comprises VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises: VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 36; and VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 8.

[0196] In one embodiment of the multispecific TRGV9 antibody provided herein, the first binding domain for binding to TRGV9 comprises the VH and VL amino acid sequences of TRGV9Ab_var17. In one embodiment, the first binding domain comprises VH, which contains VH CDR1, VH CDR2, and VHCDR3 having the amino acid sequences VH CDR1, VH CDR2, and VH CDR3, respectively, belonging to the VH having the amino acid sequence of SEQ ID NO: 65. In one embodiment, the first binding domain comprises VL, which contains VL CDR1, VLCDR2, and VL CDR3 having the amino acid sequences VL CDR1, VL CDR2, and VL CDR3, respectively, belonging to the VL having the amino acid sequence of SEQ ID NO: 66. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, these VH CDRs belonging to the VH having the amino acid sequence of SEQ ID NO: 65; and (ii) VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, these VH CDR1, VH CDR2, and VH CDR3 belonging to the VL having the amino acid sequence of SEQ ID NO: 66. In one embodiment of the multispecific TRGV9 antibody provided herein, the first binding domain comprises the VH and VL amino acid sequences of TRGV9Ab_var29. In one embodiment, the first binding domain comprises VH, which includes VH CDR1, VH CDR2, and VHCDR3 having amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, and these VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 67. In one embodiment, the first binding domain comprises VL, which includes VL CDR1, VLCDR2, and VL CDR3 having amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, and these VH CDR1, VH CDR2, and VH CDR3 belong to the VL having the amino acid sequence of SEQ ID NO: 68.In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, the VH CDRs belonging to the amino acid sequence of SEQ ID NO: 67; and (ii) VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, the VH CDR1, VH CDR2, and VH CDR3 belonging to the amino acid sequence of SEQ ID NO: 68. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 1, VH CDR2 having the amino acid sequence of SEQ ID NO: 76, and VH CDR3 having the amino acid sequence of SEQ ID NO: 3; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 77, VL CDR2 having the amino acid sequence of SEQ ID NO: 5, and VLCDR3 having the amino acid sequence of SEQ ID NO: 6. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 60, VH CDR2 having the amino acid sequence of SEQ ID NO: 61, and VH CDR3 having the amino acid sequence of SEQ ID NO: 62; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 63, VL CDR2 having the amino acid sequence of SEQ ID NO: 64, and VL CDR3 having the amino acid sequence of SEQ ID NO: 6. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 304, VH CDR2 having the amino acid sequence of SEQ ID NO: 305, and VH CDR3 having the amino acid sequence of SEQ ID NO: 306; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 307, VL CDR2 having the amino acid sequence of SEQ ID NO: 308, and VL CDR3 having the amino acid sequence of SEQ ID NO: 309.In one embodiment, the first binding domain comprises: (i) VH, which comprises VHCDR1 having the amino acid sequence of SEQ ID NO: 310, VH CDR2 having the amino acid sequence of SEQ ID NO: 311, and VH CDR3 having the amino acid sequence of SEQ ID NO: 312; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 313, VL CDR2 having the amino acid sequence of SEQ ID NO: 314, and VL CDR3 having the amino acid sequence of SEQ ID NO: 315. In one embodiment, the first binding domain comprises: (i) VH, which comprises VHCDR1 having the amino acid sequence of SEQ ID NO: 316, VH CDR2 having the amino acid sequence of SEQ ID NO: 317, and VH CDR3 having the amino acid sequence of SEQ ID NO: 318; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 319, VL CDR2 having the amino acid sequence of SEQ ID NO: 320, and VL CDR3 having the amino acid sequence of SEQ ID NO: 321. In one embodiment, the first binding domain comprises: (i) VH, which comprises VHCDR1 having the amino acid sequence of SEQ ID NO: 322, VH CDR2 having the amino acid sequence of SEQ ID NO: 323, and VH CDR3 having the amino acid sequence of SEQ ID NO: 324; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 325, VL CDR2 having the amino acid sequence of SEQ ID NO: 326, and VL CDR3 having the amino acid sequence of SEQ ID NO: 327. In one embodiment, the first binding domain comprises: (i) VH, which comprises VHCDR1 having the amino acid sequence of SEQ ID NO: 322, VH CDR2 having the amino acid sequence of SEQ ID NO: 708, and VH CDR3 having the amino acid sequence of SEQ ID NO: 709; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 325, VL CDR2 having the amino acid sequence of SEQ ID NO: 326, and VL CDR3 having the amino acid sequence of SEQ ID NO: 327.In one embodiment, the first binding domain comprises: (i) VH, which comprises VHCDR1 having the amino acid sequence of SEQ ID NO: 328, VH CDR2 having the amino acid sequence of SEQ ID NO: 329, and VH CDR3 having the amino acid sequence of SEQ ID NO: 330; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 331, VL CDR2 having the amino acid sequence of SEQ ID NO: 332, and VL CDR3 having the amino acid sequence of SEQ ID NO: 333. In one embodiment, the first binding domain comprises: (i) VH, which comprises VHCDR1 having the amino acid sequence of SEQ ID NO: 334, VH CDR2 having the amino acid sequence of SEQ ID NO: 335, and VH CDR3 having the amino acid sequence of SEQ ID NO: 336; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 337, VL CDR2 having the amino acid sequence of SEQ ID NO: 338, and VL CDR3 having the amino acid sequence of SEQ ID NO: 339. In one embodiment, the first binding domain comprises: (i) VH, which comprises VHCDR1 having the amino acid sequence of SEQ ID NO: 340, VH CDR2 having the amino acid sequence of SEQ ID NO: 341, and VH CDR3 having the amino acid sequence of SEQ ID NO: 342; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 343, VL CDR2 having the amino acid sequence of SEQ ID NO: 344, and VL CDR3 having the amino acid sequence of SEQ ID NO: 345. In one embodiment, the first binding domain comprises: (i) VH, which comprises VHCDR1 having the amino acid sequence of SEQ ID NO: 346, VH CDR2 having the amino acid sequence of SEQ ID NO: 347, and VH CDR3 having the amino acid sequence of SEQ ID NO: 348; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 349, VL CDR2 having the amino acid sequence of SEQ ID NO: 350, and VL CDR3 having the amino acid sequence of SEQ ID NO: 351.In one embodiment, the first binding domain comprises: (i) VH, which comprises VHCDR1 having the amino acid sequence of SEQ ID NO: 352, VH CDR2 having the amino acid sequence of SEQ ID NO: 353, and VH CDR3 having the amino acid sequence of SEQ ID NO: 354; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 355, VL CDR2 having the amino acid sequence of SEQ ID NO: 356, and VL CDR3 having the amino acid sequence of SEQ ID NO: 357. In one embodiment, the first binding domain comprises: (i) VH, which comprises VHCDR1 having the amino acid sequence of SEQ ID NO: 358, VH CDR2 having the amino acid sequence of SEQ ID NO: 359, and VH CDR3 having the amino acid sequence of SEQ ID NO: 360; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 361, VL CDR2 having the amino acid sequence of SEQ ID NO: 362, and VL CDR3 having the amino acid sequence of SEQ ID NO: 363. In one embodiment, the first binding domain comprises: (i) VH, which comprises VHCDR1 having the amino acid sequence of SEQ ID NO: 358, VH CDR2 having the amino acid sequence of SEQ ID NO: 710, and VH CDR3 having the amino acid sequence of SEQ ID NO: 711; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 361, VL CDR2 having the amino acid sequence of SEQ ID NO: 362, and VL CDR3 having the amino acid sequence of SEQ ID NO: 363. In one embodiment, the first binding domain comprises: (i) VH, which comprises VHCDR1 having the amino acid sequence of SEQ ID NO: 364, VH CDR2 having the amino acid sequence of SEQ ID NO: 365, and VH CDR3 having the amino acid sequence of SEQ ID NO: 366; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 367, VL CDR2 having the amino acid sequence of SEQ ID NO: 368, and VL CDR3 having the amino acid sequence of SEQ ID NO: 369.In one embodiment, the first binding domain comprises: (i) VH, which comprises VHCDR1 having the amino acid sequence of SEQ ID NO: 370, VH CDR2 having the amino acid sequence of SEQ ID NO: 371, and VH CDR3 having the amino acid sequence of SEQ ID NO: 372; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 373, VL CDR2 having the amino acid sequence of SEQ ID NO: 374, and VL CDR3 having the amino acid sequence of SEQ ID NO: 375. In some embodiments, the first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 65. In some embodiments, the first binding domain comprises VL having the amino acid sequence of SEQ ID NO: 66. In some embodiments, the first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 65 and VL having the amino acid sequence of SEQ ID NO: 66. In some embodiments, the first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 67. In some embodiments, the first binding domain comprises a VL having the amino acid sequence of SEQ ID NO: 68. In some embodiments, the first binding domain comprises 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 first binding domain comprises a heavy chain having the amino acid sequence of SEQ ID NO: 71. In some embodiments, the first binding domain comprises a light chain having the amino acid sequence of SEQ ID NO: 72. In some embodiments, the first binding domain 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 first binding domain comprises the amino acid sequence of SEQ ID NO: 70. In some embodiments, the first binding domain comprises a heavy chain having the amino acid sequence of SEQ ID NO: 74. In some embodiments, the first binding domain comprises a light chain having the amino acid sequence of SEQ ID NO: 75. In some embodiments, the first binding domain 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 first binding domain comprises the amino acid sequence of SEQ ID NO: 73. In some embodiments, the first binding domain comprises VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 65.In some embodiments, the first binding domain comprises VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 66. In some embodiments, the first binding domain comprises: VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 65; and VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 66. In some embodiments, the first binding domain comprises VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 67. In some embodiments, the first binding domain comprises VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 68. In some embodiments, the first binding domain comprises: VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 67; and VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 68. In some embodiments, the first binding domain comprises a heavy chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 71. In some embodiments, the first binding domain comprises a light chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 72. In some embodiments, the first binding domain comprises: a heavy chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 71; and a light chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 72. In some embodiments, the first binding domain contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 70. In some embodiments, the first binding domain comprises a heavy chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 74. In some embodiments, the first binding domain comprises a light chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 75. In some embodiments, the first binding domain comprises: a heavy chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 74; and a light chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 75. In some embodiments, the first binding domain contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 73.

