EP4110390A1 - Matériels et méthodes de modulation d'une réponse immunitaire - Google Patents

Matériels et méthodes de modulation d'une réponse immunitaire

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Publication number
EP4110390A1
EP4110390A1 EP21760487.5A EP21760487A EP4110390A1 EP 4110390 A1 EP4110390 A1 EP 4110390A1 EP 21760487 A EP21760487 A EP 21760487A EP 4110390 A1 EP4110390 A1 EP 4110390A1
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EP
European Patent Office
Prior art keywords
amino acid
acid sequence
antibody
seq
cdr1
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
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EP21760487.5A
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German (de)
English (en)
Inventor
Rajkumar Ganesan
Iqbal S. Grewal
Sanjaya Singh
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Janssen Biotech Inc
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Janssen Biotech Inc
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Priority claimed from PCT/US2020/031749 external-priority patent/WO2020227457A1/fr
Application filed by Janssen Biotech Inc filed Critical Janssen Biotech Inc
Publication of EP4110390A1 publication Critical patent/EP4110390A1/fr
Pending legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2809—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2878—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/3061—Blood cells
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/3069—Reproductive system, e.g. ovaria, uterus, testes, prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/51—Complete heavy chain or Fd fragment, i.e. VH + CH1
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/515—Complete light chain, i.e. VL + CL
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/74—Inducing cell proliferation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Definitions

  • This invention relates to, among other things, T Cell Receptor (TCR) redirection technologies, such as those targeting T cell Receptor Gamma Variable 9 (TRGV9) molecules, including TRGV9 antibodies, bispecific antibodies, nucleic acids and expression vectors encoding the antibodies, recombinant cells containing the vectors, and compositions comprising the antibodies.
  • TCR T Cell Receptor
  • TRGV9 antibodies T cell Receptor Gamma Variable 9
  • TRGV9 antibodies include TRGV9 antibodies, bispecific antibodies, nucleic acids and expression vectors encoding the antibodies, recombinant cells containing the vectors, and compositions comprising the antibodies.
  • This application contains a sequence listing, which is submitted electronically via EFS-Web as an ASCII formatted sequence listing with a file “ 14620-381-228_SEQLISTING” and a creation date of February 22, 2021 and having a size of 440,714 bytes.
  • the sequence listing submitted via EFS-Web is part of the specification and is herein incorporated by reference in its entirety.
  • T Cell Receptor redirection technologies including, for example, TRGV9 molecules, such as TRGV9 antibodies and multispecific antibodies, as well as nucleic acids and expression vectors encoding the antibodies, recombinant cells containing the vectors, and compositions comprising the antibodies.
  • an antibody that binds to TRGV9.
  • the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL).
  • the TRGV9 antibody has a VH and VL amino acid sequence of L7A5 2 (TRGV9 2).
  • the TRGV9 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:34; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 8.
  • the TRGV9 antibody has a VH and VL amino acid sequence of L7A5 3 (TRGV9 3).
  • the TRGV9 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:35; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 8.
  • the TRGV9 antibody has a VH and VL amino acid sequence of L7A5 4 (TRGV9 4).
  • the TRGV9 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:36; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 8.
  • the TRGV9 antibody has a VH and VL amino acid sequence of TRGV9Ab_varl7.
  • the TRGV9 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:65; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:66.
  • the TRGV9 antibody has a VH and VL amino acid sequence of TRGV9Ab_var29.
  • the TRGV9 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:67; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:68.
  • the TRGV9 antibody has a VH and VL amino acid sequence of VG9B420.
  • the TRGV9 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO: 104; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 105.
  • the TRGV9 antibody has a VH and VL amino acid sequence of VG9SB10SC1087 P18 D08.
  • the TRGV9 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO: 113; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 114.
  • the TRGV9 antibody has a VH and VL amino acid sequence of VG9SB10SC1087 P18 C12.
  • the TRGV9 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO: 123; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 124.
  • the TRGV9 antibody has a VH and VL amino acid sequence of VG9SB10SC1087 P19 C03.
  • the TRGV9 antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO: 133; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 134.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the TRGV9 antibody are according to the Rabat numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the TRGV9 antibody are according to the Chothia numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL
  • CDR3 amino acid sequences of the TRGV9 antibody are according to the AbM numbering system.
  • VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the TRGV9 antibody are according to the Contact numbering system.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the TRGV9 antibody are according to the IMGT numbering system.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the TRGV9 antibody are according to the Exemplary numbering system.
  • the antibody binds a TRGV9 antigen. In some embodiments, antibody binds a TRGV9 epitope. In some embodiments, the antibody specifically binds to TRGV9. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 form a binding site for an antigen of the TRGV9. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 form a binding site for an epitope of the TRGV9. In some embodiments, the TRGV9 is present on the surface of a T cell. In some embodiments, the T cell is a gd T cell.
  • the TRGV9 antibody is chimeric. In some embodiments, the TRGV9 antibody is human. In some embodiments, the TRGV9 antibody is humanized. In certain 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, a TRGV9 antigen binding fragment is humanized. In certain embodiments, a TRGV9 antigen binding fragment is an isolated TRGV9 antigen binding fragment. In some embodiments, the TRGV9 antibody is an IgG antibody.
  • the TRGV9 antibody is an IgGl 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 comprises a kappa light chain. In some embodiments, the TRGV9 antibody comprises a lambda 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 at least three antigens. In some embodiments, the TRGV9 antibody is capable of binding at least four antigens.
  • the TRGV9 antibody is capable of binding 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 quadraspecific antibody.
  • the TRGV9 antibody is a multispecific TRGV9 antibody. In one specific embodiment, the multispecific TRGV9 antibody is a bispecific TRGV9 antibody.
  • a multispecific TRGV9 antibody comprising a TRGV9 antibody provided herein.
  • 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.
  • the first binding domain that binds to TRGV9 comprises a VH and VL amino acid sequence of L7A5 1 (TRGV9 1).
  • the first binding domain that binds to TRGV9 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:7; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:8.
  • the first binding domain that binds to TRGV9 comprises a VH and VL amino acid sequence of L7A5 2 (TRGV9 2).
  • the first binding domain that binds to TRGV9 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:34; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:8.
  • the first binding domain that binds to TRGV9 comprises a VH and VL amino acid sequence of L7A5 3 (TRGV9 3).
  • the first binding domain that binds to TRGV9 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:35; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:8.
  • the first binding domain that binds to TRGV9 comprises a VH and VL amino acid sequence of L7A5 4 (TRGV9 4).
  • the first binding domain that binds to TRGV9 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:36; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:8.
  • the first binding domain that binds to TRGV9 comprises a VH and VL amino acid sequence of TRGV9Ab_varl7.
  • the first binding domain that binds to TRGV9 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:65; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:66.
  • the first binding domain that binds to TRGV9 comprises a VH and VL amino acid sequence of TRGV9Ab_var29.
  • the first binding domain that binds to TRGV9 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:67; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:68.
  • the first binding domain that binds to TRGV9 comprises a VH and VL amino acid sequence of VG9 B3 RN.
  • the first binding domain that binds to TRGV9 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:95; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:96.
  • the first binding domain that binds to TRGV9 comprises a VH and VL amino acid sequence of VG9B420.
  • the first binding domain that binds to TRGV9 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO: 104; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 105.
  • the first binding domain that binds to TRGV9 comprises a VH and VL amino acid sequence of VG9SB10SC1087 P18 D08.
  • the first binding domain that binds to TRGV9 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO: 113; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 114.
  • the first binding domain that binds to TRGV9 comprises a VH and VL amino acid sequence of VG9SB10SC1087 P18 C12.
  • the first binding domain that binds to TRGV9 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO: 123; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 124.
  • the first binding domain that binds to TRGV9 comprises a VH and VL amino acid sequence of VG9SB10SC1087 P19 C03.
  • the first binding domain that binds to TRGV9 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO: 133; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 134.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the first binding domain that binds TRGV9 are according to the Rabat numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the first binding domain that binds TRGV9 are according to the Chothia numbering system.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the first binding domain that binds TRGV9 are according to the AbM numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the first binding domain that binds TRGV9 are according to the Contact numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the first binding domain that binds TRGV9 are according to the IMGT numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3,
  • VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the first binding domain that binds TRGV9 are according to the Exemplary numbering system.
  • the first binding domain binds a TRGV9 antigen.
  • the first binding domain binds a TRGV9 epitope. In some embodiments, the first binding domain specifically binds to TRGV9. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the first binding domain form a binding site for an antigen of the TRGV9. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the first binding domain form a binding site for an epitope of the TRGV9. In some embodiments, the TRGV9 is present on the surface of a T cell. [0032] In some embodiments of the multispecific TRGV9 antibodies provided herein, the second target is not a TRGV9 antigen. In some embodiments of the multispecific TRGV9 antibodies provided herein, the second target is not a TRGV9 epitope.
  • the second target is CD123.
  • the second binding domain that binds to CD123 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO: 15; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 16.
  • the second target is CD33.
  • the second target is the C2 domain of CD33.
  • the second target is the V domain of CD33.
  • the second binding domain that binds to CD33 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:43; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:44.
  • the second target is TRBC1.
  • the second binding domain that binds to TRBC1 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO: 55; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:56.
  • the second target is B cell maturation antigen (BCMA).
  • BCMA B cell maturation antigen
  • the second binding domain binds to BCMA.
  • the second binding domain that binds to BCMA comprises: (i) a VH comprising a VH CDR1, a VH
  • VH CDR2 and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO: 143; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 144.
  • the second target is prostate-specific membrane antigen (PSMA).
  • PSMA prostate-specific membrane antigen
  • the second binding domain that binds to PSMA comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:775; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:776.
  • the second target is expressed by target cell. In some embodiments of the multispecific TRGV9 antibodies provided herein, the second target is on the surface of a target cell. In a specific embodiment, the target cell is an undesired cell.
  • 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 a NR 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 an erythrocyte. In one embodiment, the target cell is an endothelial cell.
  • 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 comprising a pathogen. In one embodiment, the target cell is a blood cell. In one embodiment, the target cell is a myeloid cell.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the second binding domain that binds the second target are according to the Rabat numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL
  • VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the second binding domain that binds the second target are according to the AbM numbering system.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the second binding domain that binds the second target are according to the Contact numbering system.
  • VL CDR2, and VL CDR3 amino acid sequences of the second binding domain that binds the second target are according to the IMGT numbering system.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the second binding domain that binds the second target are according to the Exemplary numbering system.
  • the second binding domain binds an antigen of the second target. In some embodiments, In some embodiments, the second binding domain binds an 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 an antigen of the second target. In some embodiments, the second binding domain specifically binds an epitope of the second target. In some embodiments, the VH CDR1, VH CDR2,
  • VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the second binding domain form a binding site for an antigen of the second target.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the second binding domain form a binding site for an epitope of the second target.
  • the second target is present on the surface of a target cell.
  • the target cell expressing the second target is killed when the multispecific TRGV9 antibody binds to TRGV9 on the surface of a T cell and the second target.
  • the T cell is a gd T cell.
  • the first binding domain of the multispecific TRGV9 antibody is multivalent. In some embodiments, the first binding domain of the multispecific TRGV9 antibody is capable of binding at least three antigens. In some embodiments, the first binding domain of the multispecific TRGV9 antibody is capable of binding at least four antigens. In some embodiments, the first binding domain of the multispecific TRGV9 antibody is capable of binding at least five antigens. In some embodiments, the second binding domain of the multispecific TRGV9 antibody is multivalent. In some embodiments, the second binding domain of the multispecific TRGV9 antibody is capable of binding at least three antigens. In some embodiments, the second binding domain of the multispecific TRGV9 antibody is capable of binding at least four antigens. In some embodiments, the second binding domain of the multispecific TRGV9 antibody is capable of binding at least five antigens.
  • the first binding domain is humanized.
  • the second binding domain is humanized.
  • both the first binding domain and the second binding domain are humanized.
  • the multispecific TRGV9 antibody comprises a kappa light chain.
  • the multispecific TRGV9 antibody comprises a lambda light chain.
  • the multispecific TRGV9 antibody is an IgG antibody.
  • the IgG antibody is an IgGl antibody.
  • the IgG antibody is an IgG2 antibody.
  • the IgG antibody is an IgG3 antibody.
  • the IgG antibody is an IgG4 antibody.
  • the multispecific TRGV9 antibody induces T cell dependent cytotoxicity of a target cell expressing the second target in vitro with an EC50 of less than about 500 pM. In some embodiments, the multispecific TRGV9 antibody induces T cell dependent cytotoxicity of a target cell expressing the second target in vitro with an EC50 of less than about 300 pM. In some embodiments, the multispecific TRGV9 antibody induces T cell dependent cytotoxicity of a target cell expressing the second target in vitro with an EC50 of less than about 160 pM. In some embodiments, the EC50 is assessed with a mixture of T cell effector cells and target cells expressing the second target.
  • the effector cell to target cell ratio is about 0.01 to 1 to about 5 to 1. In some embodiments, the effector cell to target cell ratio is about 0.1 to 1 to about 2 to 1. In some embodiments, the effector cell to target cell ratio is about 1 : 1.
  • the T cell is a gd T cell. In one embodiment, target cells are Kasumi-3 AML target cells.
  • nucleic acid encoding a TRGV9 antibody provided herein.
  • a vector comprising a nucleic acid encoding a TRGV9 antibody provided herein.
  • a host cell comprising a vector comprising a nucleic acid encoding a TRGV9 antibody provided herein.
  • a kit comprising vector comprising a nucleic acid encoding a TRGV9 antibody provided herein, and packaging for the same.
  • methods of making a TRGV9 antibody provided herein comprising culturing a cell comprising a nucleic acid encoding TRGV9 antibody under conditions to produce the TRGV9 antibody.
  • kits comprising a TRGV9 antibody provided herein, and packaging for the same.
  • a pharmaceutical composition comprising a TRGV9 antibody provided herein, and a pharmaceutically acceptable carrier.
  • the TRGV9 antibody is a multispecific TRGV9 antibody provided herein.
  • a multispecific TRGV9 antibody comprising: a first means capable of binding TRGV9; and a second means capable of binding a second target.
  • the second target is not TRGV9.
  • a multispecific TRGV9 antibody comprising: a first means that binds to TRGV9; and a second means that binds to a second target.
  • the second target is not TRGV9.
  • the TRGV9 is on the surface of a T cell.
  • the T cell is a gd T cell.
  • the first means is capable of specifically binding the TRGV9.
  • the first means specifically binds the TRGV9.
  • the TRGV9 is a TRGV9 antigen. In another embodiment, the TRGV9 is a TRGV9 epitope.
  • the first means is a paratope. In some embodiments, the paratope is a paratope of a TRGV9 antibody provided herein. In one embodiment, the first means is an antibody. In some embodiments, the antibody is TRGV9 antibody provided herein. In some embodiments, the TRGV9 antibody is an antigen binding fragment.
  • the second means is capable of specifically binding the second target. In some embodiments, the second means specifically binds the 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.
  • the second target is on the surface of a target cell. In some embodiments, the second target is CD 123. In some embodiments, the second target is CD33. In some embodiments, the second target is TRBC1. In some embodiments, the second target is BCMA. In some embodiments, the second target is PSMA. In one embodiment, the second means is a paratope. In some embodiments, the paratope is a paratope of a second binding arm provided herein. In some embodiments, the paratope is a paratope of a CD 123 antibody provided herein. In some embodiments, the paratope is a paratope of a CD33 antibody provided herein.
  • the paratope is a paratope of a TRBC1 antibody provided herein. In some embodiments, the paratope is a paratope of a BCMA antibody provided herein. In some embodiments, the paratope is a paratope of a PSMA antibody provided herein.
  • the second means is an antibody that binds a second target provided herein. In some embodiments, the second means is a CD123 antibody provided herein. In one embodiments, the CD123 antibody is an antigen binding fragment thereof. In some embodiments, the second means is a CD33 antibody provided herein. In one embodiments, the CD33 antibody is an antigen binding fragment thereof. In some embodiments, the second means is a TRBC1 antibody provided herein.
  • the TRBC1 antibody is an antigen binding fragment thereof.
  • the second means is a BCMA antibody provided herein.
  • the BCMA antibody is an antigen binding fragment thereof.
  • the second means is a PSMA antibody provided herein.
  • the PSMA antibody is an antigen binding fragment thereof.
  • a process for making an antibody that binds to more than one target comprising: a step for performing a function of obtaining a first binding domain capable of binding to TRGV9; a step for performing a function of obtaining a second binding domain capable of binding to a second target; and a step for performing a function of providing an antibody capable of binding to TRGV9 and the second target.
  • the step for performing a function of obtaining a second binding domain capable of binding to second target is repeated n times and further comprises n steps for performing a function of providing a first binding domain capable of binding to TRGV9 and n number of targets, wherein n is at least 2.
  • the second target is not TRGV9.
  • the first binding domain is capable of specifically binding to the TRGV9.
  • the TRGV9 is a TRGV9 antigen.
  • the TRGV9 is a TRGV9 epitope.
  • the first binding domain binds a TRGV9 antigen.
  • the first binding domain binds a TRGV9 epitope.
  • the TRGV9 is on the surface of a T cell.
  • the T cell is a gd T cell.
  • the second binding domain is capable of specifically binding to the second target.
  • the second binding domain binds an antigen of the second target.
  • the second binding domain binds an epitope of the second target.
  • the second target is on the surface of a target cell. In some embodiments, the second target is CD 123. 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.
  • a method of activating a T cell expressing TRGV9 comprising contacting the T cell with a TRGV9 antibody provided herein.
  • the contacting results in an increase in CD69, CD25, and/or Granzyme B expression, as compared to a control T cell expressing TRGV9.
  • a method of inactivating a T cell expressing TRGV9 comprising contacting the T cell with an antibody that binds to a TRGV9 provided herein.
  • a method of blocking activation a T cell expressing TRGV9 comprising contacting the T cell with an antibody that binds to a TRGV9 provided herein.
  • a method of modulating the activity of a T cell expressing TRGV9 comprising contacting the T cell with an antibody that binds to a TRGV9 provided herein.
  • the T cell is a gd T cell.
  • the TRGV9 antibody is a multispecific TRGV9 antibody provided herein.
  • a method of directing a T cell expressing TRGV9 to a target cell comprising contacting the T cell with a multispecific TRGV9 antibody provided herein, wherein the contacting directs the T cell to the target cell.
  • a method of inhibiting growth or proliferation of a target cell comprising contacting the target cell with a multispecific TRGV9 antibody provided herein, wherein the contacting inhibits growth or proliferation of the target cell.
  • the target cell is in the presence of the T cell expressing TRGV9 while in contact with the multispecific TRGV9 antibody.
  • the target cell expresses a second target that is not TRGV9.
  • the T cell is a gd T cell.
  • the second target is an antigen of the second target.
  • the second target is an epitope of the second target.
  • the second target is on the surface of the target cell.
  • the second target is CD123.
  • the second target is CD33.
  • the second target is TRBC1.
  • the second target is BCMA.
  • the second target is PSMA.
  • the target cell is a cancer cell.
  • a method for eliminating target cells in a subject comprising administering an effective amount of a multispecific TRGV9 antibody provided herein to the subject.
  • a method for treating a disease, disorder or condition hereafter “disease” caused all or in part by a target cell in a subject, comprising administering an effective amount of a multispecific TRGV9 antibody provided herein to the subject.
  • a method for preventing a disease caused all or in part by a target cell in a subject comprising administering an effective amount of a multispecific TRGV9 antibody provided herein to the subject.
  • a method for modulating a disease caused all or in part by a target cell in a subject comprising administering an effective amount of a multispecific TRGV9 antibody provided herein to the subject.
  • the target cell expresses a second target that is not TRGV9.
  • the second target is on the surface of the target cell.
  • the second target is CD123.
  • the second target is CD33.
  • the second target is TRBC1.
  • the second target is BCMA.
  • the second target is PSMA.
  • the target cell is a cancer cell.
  • the target cell is a T cell.
  • the target cell is a B cell.
  • the target cell is a dendritic cell. In one embodiment, the target cell is a 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 an erythrocyte. 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 comprising a pathogen.
  • the target cell is a blood cell. In one embodiment, the target cell is a myeloid cell. In some embodiments, the second target is on a cancer cell. In some embodiments, the target cell is a cancer cell. In a specific embodiment, the second target is on the surface of a cancer cell. In certain embodiments, the second target is an antigen on the surface of a cancer cell. In some embodiments, the antigen on the surface of the cancer cell is a tumor-specific antigen, a tumor-associated antigen, or a neoantigen In a specific embodiment, the disease is a cancer. In some embodiments, the subject is a subject in need thereof. In some embodiments, the subject is a human. In certain embodiments, the method further comprises identifying a subject in need thereof.
  • FIG. 1 shows a schematic demonstrating the binding of an exemplary multispecific TRGV9 antibody comprising 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 gd T cells to the target cell and to induce target cell death.
  • the second target antigen can be a tumor associated antigen (TAA), and the target cell can be a tumor cell, wherein the anti-TRGV9/anti-TAA bispecific antibody can to recruit gd T cells to the cancer cell and to induce cancer cell death.
  • TAA tumor associated antigen
  • FIG. 2 shows a graph demonstrating that Zoledronic acid selectively expands V ⁇ 9Vb2 cells from whole peripheral blood mononuclear cells (PBMCs).