[0197] In one embodiment of the multispecific TRGV9 antibody provided herein, the first binding domain for binding to TRGV9 comprises the VH and VL amino acid sequences of VG9_B3_RN. In one embodiment, the first binding domain comprises VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences VH CDR1, VH CDR2, and VH CDR3, respectively, belonging to the VH having the amino acid sequence of SEQ ID NO: 95. In one embodiment, the first binding domain comprises VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences VL CDR1, VL CDR2, and VL CDR3, respectively, belonging to the VL having the amino acid sequence of SEQ ID NO: 96. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of VH CDR1, VH CDR2, and VH CDR3, respectively, the VH CDRs belonging to the amino acid sequence of VH having SEQ ID NO: 95; and (ii) VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, the VH CDR1, VH CDR2, and VH CDR3 belonging to the amino acid sequence of VL having SEQ ID NO: 96. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 89, VH CDR2 having the amino acid sequence of SEQ ID NO: 90, and VH CDR3 having the amino acid sequence of SEQ ID NO: 91; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 92, VL CDR2 having the amino acid sequence of SEQ ID NO: 93, and VL CDR3 having the amino acid sequence of SEQ ID NO: 94. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 376, VH CDR2 having the amino acid sequence of SEQ ID NO: 377, and VH CDR3 having the amino acid sequence of SEQ ID NO: 378; and (ii) VL, which comprises VLCDR1 having the amino acid sequence of SEQ ID NO: 379, VL CDR2 having the amino acid sequence of SEQ ID NO: 380, and VL CDR3 having the amino acid sequence of SEQ ID NO: 381.In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 382, ​​VH CDR2 having the amino acid sequence of SEQ ID NO: 383, and VH CDR3 having the amino acid sequence of SEQ ID NO: 384; and (ii) VL, which comprises VLCDR1 having the amino acid sequence of SEQ ID NO: 385, VL CDR2 having the amino acid sequence of SEQ ID NO: 386, and VL CDR3 having the amino acid sequence of SEQ ID NO: 387. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 388, VH CDR2 having the amino acid sequence of SEQ ID NO: 389, and VH CDR3 having the amino acid sequence of SEQ ID NO: 390; and (ii) VL, which comprises VLCDR1 having the amino acid sequence of SEQ ID NO: 391, VL CDR2 having the amino acid sequence of SEQ ID NO: 392, and VL CDR3 having the amino acid sequence of SEQ ID NO: 393. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 394, VH CDR2 having the amino acid sequence of SEQ ID NO: 395, and VH CDR3 having the amino acid sequence of SEQ ID NO: 396; and (ii) VL, which comprises VLCDR1 having the amino acid sequence of SEQ ID NO: 397, VL CDR2 having the amino acid sequence of SEQ ID NO: 398, and VL CDR3 having the amino acid sequence of SEQ ID NO: 399. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 394, VH CDR2 having the amino acid sequence of SEQ ID NO: 712, and VH CDR3 having the amino acid sequence of SEQ ID NO: 713; and (ii) VL, which comprises VLCDR1 having the amino acid sequence of SEQ ID NO: 397, VL CDR2 having the amino acid sequence of SEQ ID NO: 398, and VL CDR3 having the amino acid sequence of SEQ ID NO: 399.In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 400, VH CDR2 having the amino acid sequence of SEQ ID NO: 401, and VH CDR3 having the amino acid sequence of SEQ ID NO: 402; and (ii) VL, which comprises VLCDR1 having the amino acid sequence of SEQ ID NO: 403, VL CDR2 having the amino acid sequence of SEQ ID NO: 404, and VL CDR3 having the amino acid sequence of SEQ ID NO: 405. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 406, VH CDR2 having the amino acid sequence of SEQ ID NO: 407, and VH CDR3 having the amino acid sequence of SEQ ID NO: 408; and (ii) VL, which comprises VLCDR1 having the amino acid sequence of SEQ ID NO: 409, VL CDR2 having the amino acid sequence of SEQ ID NO: 410, and VL CDR3 having the amino acid sequence of SEQ ID NO: 411. In some embodiments, the first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 95. In some embodiments, the first binding domain comprises VL having the amino acid sequence of SEQ ID NO: 96. In some embodiments, the first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 95 and VL having the amino acid sequence of SEQ ID NO: 96. In some embodiments, the first binding domain comprises the amino acid sequence of SEQ ID NO: 97. In some embodiments, the first binding domain comprises VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 95. In some embodiments, the first binding domain comprises VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 96. In some embodiments, the first binding domain comprises: VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 95; and VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 96. In some embodiments, the first binding domain contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 97.

[0198] In one embodiment of the multispecific TRGV9 antibody provided herein, the first binding domain for binding to TRGV9 comprises the VH and VL amino acid sequences of VG9B420. In one embodiment, the first binding domain comprises VH, which includes VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences VH CDR1, VH CDR2, and VH CDR3, respectively, and these VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 104. In one embodiment, the first binding domain comprises VL, which includes VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences VL CDR1, VL CDR2, and VL CDR3, respectively, and these VH CDR1, VH CDR2, and VH CDR3 belong to the VL having the amino acid sequence of SEQ ID NO: 105. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of VH CDR1, VH CDR2, and VHCDR3, respectively, wherein these VH CDRs belong to the amino acid sequence of VH having SEQ ID NO: 104; and (ii) VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences of VL CDR1, VL CDR2, and VL CDR3, respectively, wherein these VH CDR1, VH CDR2, and VH CDR3 belong to the amino acid sequence of VL having SEQ ID NO: 105. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 98, VH CDR2 having the amino acid sequence of SEQ ID NO: 99, and VH CDR3 having the amino acid sequence of SEQ ID NO: 100, and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 101, VL CDR2 having the amino acid sequence of SEQ ID NO: 102, and VL CDR3 having the amino acid sequence of SEQ ID NO: 103.In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 412, VH CDR2 having the amino acid sequence of SEQ ID NO: 413, and VH CDR3 having the amino acid sequence of SEQ ID NO: 414; and (ii) VL, which comprises VLCDR1 having the amino acid sequence of SEQ ID NO: 415, VL CDR2 having the amino acid sequence of SEQ ID NO: 416, and VL CDR3 having the amino acid sequence of SEQ ID NO: 417. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 418, VH CDR2 having the amino acid sequence of SEQ ID NO: 419, and VH CDR3 having the amino acid sequence of SEQ ID NO: 420; and (ii) VL, which comprises VLCDR1 having the amino acid sequence of SEQ ID NO: 421, VL CDR2 having the amino acid sequence of SEQ ID NO: 422, and VL CDR3 having the amino acid sequence of SEQ ID NO: 423. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 424, VH CDR2 having the amino acid sequence of SEQ ID NO: 425, and VH CDR3 having the amino acid sequence of SEQ ID NO: 426; and (ii) VL, which comprises VLCDR1 having the amino acid sequence of SEQ ID NO: 427, VL CDR2 having the amino acid sequence of SEQ ID NO: 428, and VL CDR3 having the amino acid sequence of SEQ ID NO: 429. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 430, VH CDR2 having the amino acid sequence of SEQ ID NO: 431, and VH CDR3 having the amino acid sequence of SEQ ID NO: 432; and (ii) VL, which comprises VLCDR1 having the amino acid sequence of SEQ ID NO: 433, VL CDR2 having the amino acid sequence of SEQ ID NO: 434, and VL CDR3 having the amino acid sequence of SEQ ID NO: 435.In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 430, VH CDR2 having the amino acid sequence of SEQ ID NO: 714, and VH CDR3 having the amino acid sequence of SEQ ID NO: 715; and (ii) VL, which comprises VLCDR1 having the amino acid sequence of SEQ ID NO: 433, VL CDR2 having the amino acid sequence of SEQ ID NO: 434, and VL CDR3 having the amino acid sequence of SEQ ID NO: 435. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 436, VH CDR2 having the amino acid sequence of SEQ ID NO: 437, and VH CDR3 having the amino acid sequence of SEQ ID NO: 438; and (ii) VL, which comprises VLCDR1 having the amino acid sequence of SEQ ID NO: 439, VL CDR2 having the amino acid sequence of SEQ ID NO: 440, and VL CDR3 having the amino acid sequence of SEQ ID NO: 441. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 442, VH CDR2 having the amino acid sequence of SEQ ID NO: 443, and VH CDR3 having the amino acid sequence of SEQ ID NO: 444; and (ii) VL, which comprises VLCDR1 having the amino acid sequence of SEQ ID NO: 445, VL CDR2 having the amino acid sequence of SEQ ID NO: 446, and VL CDR3 having the amino acid sequence of SEQ ID NO: 447. In some embodiments, the first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 104. In some embodiments, the first binding domain comprises VL having the amino acid sequence of SEQ ID NO: 105. In some embodiments, the first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 104 and VL having the amino acid sequence of SEQ ID NO: 105. In some embodiments, the first binding domain comprises the amino acid sequence of SEQ ID NO: 106. In some embodiments, the first binding domain comprises VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 104. In some embodiments, the first binding domain comprises VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 105.In some embodiments, the first binding domain comprises: VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 104; and VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 105. In some embodiments, the first binding domain contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 106.