  • FIGS. 3A-3E show phenotypic characterization of V ⁇ 9+ gd T cells.
  • FIG. 3A shows a schematic depiction of gates used to describe the differentiation of gd T cells (left).
  • Representative FACS-dot plots show the differentiation profile of V ⁇ 9 + gd T cells from fresh PBMCs (left) and PBMCs cultured ex vivo with Zoledronic acid + IL-2 + IL-15 for 14 days (right).
  • Numbers in quadrants mirror the frequency (mean ⁇ SEM) of the respective population among fresh and activated ng9 + gd T cells.
  • FIG. 3B shows numbers in representative dot plots mirroring the frequency (mean ⁇ SEM) of ng9 + gd T cells positive for respective activation marker either from fresh PBMCs (upper row) or PBMCs cultured with Zoledronic acid + IL- 2 + IL-15 for 14 days (lower row).
  • 3D shows representative FACS dot plots demonstrating the frequency (mean ⁇ SEM) of V ⁇ 9 + gd T cells expressing intracellular Granzyme B (left column) and Perforin (right column) from fresh PBMCs (upper row) and PBMCs cultured ex vivo with Zoledronic acid + IL-2 + IL-15 for 14 days (lower row).
  • FIG. 4 shows a histogram demonstrating that VG1 (an anti-TRGV9/anti- CD123 bispecific antibody) recruits V ⁇ 9+ T cells as demonstrated by conjugate formation between gd T cells and Kasumi-3 cells.
  • FIGS. 5A-5C show graphs demonstrating VG1 (anti-TRGV9/anti-CD123 bispecific antibody) bispecific mediated gd T cell cytotoxicity against Kasumi-3 cells at different effector to target cell ratios (1 : 1 for FIG. 5A; 5:1 for FIG. 5B; and 10: 1 for FIG. 5C)
  • FIGS. 6A-6C show graphs demonstrating CD69 (FIG. 6A), CD25 (FIG. 6B), or Granzyme B (FIG. 6C) expression on V ⁇ 9+ gd T cells, non-V ⁇ 9+ gd T cells, and Pan-T cells (non gd T cells) co-cultured with Kasumi-3 cells and VG1, VG3, or no bispecific antibody.
  • FIG. 7 shows a schematic demonstrating the binding of an anti- TRGV9/anti-CD33 bispecific antibody to recruit gd T-cells to a cancer cell that is CD33+ and to induce cancer cell death.
  • FIG. 8 shows an SDS-PAGE (non-reducing) gel demonstrating the integrity of the VG4 bispecific antibody.
  • FIG. 9 shows a graph demonstrating the binding of anti-CD33 antibody (clone C33B904) to MOLM-13 tumor cell line as measured by FACS.
  • FIG. 10 shows a graph demonstrating the binding of anti-CD33 antibody (clone C33B904) to Kasumi-1 tumor cell line as measured by FACS.
  • FIG. 11 shows a graph demonstrating the binding of anti-CD33 antibody (clone C33B904) to OCI-AML-3 tumor cell line as measured by FACS.
  • FIG. 12 shows a graph demonstrating that the anti-TRGV9/anti-CD33 bispecific antibody mediated gd T cell cytotoxicity against CD33 expressing Kasumi- 3 cells at 1 : 1 effector to target cell ratio.
  • the effector cells were enriched gd T cells isolated from PBMCs.
  • FIG. 13 shows a graph demonstrating that the anti-TRGV9/anti-CD33 bispecific antibody mediated gd T cell cytotoxicity against CD33 expressing Kasumi- 3 cells at 5: 1 effector to target cell ratio.
  • the effector cells were enriched gd T cells isolated from PBMCs.
  • FIG. 14 shows a graph demonstrating that the anti-TRGV9/anti-CD33 bispecific antibody mediated gd T cell cytotoxicity against CD33 expressing Kasumi- 3 cells at 1 : 1 effector to target cell ratio.
  • the effector cells were healthy donor derived PBMCs.
  • FIG. 15 shows a schematic demonstrating the binding of anti- TRGV9/anti-TRBCl bispecific antibody to recruit gd T-cells to a cancer cell that is TRBC1+ and to induce cancer cell death.
  • FIG. 16 shows selective cell binding of anti-TRBCl (JOVI-1 mIgG2a, TRBIBI) to transfected Jurkat cells.
  • the EC 50 for binding was ⁇ 1 to 2 nM.
  • TRBIBI did not show any significant binding to HPB-ALL cell line that endogenously expresses TRBC2 TCR.
  • FIG. 17 shows selective protein binding of anti-TRBCl (JOVI-1 mIgG2a, TRBIBI) to a recombinant TCR comprising of TRBCl constant domain (TRB1W16).
  • TRB1B1 did not show any significant binding to a recombinant TCR with TRBC2 constant domain (TRB2W16).
  • FIG. 18 shows phenotyping of V ⁇ 9+ cells used for cytotoxicity studies of JOVI-1 x Vg9 bispecific (TRB1B50) from a healthy donor.
  • FIG. 19 shows that the anti-TRGV9/anti-TRBCl bispecific antibody mediates gd T cell cytotoxicity against TRBCl expressing Jurkat cells in vitro. Cytotoxicity values represented here were subtracted of basal cytotoxicity value observed in the absence of bispecific antibody. EC 50 values were calculated as described in methods. Representative data shown here are from a single experiment.
  • FIG. 20 shows bispecific antibody mediated cytotoxicity. Expanded and enriched V ⁇ 9V62 T cells from various donors were used to induce cytotoxicity to Jurkat cell line (E:T ratio 1:1) in presence of V ⁇ 9xJovi at indicated concentrations. Assay was conducted for 16 hrs. Percent dead target cells for various conditions are given in the figure.
  • FIG. 21 shows that the anti-TRGV9/anti-BCMA bispecific antibody (BCV9B106 (B3)) binds gd T cells (left panel) and mediates gd T cell cytotoxicity against BCMA expressing H929 cells in vitro (right panel).
  • EC 50 values were calculated as described in methods. Representative data shown here are from a single experiment.
  • FIG. 22 shows that the anti-TRGV9/anti-BCMA bispecific antibody (HC1: VG9B420-LH-scFv; HC2: BCMA-Fab (BCMB519-Fab) (BCV9B71.001)) binds gd T cells (left panel) and mediates gd T cell cytotoxicity against BCMA expressing H929 cells in vitro (right panel).
  • EC 50 values were calculated as described in methods. Representative data shown here are from a single experiment.
  • FIG. 23 shows that the anti-TRGV9/anti-BCMA bispecific antibody (VG9SB10SC1087_P18_D08-Fab RF, BCMA-scFv (BCMB519-scFv ) (BCV9B100.001)) binds gd T cells (left panel) and mediates gd T cell cytotoxicity against BCMA expressing H929 cells in vitro (right panel).
  • EC 50 values were calculated as described in methods. Representative data shown here are from a single experiment.
  • FIG. 24 shows that the anti-TRGV9/anti-BCMA bispecific antibody (VG9SB10SC1087_P18_C12-Fab RF, BCMA-scFv (BCMB519-scFv ) (BCV9B101.001)) binds gd T cells (left panel) and mediates gd T cell cytotoxicity against BCMA expressing H929 cells in vitro (right panel).
  • EC 50 values were calculated as described in methods. Representative data shown here are from a single experiment.
  • FIG. 25 shows that the anti-TRGV9/anti-BCMA bispecific antibody (VG9SB10SC1087_P19_C03-Fab RF, BCMA-scFv (BCMB519-scFv ) (BCV9B103.001)) binds gd T cells (left panel) and mediates gd T cell cytotoxicity against BCMA expressing H929 cells in vitro (right panel).
  • EC 50 values were calculated as described in methods. Representative data shown here are from a single experiment.
  • FIG. 26 shows humanization of murine anti-V ⁇ 9 antibody.
  • Humanization of murine clone 7A5 was performed following the process outlined by Singh et al. , Mabs. 2015. 7:778-791. Based on sequence homology, germline IGHV1-8*01 and IGKV4-1*01 was chosen for framework adaption. A potential Iso- Asp isomerization site (DG motif) was also included in the design.
  • DG motif Iso- Asp isomerization site
  • FIGS. 27A-27B show epitope and paratope mapping.
  • FIG. 27A shows HX-MS epitope mapping for the mouse anti-human TCR V ⁇ 9 [clone 7A5] mAh and ng9/nd2 fused to human Fc. 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.
  • the peptide region comprising amino acids 49-68 of SEQ ID NO: 789 (L49VSISYDGTVRKESGIPSGK68 (SEQ ID NO: 774) (italicized)), was protected by mAh 7A5.
  • a molecular model (using crystal structure PBD: 1HXM, see Allison etal. , Nature. 2001. 411:820-824) of TCR ng9-nd2 and residues in the epitope are highlighted in the sphere representation.
  • FIG. 27B shows HDX paratope mapping on the murine clone 7A5 (Vg9_7A5_VH SEQ ID NO: 7; Vg9_7A5_VL SEQ ID NO:8).
  • a molecular model of the Fab with residues in the paratope are highlighted.
  • FIGS. 28A-28B show healthy individuals harbor a wide range of V ⁇ 9 gd T cells among whole PBMCs.
  • FIG. 28A shows the frequency of V ⁇ 9 gd T
  • FIG. 28B shows scatter dot plot
  • FIGS. 29A-29C show characterisation of ng9 + gd T cells.
  • FIG. 29A, left and middle panels, show graphs summarizing the frequency of V ⁇ 9+ gd T cells among whole PBMCs on day 0 and day 14 of culture containing Zoledronic acid that selectively activates and expands V ⁇ 9+ gd T cells.
  • FIG. 29B left two panels, shows numbers in representative FACS plots depict the differentiation profile of V ⁇ 9+ gd T cells on day 0 and 14 of culture containing Zoledronic acid.
  • 29C shows numbers in representative FACS plots, which depict the frequency (mean ⁇ SEM) of V ⁇ 9+ gd T cells on day 0 (top row) and day 14 (bottom row) positive for Granzyme B and Perforin intracellular expression.
  • FIGS. 30A-30D show anti-TRGV9/anti-CD123 bispecific antibody binds to V ⁇ 9+ gd T cells and CD123 expressing tumor cells.
  • CD123 expressing target cells and PBMCs that were activated and expanded with Zoledronic acid for day 14 were incubated in the presence or absence of indicated V ⁇ 9 bispecific and Null arm control bispecific antibodies. Bound bispecific antibody staining was assessed by flow cytometry.
  • FIG. 30A shows the frequency of V ⁇ 9 bispecific bound Kasumi-3 cells in 3 independent experiments for Kasumi-3 cell line. The EC 50 values shown in the graphs refers to mean of 3 independent experiments.
  • FIG. 30B shows V ⁇ 9+ gd T cells at various concentrations in 2 independent experiments with 8 healthy donors.
  • EC50 values shown in the graphs refers to 2 healthy donors. Right and left lines reflect the indicated V ⁇ 9 bispecific antibody and its corresponding V ⁇ 9 null arm bispecific control antibodies respectively. EC50 values shown in the graph were derived using a 4-parameter dose-response curve with the concentration of indicated bispecific antibody on the x-axis (log scale) and specific binding on the y-axis (linear scale).
  • FIG. 30C shows V ⁇ 9+ gd T cells were FACS-sort depleted from Pan-T cells of whole PBMCs. Total Pan-T cells and Pan-T cells depleted of V ⁇ 9+ gd T cells were incubated in the presence and absence of indicated bispecific antibodies at various concentrations.
  • FIG. 30D shows CD 123 expressing Kasumi-3 and non-expressing 22Rvl cell lines were stained with anti-CD123 monoclonal antibody.
  • the representative overlaid histogram show the staining of CD123, isotype control and FMO control on Kasumi- 3 (left) and 22Rvl (right) cell lines (upper panels).
  • the representative graphs show the binding of V ⁇ 9/CD123 and V ⁇ 9/NULL bispecific antibodies to Kasumi-3 (left) cells lines at indicated concentrations.
  • EC 50 values shown in the graph were derived using a 4-parameter dose-response curve with the concentration of indicated bispecific antibody on the x-axis (log scale) and specific binding on the y-axis (linear scale).
  • FIGS. 31A-31F shows that V ⁇ 9/CD123 bispecific antibody selectively recruits, activates and induces cytotoxicity mediated by V ⁇ 9+ gd T cells.
  • FIG. 31A shows cell trace labelled enriched gd T cells that were co-cultured with cell trace yellow labelled kasumi-3 cells at 1:1 ET ratio in the presence of lpg/mL of indicated bispecific antibody at 37°C for 1 hour. Cell-cell association was determined using flow cytometry and quantified as double positive, cells in upper right quadrant of FACS plot. Numbers in quadrants indicate the frequency of respective population.
  • FIGS. 31A shows cell trace labelled enriched gd T cells that were co-cultured with cell trace yellow labelled kasumi-3 cells at 1:1 ET ratio in the presence of lpg/mL of indicated bispecific antibody at 37°C for 1 hour. Cell-cell association was determined using flow cytometry and quantified as double positive, cells in upper right quadrant of FACS plot. Numbers in quadrants indicate the frequency
  • FIG. 31B and 31C show Pan T cells (effectors) from fresh PBMCs that were co cultured with Kasumi-3 cells (Targets) at 1 : 1 ET ratio in the presence or absence of indicated bispecific antibodies at 37°C for 72 hours.
  • V ⁇ 9+ gd T cells, V ⁇ 9- gd T cells and Non- gd T cells that were positive for CD69 (left), CD25 (right) surface expression and intra cellular Granzyme B expression are shown.
  • FIG. 31D shows V ⁇ 9/CD123 bispecific mediated gd T cells cytotoxicity against CD123 cells.
  • PBMCs cultured with Zoledronic acid for 14 of (effectors) were co-cultured with CFSE labelled target (Kasumi-3) cells at ET ratio 1 : 1 (by normalizing ET ratio to V ⁇ 9+ gd T cell frequency in expanded PBMCs) in the presence of indicated concentration of V ⁇ 9 bispecifics and V ⁇ 9 NULL arm control antibodies for a period of 16 hours.
  • Target cell lysis was determined by the 7-AAD staining and flow cytometry.
  • Graphs represent the frequency of specific target cell lysis at the indicated of concentration of V ⁇ 9 bispecific antibodies and their respective V ⁇ 9/NULL arm controls.
  • EC 50 values shown in representative graphs are mean of 8 healthy donors for V ⁇ 9/CD 123 from 3 independent experiments.
  • FIG. 31E shows V ⁇ 9/CD 123 bispecific effectively mediates AML gd T cells cytotoxicity against Kasumi-3 cells.
  • the upper and the lower lines in representative graphs show the frequency of target (kasumi-3) cell lysis (%7-AAD + cells) mediated by V ⁇ 9/CD 123 and V ⁇ 9/Null bispecific antibodies respectively, upon co-culture of day 14 Zol AML patient PBMCs with target cells for 16 hours.
  • FIG. 31F shows the depletion efficacy of ng9 + gd T cells among pan-T cells. Numbers in quadrants represent the frequency of the respective population.
  • Graphs show the frequency of target cell lysis (% 7-AAD + cells) mediated by V ⁇ 9/CD 123 and V ⁇ 9/NULL bispecific antibodies respectively at indicated concentrations, upon co-culture of pan-T cells (V ⁇ 9 non-depleted) and pan-T cells depleted of V ⁇ 9 + gd T cells (V ⁇ 9 depleted) with target (Kasumi-3) cells (middle graph).
  • Bottom graph shows the target cell lysis mediated by CD3/CD123 and CD3/NULL bispecific antibodies respectively at indicated concentrations.
  • FIGS. 32A-32C show V ⁇ 9/CD 123 bispecific antibody potently mediates activation, proliferation and effector functions of V ⁇ 9 + gd T cells among whole PBMCs.
  • CFSE labelled whole PBMCs were cultured in the presence or absence kasumi-3 cells in the presence plus indicated bispecific antibodies at a concentration of 3ng/mL.
  • FIG. 32A shows frequency of V ⁇ 9 + cells positive for surface expression of CD69 and CD25.
  • FIG. 32B shows CFSE dilution (proliferation profile).
  • FIG. 33 shows V ⁇ 9+ gd T cell selective redirection does not elicit cytokine storm compared to Pan-T cell re-direction.
  • Whole PBMCs were cultured in the presence or absence of spiked-in kasumi-3 cells in the presence or absence of indicated bispecific antibodies (3ng/ml) as described in FIG. 30. From day 3 of culture onwards, 100 pL of culture medium was removed every day from the wells, without disturbing the cells, and replenished with fresh medium until day 8 of culture. Cytokines were assessed from day 3 to day 8 cell culture supernatant.
  • FIG. 34 shows mean tumor growth kinetics of NOD SCID mice bearing subcutaneous KG-1 tumor xenograft.
  • Female NOD SCID mice inoculated subcutaneously with 1.5 x 10 6 KG-1 cells were weekly treated subcutaneously with PBS or V ⁇ 9Vd2 gd T cells. All mice received 15 pg/kg IL-2, and, as indicated, 1. 5 mg/kg (nb17 x DLL3).
  • Tumor volume (left) of each mouse was measured once every three days during experimental period. Values are expressed as Mean ⁇ SEM of 6 animals in each group.
  • Statistical analysis carried out by Two-way ANOVA followed by Bonferroni post tests using Graph Pad Prism (Version 8.3.0). * p ⁇ 0.05 & **** p ⁇ 0.0001 when respective test groups were compared to Group 1- Tumor + PBS (control) group.
  • FIG. 35 shows binding kinetics of mouse anti-human TCR V ⁇ 9 [clone 7A5] and recombinant V ⁇ 9-V52-Fc antigen by SPR at 25 °C. Different concentrations of antigen (100 nM, from top to bottom in the plot) were flowed through anti-V ⁇ 9 mAh that was captured on the surface. Experimental data (black dotted line) and 1:1 Langmuir binding fitting (smooth line) is shown. The association phase between (first -250 sec) is follow by the dissociation phase.
  • FIGS. 36A-36D show that V ⁇ 9+ subset of gd T cell are suitable for redirecting for tumor elimination.
  • FIG. 36A shows the frequency (mean ⁇ SEM) of Vg9+ gd T cells on day 0 (top row) and day 14 (bottom row) positive for activation markers.
  • FIG. 36B shows an antigen presenting cell characteristics.
  • FIG 36C shows exhaustion markers.
  • FIGS. 37A-37B show V ⁇ 9 bispecific binding to V ⁇ 9 + y6 T cells and TAA expressing tumor cells.
  • Tumor Associated Antigen (TAA) expressing target cells and day 14 Zol expanded PBMCs were incubated in the presence or absence of indicated V ⁇ 9 bispecific (V ⁇ 9/CD123 or V ⁇ 9/PSMA) and Null arm control bispecific antibodies. Bound bispecific antibody staining was assessed by flow cytometry. Representative graphs show the frequency of V ⁇ 9 bispecific bound cells at various concentrations. V ⁇ 9 bispecific antibody and its corresponding V ⁇ 9 null arm bispecific control antibodies are indicated.
  • EC 50 values shown in the graphs refers to mean of 3 independent experiments (for FIG. 37A) and 9 and 2 healthy donors (for FIG. 37B).
  • FIG. 38A-38B show that V ⁇ 9/CD123 bispecific selectively binds to V ⁇ 9 + gd T cells and CD123 expressing cell line.
  • V ⁇ 9 + gd T cells were FACS-sort depleted from enriched Pan- T cells of whole PBMCs from healthy individuals. Total Pan-T cells and Pan-T cells depleted of V ⁇ 9 + gd T cells were incubated in the presence and absence of indicated bispecific antibodies at various concentrations.
  • FIG. 38A depicts representative FACS plots showing the depletion efficacy of V ⁇ 9 + y6 T cells among pan-T cells. Numbers in quadrants represent the frequency of the respective population.
  • FIG. 38A reflects the binding of V ⁇ 9/CD123 and V ⁇ 9/NULL bispecific antibodies at indicated concentrations to pan-T cells (V ⁇ 9 non-depleted Pan-T cells) and pan-T cells depleted of V ⁇ 9 + gd T cells (V ⁇ 9 depleted Pan-T cells).
  • CD123 TAA expressing Kasumi-3 and non-expressing 22Rvl cell lines were stained with anti- CD123 monoclonal antibody.
  • the upper panels of FIG. 38B show the staining of CD123, isotype control and FMO control respectively on Kasumi-3 (left) and 22Rvl (right) cell lines.
  • V ⁇ 9/CD123 and VY9/NULL bispecific antibodies respectively to Kasumi-3 (left) and 22Rvl (right) cells lines at indicated concentrations.
  • EC 50 values shown in the graph were derived using a 4-parameter dose-response curve with the concentration of indicated bispecific antibody on the x-axis (log scale) and specific binding on the y-axis (linear scale).
  • FIGS. 39A-39B show that V ⁇ 9 bispecific mediated re-direction of gd T cells effectively eliminates liquid and solid tumors.
  • Whole PBMCs were cultured in the presence of Zol+IL-2+Il-15 for 14 days.
  • V ⁇ 9 + gd T cell frequency was assessed among whole PBMCs by flow cytotmetry.