[0199] In one embodiment of the multispecific TRGV9 antibody provided herein, the first binding domain for binding to TRGV9 comprises the VH and VL amino acid sequences of VG9SB10SC1087_P18_D08. In one embodiment, the first binding domain comprises VH, which contains VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences VH CDR1, VH CDR2, and VH CDR3, respectively, and these VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 113. In one embodiment, the first binding domain comprises VL, which contains VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences VL CDR1, VL CDR2, and VL CDR3, respectively, and these VH CDR1, VH CDR2, and VH CDR3 belong to the VL having the amino acid sequence of SEQ ID NO: 114. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of VHCDR1, VH CDR2, and VH CDR3, respectively, the VH CDRs belonging to the amino acid sequence of SEQ ID NO: 113; and (ii) VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences of VL CDR1, VL CDR2, and VLCDR3, respectively, the VH CDR1, VH CDR2, and VH CDR3 belonging to the amino acid sequence of SEQ ID NO: 114. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 107, VH CDR2 having the amino acid sequence of SEQ ID NO: 108, and VH CDR3 having the amino acid sequence of SEQ ID NO: 109, and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 110, VL CDR2 having the amino acid sequence of SEQ ID NO: 111, and VL CDR3 having the amino acid sequence of SEQ ID NO: 112.In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 448, VHCDR2 having the amino acid sequence of SEQ ID NO: 449, and VH CDR3 having the amino acid sequence of SEQ ID NO: 450; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 451, VL CDR2 having the amino acid sequence of SEQ ID NO: 452, and VL CDR3 having the amino acid sequence of SEQ ID NO: 453. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 454, VHCDR2 having the amino acid sequence of SEQ ID NO: 455, and VH CDR3 having the amino acid sequence of SEQ ID NO: 456; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 457, VL CDR2 having the amino acid sequence of SEQ ID NO: 458, and VL CDR3 having the amino acid sequence of SEQ ID NO: 459. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 460, VHCDR2 having the amino acid sequence of SEQ ID NO: 461, and VH CDR3 having the amino acid sequence of SEQ ID NO: 462; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 463, VL CDR2 having the amino acid sequence of SEQ ID NO: 464, and VL CDR3 having the amino acid sequence of SEQ ID NO: 465. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 466, VHCDR2 having the amino acid sequence of SEQ ID NO: 467, and VH CDR3 having the amino acid sequence of SEQ ID NO: 468; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 469, VL CDR2 having the amino acid sequence of SEQ ID NO: 470, and VL CDR3 having the amino acid sequence of SEQ ID NO: 471.In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 466, VHCDR2 having the amino acid sequence of SEQ ID NO: 716, and VH CDR3 having the amino acid sequence of SEQ ID NO: 717; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 469, VL CDR2 having the amino acid sequence of SEQ ID NO: 470, and VL CDR3 having the amino acid sequence of SEQ ID NO: 471. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 472, VHCDR2 having the amino acid sequence of SEQ ID NO: 473, and VH CDR3 having the amino acid sequence of SEQ ID NO: 474; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 475, VL CDR2 having the amino acid sequence of SEQ ID NO: 476, and VL CDR3 having the amino acid sequence of SEQ ID NO: 477. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 478, VHCDR2 having the amino acid sequence of SEQ ID NO: 479, and VH CDR3 having the amino acid sequence of SEQ ID NO: 480; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 481, VL CDR2 having the amino acid sequence of SEQ ID NO: 482, and VL CDR3 having the amino acid sequence of SEQ ID NO: 483. In some embodiments, the first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 113. In some embodiments, the first binding domain comprises VL having the amino acid sequence of SEQ ID NO: 114. In some embodiments, the first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 113 and VL having the amino acid sequence of SEQ ID NO: 114. In some embodiments, the first binding domain comprises a heavy chain having the amino acid sequence of SEQ ID NO: 115. In some embodiments, the first binding domain comprises a light chain having the amino acid sequence of SEQ ID NO: 116. In some embodiments, the first binding domain 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 first binding domain comprises VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 113. In some embodiments, the first binding domain comprises VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 114. In some embodiments, the first binding domain comprises: VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 113; and VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 114. In some embodiments, the first binding domain comprises a heavy chain, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 115. In some embodiments, the first binding domain comprises a light chain, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 116. In some embodiments, the first binding domain comprises: a heavy chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 115; and a light chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 116.

[0200] In one embodiment of the multispecific TRGV9 antibody provided herein, the first binding domain for binding to TRGV9 comprises the VH and VL amino acid sequences of VG9SB10SC1087_P18_C12. In one embodiment, the first binding domain comprises VH, which contains VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences VH CDR1, VH CDR2, and VH CDR3, respectively, and these VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 123. In one embodiment, the first binding domain comprises VL, which contains VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences VL CDR1, VL CDR2, and VL CDR3, respectively, and these VH CDR1, VH CDR2, and VH CDR3 belong to the VL having the amino acid sequence of SEQ ID NO: 124. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of VHCDR1, VH CDR2, and VH CDR3, respectively, the VH CDRs belonging to the amino acid sequence of SEQ ID NO: 123; and (ii) VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences of VL CDR1, VL CDR2, and VLCDR3, respectively, the VH CDR1, VH CDR2, and VH CDR3 belonging to the amino acid sequence of SEQ ID NO: 124. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 117, VH CDR2 having the amino acid sequence of SEQ ID NO: 118, and VH CDR3 having the amino acid sequence of SEQ ID NO: 119, and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 120, VL CDR2 having the amino acid sequence of SEQ ID NO: 121, and VL CDR3 having the amino acid sequence of SEQ ID NO: 122.In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 484, VHCDR2 having the amino acid sequence of SEQ ID NO: 485, and VH CDR3 having the amino acid sequence of SEQ ID NO: 486; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 487, VL CDR2 having the amino acid sequence of SEQ ID NO: 488, and VL CDR3 having the amino acid sequence of SEQ ID NO: 489. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 490, VHCDR2 having the amino acid sequence of SEQ ID NO: 491, and VH CDR3 having the amino acid sequence of SEQ ID NO: 492; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 493, VL CDR2 having the amino acid sequence of SEQ ID NO: 494, and VL CDR3 having the amino acid sequence of SEQ ID NO: 495. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 496, VHCDR2 having the amino acid sequence of SEQ ID NO: 497, and VH CDR3 having the amino acid sequence of SEQ ID NO: 498; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 499, VL CDR2 having the amino acid sequence of SEQ ID NO: 500, and VL CDR3 having the amino acid sequence of SEQ ID NO: 501. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 502, VHCDR2 having the amino acid sequence of SEQ ID NO: 503, and VH CDR3 having the amino acid sequence of SEQ ID NO: 504; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 505, VL CDR2 having the amino acid sequence of SEQ ID NO: 506, and VL CDR3 having the amino acid sequence of SEQ ID NO: 507.In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 502, VHCDR2 having the amino acid sequence of SEQ ID NO: 718, and VH CDR3 having the amino acid sequence of SEQ ID NO: 719; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 505, VL CDR2 having the amino acid sequence of SEQ ID NO: 506, and VL CDR3 having the amino acid sequence of SEQ ID NO: 507. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 508, VHCDR2 having the amino acid sequence of SEQ ID NO: 509, and VH CDR3 having the amino acid sequence of SEQ ID NO: 510; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 511, VL CDR2 having the amino acid sequence of SEQ ID NO: 512, and VL CDR3 having the amino acid sequence of SEQ ID NO: 513. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 514, VHCDR2 having the amino acid sequence of SEQ ID NO: 515, and VH CDR3 having the amino acid sequence of SEQ ID NO: 516; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 517, VL CDR2 having the amino acid sequence of SEQ ID NO: 518, and VL CDR3 having the amino acid sequence of SEQ ID NO: 519. In some embodiments, the first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 123. In some embodiments, the first binding domain comprises VL having the amino acid sequence of SEQ ID NO: 124. In some embodiments, the first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 123 and VL having the amino acid sequence of SEQ ID NO: 124. In some embodiments, the first binding domain comprises a heavy chain having the amino acid sequence of SEQ ID NO: 125. In some embodiments, the first binding domain comprises a light chain having the amino acid sequence of SEQ ID NO: 126. In some embodiments, the first binding domain 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 first binding domain comprises VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 123. In some embodiments, the first binding domain comprises VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 124. In some embodiments, the first binding domain comprises: VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 123; and VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 124. In some embodiments, the first binding domain comprises a heavy chain, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 125. In some embodiments, the first binding domain comprises a light chain, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 126. In some embodiments, the first binding domain comprises: a heavy chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 125; and a light chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 126.