  • FIG. 39B represent the frequency of specific target cell lysis at the indicated concentration of V ⁇ 9 bispecific antibodies and their respective VY9/NULL arm controls.
  • EC 50 values shown in representative graphs are mean of 8 and 2 healthy donors for VY9/CD123 (FIG. 39 A) and VY9/PSMA (FIG. 39B) bispecific antibodies respectively from 3 (for FIG. 39A) and one (for FIG. 39B) independent experiments.
  • FIGS. 40A-40E show that VY9/CD123 bispecific antibody potently mediates activation, proliferation and effector functions of ng9 + gd T cells among whole PBMCs.
  • FIG. 40A shows how CFSE labelled whole PBMCs were cultured in the presence or absence of spiked-in kasumi-3 cells in the presence of indicated bispecific antibodies at a concentration of 3ng/mL. As a control, CFSE labelled whole PBMCs (with or without spiked in Kasumi-3 cells) were cultured in the absence of any bispecific antibody.
  • FIG. 40B depicts graphs that represent the mean ( ⁇ SEM) frequency of V ⁇ 9 + cells positive for surface expression of CD69, CD25 and CD71 (activation markers).
  • FIG. 40C shows CFSE dilution (proliferation profile) and FIG. 40D shows ability to eliminate exogenously added Kasumi-3 cells or endogenous CD123 + cells (as shown in FIG. 40E) among whole PBMCs (effector profile) upon culture in the absence or presence of indicated bispecific antibodies (FIGS. 40C-40E).
  • FIGS. 41A-41C show that V ⁇ 9+ gd T cell selective redirection do not elicit cytokine storm compared to Pan-T cell re-direction.
  • Whole PBMCs were cultured in the presence or absence of spiked-in kasumi-3 cells in the presence or absence of indicated bispecific antibodies (3ng/ml) as described in FIG. 40. From day 3 of culture onwards, 100 pL of culture medium was removed every day from the wells, without disturbing the cells, and replenished with fresh medium until day 8 of culture. Cytokines were assessed from day 3 to day 8 cell culture supernatant.
  • FIGS. 42A-42D show V ⁇ 9/CD123 bispecific mediated gd T cells redirection in AML patients PBMCs.
  • FIG. 42A shows TCR V ⁇ 9 + gd T cells from AML patients can be expanded via ZoL. Numbers in representative FACS plots show the frequency of V ⁇ 9 + and V ⁇ 9 gd T cells on day 0 (left) and day 14 (right) AML patients PBMCs culture with Zol+IL-2+IL-15.
  • FIG. 42B shows the fold of expansion of TCRV ⁇ 9 + gd T cells from four AML patients PBMCs.
  • FIG. 42C shows TCR V ⁇ 9 + gd T cells from LC patients PBMCs exhibit more activated phenotype.
  • Scatter dot plot graphs shows the frequency of V ⁇ 9 + gd T cells, from fresh PBMCs, positive for naive (CD27 + CD45RA + ), Central Memory (TCM: CD27 + CD45RA ), Effector Memory (TEM: CD27 CD45RA) and Effector Memory cells that re-express CD45RA (EMRA: CD27 CD45RA + ) phenotype.
  • Each dot represented data from an a Lung Cancer patient sample.
  • FIG. 42D shows V ⁇ 9/CD 123 bispecific effectively mediates AML gd T cells cytotoxicity against Kasumi-3 cells.
  • any numerical values such as a concentration or a concentration range described herein, are to be understood as being modified in all instances by the term “about.”
  • a numerical value typically includes ⁇ 10% of the recited value.
  • a concentration of 1 mg/mL includes 0.9 mg/mL to 1.1 mg/mL.
  • a concentration range of 1% to 10% (w/v) includes 0.9%
  • compositions, a mixture, a process, a method, an article, or an apparatus that comprises a list of elements is not necessarily limited to only those elements but can include other elements not expressly listed or inherent to such composition, mixture, process, method, article, or apparatus.
  • “or” refers to an inclusive or and not to an exclusive or. For example, a condition A or B is satisfied by any one of the following: A is true (or present) and B is false (or not present), A is false (or not present) and B is true (or present), and both A and B are true (or present).
  • the conjunctive term “and/or” between multiple recited elements is understood as encompassing both individual and combined options. For instance, where two elements are conjoined by “and/or,” a first option refers to the applicability of the first element without the second. A second option refers to the applicability of the second element without the first. A third option refers to the applicability of the first and second elements together. Any one of these options is understood to fall within the meaning, and therefore satisfy the requirement of the term “and/or” as used herein. Concurrent applicability of more than one of the options is also understood to fall within the meaning, and therefore satisfy the requirement of the term “and/or.”
  • subject means any animal, preferably a mammal, most preferably a human.
  • mammal encompasses any mammal. Examples of mammals include, but are not limited to, cows, horses, sheep, pigs, cats, dogs, mice, rats, rabbits, guinea pigs, monkeys, humans, etc ., more preferably a human.
  • nucleic acids or polypeptide sequences e.g., anti-TRGV9/anti-cancer-associated antigen bispecific antibodies and polynucleotides that encode them, anti- TRGV9/anti-CD123 bispecific antibodies and polynucleotides that encode them, TRGV9 polypeptides and TRGV9 polynucleotides that encode them, CD123 polypeptides and CD 123 polynucleotides that encode them
  • nucleic acids or polypeptide sequences e.g., anti-TRGV9/anti-cancer-associated antigen bispecific antibodies and polynucleotides that encode them, anti- TRGV9/anti-CD123 bispecific antibodies and polynucleotides that encode them, TRGV9 polypeptides and TRGV9 polynucleotides that encode them, CD123 polypeptides and CD 123 polynucleotides that encode them
  • sequences or subsequences that are the same or have a specified percentage of amino acid residues or nu
  • sequence comparison typically one sequence acts as a reference sequence, to which test sequences are compared.
  • test and reference sequences are input into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated.
  • sequence comparison algorithm then calculates the percent sequence identity for the test sequence(s) relative to the reference sequence, based on the designated program parameters.
  • Optimal alignment of sequences for comparison can be conducted, e.g, by the local homology algorithm of Smith & Waterman, Adv. Appl. Math. 2:482 (1981), by the homology alignment algorithm of Needleman & Wunsch, J. Mol.
  • BLAST and BLAST 2.0 algorithms are described in Altschul et al. (1990) J. Mol. Biol. 215: 403-410 and Altschul etal. (1997) Nucleic Acids Res. 25: 3389-3402, respectively.
  • Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information.
  • This algorithm involves first identifying high scoring sequence pairs (HSPs) by identifying short words of length W in the query sequence, which either match or satisfy some positive-valued threshold score T when aligned with a word of the same length in a database sequence. T is referred to as the neighborhood word score threshold (Altschul etal ., supra).
  • HSPs high scoring sequence pairs
  • T is referred to as the neighborhood word score threshold (Altschul etal ., supra).
  • These initial neighborhood 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 for as far as the cumulative alignment score can be increased.
  • Cumulative scores are calculated using, for nucleotide sequences, the parameters M (reward score for a pair of matching residues; always > 0) and N (penalty score for mismatching residues; always ⁇ 0).
  • M forward score for a pair of matching residues; always > 0
  • N penalty score for mismatching residues; always ⁇ 0.
  • a scoring matrix is used to calculate the cumulative score. Extension of the word hits in each direction are halted when: the cumulative alignment score falls off by the quantity X from its maximum achieved value; the cumulative score goes to zero or below, due to the accumulation of one or more negative-scoring residue alignments; or the end of either sequence is reached.
  • the BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment.
  • the BLASTP program uses as defaults a word length (W) of 3, an expectation (E) of 10, and the BLOSUM62 scoring matrix (see Henikoff & Henikoff, Proc. Natl. Acad. Sci. USA 89:10915 (1989)).
  • the BLAST algorithm In addition to calculating percent sequence identity, the BLAST algorithm also performs a statistical analysis of the similarity between two sequences (see, e.g ., Karlin & Altschul, Proc. Nat’l. Acad. Sci.
  • nucleic acid is considered similar to a reference sequence if the smallest sum probability in a comparison of the test nucleic acid to the reference nucleic acid is less than about 0.1, more preferably less than about 0.01, and most preferably less than about 0.001.
  • a further indication that two nucleic acid sequences or polypeptides are substantially identical is that the polypeptide encoded by the first nucleic acid is immunologically cross reactive with the polypeptide encoded by the second nucleic acid, as described below.
  • a polypeptide is typically substantially identical to a second polypeptide, for example, where the two peptides differ only by conservative substitutions.
  • Another indication that two nucleic acid sequences are substantially identical is that the two molecules hybridize to each other under stringent conditions.
  • nucleic acid molecule refers to any polyribonucleotide or polydeoxyribonucleotide, which can be unmodified RNA or DNA or modified RNA or DNA.
  • Polynucleotides include, without limitation single- and double-stranded DNA, DNA that is a mixture of single- and double- stranded regions, single- and double-stranded RNA, and RNA that is mixture of single- and double-stranded regions, hybrid molecules comprising DNA and RNA that can be single-stranded or, more typically, double-stranded or a mixture of single- and double-stranded regions.
  • polynucleotide refers to triple-stranded regions comprising RNA or DNA or both RNA and DNA.
  • the term polynucleotide also includes DNAs or RNAs containing one or more modified bases and DNAs or RNAs with backbones modified for stability or for other reasons.
  • Modified bases include, for example, tritylated bases and unusual bases such as inosine.
  • polynucleotide embraces chemically, enzymatically or metabolically modified forms of polynucleotides as typically found in nature, as well as the chemical forms of DNA and RNA characteristic of viruses and cells.
  • Polynucleotide also embraces relatively short nucleic acid chains, often referred to as oligonucleotides.
  • vector is a replicon in which another nucleic acid segment can be operably inserted so as to bring about the replication or expression of the segment.
  • the term “host cell” refers to a cell comprising a nucleic acid molecule of the invention.
  • the “host cell” can be any type of cell, e.g ., a primary cell, a cell in culture, or a cell from a cell line.
  • a “host cell” is a cell transfected with a nucleic acid molecule of the invention.
  • a “host cell” is a progeny or potential progeny of such a transfected cell.
  • a progeny of a cell may or may not be identical to the parent cell, e.g., due to mutations or environmental influences that can occur in succeeding generations or integration of the nucleic acid molecule into the host cell genome.
  • the term “expression” as used herein, refers to the biosynthesis of a gene product.
  • the term encompasses the transcription of a gene into RNA.
  • the term also encompasses translation of RNA into one or more polypeptides, and further encompasses all naturally occurring post-transcriptional and post-translational modifications.
  • the expressed bispecific antibody can be within the cytoplasm of a host cell, into the extracellular milieu such as the growth medium of a cell culture or anchored to the cell membrane.
  • peptide can refer to a molecule comprised of amino acids and can be recognized as a protein by those of skill in the art.
  • the conventional one-letter or three-letter code for amino acid residues is used herein.
  • peptide can be used interchangeably herein to refer to polymers of amino acids of any length.
  • the polymer can be linear or branched, it can comprise modified amino acids, and it can be interrupted by non-amino acids.
  • the terms also encompass an amino acid polymer that has been modified naturally or by intervention; for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation or modification, such as conjugation with a labeling component. Also included within the definition are, for example, polypeptides containing one or more analogs of an amino acid (including, for example, unnatural amino acids, etc.), as well as other modifications known in the art. [0072] The peptide sequences described herein are written according to the usual convention whereby the N-terminal region of the peptide is on the left and the C- terminal region is on the right. Although isomeric forms of the amino acids are known, it is the L-form of the amino acid that is represented unless otherwise expressly indicated.
  • TRGV9 antibodies are provided herein.
  • nucleic acids and expression vectors encoding the antibodies, recombinant cells containing the vectors, and compositions comprising the antibodies.
  • Methods of making the antibodies, and methods of using the antibodies to treat diseases are also provided.
  • the antibodies disclosed herein possess one or more desirable functional properties, including but not limited to high-affinity binding to TRGV9 or high specificity to TRGV9.
  • the antibodies disclosed herein possess the ability to treat or prevent a disease or disorder when administered to a subject alone or in combination with other therapies.
  • the TRGV9 antibody comprises a TRGV9 antigen binding fragment. In some embodiments, the TRGV9 antibody consists of a TRGV9 antigen binding fragment. In other embodiments, the TRGV9 antibody is a multispecific TRGV9 antibody. In yet other embodiments, the multispecific TRGV9 antibody is a bispecific TRGV9 antibody. While TRGV9 antibodies are exemplified herein, it is understood that other molecules that bind to TRGV9 are also contemplated. Such molecules include other alternative binding agents, including equivalents of the antibodies and other antibody binding fragments provided herein.
  • TRGV9 multispecific antibodies nucleic acids and expression vectors encoding the multispecific antibodies, recombinant cells containing the vectors, and compositions comprising the multispecific antibodies.
  • Methods of making the antibodies, and methods of using the multispecific antibodies to treat diseases, including cancer, are also provided.
  • the antibodies disclosed herein possess one or more desirable functional properties.
  • the multispecific antibodies provided herein have high-affinity binding to TRGV9.
  • the multispecific antibodies provided herein have high-affinity binding to a second target antigen.
  • the multispecific antibodies provided herein have high specificity to TRGV9.
  • the multispecific antibodies provided herein have high specificity to a second target antigen.
  • the multispecific antibodies provided herein have the ability to treat or prevent a disease or disorder when administered alone. In some embodiments, the multispecific antibodies provided herein have the ability to treat or prevent a disease or disorder when administered in combination with other therapies. In a specific embodiment, the multispecific antibody is a bispecific antibody. In some embodiments, the TRGV9 antibody comprise an antigen binding fragment thereof.
  • the term “antibody” is used in a broad sense and includes immunoglobulin or antibody molecules including human, humanized, composite and chimeric antibodies and antibody fragments that are monoclonal or polyclonal. In general, antibodies are proteins or peptide chains that exhibit binding specificity to a specific antigen. Antibody structures are well known. Immunoglobulins can be assigned to five major classes (i.e., IgA, IgD, IgE, IgG and IgM), depending on the heavy chain constant domain amino acid sequence. IgA and IgG are further sub- classified as the isotypes IgAl, IgA2, IgGl, IgG2, IgG3 and IgG4. Accordingly, the antibodies of the invention can be of any of the five major classes or corresponding sub-classes. In specific embodiments, the antibodies provided herein are IgGl,
  • Antibody light chains of vertebrate species can be assigned to one of two clearly distinct types, namely kappa and lambda, based on the amino acid sequences of their constant domains. Accordingly, the antibodies provided herein can contain a kappa or lambda light chain constant domain. According to particular embodiments, the antibodies of the invention include heavy and/or light chain constant regions from rat or human antibodies.
  • antibodies contain an antigen-binding region that is made up 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), CDR2 and CDR3.
  • a “CDR” refers to one of three hypervariable regions (HCDR1, HCDR2 or HCDR3) within the non- framework region of the immunoglobulin (Ig or antibody) VH b-sheet framework, or one of three hypervariable regions (LCDR1, LCDR2 or LCDR3) within the non- framework region of the antibody VL b-sheet framework.
  • CDRs are variable region sequences interspersed within the framework region sequences.
  • CDR regions are well known to those skilled in the art and have been defined by, for example, Kabat as the regions of most hypervariability within the antibody variable (V) domains (Kabat etal, J. Biol. Chem. 252:6609-6616 (1977); Kabat, A civ. Prot. Chem. 32:1-75 (1978)).
  • CDR region sequences also have been defined structurally by Chothia as those residues that are not part of the conserved b-sheet framework, and thus are able to adapt different conformations (Chothia and Lesk, J. Mol. Biol. 196:901-917 (1987)). Both terminologies are well recognized in the art.
  • CDR region sequences have also been defined by AbM, Contact and IMGT. Exemplary CDR region sequences are illustrated herein, for example, in the Sequence Listing, and tables provided in the Examples below. The positions of CDRs within a canonical antibody variable region have been determined by comparison of numerous structures (Al-Lazikani etal, J. Mol. Biol. 273:927-948 (1997); Morea et ah, Methods 20:267-279 (2000)).
  • the light chain variable region CDR1 domain is interchangeably referred to herein as LCDR1 or VL CDR1.
  • the light chain variable region CDR2 domain is interchangeably referred to herein as LCDR2 or VL CDR2.
  • the light chain variable region CDR3 domain is interchangeably referred to herein as LCDR3 or VL CDR3.
  • the heavy chain variable region CDR1 domain is interchangeably referred to herein as HCDR1 or VH CDR1.
  • the heavy chain variable region CDR2 domain is interchangeably referred to herein as HCDR2 or VH CDR2.
  • the heavy chain variable region CDR1 domain is interchangeably referred to herein as HCDR3 or VH CDR3.
  • hypervariable region such as a VH or VL
  • VH antibody variable region
  • VL VL
  • hypervariable region delineations are in use and are encompassed herein.
  • Kabat CDRs are based on sequence variability and are the most commonly used (see, e.g., Kabat etal. , Sequences of Proteins of Immunological Interest. 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD.
  • Chothia refers instead to the location of the structural loops (see, e.g., Chothia and Lesk, ./. Mol. Biol. 196:901-917 (1987)).
  • the end of the Chothia CDR-HCDR1 loop when numbered using the Rabat numbering convention varies between H32 and H34 depending on the length of the loop (this is because the Rabat numbering scheme places the insertions at H35A and H35B; if neither 35 A nor 35B is present, the loop ends at 32; if only 35 A is present, the loop ends at 33; if both 35A and 35B are present, the loop ends at 34).
  • the “AbM” hypervariable regions represent a compromise between the Rabat CDRs and Chothia structural loops, and are used by Oxford Molecular’s AbM antibody modeling software (see, e.g, Martin, in Antibody Engineering. Vol. 2, Chapter 3, Springer Verlag). “Contact” hypervariable regions are based on an analysis of the available complex crystal structures.
  • ImMunoGeneTics (IMGT) Information System ® (Lafranc etal. , Dev.
  • IMGT immunoglobulins
  • TR T cell receptors
  • MHC major histocompatibility complex
  • the CDRs are referred to in terms of both the amino acid sequence and the location within the light or heavy chain.
  • location of the CDRs within the structure of the immunoglobulin variable domain is conserved between species and present in structures called loops, by using numbering systems that align variable domain sequences according to structural features, CDR and framework residues and are readily identified.
  • This information can be used in grafting and replacement of CDR residues from immunoglobulins of one species into an acceptor framework from, typically, a human antibody.
  • An additional numbering system (AHon) has been developed by Honegger and Pluckthun, ./. Mol. Biol. 309: 657-670 (2001).
  • the numbering system including, for example, the Rabat numbering and the IMGT unique numbering system, is well known to one skilled in the art (see, e.g., Rabat, supra ; Chothia and Lesk, supra ; Martin, supra ; Lefranc et al. , supra).
  • An Exemplary system shown herein, combines Rabat and Chothia.
  • Hypervariable regions may comprise “extended hypervariable regions” as follows: 24-36 or 24-34 (LCDR1), 46-56 or 50-56 (LCDR2) and 89-97 or 89-96 (LCDR3) in the VL and 26-35 or 26-35A (HCDR1), 50-65 or 49-65 (HCDR2) and 93-102, 94-102, or 95-102 (HCDR3) in the VH.
  • CDR sequences reflecting each of the above numbering schemes, are provided herein, including in the Sequence Listing.
  • constant region refers to a carboxy terminal portion of the light and heavy chain which is not directly involved in binding of the antibody to antigen but exhibits various effector function, such as interaction with the Fc receptor.
  • the terms refer to the portion of an immunoglobulin molecule having a more conserved amino acid sequence relative to the other portion of the immunoglobulin, the variable region, which contains the antigen binding site.
  • the constant region may contain the CHI, CH2 and CH3 regions of the heavy chain and the CL region of the light chain.
  • FR residues are those variable region residues flanking the CDRs. FR residues are present, for example, in chimeric, humanized, human, domain antibodies, diabodies, linear antibodies, and bispecific antibodies. FR residues are those variable domain residues other than the hypervariable region residues or CDR residues.
  • an “isolated antibody” refers to an antibody which is substantially free of other antibodies having different antigenic specificities (e.g ., an isolated antibody that specifically binds to TRGV9 is substantially free of antibodies that do not bind to V ⁇ 9; 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).
  • an isolated antibody is substantially free of other cellular material and/or chemicals.
  • the term “monoclonal antibody” refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that can be present in minor amounts.
  • the monoclonal antibodies of the invention can be made by the hybridoma method, phage display technology, single lymphocyte gene cloning technology, or by recombinant DNA methods.
  • the monoclonal antibodies can be produced by a hybridoma which includes a B cell obtained from a transgenic nonhuman animal, such as a transgenic mouse or rat, having a genome comprising a human heavy chain transgene and a light chain transgene.
  • the term “antigen-binding fragment” refers to an antibody fragment such as, for example, a diabody, a Fab, a Fab’, a F(ab’)2, an Fv fragment, a disulfide stabilized Fv fragment (dsFv), a (dsFv)2, a bispecific dsFv (dsFv-dsFv’), a disulfide stabilized diabody (ds diabody), a single-chain antibody molecule (scFv), a single domain antibody (sdAb) an scFv dimer (bivalent diabody), a multispecific antibody formed from a portion of an antibody comprising one or more CDRs, a camelized single domain antibody, a nanobody, a domain antibody, a bivalent domain antibody, or any other antibody fragment that binds to an antigen but does not comprise a complete antibody structure.