[0201] In one embodiment of the multispecific TRGV9 antibody provided herein, the first binding domain binding to TRGV9 comprises the VH and VL amino acid sequences of VG9SB10SC1087_P19_C03. In one embodiment, the first binding domain comprises VH, which contains VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences VH CDR1, VH CDR2, and VH CDR3, respectively, and these VH CDRs belong to the VH having the amino acid sequence of SEQ ID NO: 133. In one embodiment, the first binding domain comprises VL, which contains VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences VL CDR1, VL CDR2, and VL CDR3, respectively, and these VH CDR1, VH CDR2, and VH CDR3 belong to the VL having the amino acid sequence of SEQ ID NO: 134. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1, VH CDR2, and VH CDR3 having amino acid sequences of VHCDR1, VH CDR2, and VH CDR3, respectively, the VH CDRs belonging to the amino acid sequence of SEQ ID NO: 133; and (ii) VL, which comprises VL CDR1, VL CDR2, and VL CDR3 having amino acid sequences of VL CDR1, VL CDR2, and VLCDR3, respectively, the VH CDR1, VH CDR2, and VH CDR3 belonging to the amino acid sequence of SEQ ID NO: 134. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 127, VH CDR2 having the amino acid sequence of SEQ ID NO: 128, and VH CDR3 having the amino acid sequence of SEQ ID NO: 129, and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 130, VL CDR2 having the amino acid sequence of SEQ ID NO: 131, and VL CDR3 having the amino acid sequence of SEQ ID NO: 132.In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 520, VHCDR2 having the amino acid sequence of SEQ ID NO: 521, and VH CDR3 having the amino acid sequence of SEQ ID NO: 522; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 523, VL CDR2 having the amino acid sequence of SEQ ID NO: 524, and VL CDR3 having the amino acid sequence of SEQ ID NO: 525. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 526, VHCDR2 having the amino acid sequence of SEQ ID NO: 527, and VH CDR3 having the amino acid sequence of SEQ ID NO: 528; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 529, VL CDR2 having the amino acid sequence of SEQ ID NO: 530, and VL CDR3 having the amino acid sequence of SEQ ID NO: 531. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 532, VHCDR2 having the amino acid sequence of SEQ ID NO: 533, and VH CDR3 having the amino acid sequence of SEQ ID NO: 534; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 535, VL CDR2 having the amino acid sequence of SEQ ID NO: 536, and VL CDR3 having the amino acid sequence of SEQ ID NO: 537. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 538, VHCDR2 having the amino acid sequence of SEQ ID NO: 539, and VH CDR3 having the amino acid sequence of SEQ ID NO: 540; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 541, VL CDR2 having the amino acid sequence of SEQ ID NO: 542, and VL CDR3 having the amino acid sequence of SEQ ID NO: 543.In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 538, VHCDR2 having the amino acid sequence of SEQ ID NO: 720, and VH CDR3 having the amino acid sequence of SEQ ID NO: 721; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 541, VL CDR2 having the amino acid sequence of SEQ ID NO: 542, and VL CDR3 having the amino acid sequence of SEQ ID NO: 543. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 544, VHCDR2 having the amino acid sequence of SEQ ID NO: 545, and VH CDR3 having the amino acid sequence of SEQ ID NO: 546; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 547, VL CDR2 having the amino acid sequence of SEQ ID NO: 548, and VL CDR3 having the amino acid sequence of SEQ ID NO: 549. In one embodiment, the first binding domain comprises: (i) VH, which comprises VH CDR1 having the amino acid sequence of SEQ ID NO: 550, VHCDR2 having the amino acid sequence of SEQ ID NO: 551, and VH CDR3 having the amino acid sequence of SEQ ID NO: 552; and (ii) VL, which comprises VL CDR1 having the amino acid sequence of SEQ ID NO: 553, VL CDR2 having the amino acid sequence of SEQ ID NO: 554, and VL CDR3 having the amino acid sequence of SEQ ID NO: 555. In some embodiments, the first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 133. In some embodiments, the first binding domain comprises VL having the amino acid sequence of SEQ ID NO: 134. In some embodiments, the first binding domain comprises VH having the amino acid sequence of SEQ ID NO: 133 and VL having the amino acid sequence of SEQ ID NO: 134. In some embodiments, the first binding domain comprises a heavy chain having the amino acid sequence of SEQ ID NO: 135. In some embodiments, the first binding domain comprises a light chain having the amino acid sequence of SEQ ID NO: 136. In some embodiments, the first binding domain 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 first binding domain comprises VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 133. In some embodiments, the first binding domain comprises VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 134. In some embodiments, the first binding domain comprises: VH, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 133; and VL, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 134. In some embodiments, the first binding domain comprises a heavy chain, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 135. In some embodiments, the first binding domain comprises a light chain, which contains an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 136. In some embodiments, the first binding domain comprises: a heavy chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 135; and a light chain containing an amino acid sequence having at least 95% identity with the amino acid sequence of SEQ ID NO: 136.

[0202] In some embodiments, the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 binding to the first binding domain of TRGV9 are defined according to the Kabat numbering system. In some embodiments, the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 binding to the first binding domain of TRGV9 are defined according to the Chothia numbering system. In some embodiments, the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 binding to the first binding domain of TRGV9 are defined according to the AbM numbering system. In some embodiments, the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 binding to the first binding domain of TRGV9 are defined according to the Contact numbering system. In some embodiments, the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 binding to the first binding domain of TRGV9 are defined according to the IMGT numbering system. In some embodiments, the amino acid sequences of VH CDR1, VH CDR2, and VH CDR3 binding to the first binding domain of TRGV9 are defined according to an exemplary numbering system. In some embodiments, the amino acid sequences of VL CDR1, VL CDR2, and VL CDR3 binding to the first binding domain of TRGV9 are ...