  • an antibody fragment such as, for example, a diabody, a Fab, a
  • an antigen-binding fragment is capable of binding to the same antigen to which the parent antibody or a parent antibody fragment binds.
  • the antigen-binding fragment comprises a light chain variable region, a light chain constant region, and an Fd segment of the heavy chain.
  • the antigen binding fragment comprises Fab and F(ab’).
  • single-chain antibody refers to a conventional single-chain antibody in the field, which comprises a heavy chain variable region and a light chain variable region connected by a short peptide of about 15 to about 20 amino acids.
  • single domain antibody refers to a conventional single domain antibody in the field, which comprises a heavy chain variable region and a heavy chain constant region or which comprises only a heavy chain variable region.
  • human antibody refers to an antibody produced by a human or an antibody having an amino acid sequence corresponding to an antibody produced by a human made using any technique known in the art. This definition of a human antibody includes intact or full-length antibodies, fragments thereof, and/or antibodies comprising at least one human heavy and/or light chain polypeptide.
  • humanized antibody refers to a non-human antibody that is modified to increase the sequence homology to that of a human antibody, such that the antigen-binding properties of the antibody are retained, but its antigenicity in the human body is reduced.
  • chimeric antibody refers to an antibody wherein the amino acid sequence of the immunoglobulin molecule is derived from two or more species.
  • the variable region of both the light and heavy chains often corresponds to the variable region of an antibody derived from one species of mammal (e.g ., mouse, rat, rabbit, etc.) having the desired specificity, affinity, and capability, while the constant regions correspond to the sequences of an antibody derived from another species of mammal (e.g., human) to avoid eliciting an immune response in that species.
  • multispecific antibody refers to an antibody that comprises a plurality of immunoglobulin variable domain sequences, wherein a first immunoglobulin variable domain sequence of the plurality has binding specificity for a first epitope and a second immunoglobulin variable domain sequence of the plurality has binding specificity for a second epitope.
  • the first and second epitopes do not overlap or do not substantially overlap.
  • the first and second epitopes are on different antigens, e.g, the different proteins (or different subunits of a multimeric protein).
  • a multispecific antibody comprises a third, fourth, or fifth immunoglobulin variable domain.
  • a multispecific antibody is a bispecific antibody molecule, a trispecific antibody molecule, or a tetraspecific antibody molecule.
  • bispecific antibody refers to a multispecific antibody that binds no more than two epitopes or two antigens.
  • a bispecific antibody is characterized by a first immunoglobulin variable domain sequence which has binding specificity for a first epitope (e.g, an epitope on a TRGV9 antigen) and a second immunoglobulin variable domain sequence that has binding specificity for a second epitope.
  • the first and second epitopes are on different antigens, e.g, the different proteins (or different subunits of a multimeric protein).
  • a bispecific antibody comprises a heavy chain variable domain sequence and a light chain variable domain sequence which have binding specificity for a first epitope and a heavy chain variable domain sequence and a light chain variable domain sequence which have binding specificity for a second epitope.
  • a bispecific antibody comprises a half antibody, or fragment thereof, having binding specificity for a first epitope and a half antibody, or fragment thereof, having binding specificity for a second epitope.
  • a bispecific antibody comprises a scFv, or fragment thereof, having binding specificity for a first epitope, and a scFv, or fragment thereof, having binding specificity for a second epitope.
  • the first epitope is located on TRGV9 and the second epitope is located on CD123. In an embodiment, the first epitope is located on TRGV9 and the second epitope is located on CD33. In an embodiment, the first epitope is located on TRGV9 and the second epitope is located on TRBC1. In an embodiment, the first epitope is located on TRGV9 and the second epitope is located on BCMA. In an embodiment, the first epitope is located on TRGV9 and the second epitope is located on PSMA.
  • the first epitope is located on TRGV9 and the second epitope is located on PD-1, PD-L1, CTLA-4, EGFR, HER-2, CD 19, CD20, CD3 and/or other cancer associated immune suppressors or surface antigens.
  • half antibody refers to one immunoglobulin heavy chain associated with one immunoglobulin light chain.
  • An exemplary half antibody is depicted in SEQ ID NO: 17.
  • a half-antibody can encompass a fragment thereof and can also have an antigen binding domain consisting of a single variable domain, e.g ., originating from a camelidae.
  • TRGV9 refers to a polypeptide capable of forming a T cell receptor when expressed on the surface of gd T cells.
  • TRGV9- expressing gd T cells are among the first T cells to develop in the human fetus and are the predominant gd T cell subset in healthy adult peripheral blood cells.
  • TRGV9 includes any TRGV9 variant, isoform, and species homolog, which is naturally expressed by cells (including T cells) or can be expressed on cells transfected with genes or cDNA encoding the polypeptide.
  • the TRGV9 is a human TRGV9.
  • An exemplary human TRGV9 amino acid sequence is provided by GenBank Accession Number NG_001336.2.
  • An exemplary human TRGV9 is also provided in FIG. 27A and SEQ ID NO:789.
  • CD123 refers to a molecule that is found on cells which helps transmit the signal of interleukin-3, a soluble cytokine that is important in the immune system. CD123 can also be referred to as the “interleukin-3 receptor.”
  • the receptor belongs to the type I cytokine receptor family and is a heterodimer with a unique alpha chain paired with the common beta subunit (beta c or CD131).
  • the CD123 receptor can be found on pluripotent progenitor cells and can induce tyrosine phosphorylation within the cell and promote proliferation and differentiation within hematopoietic cell lines. CD123 can also be expressed in acute myeloid leukemia (AML) subtypes.
  • AML acute myeloid leukemia
  • CD123 includes any CD123 variant, isoform, and species homolog, which is naturally expressed by cells (including T cells) or can be expressed on cells transfected with genes or cDNA encoding those polypeptides, unless noted, in specific embodiments the “CD123” is a human CD123.
  • a human CD123 amino acid sequence is provided by GenBank Accession Number AY789109.1.
  • CD33 refers to a 67kD single pass transmembrane glycoprotein and is a member of the sialic acid-binding immunoglobulin-like lectins (Siglecs) family. While its exact biological function is unclear, in normal individuals, it is primarily considered to be a myeloid differentiation antigen, with low expression in myeloid progenitors, neutrophils and macrophages while being highly expressed in circulating monocytes and dendritic cells. CD33 has been detected on blasts and leukemic stem cells of 85-90% of patients presenting with in acute myeloid leukemia (AML).
  • AML acute myeloid leukemia
  • CD33 includes any CD33 variant, isoform, and species homolog, which is naturally expressed by cells or can be expressed on cells transfected with genes or cDNA encoding those polypeptides, unless noted, the “CD33” is a human CD33.
  • a human CD33 amino acid sequence is provided by GenBank Accession Number BC028152.1.
  • an antibody that “specifically binds” to a target refers to an antibody that binds to a target with a KD of 1 x 10 -7 M or less, such as 1 x 10 -8 M or less, 5 x 10 -9 M or less, 1 x 10 -9 M or less, 5 x 10 -10 M or less, or 1x110 -10 M or less.
  • the target is a human target.
  • the target can be, e.g.,
  • KD refers to the dissociation constant, which is obtained from the ratio of Kd to Ka (i.e., Kd/Ka) and is expressed as a molar concentration (M).
  • KD values for antibodies can be determined using methods in the art in view of the present disclosure.
  • the KD of an antibody can be determined by using surface plasmon resonance, such as by using a biosensor system, e.g ., a Biacore® system, or by using bio-layer interferometry technology, such as an Octet RED96 system.
  • the smaller the value of the KD of an antibody the higher affinity that the antibody binds to a target antigen.
  • an antibody that binds to TRGV9.
  • the antibody comprises a heavy chain variable (VH) region and a light chain variable (VL) region.
  • the TRGV9 antibody is not a single domain antibody or nanobody. In some embodiments, the TRGV9 antibody is a humanized antibody.
  • a TRGV9 antibody comprising a VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and/or VL CDR3 of any one of the antibodies described herein.
  • a TRGV9 antibody comprising a VH region of any one of the antibodies described herein.
  • a TRGV9 antibody comprising a VL region of any one of the antibodies described herein.
  • a TRGV9 antibody comprising a VH region of any one of the antibodies described herein, and a VL region of any one of the antibodies described herein.
  • a TRGV9 antibody comprising a VH CDR1, VH CDR2, and VH CDR3 of any one of the antibodies described herein. In some embodiments, provided herein is a TRGV9 antibody comprising a VL CDR1, VL CDR2, and VL CDR3 of any one of the antibodies described herein. In some embodiments, provided herein is a TRGV9 antibody comprising a VH CDR1, VH CDR2, and VH CDR3 of any one of the antibodies described herein; and a VL CDR1, VL CDR2, and VL CDR3 of any one of the antibodies described herein.
  • VH and VL amino acid sequences including VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 amino acid sequences, of TRGV9 antibodies provided herein are provided in the Sequence Listing, as well as Tables 1-39.
  • the TRGV9 antibody is a multispecific TRGV9 antibody provided herein. In some embodiments, the multispecific TRGV9 antibody is a bispecific TRGV9 antibody. In one embodiment, the multispecific TRGV9 antibody comprises: (a) a first binding domain that binds to TRGV9, and (b) a second binding domain that binds to a second target that is not TRGV9.
  • the first binding domain that binds to TRGV9 comprises a VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and/or VL CDR3 of any one of the TRGV9 antibodies described herein.
  • the first binding domain that binds to TRGV9 comprises a VH region of any one of the TRGV9 antibodies described herein.
  • the first binding domain that binds to TRGV9 comprises a VL region of any one of the TRGV9 antibodies described herein.
  • the first binding domain that binds to TRGV9 comprises a VH region and a VL region of any one of the TRGV9 antibodies described herein.
  • the first binding domain that binds to TRGV9 comprises a VH CDR1, VH CDR2, and VH CDR3 of any one of the TRGV9 antibodies described herein. In some embodiments, the first binding domain that binds to TRGV9 comprises a VL CDR1, VL CDR2, and VL CDR3 of any one of the TRGV9 antibodies described herein. In some embodiments, the first binding domain that binds to TRGV9 comprises a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of any one of the TRGV9 antibodies described herein.
  • VH and VL amino acid sequences including VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 amino acid sequences, of TRGV9 antibodies provided herein are provided in the Sequence Listing, as well as Tables 1-39.
  • the second target is CD 123.
  • second binding domain that binds CD 123 has a VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and/or VL CDR3 of a CD 123 antibody provided herein.
  • second binding domain that binds CD 123 has a VH region of a CD 123 antibody provided herein.
  • second binding domain that binds CD 123 has a VL region of a CD 123 antibody provided herein.
  • second binding domain that binds CD 123 has a VH region and a VL region of a CD 123 antibody provided herein.
  • second binding domain that binds CD123 has a VH CDR1, VH CDR2, and VH CDR3 of a CD 123 antibody provided herein. In some embodiments, second binding domain that binds CD 123 has a VL CDR1, VL CDR2, and VL
  • second binding domain that binds CD123 has a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of a CD 123 antibody provided herein.
  • the second target is CD33.
  • second binding domain that binds CD33 has a VH region, VL region, VH CDR1,
  • second binding domain that binds CD33 has a VH region of a CD33 antibody provided herein. In some embodiments, second binding domain that binds CD33 has a VL region of a CD33 antibody provided herein. In some embodiments, second binding domain that binds CD33 has a VH region and a VL region of a CD33 antibody provided herein. In some embodiments, second binding domain that binds CD33 has a VH CDR1, VH CDR2, and VH CDR3 of a CD33 antibody provided herein.
  • second binding domain that binds CD33 has a VL CDR1, VL CDR2, and VL CDR3 of a CD33 antibody provided herein. In some embodiments, second binding domain that binds CD33 has a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of a CD33 antibody provided herein.
  • the second target is TRBCl.
  • second binding domain that binds TRBCl has a VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and/or VL CDR3 of a TRBCl antibody provided herein.
  • second binding domain that binds TRBCl has a VH region of a TRBCl antibody provided herein.
  • second binding domain that binds TRBCl has a VL region of a TRBCl antibody provided herein.
  • second binding domain that binds TRBCl has a VH region and a VL region of a TRBCl antibody provided herein.
  • second binding domain that binds TRBCl has a VH CDR1, VH CDR2, and VH CDR3 of a TRBCl antibody provided herein. In some embodiments, second binding domain that binds TRBCl has a VL CDR1, VL CDR2, and VL CDR3 of a TRBCl antibody provided herein. In some embodiments, second binding domain that binds TRBCl has a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of a TRBCl antibody provided herein.
  • the second target is BCMA.
  • second binding domain that binds BCMA has a VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, V CDR2, and/or VL CDR3 of a BCMA antibody provided herein.
  • second binding domain that binds BCMA has a VH region of a BCMA antibody provided herein.
  • second binding domain that binds BCMA has a VL region of a BCMA antibody provided herein.
  • second binding domain that binds BCMA has a VH region and a VL region of a BCMA antibody provided herein.
  • second binding domain that binds BCMA has a VH CDR1, VH CDR2, and VH CDR3 of a BCMA antibody provided herein. In some embodiments, second binding domain that binds BCMA has a VL CDR1, VL CDR2, and VL CDR3 of a BCMA antibody provided herein. In some embodiments, second binding domain that binds BCMA has a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of a BCMA antibody provided herein.
  • the second target is PSMA.
  • second binding domain that binds PSMA has a VH region, VL region, VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and/or VL CDR3 of a PSMA antibody provided herein.
  • second binding domain that binds PSMA has a VH region of a PSMA antibody provided herein.
  • second binding domain that binds PSMA has a VL region of a PSMA antibody provided herein.
  • second binding domain that binds PSMA has a VH region and a VL region of a PSMA antibody provided herein.
  • second binding domain that binds PSMA has a VH CDR1, VH CDR2, and VH CDR3 of a PSMA antibody provided herein. In some embodiments, second binding domain that binds PSMA has a VL CDR1, VL CDR2, and VL CDR3 of a PSMA antibody provided herein. In some embodiments, second binding domain that binds PSMA has a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of a PSMA antibody provided herein.
  • the antibody specifically binds TRGV9.
  • the TRGV9 is present on the surface of a T cell.
  • the TRGV9 antibody is chimeric. In some embodiments, the TRGV9 antibody is human. In some embodiments, the TRGV9 antibody is humanized. In certain embodiments, the TRGV9 antibody is an isolated TRGV9 antibody. In certain embodiments, provided is a TRGV9 antibody that is an intact antibody.
  • the TRGV9 antibody is an IgG antibody. In some embodiments, the TRGV9 antibody is an IgGl 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 comprises a kappa light chain. In some embodiments, the TRGV9 antibody comprises a lambda 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 at least three antigens. In some embodiments, the TRGV9 antibody is capable of binding at least four antigens. In some embodiments, the TRGV9 antibody is capable of binding at least five antigens.
  • 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 quadraspecific antibody.
  • a TRGV9 antibody is an antigen binding fragment of the TRGV9 antibody.
  • the antigen binding fragment of the TRGV9 antibody is a functional fragment.
  • the TRGV9 antigen binding fragment is chimeric.
  • the TRGV9 antigen binding fragment is human.
  • a TRGV9 antigen binding fragment is humanized.
  • a TRGV9 antigen binding fragment is an isolated TRGV9 antigen binding fragment.
  • the antigen binding fragment is a diabody. In some embodiments, the antigen binding fragment is a Fab. In some embodiments, the antigen binding fragment is a Fab’. In some embodiments, the antigen binding fragment is a F(ab’)2. In some embodiments, the antigen binding fragment is a Fv fragment. In some embodiments, the antigen binding fragment is a disulfide stabilized Fv fragment (dsFv). In some embodiments, the antigen binding fragment is a (dsFv)2. In some embodiments, the antigen binding fragment is a bispecific dsFv (dsFv-dsFv’).
  • the antigen binding fragment is a disulfide stabilized diabody (ds diabody). In some embodiments, the antigen binding fragment is a single-chain antibody molecule (scFv). In some embodiments, the antigen binding fragment is a single domain antibody (sdAb). In some embodiments, the antigen binding fragment is an scFv dimer (bivalent diabody). In some embodiments, the antigen binding fragment is a multispecific antibody formed from a portion of an antibody comprising one or more CDRs. In some embodiments, the antigen binding fragment is a camelized single domain antibody. In some embodiments, the antigen binding fragment is a nanobody. In some embodiments, the antigen binding fragment is a domain antibody. In some embodiments, the antigen binding fragment is a bivalent domain antibody. In some embodiments, the antigen binding fragment is an antibody fragment that binds to an antigen but does not comprise a complete antibody structure.
  • the TRGV9 antibody is a multispecific antibody. In other embodiments, the TRGV9 antibody is a bispecific antibody. In certain embodiments, the multispecific antibody comprises an antigen binding fragment of a TRGV9 antibody provided herein. In other embodiments, the bispecific antibody comprises an antigen binding fragment of a TRGV9 antibody provided herein. In some embodiments, the TRGV9 antibody is an agonistic antibody. In certain embodiments, the TRGV9 antibody activates T cells. In other embodiments, the TRGV9 antibody is an antagonistic antibody. In certain embodiments, the TRGV9 antibody inactivates T cells. In some embodiments, the TRGV9 antibody blocks activation of T cells. In some embodiments, the TRGV9 antibody modulates the activity of T cells. In some embodiments, the TRGV9 antibody neither activates or inactivates the activity of gd T cells. In a specific embodiment, the T cells are gd T cells.
  • the gd T cells are human gd T cells.
  • a bispecific antibody comprising a TRGV9 antibody provided herein in a knob-in-hole format.
  • a TRGV9 antibody provided herein may be comprised in a bispecific antibody.
  • a TRGV9 bispecific antibody provided herein may be comprised in a multispecific antibody.
  • a bispecific antibody provided herein comprises a first binding domain comprising a TRGV9 antibody provided herein that binds to a first TRGV9 epitope, and a second binding domain comprising a TRGV9 antibody provided herein that binds to a second TRGV9 epitope, wherein the first TRGV9 epitope and the second TRGV9 epitope are not the same.
  • a TRGV9 antibody, or antigen binding fragment thereof, provided herein specifically binds to TRGV9.
  • a TRGV9 antibody, or antigen binding fragment thereof, provided herein does not bind to an epitope of Vb2.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences are according to the Rabat numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences are according to the Chothia numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences are according to the Exemplary numbering system.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences are according to the Contact numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences are according to the IMGT numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences are according to the AbM numbering system. Exemplary sets of 6 CDRs (VH CDRl-3 and VL CDRl-3) of certain antibody embodiments are provided herein. Other sets of CDRs are contemplated and within the scope of the antibody embodiments provided herein.
  • a TRGV9 antibody provided herein has a VH and VL amino acid sequence of L7A5 1 (TRGV9 1).
  • TRGV9 a TRGV9 antibody, wherein the antibody comprises a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:7.
  • a TRGV9 antibody wherein the antibody comprises a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 8.
  • a TRGV9 antibody wherein the antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:7; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:8.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 1, a VH CDR2 having an amino acid sequence of SEQ ID NO:2, and a VH CDR3 having an amino acid sequence of SEQ ID NO:3; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:4, a VL
  • a TRGV9 antibody wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 160, a VH CDR2 having an amino acid sequence of SEQ ID NO: 161, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 162; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 163, a VL CDR2 having an amino acid sequence of SEQ ID NO: 164, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 165.
  • a TRGV9 antibody wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 166, a VH CDR2 having an amino acid sequence of SEQ ID NO: 167, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 168; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 169, a VL CDR2 having an amino acid sequence of SEQ ID NO: 170, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 171.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 172, a VH CDR2 having an amino acid sequence of SEQ ID NO: 173, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 174; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 175, a VL CDR2 having an amino acid sequence of SEQ ID NO: 176, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 177.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 178, a VH CDR2 having an amino acid sequence of SEQ ID NO: 179, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 180; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 181, a VL CDR2 having an amino acid sequence of SEQ ID NO: 182, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 183.
  • a TRGV9 antibody wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 178, a VH CDR2 having an amino acid sequence of SEQ ID NO:700, and a VH CDR3 having an amino acid sequence of SEQ ID NO:701; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 181, a VL CDR2 having an amino acid sequence of SEQ ID NO: 182, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 183.
  • a TRGV9 antibody wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 184, a VH CDR2 having an amino acid sequence of SEQ ID NO: 185, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 186; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 187, a VL CDR2 having an amino acid sequence of SEQ ID NO: 188, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 189.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 190, a VH CDR2 having an amino acid sequence of SEQ ID NO: 191, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 192; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 193, a VL CDR2 having an amino acid sequence of SEQ ID NO: 194, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 195.
  • the antibody comprises a VH having an amino acid sequence of SEQ ID NO:7.
  • the antibody comprises a VL having an amino acid sequence of SEQ ID NO:8. In some embodiments, the antibody comprises a VH having an amino acid sequence of SEQ ID NO: 7, and a VL having an amino acid sequence of SEQ ID NO:8. In some embodiments, the antibody comprises a heavy chain having an amino acid sequence of SEQ ID NO:23. In some embodiments, the antibody comprises a light chain having an amino acid sequence of SEQ ID NO:24. In some embodiments, the antibody comprises a heavy chain having an amino acid sequence of SEQ ID NO:23, and a light chain having an amino acid sequence of SEQ ID NO:24. In some embodiments, the antibody comprises an amino acid sequence of SEQ ID NO: 17.
  • the antibody comprises a heavy chain having an amino acid sequence of SEQ ID NO:69. In some embodiments, the antibody comprises a light chain having an amino acid sequence of SEQ ID NO:24. In some embodiments, the antibody comprises a heavy chain having an amino acid sequence of SEQ ID NO: 69, and a light chain having an amino acid sequence of SEQ ID NO:24. In some embodiments, the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:7. In some embodiments, the antibody comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8. In some embodiments, the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:
  • the antibody comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:23. In some embodiments, the antibody comprises a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:24. In some embodiments, the antibody comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:23, and a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:24.
  • the antibody comprises an amino acid sequence of SEQ ID NO: 17. In some embodiments, the antibody comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:69. In some embodiments, the antibody comprises a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:24. In some embodiments, the antibody comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 69, and a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 24.
  • a TRGV9 antibody provided herein has a VH and VL amino acid sequence of TRGV9Ab_2 (L7A5 2).
  • a TRGV9 antibody wherein the antibody comprises a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of the VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO:34.
  • a TRGV9 antibody wherein the antibody comprises a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of the VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 8.
  • a TRGV9 antibody wherein the antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of the VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO:34; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of the VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO:8.
  • a TRGV9 antibody wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ
  • VH CDR2 having an amino acid sequence of SEQ ID NO:2
  • VH CDR3 having an amino acid sequence of SEQ ID NO:31
  • VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:4, a VL CDR2 having an amino acid sequence of SEQ ID NO:5, and a VL CDR3 having an amino acid sequence of SEQ ID NO:6.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 196, a VH CDR2 having an amino acid sequence of SEQ ID NO: 197, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 198; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 199, a VL CDR2 having an amino acid sequence of SEQ ID NO:200, and a VL CDR3 having an amino acid sequence of SEQ ID NO:201.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:202, a VH CDR2 having an amino acid sequence of SEQ ID NO:203, and a VH CDR3 having an amino acid sequence of SEQ ID NO:204; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:205, a VL CDR2 having an amino acid sequence of SEQ ID NO:206, and a VL CDR3 having an amino acid sequence of SEQ ID NO:207.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:208, a VH CDR2 having an amino acid sequence of SEQ ID NO:209, and a VH CDR3 having an amino acid sequence of SEQ ID NO:210; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:211, a VL CDR2 having an amino acid sequence of SEQ ID NO:212, and a VL CDR3 having an amino acid sequence of SEQ ID NO:213.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:214, a VH CDR2 having an amino acid sequence of SEQ ID NO:215, and a VH CDR3 having an amino acid sequence of SEQ ID NO:216; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:217, a VL CDR2 having an amino acid sequence of SEQ ID NO:218, and a VL CDR3 having an amino acid sequence of SEQ ID NO:219.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:214, a VH CDR2 having an amino acid sequence of SEQ ID NO:702, and a VH CDR3 having an amino acid sequence of SEQ ID NO:703; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:217, a VL CDR2 having an amino acid sequence of SEQ ID NO:218, and a VL CDR3 having an amino acid sequence of SEQ ID NO:219.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:220, a VH CDR2 having an amino acid sequence of SEQ ID NO:221, and a VH CDR3 having an amino acid sequence of SEQ ID NO:222; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:223, a VL CDR2 having an amino acid sequence of SEQ ID NO:224, and a VL CDR3 having an amino acid sequence of SEQ ID NO:225.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:226, a VH CDR2 having an amino acid sequence of SEQ ID NO:227, and a VH CDR3 having an amino acid sequence of SEQ ID NO:228; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:229, a VL CDR2 having an amino acid sequence of SEQ ID NO:230, and a VL CDR3 having an amino acid sequence of SEQ ID NO:231.
  • the antibody comprises a VH having an amino acid sequence of SEQ ID NO:34.
  • the antibody comprises a VL having an amino acid sequence of SEQ ID NO:8. In some embodiments, the antibody comprises a VH having an amino acid sequence of SEQ ID NO:34, and a VL having an amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:34. In some embodiments, the antibody comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8.
  • the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:34, and a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 8.
  • a TRGV9 antibody provided herein has a VH and VL amino acid sequence of TRGV9Ab_3 (L7A5 3).
  • the antibody comprises a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of the VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO:35.
  • a TRGV9 antibody wherein the antibody comprises a VL comprising a VL
  • a TRGV9 antibody wherein the antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of the VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO:35; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of the VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO:8.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 1, a VH CDR2 having an amino acid sequence of SEQ ID NO:2, and a VH CDR3 having an amino acid sequence of SEQ ID NO:32; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:4, a VL CDR2 having an amino acid sequence of SEQ ID NO:5, and a VL CDR3 having an amino acid sequence of SEQ ID NO:6.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:232, a VH CDR2 having an amino acid sequence of SEQ ID NO:233, and a VH CDR3 having an amino acid sequence of SEQ ID NO:234; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:235, a VL CDR2 having an amino acid sequence of SEQ ID NO:236, and a VL CDR3 having an amino acid sequence of SEQ ID NO:237.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:238, a VH CDR2 having an amino acid sequence of SEQ ID NO:239, and a VH CDR3 having an amino acid sequence of SEQ ID NO:240; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:241, a VL CDR2 having an amino acid sequence of SEQ ID NO:242, and a VL CDR3 having an amino acid sequence of SEQ ID NO:243.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:244, a VH CDR2 having an amino acid sequence of SEQ ID NO:245, and a VH CDR3 having an amino acid sequence of SEQ ID NO:246; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:247, a VL CDR2 having an amino acid sequence of SEQ ID NO:248, and a VL CDR3 having an amino acid sequence of SEQ ID NO:249.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:250, a VH CDR2 having an amino acid sequence of SEQ ID NO:251, and a VH CDR3 having an amino acid sequence of SEQ ID NO:252; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:253, a VL CDR2 having an amino acid sequence of SEQ ID NO:254, and a VL CDR3 having an amino acid sequence of SEQ ID NO:255.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:250, a VH CDR2 having an amino acid sequence of SEQ ID NO:704, and a VH CDR3 having an amino acid sequence of SEQ ID NO:705; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:253, a VL CDR2 having an amino acid sequence of SEQ ID NO:254, and a VL CDR3 having an amino acid sequence of SEQ ID NO:255.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:256, a VH CDR2 having an amino acid sequence of SEQ ID NO:257, and a VH CDR3 having an amino acid sequence of SEQ ID NO:258; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:259, a VL CDR2 having an amino acid sequence of SEQ ID NO:260, and a VL CDR3 having an amino acid sequence of SEQ ID NO:261.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:262, a VH CDR2 having an amino acid sequence of SEQ ID NO:263, and a VH CDR3 having an amino acid sequence of SEQ ID NO:264; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:265, a VL CDR2 having an amino acid sequence of SEQ ID NO:266, and a VL CDR3 having an amino acid sequence of SEQ ID NO:267.
  • the antibody comprises a VH having an amino acid sequence of SEQ ID NO:35.
  • the antibody comprises a VL having an amino acid sequence of SEQ ID NO:8. In some embodiments, the antibody comprises a VH having an amino acid sequence of SEQ ID NO:35, and a VL having an amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:35. In some embodiments, the antibody comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8.
  • the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:35, and a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 8.
  • a TRGV9 antibody provided herein has a VH and VL amino acid sequence of TRGV9Ab_4 (L7A5 4).
  • a TRGV9 antibody wherein the antibody comprises a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of the VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO:36.
  • a TRGV9 antibody wherein the antibody comprises a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of the VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 8.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of the VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 36; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of the VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO:8.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 1, a VH CDR2 having an amino acid sequence of SEQ ID NO:2, and a VH CDR3 having an amino acid sequence of SEQ ID NO:33; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:4, a VL CDR2 having an amino acid sequence of SEQ ID NO:5, and a VL CDR3 having an amino acid sequence of SEQ ID NO:6.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:268, a VH CDR2 having an amino acid sequence of SEQ ID NO:269, and a VH CDR3 having an amino acid sequence of SEQ ID NO:270; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:271, a VL CDR2 having an amino acid sequence of SEQ ID NO:272, and a VL CDR3 having an amino acid sequence of SEQ ID NO:273.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:274, a VH CDR2 having an amino acid sequence of SEQ ID NO:275, and a VH CDR3 having an amino acid sequence of SEQ ID NO:276; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:277, a VL CDR2 having an amino acid sequence of SEQ ID NO:278, and a VL CDR3 having an amino acid sequence of SEQ ID NO:279.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:280, a VH CDR2 having an amino acid sequence of SEQ ID NO:281, and a VH CDR3 having an amino acid sequence of SEQ ID NO:282; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:283, a VL CDR2 having an amino acid sequence of SEQ ID NO:284, and a VL CDR3 having an amino acid sequence of SEQ ID NO:285.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:286, a VH CDR2 having an amino acid sequence of SEQ ID NO:287, and a VH CDR3 having an amino acid sequence of SEQ ID NO:288; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:289, a VL CDR2 having an amino acid sequence of SEQ ID NO:290, and a VL CDR3 having an amino acid sequence of SEQ ID NO:291.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:286, a VH CDR2 having an amino acid sequence of SEQ ID NO:706, and a VH CDR3 having an amino acid sequence of SEQ ID NO:707; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:289, a VL CDR2 having an amino acid sequence of SEQ ID NO:290, and a VL CDR3 having an amino acid sequence of SEQ ID NO:291.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:292, a VH CDR2 having an amino acid sequence of SEQ ID NO:293, and a VH CDR3 having an amino acid sequence of SEQ ID NO:294; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:295, a VL CDR2 having an amino acid sequence of SEQ ID NO:296, and a VL CDR3 having an amino acid sequence of SEQ ID NO:297.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:298, a VH CDR2 having an amino acid sequence of SEQ ID NO:299, and a VH CDR3 having an amino acid sequence of SEQ ID NO:300; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:301, a VL CDR2 having an amino acid sequence of SEQ ID NO: 302, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 303.
  • the antibody comprises a VH having an amino acid sequence of SEQ ID NO:36.
  • the antibody comprises a VL having an amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody comprises a VH having an amino acid sequence of SEQ ID NO:36, and a VL having an amino acid sequence of SEQ ID NO: 8. In some embodiments, the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:36. In some embodiments, the antibody comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 8.
  • the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:36, and a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 8.
  • a TRGV9 antibody provided herein has a VH and VL amino acid sequence of TRGV9Ab_varl7.
  • a TRGV9 antibody provided herein has a VH and VL amino acid sequence of TRGV9Ab_var29.
  • a TRGV9 antibody wherein the antibody comprises a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of the VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 65.
  • a TRGV9 antibody wherein the antibody comprises a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of the VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO:66.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of the VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO:65; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of the VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO:66.
  • a TRGV9 antibody wherein the antibody comprises a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of the VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO:67.
  • a TRGV9 antibody wherein the antibody comprises a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of the VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 68.
  • a TRGV9 antibody wherein the antibody comprises: (i) a VH comprising a
  • VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of the VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 67; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of the VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 68.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 1, a VH CDR2 having an amino acid sequence of SEQ ID NO:76, and a VH CDR3 having an amino acid sequence of SEQ ID NO:3; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:77, a VL CDR2 having an amino acid sequence of SEQ ID NO:5, and a VL CDR3 having an amino acid sequence of SEQ ID NO:6.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 60, a VH CDR2 having an amino acid sequence of SEQ ID NO:61, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 62; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:63, a VL CDR2 having an amino acid sequence of SEQ ID NO:64, and a VL CDR3 having an amino acid sequence of SEQ ID NO:6.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 304, a VH CDR2 having an amino acid sequence of SEQ ID NO:305, and a VH CDR3 having an amino acid sequence of SEQ ID NO:306; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 307, a VL CDR2 having an amino acid sequence of SEQ ID NO: 308, and a VL CDR3 having an amino acid sequence of SEQ ID NO:309.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 310, a VH CDR2 having an amino acid sequence of SEQ ID NO: 311, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 312; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 313, a VL CDR2 having an amino acid sequence of SEQ ID NO: 314, and a VL CDR3 having an amino acid sequence of SEQ ID NO:315.
  • a TRGV9 antibody wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:316, a VH CDR2 having an amino acid sequence of SEQ ID NO: 317, and a VH CDR3 having an amino acid sequence of SEQ ID NO:318; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 319, a VL CDR2 having an amino acid sequence of SEQ ID NO:320, and a VL CDR3 having an amino acid sequence of SEQ ID NO:321.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:322, a VH CDR2 having an amino acid sequence of SEQ ID NO:323, and a VH CDR3 having an amino acid sequence of SEQ ID NO:324; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:325, a VL CDR2 having an amino acid sequence of SEQ ID NO:326, and a VL CDR3 having an amino acid sequence of SEQ ID NO:327.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:322, a VH CDR2 having an amino acid sequence of SEQ ID NO:708, and a VH CDR3 having an amino acid sequence of SEQ ID NO:709; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:325, a VL CDR2 having an amino acid sequence of SEQ ID NO:326, and a VL CDR3 having an amino acid sequence of SEQ ID NO:327.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:328, a VH CDR2 having an amino acid sequence of SEQ ID NO:329, and a VH CDR3 having an amino acid sequence of SEQ ID NO:330; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:331, a VL CDR2 having an amino acid sequence of SEQ ID NO:332, and a VL CDR3 having an amino acid sequence of SEQ ID NO:333.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:334, a VH CDR2 having an amino acid sequence of SEQ ID NO:335, and a VH CDR3 having an amino acid sequence of SEQ ID NO:336; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:337, a VL CDR2 having an amino acid sequence of SEQ ID NO:338, and a VL CDR3 having an amino acid sequence of SEQ ID NO:339.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:340, a VH CDR2 having an amino acid sequence of SEQ ID NO:341, and a VH CDR3 having an amino acid sequence of SEQ ID NO:342; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:343, a VL CDR2 having an amino acid sequence of SEQ
  • a TRGV9 antibody wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:346, a VH CDR2 having an amino acid sequence of SEQ ID NO:347, and a VH CDR3 having an amino acid sequence of SEQ ID NO:348; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:349, a VL CDR2 having an amino acid sequence of SEQ ID NO:350, and a VL CDR3 having an amino acid sequence of SEQ ID NO:351.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 352, a VH CDR2 having an amino acid sequence of SEQ ID NO:353, and a VH CDR3 having an amino acid sequence of SEQ ID NO:354; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:355, a VL CDR2 having an amino acid sequence of SEQ ID NO:356, and a VL CDR3 having an amino acid sequence of SEQ ID NO:357.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:358, a VH CDR2 having an amino acid sequence of SEQ ID NO:359, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 360; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:361, a VL CDR2 having an amino acid sequence of SEQ ID NO: 362, and a VL CDR3 having an amino acid sequence of SEQ ID NO:363.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:358, a VH CDR2 having an amino acid sequence of SEQ ID NO:710, and a VH CDR3 having an amino acid sequence of SEQ ID NO:711; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:361, a VL CDR2 having an amino acid sequence of SEQ ID NO: 362, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 363.
  • a TRGV9 antibody wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:364, a VH CDR2 having an amino acid sequence of SEQ ID NO:365, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 366; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:367, a VL CDR2 having an amino acid sequence of SEQ ID NO: 368, and a VL CDR3 having an amino acid sequence of SEQ ID NO:369.
  • a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:364, a VH CDR2 having an amino acid sequence of SEQ ID NO:365, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 366
  • the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:370, a VH CDR2 having an amino acid sequence of SEQ ID NO:371, and a VH CDR3 having an amino acid sequence of SEQ ID NO:372; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 373, a VL CDR2 having an amino acid sequence of SEQ ID NO: 374, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 375.
  • the antibody comprises a VH having an amino acid sequence of SEQ ID NO:65.
  • the antibody comprises a VL having an amino acid sequence of SEQ ID NO:66. In some embodiments, the antibody comprises a VH having an amino acid sequence of SEQ ID NO:65, and a VL having an amino acid sequence of SEQ ID NO:66. In some embodiments, the antibody comprises a VH having an amino acid sequence of SEQ ID NO:67. In some embodiments, the antibody comprises a VL having an amino acid sequence of SEQ ID NO:68. In some embodiments, the antibody comprises a VH having an amino acid sequence of SEQ ID NO: 67, and a VL having an amino acid sequence of SEQ ID NO:68. In some embodiments, the antibody comprises a heavy chain having an amino acid sequence of SEQ ID NO:71.
  • the antibody comprises a light chain having an amino acid sequence of SEQ ID NO:72. In some embodiments, the antibody comprises a heavy chain having an amino acid sequence of SEQ ID NO:71, and a light chain having an amino acid sequence of SEQ ID NO:72. In some embodiments, the antibody comprises an amino acid sequence of SEQ ID NO:70. In some embodiments, the antibody comprises a heavy chain having an amino acid sequence of SEQ ID NO:74. In some embodiments, the antibody comprises a light chain having an amino acid sequence of SEQ ID NO:75. In some embodiments, the antibody comprises a heavy chain having an amino acid sequence of SEQ ID NO: 74, and a light chain having an amino acid sequence of SEQ ID NO:75.
  • the antibody comprises an amino acid sequence of SEQ ID NO:73. In some embodiments, the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:65. In some embodiments, the antibody comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:66. In some embodiments, the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:65, and a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:66.
  • the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:67. In some embodiments, the antibody comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:68. In some embodiments, the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:67, and a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 68. In some embodiments, the antibody comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:71.
  • the antibody comprises a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:72. In some embodiments, the antibody comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:71, and a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:72. In some embodiments, the antibody comprises an amino acid sequence of SEQ ID NO:70. In some embodiments, the antibody comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:74.
  • the antibody comprises a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:75. In some embodiments, the antibody comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:74, and a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 75. In some embodiments, the antibody comprises an amino acid sequence of SEQ ID NO:73.
  • a TRGV9 antibody provided herein has a VH and VL amino acid sequence of VG3 B3 RN.
  • a TRGV9 antibody wherein the antibody comprises a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of the VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO:95.
  • a TRGV9 antibody wherein the antibody comprises a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of the VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO:96.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of the VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 95; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of the VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO:96.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 89, a VH CDR2 having an amino acid sequence of SEQ ID NO: 90, and a VH CDR3 having an amino acid sequence of SEQ ID NO:91; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:92, a VL CDR2 having an amino acid sequence of SEQ ID NO: 93, and a VL CDR3 having an amino acid sequence of SEQ ID NO:94.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:376, a VH CDR2 having an amino acid sequence of SEQ ID NO:377, and a VH CDR3 having an amino acid sequence of SEQ ID NO:378; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:379, a VL CDR2 having an amino acid sequence of SEQ ID NO: 380, and a VL CDR3 having an amino acid sequence of SEQ ID NO:381.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 382, a VH CDR2 having an amino acid sequence of SEQ ID NO: 383, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 384; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 385, a VL CDR2 having an amino acid sequence of SEQ ID NO: 386, and a VL CDR3 having an amino acid sequence of SEQ ID NO:387.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:388, a VH CDR2 having an amino acid sequence of SEQ ID NO: 389, and a VH CDR3 having an amino acid sequence of SEQ ID NO:390; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:391, a VL CDR2 having an amino acid sequence of SEQ ID NO: 392, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 393.
  • a TRGV9 antibody wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:394, a VH CDR2 having an amino acid sequence of SEQ ID NO:395, and a
  • VH CDR3 having an amino acid sequence of SEQ ID NO: 396; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:397, a VL CDR2 having an amino acid sequence of SEQ ID NO: 398, and a VL CDR3 having an amino acid sequence of SEQ ID NO:399.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 394, a VH CDR2 having an amino acid sequence of SEQ ID NO:712, and a VH CDR3 having an amino acid sequence of SEQ ID NO:713; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 397, a VL CDR2 having an amino acid sequence of SEQ ID NO:398, and a VL CDR3 having an amino acid sequence of SEQ ID NO:399.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:400, a VH CDR2 having an amino acid sequence of SEQ ID NO:401, and a VH CDR3 having an amino acid sequence of SEQ ID NO:402; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:403, a VL CDR2 having an amino acid sequence of SEQ ID NO:404, and a VL CDR3 having an amino acid sequence of SEQ ID NO:405.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:406, a VH CDR2 having an amino acid sequence of SEQ ID NO:407, and a VH CDR3 having an amino acid sequence of SEQ ID NO:408; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:409, a VL CDR2 having an amino acid sequence of SEQ ID NO:410, and a VL CDR3 having an amino acid sequence of SEQ ID NO:411.
  • the antibody comprises a VH having an amino acid sequence of SEQ ID NO:95.
  • the antibody comprises a VL having an amino acid sequence of SEQ ID NO:96. In some embodiments, the antibody comprises a VH having an amino acid sequence of SEQ ID NO:95, and a VL having an amino acid sequence of SEQ ID NO:96. In some embodiments, the antibody comprises an amino acid sequence of SEQ ID NO:97. In some embodiments, the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 95. In some embodiments, the antibody comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:96.