Claims

1. A bispecific TRGV9 antibody, said bispecific TRGV9 antibody comprising... (a) A first binding domain, the first binding domain being bound to TRGV9, wherein the first binding domain comprises: (i) VH, said VH comprising VH CDR1 shown in the amino acid sequence of SEQ ID NO: 1, VH CDR2 shown in the amino acid sequence of SEQ ID NO: 2, and VH CDR3 shown in the amino acid sequence of SEQ ID NO: 31; and (ii) VL, said VL comprising VL CDR1 shown in the amino acid sequence of SEQ ID NO: 4, VL CDR2 shown in the amino acid sequence of SEQ ID NO: 5, and VL CDR3 shown in the amino acid sequence of SEQ ID NO: 6, and (b) A second binding domain, which binds to a second target, which is CD33, TRBC1, BCMA or PSMA.

2. The bispecific TRGV9 antibody according to claim 1, wherein the first binding domain comprises VH of the amino acid sequence of SEQ ID NO: 34 and VL of the amino acid sequence of SEQ ID NO:

8.

3. The bispecific TRGV9 antibody according to claim 1, wherein the second binding domain binds to the antigen of the second target.

4. The bispecific TRGV9 antibody according to claim 1, wherein the second binding domain binds to the epitope of the second target.

5. The bispecific TRGV9 antibody according to claim 1, wherein the second binding domain specifically binds to the second target.

6. The bispecific TRGV9 antibody according to any one of claims 1 to 5, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the second binding domain form a binding site for the antigen of the second target.

7. The bispecific TRGV9 antibody according to any one of claims 1 to 5, wherein the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the second binding domain form binding sites for the epitope of the second target.

8. The bispecific TRGV9 antibody according to any one of claims 1 to 5, wherein the second target is present on the surface of the target cell.

9. The bispecific TRGV9 antibody according to any one of claims 1 to 5, wherein the second target is CD33.

10. The bispecific TRGV9 antibody of claim 9, wherein the second binding arm binding to CD33 comprises: (i) VH, wherein the VH comprises VH CDR1 shown in the amino acid sequence of SEQ ID NO: 37, VH CDR2 shown in the amino acid sequence of SEQ ID NO: 38, and VH CDR3 shown in the amino acid sequence of SEQ ID NO: 39; and (ii) VL, wherein the VL comprises VL CDR1 shown in the amino acid sequence of SEQ ID NO: 40, VL CDR2 shown in the amino acid sequence of SEQ ID NO: 41 and VL CDR3 shown in the amino acid sequence of SEQ ID NO:

42.

11. The bispecific TRGV9 antibody according to claim 10, wherein the second binding arm binding to CD33 comprises VH of the amino acid sequence of SEQ ID NO:43 and VL of the amino acid sequence of SEQ ID NO:

44.

12. The bispecific TRGV9 antibody according to any one of claims 1 to 5, wherein the second target is TRBC1.

13. The bispecific TRGV9 antibody according to any one of claims 1 to 5, wherein the second binding arm binding TRBC1 comprises: (i) VH, said VH comprising VH CDR1 shown in the amino acid sequence of SEQ ID NO: 49, VH CDR2 shown in the amino acid sequence of SEQ ID NO: 50, and VH CDR3 shown in the amino acid sequence of SEQ ID NO: 51; and (ii) VL, wherein the VL comprises VL CDR1 shown in the amino acid sequence of SEQ ID NO: 52, VL CDR2 shown in the amino acid sequence of SEQ ID NO: 53 and VL CDR3 shown in the amino acid sequence of SEQ ID NO:

54.

14. The bispecific TRGV9 antibody according to claim 13, wherein the second binding arm binding TRBC1 comprises VH of the amino acid sequence of SEQ ID NO:55 and VL of the amino acid sequence of SEQ ID NO:

56.

15. The bispecific TRGV9 antibody according to any one of claims 1 to 5, wherein the second target is BCMA.

16. The bispecific TRGV9 antibody of claim 15, wherein the second binding arm binding to BCMA comprises: (i) VH, wherein the VH comprises VH CDR1 shown in the amino acid sequence of SEQ ID NO: 137, VH CDR2 shown in the amino acid sequence of SEQ ID NO: 138, and VH CDR3 shown in the amino acid sequence of SEQ ID NO: 139; and (ii) VL, wherein the VL comprises VL CDR1 shown in the amino acid sequence of SEQ ID NO: 140, VL CDR2 shown in the amino acid sequence of SEQ ID NO: 141 and VL CDR3 shown in the amino acid sequence of SEQ ID NO:

142.

17. The bispecific TRGV9 antibody of claim 16, wherein the second binding arm binding to BCMA comprises VH of the amino acid sequence of SEQ ID NO:143 and VL of the amino acid sequence of SEQ ID NO:

144.

18. The bispecific TRGV9 antibody according to any one of claims 1 to 5, wherein the second target is PSMA.

19. The bispecific TRGV9 antibody of claim 18, wherein the second binding arm binding PSMA comprises: (i) VH, said VH comprising VH CDR1 shown in the amino acid sequence of SEQ ID NO: 783, VH CDR2 shown in the amino acid sequence of SEQ ID NO: 784, and VH CDR3 shown in the amino acid sequence of SEQ ID NO: 785; and (ii) VL, wherein the VL comprises VL CDR1 shown in the amino acid sequence of SEQ ID NO: 786, VL CDR2 shown in the amino acid sequence of SEQ ID NO: 787 and VL CDR3 shown in the amino acid sequence of SEQ ID NO:

788.

20. The bispecific TRGV9 antibody of claim 19, wherein the second binding arm binding to PSMA comprises VH of the amino acid sequence of SEQ ID NO:775 and VL of the amino acid sequence of SEQ ID NO:

776.