  • the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:95, and a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:96. In some embodiments, the antibody comprises an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:97.
  • a TRGV9 antibody provided herein has a VH and VL amino acid sequence of VG9B420.
  • a TRGV9 antibody wherein the antibody comprises a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of the VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 104.
  • a TRGV9 antibody wherein the antibody comprises a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of the VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 105.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of the VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 104; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of the VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 105.
  • a TRGV9 antibody wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 98, a VH CDR2 having an amino acid sequence of SEQ ID NO: 99, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 100; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 101, a VL CDR2 having an amino acid sequence of SEQ ID NO: 102, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 103.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:412, a VH CDR2 having an amino acid sequence of SEQ ID NO:413, and a VH CDR3 having an amino acid sequence of SEQ ID NO:414; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:415, a VL CDR2 having an amino acid sequence of SEQ ID NO:416, and a VL CDR3 having an amino acid sequence of SEQ ID NO:417.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:418, a VH CDR2 having an amino acid sequence of SEQ ID NO:419, and a VH CDR3 having an amino acid sequence of SEQ ID NO:420; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:421, a VL CDR2 having an amino acid sequence of SEQ ID NO:422, and a VL CDR3 having an amino acid sequence of SEQ ID NO:423.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:424, a VH CDR2 having an amino acid sequence of SEQ ID NO:425, and a VH CDR3 having an amino acid sequence of SEQ ID NO:426; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:427, a VL CDR2 having an amino acid sequence of SEQ ID NO:428, and a VL CDR3 having an amino acid sequence of SEQ ID NO:429.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:430, a VH CDR2 having an amino acid sequence of SEQ ID NO:431, and a VH CDR3 having an amino acid sequence of SEQ ID NO:432; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:433, a VL CDR2 having an amino acid sequence of SEQ ID NO:434, and a VL CDR3 having an amino acid sequence of SEQ ID NO:435.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:430, a VH CDR2 having an amino acid sequence of SEQ ID NO:714, and a VH CDR3 having an amino acid sequence of SEQ ID NO:715; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:433, a VL CDR2 having an amino acid sequence of SEQ ID NO:434, and a VL CDR3 having an amino acid sequence of SEQ ID NO:435.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:436, a VH CDR2 having an amino acid sequence of SEQ ID NO:437, and a VH CDR3 having an amino acid sequence of SEQ ID NO:438; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:439, a VL CDR2 having an amino acid sequence of SEQ ID NO:440, and a VL CDR3 having an amino acid sequence of SEQ ID NO:441.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:442, a VH CDR2 having an amino acid sequence of SEQ ID NO:443, and a VH CDR3 having an amino acid sequence of SEQ ID NO:444; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:445, a VL CDR2 having an amino acid sequence of SEQ
  • the antibody comprises a VH having an amino acid sequence of SEQ ID NO: 104. In some embodiments, the antibody comprises a VL having an amino acid sequence of SEQ ID NO: 105. In some embodiments, the antibody comprises a VH having an amino acid sequence of SEQ ID NO: 104, and a VL having an amino acid sequence of SEQ ID NO: 105. In some embodiments, the antibody comprises an amino acid sequence of SEQ ID NO: 106. In some embodiments, the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 104.
  • the antibody comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 105. In some embodiments, the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 104, and a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 105. In some embodiments, the antibody comprises an amino acid sequence of SEQ ID NO: 106.
  • a TRGV9 antibody provided herein has a VH and VL amino acid sequence of VG9SB10SC1087 P18 D08.
  • a TRGV9 antibody wherein the antibody comprises a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of the VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 113.
  • a TRGV9 antibody wherein the antibody comprises a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of the VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 114.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of the VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 113; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of the VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 114.
  • a TRGV9 antibody wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 107, a VH CDR2 having an amino acid sequence of SEQ ID NO: 108, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 109; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:
  • a TRGV9 antibody wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:448, a VH CDR2 having an amino acid sequence of SEQ ID NO:449, and a VH CDR3 having an amino acid sequence of SEQ ID NO:450; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:451, a VL CDR2 having an amino acid sequence of SEQ ID NO:452, and a VL CDR3 having an amino acid sequence of SEQ ID NO:453.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:454, a VH CDR2 having an amino acid sequence of SEQ ID NO:455, and a VH CDR3 having an amino acid sequence of SEQ ID NO:456; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:457, a VL CDR2 having an amino acid sequence of SEQ ID NO:458, and a VL CDR3 having an amino acid sequence of SEQ ID NO:459.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:460, a VH CDR2 having an amino acid sequence of SEQ ID NO:461, and a VH CDR3 having an amino acid sequence of SEQ ID NO:462; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:463, a VL CDR2 having an amino acid sequence of SEQ ID NO:464, and a VL CDR3 having an amino acid sequence of SEQ ID NO:465.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:466, a VH CDR2 having an amino acid sequence of SEQ ID NO:467, and a VH CDR3 having an amino acid sequence of SEQ ID NO:468; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:469, a VL CDR2 having an amino acid sequence of SEQ ID NO:470, and a VL CDR3 having an amino acid sequence of SEQ ID NO:471.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:466, a VH CDR2 having an amino acid sequence of SEQ ID NO:716, and a VH CDR3 having an amino acid sequence of SEQ ID NO:717; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:469, a VL CDR2 having an amino acid sequence of SEQ ID NO:470, and a VL CDR3 having an amino acid sequence of SEQ ID NO:471.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:472, a VH CDR2 having an amino acid sequence of SEQ ID NO:473, and a VH CDR3 having an amino acid sequence of SEQ ID NO:474; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:475, a VL CDR2 having an amino acid sequence of SEQ ID NO:476, and a VL CDR3 having an amino acid sequence of SEQ ID NO:477.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:478, a VH CDR2 having an amino acid sequence of SEQ ID NO:479, and a VH CDR3 having an amino acid sequence of SEQ ID NO:480; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:481, a VL CDR2 having an amino acid sequence of SEQ ID NO:482, and a VL CDR3 having an amino acid sequence of SEQ ID NO:483.
  • the antibody comprises a VH having an amino acid sequence of SEQ ID NO:l 13.
  • the antibody comprises a VL having an amino acid sequence of SEQ ID NO:l 14. In some embodiments, the antibody comprises a VH having an amino acid sequence of SEQ ID NO: 113, and a VL having an amino acid sequence of SEQ ID NO:l 14. In some embodiments, the antibody comprises a heavy chain having an amino acid sequence of SEQ ID NO:l 15. In some embodiments, the antibody comprises a light chain having an amino acid sequence of SEQ ID NO: 116. In some embodiments, the antibody comprises a heavy chain having an amino acid sequence of SEQ ID NO: 115, and a light chain having an amino acid sequence of SEQ ID NO: 116.
  • the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 113. In some embodiments, the antibody comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 114. In some embodiments, the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 113, and a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 114. In some embodiments, the antibody comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 115. In some embodiments, the antibody comprises a light chain comprising an amino acid sequence having at least
  • the antibody comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 115, and a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 116.
  • a TRGV9 antibody provided herein has a VH and VL amino acid sequence of VG9SB10SC1087 P18 C12.
  • a TRGV9 antibody wherein the antibody comprises a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of the VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 123.
  • a TRGV9 antibody wherein the antibody comprises a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of the VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 124.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of the VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 123; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of the VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 124.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 117, a VH CDR2 having an amino acid sequence of SEQ ID NO: 118, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 119; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 120, a VL CDR2 having an amino acid sequence of SEQ ID NO: 121, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 122.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:484, a VH CDR2 having an amino acid sequence of SEQ ID NO:485, and a VH CDR3 having an amino acid sequence of SEQ ID NO:486; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:487, a VL CDR2 having an amino acid sequence of SEQ ID NO:488, and a VL CDR3 having an amino acid sequence of SEQ ID NO:489.
  • a TRGV9 antibody wherein the antibody comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:490, a VH CDR2 having an amino acid sequence of
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:496, a VH CDR2 having an amino acid sequence of SEQ ID NO:497, and a VH CDR3 having an amino acid sequence of SEQ ID NO:498; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:499, a VL CDR2 having an amino acid sequence of SEQ ID NO:500, and a VL CDR3 having an amino acid sequence of SEQ ID NO:501.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:502, a VH CDR2 having an amino acid sequence of SEQ ID NO:503, and a VH CDR3 having an amino acid sequence of SEQ ID NO:504; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:505, a VL CDR2 having an amino acid sequence of SEQ ID NO:506, and a VL CDR3 having an amino acid sequence of SEQ ID NO:507.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:502, a VH CDR2 having an amino acid sequence of SEQ ID NO:718, and a VH CDR3 having an amino acid sequence of SEQ ID NO:719; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:505, a VL CDR2 having an amino acid sequence of SEQ ID NO:506, and a VL CDR3 having an amino acid sequence of SEQ ID NO:507.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:508, a VH CDR2 having an amino acid sequence of SEQ ID NO:509, and a VH CDR3 having an amino acid sequence of SEQ ID NO:510; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:511, a VL CDR2 having an amino acid sequence of SEQ ID NO: 512, and a VL CDR3 having an amino acid sequence of SEQ ID NO:513.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:514, a VH CDR2 having an amino acid sequence of SEQ ID NO:515, and a VH CDR3 having an amino acid sequence of SEQ ID NO:516; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:517, a VL CDR2 having an amino acid sequence of SEQ ID NO: 518, and a VL CDR3 having an amino acid sequence of SEQ ID NO:519.
  • the antibody comprises a VH having an amino acid sequence of SEQ ID NO: 123.
  • the antibody comprises a VL having an amino acid sequence of SEQ ID NO: 124. In some embodiments, the antibody comprises a VH having an amino acid sequence of SEQ ID NO: 123, and a VL having an amino acid sequence of SEQ ID NO: 124. In some embodiments, the antibody comprises a heavy chain having an amino acid sequence of SEQ ID NO: 125. In some embodiments, the antibody comprises a light chain having an amino acid sequence of SEQ ID NO: 126. In some embodiments, the antibody comprises a heavy chain having an amino acid sequence of SEQ ID NO: 125, and a light chain having an amino acid sequence of SEQ ID NO: 126.
  • the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 123. In some embodiments, the antibody comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 124. In some embodiments, the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 123, and a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 124. In some embodiments, the antibody comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 125.
  • the antibody comprises a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 126. In some embodiments, the antibody comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 125, and a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 126.
  • a TRGV9 antibody provided herein has a VH and VL amino acid sequence of VG9SB10SC1087 P19 C03.
  • a TRGV9 antibody wherein the antibody comprises a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of the VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 133.
  • a TRGV9 antibody wherein the antibody comprises a VL comprising a VL
  • a TRGV9 antibody wherein the antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of the VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 133; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of the VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 134.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 127, a VH CDR2 having an amino acid sequence of SEQ ID NO: 128, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 129; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 130, a VL CDR2 having an amino acid sequence of SEQ ID NO: 131, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 132.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:520, a VH CDR2 having an amino acid sequence of SEQ ID NO: 521, and a VH CDR3 having an amino acid sequence of SEQ ID NO:522; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 523, a VL CDR2 having an amino acid sequence of SEQ ID NO: 524, and a VL CDR3 having an amino acid sequence of SEQ ID NO:525.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 526, a VH CDR2 having an amino acid sequence of SEQ ID NO: 527, and a VH CDR3 having an amino acid sequence of SEQ ID NO:528; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:529, a VL CDR2 having an amino acid sequence of SEQ ID NO:530, and a VL CDR3 having an amino acid sequence of SEQ ID NO:531.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:532, a VH CDR2 having an amino acid sequence of SEQ ID NO:533, and a VH CDR3 having an amino acid sequence of SEQ ID NO:534; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:535, a VL CDR2 having an amino acid sequence of SEQ ID NO:536, and a VL CDR3 having an amino acid sequence of SEQ ID NO:537.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:538, a VH CDR2 having an amino acid sequence of SEQ ID NO:539, and a VH CDR3 having an amino acid sequence of SEQ ID NO:540; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 541, a VL CDR2 having an amino acid sequence of SEQ ID NO: 542, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 543.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:538, a VH CDR2 having an amino acid sequence of SEQ ID NO:720, and a VH CDR3 having an amino acid sequence of SEQ ID NO:721; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:541, a VL CDR2 having an amino acid sequence of SEQ ID NO: 542, and a VL CDR3 having an amino acid sequence of SEQ ID NO:543.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 544, a VH CDR2 having an amino acid sequence of SEQ ID NO:545, and a VH CDR3 having an amino acid sequence of SEQ ID NO:546; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 547, a VL CDR2 having an amino acid sequence of SEQ ID NO:548, and a VL CDR3 having an amino acid sequence of SEQ ID NO:549.
  • a TRGV9 antibody comprising: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:550, a VH CDR2 having an amino acid sequence of SEQ ID NO:551, and a VH CDR3 having an amino acid sequence of SEQ ID NO:552; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:553, a VL CDR2 having an amino acid sequence of SEQ ID NO: 554, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 555.
  • the antibody comprises a VH having an amino acid sequence of SEQ ID NO: 133.
  • the antibody comprises a VL having an amino acid sequence of SEQ ID NO: 134. In some embodiments, the antibody comprises a VH having an amino acid sequence of SEQ ID NO: 133, and a VL having an amino acid sequence of SEQ ID NO: 134. In some embodiments, the antibody comprises a heavy chain having an amino acid sequence of SEQ ID NO: 135. In some embodiments, the antibody comprises a light chain having an amino acid sequence of SEQ ID NO: 136. In some embodiments, the antibody comprises a heavy chain having an amino acid sequence of SEQ ID NO: 135, and a light chain having an amino acid sequence of SEQ ID NO: 136.
  • the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 133. In some embodiments, the antibody comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 134. In some embodiments, the antibody comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 133, and a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 134. In some embodiments, the antibody comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 135.
  • the antibody comprises a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 136. In some embodiments, the antibody comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 135, and a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 136.
  • the VH CDR1, VH CDR2 and VH CDR3 amino acid sequences of the TRGV9 antibody are according to the Rabat numbering system. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 amino acid sequences of the TRGV9 antibody are according to the Chothia numbering system.
  • the VH CDR1, VH CDR2 and VH CDR3 amino acid sequences of the TRGV9 antibody are according to the AbM numbering system. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 amino acid sequences of the TRGV9 antibody are according to the Contact numbering system. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 amino acid sequences of the TRGV9 antibody are according to the IMGT numbering system. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 amino acid sequences of the TRGV9 antibody are according to the Exemplary numbering system.
  • the VL CDR1, VL CDR2 and VL CDR3 amino acid sequences of the TRGV9 antibody are according to the Rabat numbering system. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 amino acid sequences of the TRGV9 antibody are according to the Chothia numbering system. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 amino acid sequences of the
  • TRGV9 antibody are according to the AbM numbering system. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 amino acid sequences of the TRGV9 antibody are according to the Contact numbering system. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 amino acid sequences of the TRGV9 antibody are according to the IMGT numbering system. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 amino acid sequences of the TRGV9 antibody are according to the Exemplary numbering system.
  • the TRGV9 antibody is a multispecific antibody. In other embodiments, the TRGV9 antibody is a bispecific antibody. In certain embodiments, the multispecific antibody comprises an antigen binding fragment of a TRGV9 antibody provided herein. In some embodiments, the multispecific antibody comprises a first binding domain that binds to a first TRGV9 epitope and a second domain that binds to a second TRGV9 epitope, wherein the first TRGV9 epitope and the second TRGV9 epitope are different. In certain embodiments, the multispecific antibody further comprises a third binding domain that binds to a target that is not TRGV9. In some embodiments, the multispecific antibody comprises heavy chain variable regions and light chain variable region.
  • the first binding domain comprises a heavy chain variable region and a light chain variable region.
  • the second binding domain comprises a heavy chain variable region and a light chain variable region.
  • the first binding domain comprises a heavy chain variable region and a light chain variable region
  • the second binding domain comprises a heavy chain variable region and a light chain variable region.
  • the first binding domain of the TRGV9 antibody is not a single domain antibody or nanobody.
  • the second binding domain of the TRGV9 antibody is not a single domain antibody or nanobody.
  • the TRGV9 antibody comprises 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 certain embodiments, the TRGV9 antibody is not a VHH antibody. In certain embodiments, the TRGV9 antibody is not a llama antibody. In some embodiments, the TRGV9 bispecific antibody does not comprise a single chain antibody. In some embodiments, the TRGV9 bispecific antibody does not comprise a single domain antibody. In certain embodiments, the TRGV9 bispecific antibody does not comprise a nanobody. In certain embodiments, the TRGV9 bispecific antibody does not comprise a VHH antibody. In certain embodiments, the TRGV9 bispecific antibody does not comprise a llama antibody.
  • a TRGV9 antibody provided herein does not comprise a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NOs:730, 731, and 732, respectively. In some embodiments, a TRGV9 antibody provided herein does not comprise a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NOs:733, 734, and 735, respectively. In some embodiments, a TRGV9 antibody provided herein does not comprise a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NOs:736, 737, and 738, respectively.
  • a TRGV9 antibody provided herein does not comprise a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NOs:739, 740, and 741, respectively. In some embodiments, a TRGV9 antibody provided herein does not comprise a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NOs:742,
  • a TRGV9 antibody provided herein does not comprise a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NOs:745, 746, and 747, respectively. In some embodiments, a TRGV9 antibody provided herein does not comprise a VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequence of SEQ ID NOs:748,
  • a TRGV9 antibody provided herein does not comprise a VH domain having the amino acid sequence of SEQ ID NO:751. In some embodiments, a TRGV9 antibody provided herein does not comprise a VH domain having the amino acid sequence of SEQ ID NO:752. In some embodiments, a TRGV9 antibody provided herein does not comprise a VH domain having the amino acid sequence of SEQ ID NO:753. In some embodiments, a TRGV9 antibody provided herein does not comprise a VH domain having the amino acid sequence of SEQ ID NO:754. In some embodiments, a TRGV9 antibody provided herein does not comprise a VH domain having the amino acid sequence of SEQ ID NO:755.
  • a TRGV9 antibody provided herein does not comprise a VH domain having the amino acid sequence of SEQ ID NO:756. In some embodiments, a TRGV9 antibody provided herein does not comprise a VH domain having the amino acid sequence of SEQ ID NO:757. [00129] In another aspect, provided herein is a TRGV9 antibody, comprising a VH domain comprising a VH CDR3 having the amino acid sequence of APNxGzYTbDF (SEQ ID NO:758), wherein x is Y or M, z is M or D, and b is I or L.
  • APNxGzYTbDF SEQ ID NO:758
  • a TRGV9 antibody comprising a VH domain comprising the amino acid sequence of SEQ ID NO: 758.
  • a TRGV9 antibody comprising a VH domain comprising a VH CDR1 having the amino acid sequence of GxTFzz (SEQ ID NO:761), wherein x is F, D or G, and z is S or N.
  • a TRGV9 antibody comprising a VH domain comprising the amino acid sequence of SEQ ID NO:761.
  • a TRGV9 antibody comprising a VL domain comprising a VL CDR1 having the amino acid sequence of RxSQSz (SEQ ID NO:762), wherein x is A or S, and z is V or L.
  • a TRGV9 antibody comprising a VL domain comprising the amino acid sequence of SEQ ID NO:761.
  • an antibody that binds to TRGV9 comprising: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3.
  • the VH CDR1 comprises a first polar amino acid.
  • the VH CDR1 comprises a last polar uncharged amino acid.
  • the VH CDR1 comprises at least one tyrosine.
  • the VH CDR1 comprises at least 20% hydrophobic amino acids.
  • the VH CDR1 comprises at least two hydrophobic amino acids. In some embodiments, the VH CDR1 comprises at least about 40% hydrophobic amino acids. In some embodiments, the VH CDR1 comprises the 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-mentioned VH CDR1 structural features are also contemplated. In some embodiments, the VH CDR2 comprises a polar amino acid at residue 13. In some embodiments, the VH CDR2 comprises a hydrophobic at amino acid position 15.
  • the VH CDR2 comprises a phenylalanine (F) or leucine (L) at position 15. In some embodiments, the VH CDR2 comprises a polar amino acid at position 14. In some embodiments, the VH CDR2 comprises a lysine (K) or serine (S) at position 14. In some embodiments, the VH CDR2 comprises a hydrophobic amino acid at position 2. In some embodiments, the VH CDR2 comprises a hydrophobic amino acid at position 3. In some embodiments, the VH CDR2 comprises and a polar penultimate amino acid.
  • the VH CDR2 comprises a polar amino acid at residue 13, a hydrophobic at amino acid position 15, a phenylalanine (F) or leucine (L) at position 15, a polar amino acid at position 14, a lysine (K) or serine (S) at position 14, a hydrophobic amino acid at position 2 or 3, and a polar penultimate amino acid. Any combination of two or more of the above- mentioned VH CDR2 structural features are also contemplated.
  • the VH CDR3 does not comprise a polar charged amino acid at position 3.
  • the VH CDR3 comprises a hydrophobic or polar charged amino acid at position 7.
  • the VH CDR3 comprises a polar uncharged or hydrophobic amino acid at position 6. In some embodiments, the VH CDR3 comprises no polar charged amino acid at position 3, a hydrophobic or polar charged amino acid at position 7, and a polar uncharged or hydrophobic amino acid at position 6. Any combination of two or more of the above-mentioned VH CDR3 structural features are also contemplated.
  • the VL CDR1 comprises a polar amino acid at position 4 . In some embodiments, the VL CDR1 comprises a first amino acid that is polar charged. In some embodiments, the VL CDR1 comprises a polar uncharged or hydrophobic amino acid at position 2.
  • the VL CDR1 comprises a serine at position 3. In some embodiments, the VL CDR1 comprises a polar amino acid at position 5. In some embodiments, the VL CDR1 comprises a hydrophobic amino acid at position 6. In some embodiments, the VL CDR1 comprises a polar amino acid at position 4, a first amino acid that is polar charged, a polar uncharged or hydrophobic amino acid at position 2, a serine at position 3, a polar amino acid at position 5, and a hydrophobic amino acid at position 6. Any combination of two or more of the above-mentioned VL CDR1 structural features are also contemplated. In some embodiments, the VL CDR2 comprises a polar amino acid at position 7.
  • the VL CDR2 comprises a polar charged or hydrophobic amino acid at position 6. In some embodiments, the VL CDR2 comprises a polar charged amino acid at position 3. In some embodiments, the VL CDR2 comprises a polar uncharged amino acid at position 4. In some embodiments, the VL CDR2 comprises a hydrophobic amino acid at position 2. In some embodiments, the VL CDR2 comprises a polar amino acid at position 7, a polar charged 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- mentioned VL CDR2 structural features are also contemplated.
  • the VL CDR3 comprises a hydrophobic terminal amino acid. In some embodiments, the VL CDR3 comprises a terminal tyrosine. In some embodiments, the VL CDR3 comprises a polar uncharged amino acid at position 5. In some embodiments, the VL CDR3 comprises a polar amino acid at position 2. In some embodiments, the VL CDR3 comprises a polar uncharged or hydrophobic amino acid at position 1. In some embodiments, the VL CDR3 comprises a hydrophobic amino acid at position 3. In some embodiments, the VL CDR3 comprises a hydrophilic or polar uncharged amino acid at position 6. In some embodiments, the VL CDR3 comprises no polar or hydrophobic amino acid at position 7.
  • the VL CDR3 comprises a hydrophobic terminal amino acid, a terminal tyrosine, a polar uncharged amino acid at position 5, a polar amino acid at position 2, a polar uncharged 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-mentioned VL CDR3 structural features are also contemplated. In specific embodiments, residue position numbering is according to Exemplary numbering.
  • an antibody that binds to TRGV9 wherein the antibody comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3.
  • the VH CDR1 comprises at least three polar amino acids.
  • the VH CDR1 comprises at least 40% polar amino acids.
  • the VH CDR1 comprises a glycine (G) at position 1.
  • the VH CDR1 does not comprise a polar uncharged amino acid at position 2. In some embodiments, the VH CDR1 comprises a polar uncharged amino acid at position 3. In some embodiments, the VH CDR1 comprises a threonine (T) or a serine (S) at position 3. In some embodiments, the VH CDR1 comprises a hydrophobic amino acid at position 4. In some embodiments, the VH CDR1 comprises a phenylalanine (F) or an isoleucine (I) at position 4. In some embodiments, the VH CDR1 comprises a polar uncharged amino acid at position 5. In some embodiments, the VH CDR1 comprises a polar uncharged amino acid at position 3. In some embodiments, the VH CDR1 comprises a polar uncharged amino acid at position 3. In some embodiments, the VH CDR1 comprises a polar uncharged amino acid at position 3. In some embodiments, the VH CDR1 comprises a polar uncharged amino acid at
  • VH CDR1 comprises a threonine (T), a serine (S), or an asparagine (N) at position 5.
  • the VH CDR1 comprises a polar amino acid at position 6.
  • the VH CDR1 comprises an acid amino acid or a polar uncharged amino acid at position 6.
  • the VH CDR1 does not comprise a polar uncharged amino acid at position 7. Any combination of two or more of the above-mentioned VH CDR1 structural features are also contemplated.
  • the amino acid residue numbering is according to Chothia. [00133]
  • the VH CDR2 does not comprise a charged amino acid at position 1.
  • the VH CDR2 does not comprise a charged amino acid at position 2.
  • the VH CDR2 comprises a glycine (G), a hydrophobic, or a polar uncharged amino acid at position 2.
  • the VH CDR2 does not comprises a hydrophobic or a polar charged amino acid at position 4.
  • the VH CDR2 does not comprise a hydrophobic or a polar uncharged amino acid at the last position.
  • the VH CDR2 comprises a glycine (G) or a polar uncharged amino acid at the last position. Any combination of two or more of the above-mentioned VH CDR2 structural features are also contemplated.
  • the amino acid residue numbering is according to Chothia.
  • the VH CDR3 does not comprise a polar charged amino acid at position 1. In some embodiments, the VH CDR3 does not comprise a polar charged amino acid at position 2. In some embodiments, the VH CDR3 comprises a glycine (G), a tyrosine (Y), or a polar uncharged amino acid at position 2. In some embodiments, the VH CDR3 does not comprise a polar uncharged amino acid at position 3. In some embodiments, the VH CDR3 comprises a glycine (G), an aspartic acid (D), or a hydrophobic amino acid at position 3.
  • the VH CDR3 does not comprise a polar charged amino acid at position 5. In some embodiments, the VH CDR3 does not comprise a polar uncharged amino acid at position 6. In some embodiments, the VH CDR3 comprises an aspartic acid (D) or a hydrophobic amino acid at position 6. In some embodiments, the VH CDR3 comprises a hydrophobic penultimate amino acid. In some embodiments, the VH CDR3 does not comprise a polar uncharged amino acid at position 7. In some embodiments, the VH CDR3 comprises a terminal aspartic acid (D) or a terminal alanine (A). Any combination of two or more of the above-mentioned VH CDR3 structural features are also contemplated. In certain embodiments, the amino acid residue numbering is according to Chothia.
  • the VL CDR1 comprises a serine (S) at position 1. In some embodiments, the VL CDR1 comprises a glutamine (G) or a glutamic acid (E) at position 2. In some embodiments, the VL CDR1 comprises a polar uncharged amino acid at position 3.
  • the VL CDR1 comprises a serine (S) or an asparagine (N) at position 3. In some embodiments, the VL CDR1 comprises a hydrophobic amino acid at position 4. In some embodiments, the VL CDR1 comprises a leucine (L), valine (V), or isoleucine (I) at position 4. In some embodiments, the VL CDR1 comprises a serine (S) or tyrosine (Y) at position 7. In some embodiments, the VL CDR1 comprises a polar uncharged penultimate amino acid. In some embodiments, the VL CDR1 comprises a terminal tyrosine (Y) or a terminal lysine (K). Any combination of two or more of the above-mentioned VL CDR1 structural features are also contemplated. In certain embodiments, the amino acid residue numbering is according to Chothia.
  • the VL CDR2 comprises a hydrophobic amino acid at position 2.
  • the VL CDR2 comprises an alanine (A) or an isoleucine (I) at position 2.
  • the VL CDR2 comprises a polar terminal amino acid.
  • the VL CDR2 comprises a terminal serine (S) or a terminal lysine (K). Any combination of two or more of the above-mentioned VL CDR2 structural features are also contemplated.
  • the amino acid residue numbering is according to Chothia.
  • the VL CDR3 does not comprise a polar uncharged amino acid at position 1.
  • the VL CDR3 comprises an arginine (R) or a hydrophobic amino acid at position 1.
  • the VL CDR3 does not comprise a hydrophobic amino acid at position 3.
  • the VL CDR3 comprises an arginine (R) or a polar uncharged amino acid at position 3.
  • the VL CDR3 does not comprise a polar charged amino acid at position 4.
  • the VL CDR3 comprises a serine (S) or a hydrophobic amino acid at position 4.
  • the VL CDR3 comprises a tyrosine (Y) or a proline (P) as the penultimate amino acid.
  • the VL CDR3 comprises a histidine (H) or a proline (P) at position 5.
  • the VL CDR3 comprises a terminal histidine (H), a terminal lysine (L), or a terminal tyrosine (Y). Any combination of two or more of the above-mentioned VL CDR3 structural features are also contemplated.
  • the amino acid residue numbering is according to Chothia.
  • a TRGV9 antibody comprising a VH comprising a VH CDR1 having the amino acid sequence of GX1TFX2X3X4 (SEQ ID NO:777), wherein Xi is F, D, or G; X2 is T, S, or N; X3 is D, S, or N; and X4 is H, N, or Y.
  • a TRGV9 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO:777.
  • a TRGV9 antibody comprising a VH comprising a VH CDR2 having the amino acid sequence of PGXiG (SEQ ID NO:778), wherein Xi is D or S.
  • a TRGV9 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO:778.
  • a TRGV9 antibody comprising a VH comprising a VH CDR3 having the amino acid sequence of X1GX2YTX3D (SEQ ID NO:779), wherein Xi is Y or M, X 2 is D or M, and X3 is I or L.
  • a TRGV9 antibody comprising a VH comprising the amino acid sequence of SEQ ID NO:779.
  • a TRGV9 antibody comprising a VL comprising a VL CDR1 having the amino acid sequence of SQSX1LYSSNX2X3 (SEQ ID NO:780), wherein Xi is L or V, X2 is Q or N, and X3 is K or KNY.
  • a TRGV9 antibody comprising a VL comprising the amino acid sequence of SEQ ID NO:780.
  • a TRGV9 antibody comprising a VH comprising a VH CDR1, VH CDR2 and VH CDR3.
  • the VH CDR1 comprises an amino acid sequence of GX1TFX2X3X4 (SEQ ID NO:777), wherein Xi is F, D, or G; X2 is T, S, or N; X3 is D, S, or N; and X4 is H, N, or Y.
  • the VH CDR1 comprises an amino acid sequences o SEQ ID NO: 178.
  • the VH CDR1 comprises an amino acid sequences o SEQ ID NO:394.
  • the VH CDR1 comprises an amino acid sequences o SEQ ID NO:430. In some embodiments, the VH CDR1 comprises an amino acid sequences o SEQ ID NO:466. In some embodiments, the VH CDR1 comprises an amino acid sequences o SEQ ID NO:502. In some embodiments, the
  • VH CDR1 comprises an amino acid sequences o SEQ ID NO:538.
  • the VH CDR2 comprises an amino acid sequence of PGXiG (SEQ ID NO:778), wherein Xi is D or S.
  • the VH CDR3 comprises an amino acid sequence of X1GX2YTX3D (SEQ ID NO:779), wherein Xi is Y or M, X2 is D or M, and X3 is I or L.
  • a TRGV9 antibody comprising a VL comprising a VL CDR1, VL CDR2 and VL CDR3.
  • the VL CDR1 comprises an amino acid sequence of SQSX1LYSSNX2X3 (SEQ ID NO:780), wherein Xi is L or V, X2 is Q or N, and X3 is K or KNY.
  • the VL CDR2 comprises an amino acid sequence of SEQ ID NO: 182.
  • the VL CDR2 comprises an amino acid sequence of SEQ ID NO: 398.
  • the VL CDR2 comprises an amino acid sequence of SEQ ID NO:434.
  • the VL CDR2 comprises an amino acid sequence of SEQ ID NO:470.
  • the VL CDR3 comprises an amino acid sequence of SEQ ID NO:542.
  • the VL CDR3 comprises an amino acid sequence of SEQ ID NO:399. In some embodiments, the VL CDR3 comprises an amino acid sequence of SEQ ID NO:435. In some embodiments, the VL CDR3 comprises an amino acid sequence of SEQ ID NO:471. In some embodiments, the VL CDR3 comprises an amino acid sequence of SEQ ID NO:507. In some embodiments, the VL CDR3 comprises an amino acid sequence of SEQ ID NO:543.
  • a multispecific TRGV9 antibody comprising a TRGV9 antibody provided herein.
  • the multispecific TRGV9 antibody is a bispecific antibody.
  • a multispecific TRGV9 antibody wherein the antibody comprises a VH CDR1, VH CDR2 and VH CDR3 of a TRGV9 antibody provided herein.
  • a multispecific TRGV9 antibody wherein the antibody comprises a VL CDR1, VL CDR2 and VL CDR3 of a TRGV9 antibody provided herein.
  • a multispecific TRGV9 antibody wherein the antibody comprises a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of a TRGV9 antibody provided herein.
  • the antibody comprises a VH of a TRGV9 antibody provided herein.
  • the antibody comprises a VL of a TRGV9 antibody provided herein.
  • a multispecific TRGV9 antibody wherein the antibody comprises a VH and VL of a TRGV9 antibody provided herein.
  • 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.
  • the second target is not a TRGV9 antigen.
  • the second target is not a TRGV9 epitope.
  • the first binding domain that binds to TRGV9 comprises a VH and VL amino acid sequence of L7A5 1 (TRGV9 1).
  • the first binding domain comprises a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:7.
  • the first binding domain comprises a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 8.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:7; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 8.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 1, a VH CDR2 having an amino acid sequence of SEQ ID NO:2, and a VH CDR3 having an amino acid sequence of SEQ ID NO:3; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:4, a VL CDR2 having an amino acid sequence of SEQ ID NO:5, and a VL CDR3 having an amino acid sequence of SEQ ID NO:6.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 160, a VH CDR2 having an amino acid sequence of SEQ ID NO: 161, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 162; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 163, a VL CDR2 having an amino acid sequence of SEQ ID NO: 164, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 165.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 166, a VH CDR2 having an amino acid sequence of SEQ ID NO: 167, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 168; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 169, a VL CDR2 having an amino acid sequence of SEQ ID NO: 170, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 171.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 172, a VH CDR2 having an amino acid sequence of SEQ ID NO: 173, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 174; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 175, a VL CDR2 having an amino acid sequence of SEQ ID NO: 176, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 177.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 178, a VH CDR2 having an amino acid sequence of SEQ ID NO: 179, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 180; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 181, a VL CDR2 having an amino acid sequence of SEQ ID NO: 182, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 183.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 178, a VH CDR2 having an amino acid sequence of SEQ ID NO:700, and a VH CDR3 having an amino acid sequence of SEQ ID NO:701; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 181, a VL CDR2 having an amino acid sequence of SEQ ID NO: 182, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 183.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 184, a VH CDR2 having an amino acid sequence of SEQ ID NO: 185, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 186; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 187, a VL CDR2 having an amino acid sequence of SEQ ID NO: 188, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 189.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 190, a VH CDR2 having an amino acid sequence of SEQ ID NO: 191, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 192; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 193, a VL CDR2 having an amino acid sequence of SEQ ID NO: 194, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 195.
  • the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO:7.
  • the first binding domain comprises a VL having an amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO:7, and a VL having an amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises a heavy chain having an amino acid sequence of SEQ ID NO:23. In some embodiments, the first binding domain comprises a light chain having an amino acid sequence of SEQ ID NO:24. In some embodiments, the first binding domain comprises a heavy chain having an amino acid sequence of SEQ ID NO:23, and a light chain having an amino acid sequence of SEQ ID NO:24. In some embodiments, the first binding domain comprises an amino acid sequence of SEQ ID NO: 17.
  • the first binding domain comprises a heavy chain having an amino acid sequence of SEQ ID NO:69. In some embodiments, the first binding domain comprises a light chain having an amino acid sequence of SEQ ID NO:24. In some embodiments, the first binding domain comprises a heavy chain having an amino acid sequence of SEQ ID NO: 69, and a light chain having an amino acid sequence of SEQ ID NO:24. In some embodiments, the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:7. In some embodiments, the first binding domain comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 8.
  • the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:7, and a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8.
  • the first binding domain comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:23.
  • the first binding domain comprises a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:24.
  • the first binding domain comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:23, and a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:24.
  • the first binding domain comprises an amino acid sequence of SEQ ID NO: 17.
  • the first binding domain comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:69.
  • the first binding domain comprises a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:24.
  • the first binding domain comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:69, and a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:24.
  • the first binding domain that binds to TRGV9 comprises a VH and VL amino acid sequence of L7A5 2 (TRGV9 2).
  • the first binding domain comprises a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:34.
  • the first binding domain comprises a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 8.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:34; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 8.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 1, a VH CDR2 having an amino acid sequence of SEQ ID NO:2, and a VH CDR3 having an amino acid sequence of SEQ ID NO:31; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:4, a VL CDR2 having an amino acid sequence of SEQ ID NO:5, and a VL CDR3 having an amino acid sequence of SEQ ID NO:6.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 196, a VH CDR2 having an amino acid sequence of
  • VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 199, a VL CDR2 having an amino acid sequence of SEQ ID NO:200, and a VL CDR3 having an amino acid sequence of SEQ ID NO:201.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:202, a VH CDR2 having an amino acid sequence of SEQ ID NO:203, and a VH CDR3 having an amino acid sequence of SEQ ID NO:204; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:205, a VL CDR2 having an amino acid sequence of SEQ ID NO:206, and a VL CDR3 having an amino acid sequence of SEQ ID NO:207.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:208, a VH CDR2 having an amino acid sequence of SEQ ID NO:209, and a VH CDR3 having an amino acid sequence of SEQ ID NO:210; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:211, a VL CDR2 having an amino acid sequence of SEQ ID NO:212, and a VL CDR3 having an amino acid sequence of SEQ ID NO:213.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:214, a VH CDR2 having an amino acid sequence of SEQ ID NO:215, and a VH CDR3 having an amino acid sequence of SEQ ID NO:216; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:217, a VL CDR2 having an amino acid sequence of SEQ ID NO:218, and a VL CDR3 having an amino acid sequence of SEQ ID NO:219.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:214, a VH CDR2 having an amino acid sequence of SEQ ID NO:702, and a VH CDR3 having an amino acid sequence of SEQ ID NO:703; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:217, a VL CDR2 having an amino acid sequence of SEQ ID NO:218, and a VL CDR3 having an amino acid sequence of SEQ ID NO:219.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:220, a VH CDR2 having an amino acid sequence of SEQ ID NO:221, and a VH CDR3 having an amino acid sequence of SEQ ID NO:222; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:223, a VL CDR2 having an amino acid sequence of SEQ ID NO:224, and a VL CDR3 having an amino acid sequence of SEQ ID NO:225.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:226, a VH CDR2 having an amino acid sequence of SEQ ID NO:227, and a VH CDR3 having an amino acid sequence of SEQ ID NO:228; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:229, a VL CDR2 having an amino acid sequence of SEQ ID NO:230, and a VL CDR3 having an amino acid sequence of SEQ ID NO:231.
  • the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO:34.
  • the first binding domain comprises a VL having an amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO:34, and a VL having an amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:34. In some embodiments, the first binding domain comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 8.
  • the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:34, and a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8.
  • the first binding domain that binds to TRGV9 comprises a VH and VL amino acid sequence of L7A5 3 (TRGV9 3).
  • the first binding domain comprises a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:35.
  • the first binding domain comprises a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 8.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:35; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 8.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 1, a VH CDR2 having an amino acid sequence of SEQ ID NO:2, and a VH CDR3 having an amino acid sequence of SEQ ID NO:32; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:4, a VL CDR2 having an amino acid sequence of SEQ ID NO:5, and a VL CDR3 having an amino acid sequence of SEQ ID NO:6.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:232, a VH CDR2 having an amino acid sequence of SEQ ID NO:233, and a VH CDR3 having an amino acid sequence of SEQ ID NO:234; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:235, a VL CDR2 having an amino acid sequence of SEQ ID NO:236, and a VL CDR3 having an amino acid sequence of SEQ ID NO:237.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:238, a VH CDR2 having an amino acid sequence of SEQ ID NO:239, and a VH CDR3 having an amino acid sequence of SEQ ID NO:240; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:241, a VL CDR2 having an amino acid sequence of SEQ ID NO:242, and a VL CDR3 having an amino acid sequence of SEQ ID NO:243.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:244, a VH CDR2 having an amino acid sequence of SEQ ID NO:245, and a VH CDR3 having an amino acid sequence of SEQ ID NO:246; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:247, a VL CDR2 having an amino acid sequence of SEQ ID NO:248, and a VL CDR3 having an amino acid sequence of SEQ ID NO:249.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:250, a VH CDR2 having an amino acid sequence of SEQ ID NO:251, and a VH CDR3 having an amino acid sequence of SEQ ID NO:252; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:253, a VL CDR2 having an amino acid sequence of SEQ ID NO:254, and a VL CDR3 having an amino acid sequence of SEQ ID NO:255.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:250, a VH CDR2 having an amino acid sequence of SEQ ID NO:704, and a VH CDR3 having an amino acid sequence of SEQ ID NO:705; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:253, a VL CDR2 having an amino acid sequence of SEQ ID NO:254, and a VL CDR3 having an amino acid sequence of SEQ ID NO:255.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:256, a VH CDR2 having an amino acid sequence of SEQ ID NO:257, and a VH CDR3 having an amino acid sequence of SEQ ID NO:258; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:259, a VL CDR2 having an amino acid sequence of SEQ ID NO:260, and a VL CDR3 having an amino acid sequence of SEQ ID NO:261.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:262, a VH CDR2 having an amino acid sequence of SEQ ID NO:263, and a VH CDR3 having an amino acid sequence of SEQ ID NO:264; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:265, a VL CDR2 having an amino acid sequence of SEQ ID NO:266, and a VL CDR3 having an amino acid sequence of SEQ ID NO:267.