21. A nucleic acid encoding an antibody according to any one of claims 1 to 20.

22. A vector comprising the nucleic acid according to claim 21.

23. A host cell comprising the vector according to claim 22.

24. A reagent kit comprising the carrier and its packaging according to claim 22.

25. A kit comprising an antibody and its packaging according to any one of claims 1 to 20.

26. A pharmaceutical composition comprising an antibody according to any one of claims 1 to 20 and a pharmaceutically acceptable carrier.

27. A method for producing a pharmaceutical composition according to claim 26, the method comprising combining the antibody with a pharmaceutically acceptable carrier to obtain the pharmaceutical composition.

28. Use of the bispecific TRGV9 antibody according to any one of claims 1 to 20 in the preparation of a medicament for guiding TRGV9-expressing T cells to target cells, wherein the bispecific TRGV9 antibody according to any one of claims 1 to 20 is contacted with the target cells, wherein the second target is present on the surface of the target cells, and wherein the contact guides the T cells to the target cells, wherein... When the second target is CD33, the target cells are leukemia cells; When the second target is TRBC1, the target cells are leukemia cells; When the second target is BCMA, the target cells are cells of multiple myeloma; or When the second target is PSMA, the target cell is a prostate cancer cell.

29. Use of the bispecific TRGV9 antibody according to any one of claims 1 to 20 in the preparation of a medicament for inhibiting the growth or proliferation of target cells, wherein the bispecific TRGV9 antibody according to any one of claims 1 to 20 is contacted with the target cell having a second target present on the surface of the target cell, wherein the contact is in the presence of T cells expressing the TRGV9, and wherein the contact results in inhibition of the growth or proliferation of the target cell, wherein When the second target is CD33, the target cells are leukemia cells; When the second target is TRBC1, the target cells are leukemia cells; When the second target is BCMA, the target cells are cells of multiple myeloma; or When the second target is PSMA, the target cell is a prostate cancer cell.

30. Use of the bispecific TRGV9 antibody according to any one of claims 1 to 20 in the preparation of a medicament for eliminating target cells in a subject, wherein the bispecific TRGV9 antibody according to any one of claims 1 to 20 is contacted with the target cell having a second target present on the surface of the target cell, wherein the contact is in the presence of T cells expressing the TRGV9, and wherein the contact results in the elimination of the target cell, wherein When the second target is CD33, the target cells are leukemia cells; When the second target is TRBC1, the target cells are leukemia cells; When the second target is BCMA, the target cells are cells of multiple myeloma; or When the second target is PSMA, the target cell is a prostate cancer cell.

31. Use of the bispecific TRGV9 antibody according to any one of claims 1 to 20 in the preparation of a medicament for treating a disease in a subject, wherein the disease is wholly or partially caused by said target cells having a second target present on the surface of the target cells, wherein When the second target is CD33, the target cells are leukemia cells; When the second target is TRBC1, the target cells are leukemia cells; When the second target is BCMA, the target cells are cells of multiple myeloma; or When the second target is PSMA, the target cell is a prostate cancer cell.

32. The use according to claim 30 or 31, wherein the subject is a human.

33. The use according to claim 30 or 31, wherein the subject is a subject who needs it.

34. The bispecific TRGV9 antibody according to any one of claims 1 to 5, or the use according to any one of claims 28 to 31, wherein the second target is present on the surface of the target cell, and wherein... When the second target is CD33, the target cells are leukemia cells; When the second target is TRBC1, the target cells are leukemia cells; When the second target is BCMA, the target cells are cells of multiple myeloma; or When the second target is PSMA, the target cell is a prostate cancer cell.

35. The bispecific TRGV9 antibody or use according to claim 34, wherein the second target is BCMA, CD33 or PSMA.

36. The bispecific TRGV9 antibody or use according to claim 34, wherein the second target is CD33.

37. The bispecific TRGV9 antibody or use according to claim 34, wherein the second target is BCMA.

38. The bispecific TRGV9 antibody or use according to claim 34, wherein the second target is PSMA.

39. The use of the bispecific TRGV9 antibody according to any one of claims 1 to 5 or according to any one of claims 28 to 31, wherein the second target is present on the surface of the target cell, and wherein the target cell is a T cell.

40. The bispecific TRGV9 antibody or use according to claim 39, wherein the second target is TRBC1.

41. The use of the bispecific TRGV9 antibody according to any one of claims 1 to 5 or according to any one of claims 28 to 31, wherein the second target is present on the surface of the target cell, and wherein the target cell is a B cell.

42. The bispecific TRGV9 antibody according to claim 41, wherein the second target is BCMA.

43. The use of the bispecific TRGV9 antibody according to any one of claims 1 to 5 or according to any one of claims 28 to 31, wherein the second target is present on the surface of the target cell, and wherein the target cell is a dendritic cell.

44. The use of the bispecific TRGV9 antibody according to any one of claims 1 to 5 or according to any one of claims 28 to 31, wherein the second target is present on the surface of the target cell, and wherein the target cell is a stem cell or a stem cell precursor.

45. The use of the bispecific TRGV9 antibody according to any one of claims 1 to 5 or according to any one of claims 28 to 31, wherein the second target is present on the surface of the target cell, and wherein the target cell is a monocyte or a macrophage.

46. ​​The use of the bispecific TRGV9 antibody according to any one of claims 1 to 5 or according to any one of claims 28 to 31, wherein the second target is present on the surface of the target cell, and wherein the target cell is a granulocyte.

47. The use of the bispecific TRGV9 antibody according to any one of claims 1 to 5 or according to any one of claims 28 to 31, wherein the second target is present on the surface of the target cell, and wherein the target cell is an epithelial cell.

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