  • the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO:35.
  • the first binding domain comprises a VL having an amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO:35, and a VL having an amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:35. In some embodiments, the first binding domain comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 8.
  • the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:35, and a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:8.
  • the first binding domain that binds to TRGV9 comprises a VH and VL amino acid sequence of L7A5 4 (TRGV9 4).
  • the first binding domain comprises a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:36.
  • the first binding domain comprises a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 8.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:36; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 8.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 1, a VH CDR2 having an amino acid sequence of SEQ ID NO:2, and a VH CDR3 having an amino acid sequence of SEQ ID NO:33; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:4, a VL CDR2 having an amino acid sequence of SEQ ID NO:5, and a VL CDR3 having an amino acid sequence of SEQ ID NO:6.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:268, a VH CDR2 having an amino acid sequence of SEQ ID NO:269, and a VH CDR3 having an amino acid sequence of SEQ ID NO:270; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:271, a VL CDR2 having an amino acid sequence of SEQ ID NO:272, and a VL CDR3 having an amino acid sequence of SEQ ID NO:273.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:274, a VH CDR2 having an amino acid sequence of SEQ ID NO:275, and a VH CDR3 having an amino acid sequence of SEQ ID NO:276; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:277, a VL CDR2 having an amino acid sequence of SEQ ID NO:278, and a VL CDR3 having an amino acid sequence of SEQ ID NO:279.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:280, a VH CDR2 having an amino acid sequence of SEQ ID NO:281, and a VH CDR3 having an amino acid sequence of SEQ ID NO:282; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:283, a VL CDR2 having an amino acid sequence of SEQ ID NO:284, and a VL CDR3 having an amino acid sequence of SEQ ID
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:286, a VH CDR2 having an amino acid sequence of SEQ ID NO:287, and a VH CDR3 having an amino acid sequence of SEQ ID NO:288; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:289, a VL CDR2 having an amino acid sequence of SEQ ID NO:290, and a VL CDR3 having an amino acid sequence of SEQ ID NO:291.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:286, a VH CDR2 having an amino acid sequence of SEQ ID NO:706, and a VH CDR3 having an amino acid sequence of SEQ ID NO:707; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:289, a VL CDR2 having an amino acid sequence of SEQ ID NO:290, and a VL CDR3 having an amino acid sequence of SEQ ID NO:291.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:292, a VH CDR2 having an amino acid sequence of SEQ ID NO:293, and a VH CDR3 having an amino acid sequence of SEQ ID NO:294; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:295, a VL CDR2 having an amino acid sequence of SEQ ID NO:296, and a VL CDR3 having an amino acid sequence of SEQ ID NO:297.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:298, a VH CDR2 having an amino acid sequence of SEQ ID NO:299, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 300; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:301, a VL CDR2 having an amino acid sequence of SEQ ID NO: 302, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 303.
  • the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO:36.
  • the first binding domain comprises a VL having an amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO:36, and a VL having an amino acid sequence of SEQ ID NO: 8. In some embodiments, the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:36. In some embodiments, the first binding domain comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 8.
  • the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 36, and a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 8.
  • the first binding domain that binds to TRGV9 comprises a VH and VL amino acid sequence of TRGV9Ab_varl7.
  • the first binding domain comprises a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO: 65.
  • the first binding domain comprises a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:66.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:65; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:66.
  • the first binding domain comprises a VH and VL amino acid sequence of TRGV9Ab_var29.
  • the first binding domain comprises a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:67.
  • the first binding domain comprises a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 68.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO: 67; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 68.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 1, a VH CDR2 having an amino acid sequence of SEQ ID NO:76, and a VH CDR3 having an amino acid sequence of SEQ ID NO:3; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:77, a VL CDR2 having an amino acid sequence of SEQ ID NO:5, and a VL CDR3 having an amino acid sequence of SEQ ID NO:6.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 60, a VH CDR2 having an amino acid sequence of SEQ ID NO:61, and a VH CDR3 having an amino acid sequence of SEQ ID NO:62; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:63, a VL CDR2 having an amino acid sequence of SEQ ID NO: 64, and a VL CDR3 having an amino acid sequence of SEQ ID NO:6.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:304, a VH CDR2 having an amino acid sequence of SEQ ID NO:305, and a VH CDR3 having an amino acid sequence of SEQ ID NO:306; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:307, a VL CDR2 having an amino acid sequence of SEQ ID NO: 308, and a VL CDR3 having an amino acid sequence of SEQ ID NO:309.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 310, a VH CDR2 having an amino acid sequence of SEQ ID NO: 311, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 312; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 313, a VL CDR2 having an amino acid sequence of SEQ ID NO: 314, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 315.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 316, a VH CDR2 having an amino acid sequence of SEQ ID NO: 317, and a VH CDR3 having an amino acid sequence of SEQ ID NO:318; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:319, a VL CDR2 having an amino acid sequence of SEQ ID NO:320, and a VL CDR3 having an amino acid sequence of SEQ ID NO:321.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:322, a VH CDR2 having an amino acid sequence of SEQ ID NO:323, and a VH CDR3 having an amino acid sequence of SEQ ID NO:324; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 325, a VL
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:322, a VH CDR2 having an amino acid sequence of SEQ ID NO:708, and a VH CDR3 having an amino acid sequence of SEQ ID NO:709; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 325, a VL CDR2 having an amino acid sequence of SEQ ID NO:326, and a VL CDR3 having an amino acid sequence of SEQ ID NO:327.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:328, a VH CDR2 having an amino acid sequence of SEQ ID NO:329, and a VH CDR3 having an amino acid sequence of SEQ ID NO:330; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:331, a VL CDR2 having an amino acid sequence of SEQ ID NO:332, and a VL CDR3 having an amino acid sequence of SEQ ID NO:333.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:334, a VH CDR2 having an amino acid sequence of SEQ ID NO:335, and a VH CDR3 having an amino acid sequence of SEQ ID NO:336; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:337, a VL CDR2 having an amino acid sequence of SEQ ID NO:338, and a VL CDR3 having an amino acid sequence of SEQ ID NO:339.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:340, a VH CDR2 having an amino acid sequence of SEQ ID NO:341, and a VH CDR3 having an amino acid sequence of SEQ ID NO:342; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:343, a VL CDR2 having an amino acid sequence of SEQ ID NO:344, and a VL CDR3 having an amino acid sequence of SEQ ID NO:345.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:346, a VH CDR2 having an amino acid sequence of SEQ ID NO:347, and a VH CDR3 having an amino acid sequence of SEQ ID NO:348; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:349, a VL CDR2 having an amino acid sequence of SEQ ID NO:350, and a VL CDR3 having an amino acid sequence of SEQ ID NO:351.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:352, a VH CDR2 having an amino acid sequence of SEQ ID NO:353, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 354; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:355, a VL CDR2 having an amino acid sequence of SEQ ID NO:356, and a VL CDR3 having an amino acid sequence of SEQ ID NO:357.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:358, a VH CDR2 having an amino acid sequence of SEQ ID NO:359, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 360; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:361, a VL CDR2 having an amino acid sequence of SEQ ID NO: 362, and a VL CDR3 having an amino acid sequence of SEQ ID NO:363.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:358, a VH CDR2 having an amino acid sequence of SEQ ID NO:710, and a VH CDR3 having an amino acid sequence of SEQ ID NO:711; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:361, a VL CDR2 having an amino acid sequence of SEQ ID NO: 362, and a VL CDR3 having an amino acid sequence of SEQ ID NO:363.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:364, a VH CDR2 having an amino acid sequence of SEQ ID NO:365, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 366; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:367, a VL CDR2 having an amino acid sequence of SEQ ID NO: 368, and a VL CDR3 having an amino acid sequence of SEQ ID NO:369.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:370, a VH CDR2 having an amino acid sequence of SEQ ID NO:371, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 372; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 373, a VL CDR2 having an amino acid sequence of SEQ ID NO: 374, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 375.
  • the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO:65.
  • the first binding domain comprises a VL having an amino acid sequence of SEQ ID NO:66. In some embodiments, the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO:65, and a VL having an amino acid sequence of SEQ ID NO:66. In some embodiments, the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO:67. In some embodiments, the first binding domain comprises a VL having an amino acid sequence of SEQ ID NO: 68. In some embodiments, the first binding domain a VH having an amino acid sequence of SEQ ID NO: 67, and a VL having an amino acid sequence of SEQ ID NO: 68.
  • the first binding domain comprises a heavy chain having an amino acid sequence of SEQ ID NO:71. In some embodiments, the first binding domain comprises a light chain having an amino acid sequence of SEQ ID NO:72. In some embodiments, the first binding domain comprises a heavy chain having an amino acid sequence of SEQ ID NO:71, and a light chain having an amino acid sequence of SEQ ID NO:72. In some embodiments, the first binding domain comprises an amino acid sequence of SEQ ID NO:70. In some embodiments, the first binding domain comprises a heavy chain having an amino acid sequence of SEQ ID NO:74. In some embodiments, the first binding domain comprises a light chain having an amino acid sequence of SEQ ID NO:75.
  • the first binding domain comprises a heavy chain having an amino acid sequence of SEQ ID NO: 74, and a light chain having an amino acid sequence of SEQ ID NO: 75. In some embodiments, the first binding domain comprises an amino acid sequence of SEQ ID NO:73. In some embodiments, the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 65. In some embodiments, the first binding domain comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:66.
  • the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:65, and a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:66. In some embodiments, the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:67. In some embodiments, the first binding domain comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 68.
  • the first binding domain a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 67, and a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 68.
  • the first binding domain comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:71.
  • the first binding domain comprises a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:72.
  • the first binding domain comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:71, and a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:72. In some embodiments, the first binding domain comprises an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:70. In some embodiments, the first binding domain comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:74. In some embodiments, the first binding domain comprises a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 75.
  • the first binding domain comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:74, and a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 75. In some embodiments, the first binding domain comprises an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:73.
  • the first binding domain that binds to TRGV9 comprises a VH and VL amino acid sequence of VG9 B3 RN.
  • the first binding domain comprises a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:95.
  • the first binding domain comprises a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:96.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:95; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:96.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 89, a VH CDR2 having an amino acid sequence of SEQ ID NO:90, and a VH CDR3 having an amino acid sequence of SEQ ID NO:91; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 92, a VL CDR2 having an amino acid sequence of SEQ ID NO:93, and a VL CDR3 having an amino acid sequence of SEQ ID NO:94.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:376, a VH CDR2 having an amino acid sequence of SEQ ID NO:377, and a VH CDR3 having an amino acid sequence of SEQ ID NO:378; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:379, a VL CDR2 having an amino acid sequence of SEQ ID NO: 380, and a VL CDR3 having an amino acid sequence of SEQ ID NO:381.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:382, a VH CDR2 having an amino acid sequence of SEQ ID NO: 383, and a VH CDR3 having an amino acid sequence of SEQ ID NO:384; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:385, a VL CDR2 having an amino acid sequence of SEQ ID NO: 386, and a VL CDR3 having an amino acid sequence of SEQ ID NO:387.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:388, a VH CDR2 having an amino acid sequence of SEQ ID NO: 389, and a VH CDR3 having an amino acid sequence of SEQ ID NO:390; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:391, a VL CDR2 having an amino acid sequence of SEQ ID NO: 392, and a VL CDR3 having an amino acid sequence of SEQ ID NO:393. .
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:394, a VH CDR2 having an amino acid sequence of SEQ ID NO:395, and a VH CDR3 having an amino acid sequence of SEQ ID NO:396; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:397, a VL CDR2 having an amino acid sequence of SEQ ID NO: 398, and a VL CDR3 having an amino acid sequence of SEQ ID NO:399.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 394, a VH CDR2 having an amino acid sequence of SEQ ID NO:712, and a VH CDR3 having an amino acid sequence of SEQ ID NO:713; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:397, a VL CDR2 having an amino acid sequence of SEQ ID NO: 398, and a VL CDR3 having an amino acid sequence of SEQ ID NO:399.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:400, a VH CDR2 having an amino acid sequence of SEQ ID NO:401, and a VH CDR3 having an amino acid sequence of SEQ ID NO:402; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:403, a VL CDR2 having an amino acid sequence of SEQ ID NO:404, and a VL CDR3 having an amino acid sequence of SEQ ID NO:405.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:406, a VH CDR2 having an amino acid sequence of SEQ ID NO:407, and a VH CDR3 having an amino acid sequence of SEQ ID NO:408; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:409, a VL CDR2 having an amino acid sequence of SEQ ID NO:410, and a VL CDR3 having an amino acid sequence of SEQ ID NO:411.
  • the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO:95.
  • the first binding domain comprises a VL having an amino acid sequence of SEQ ID NO:96. In some embodiments, the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO:95, and a VL having an amino acid sequence of SEQ ID NO:96. In some embodiments, the first binding domain comprises an amino acid sequence of SEQ ID NO:97. In some embodiments, the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 95. In some embodiments, the first binding domain comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:96.
  • the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:95, and a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:96. In some embodiments, the first binding domain comprises an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO:97.
  • the first binding domain that binds to TRGV9 comprises a VH and VL amino acid sequence of VG9B420.
  • the first binding domain comprises a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO: 104.
  • the first binding domain comprises a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 105.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO: 104; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 105.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 98, a VH CDR2 having an amino acid sequence of SEQ ID NO:99, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 100, and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 101, a VL CDR2 having an amino acid sequence of SEQ ID NO: 102, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 103.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:412, a VH CDR2 having an amino acid sequence of SEQ ID NO:413, and a VH CDR3 having an amino acid sequence of SEQ ID NO:414; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:415, a VL CDR2 having an amino acid sequence of SEQ ID NO:416, and a VL CDR3 having an amino acid sequence of SEQ ID NO:417.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:418, a VH CDR2 having an amino acid sequence of SEQ ID NO:419, and a VH CDR3 having an amino acid sequence of SEQ ID NO:420; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:421, a VL CDR2 having an amino acid sequence of SEQ ID NO:422, and a VL CDR3 having an amino acid sequence of SEQ ID NO:423.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:424, a VH CDR2 having an amino acid sequence of SEQ ID NO:425, and a VH CDR3 having an amino acid sequence of SEQ ID NO:426; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:427, a VL CDR2 having an amino acid sequence of SEQ ID NO:428, and a VL CDR3 having an amino acid sequence of SEQ ID NO:429.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:430, a VH CDR2 having an amino acid sequence of SEQ ID NO:431, and a VH CDR3 having an amino acid sequence of SEQ ID NO:432; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:433, a VL CDR2 having an amino acid sequence of SEQ ID NO:434, and a VL CDR3 having an amino acid sequence of SEQ ID NO:435.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:430, a VH CDR2 having an amino acid sequence of SEQ ID NO:714, and a VH CDR3 having an amino acid sequence of SEQ ID NO:715; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:433, a VL CDR2 having an amino acid sequence of SEQ ID NO:434, and a VL CDR3 having an amino acid sequence of SEQ ID NO:435.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:436, a VH CDR2 having an amino acid sequence of SEQ ID NO:437, and a VH CDR3 having an amino acid sequence of SEQ ID NO:438; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:439, a VL CDR2 having an amino acid sequence of SEQ ID NO:440, and a VL CDR3 having an amino acid sequence of SEQ ID NO:441.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:442, a VH CDR2 having an amino acid sequence of SEQ ID NO:443, and a VH CDR3 having an amino acid sequence of SEQ ID NO:444; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 445, a VL CDR2 having an amino acid sequence of SEQ ID NO:446, and a VL CDR3 having an amino acid sequence of SEQ ID NO:447.
  • the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 104.
  • the first binding domain comprises a VL having an amino acid sequence of SEQ ID NO: 105. In some embodiments, the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 104, and a VL having an amino acid sequence of SEQ ID NO: 105. In some embodiments, the first binding domain comprises an amino acid sequence of SEQ ID NO: 106. In some embodiments, the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 104. In some embodiments, the first binding domain comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 105.
  • the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 104, and a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 105. In some embodiments, the first binding domain comprises an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO: 106.
  • the first binding domain that binds to TRGV9 comprises a VH and VL amino acid sequence of VG9SB10SC1087 P18 D08.
  • the first binding domain comprises a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO: 113.
  • the first binding domain comprises a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 114.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO: 113; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 114.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 107, a VH CDR2 having an amino acid sequence of SEQ ID NO: 108, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 109, and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 110, a VL CDR2 having an amino acid sequence of SEQ ID NO: 111, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 112.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:448, a VH CDR2 having an amino acid sequence of SEQ ID NO:449, and a VH CDR3 having an amino acid sequence of SEQ ID NO:450; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 451, a VL CDR2 having an amino acid sequence of SEQ ID NO:452, and a VL CDR3 having an amino acid sequence of SEQ ID NO:453.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:454, a VH CDR2 having an amino acid sequence of SEQ ID NO:455, and a VH CDR3 having an amino acid sequence of SEQ ID NO:456; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:457, a VL CDR2 having an amino acid sequence of SEQ ID NO:458, and a VL CDR3 having an amino acid sequence of SEQ ID NO:459.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:460, a VH CDR2 having an amino acid sequence of SEQ ID NO:461, and a VH CDR3 having an amino acid sequence of SEQ ID NO:462; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:463, a VL CDR2 having an amino acid sequence of SEQ ID NO:464, and a VL CDR3 having an amino acid sequence of SEQ ID NO:465.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:466, a VH CDR2 having an amino acid sequence of SEQ ID NO:467, and a VH CDR3 having an amino acid sequence of SEQ ID NO:468; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:469, a VL CDR2 having an amino acid sequence of SEQ ID NO:470, and a VL CDR3 having an amino acid sequence of SEQ ID NO:471.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:466, a VH CDR2 having an amino acid sequence of SEQ ID NO:716, and a VH CDR3 having an amino acid sequence of SEQ ID NO:717; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:469, a VL CDR2 having an amino acid sequence of SEQ ID NO:470, and a VL CDR3 having an amino acid sequence of SEQ ID NO:471.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:472, a VH CDR2 having an amino acid sequence of SEQ ID NO:473, and a VH CDR3 having an amino acid sequence of SEQ ID NO:474; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:475, a VL CDR2 having an amino acid sequence of SEQ ID NO:476, and a VL CDR3 having an amino acid sequence of SEQ ID NO:477.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:478, a VH CDR2 having an amino acid sequence of SEQ ID NO:479, and a VH CDR3 having an amino acid sequence of SEQ ID NO:480; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 481, a VL CDR2 having an amino acid sequence of SEQ ID NO:482, and a VL CDR3 having an amino acid sequence of SEQ ID NO:483.
  • the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 113.
  • the first binding domain comprises a VL having an amino acid sequence of SEQ ID NO: 114. In some embodiments, the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 113, and a VL having an amino acid sequence of SEQ ID NO:l 14. In some embodiments, the first binding domain comprises a heavy chain having an amino acid sequence of SEQ ID NO: 115. In some embodiments, the first binding domain comprises a light chain having an amino acid sequence of SEQ ID NO:l 16. In some embodiments, the first binding domain comprises a heavy chain having an amino acid sequence of SEQ ID NO: 115, and a light chain having an amino acid sequence of SEQ ID NO: 116.
  • the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 113. In some embodiments, the first binding domain comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 114. In some embodiments, the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 113, and a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 114. In some embodiments, the first binding domain comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 115.
  • the first binding domain comprises a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 116. In some embodiments, the first binding domain comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 115, and a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 116.
  • the first binding domain that binds to TRGV9 comprises a VH and VL amino acid sequence of VG9SB10SC1087 P18 C12.
  • the first binding domain comprises a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO: 123.
  • the first binding domain comprises a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 124.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO: 123; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 124.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 117, a VH CDR2 having an amino acid sequence of SEQ ID NO: 118, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 119, and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 120, a VL CDR2 having an amino acid sequence of SEQ ID NO: 121, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 122.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:484, a VH CDR2 having an amino acid sequence of SEQ ID NO:485, and a VH CDR3 having an amino acid sequence of SEQ ID NO:486; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:487, a VL CDR2 having an amino acid sequence of SEQ ID NO:488, and a VL CDR3 having an amino acid sequence of SEQ ID NO:489.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:490, a VH CDR2 having an amino acid sequence of SEQ ID NO:491, and a VH CDR3 having an amino acid sequence of SEQ ID NO:492; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:493, a VL CDR2 having an amino acid sequence of SEQ ID NO:494, and a VL CDR3 having an amino acid sequence of SEQ ID NO:495.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:496, a VH CDR2 having an amino acid sequence of SEQ ID NO:497, and a VH CDR3 having an amino acid sequence of SEQ ID NO:498; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:499, a VL CDR2 having an amino acid sequence of SEQ ID NO:500, and a VL CDR3 having an amino acid sequence of SEQ ID NO:501.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:502, a VH CDR2 having an amino acid sequence of SEQ ID NO:503, and a VH CDR3 having an amino acid sequence of SEQ ID NO:504; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 505, a VL CDR2 having an amino acid sequence of SEQ ID NO:506, and a VL CDR3 having an amino acid sequence of SEQ ID NO:507.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:502, a VH CDR2 having an amino acid sequence of SEQ ID NO:718, and a VH CDR3 having an amino acid sequence of SEQ ID NO:719; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 505, a VL CDR2 having an amino acid sequence of SEQ ID NO:506, and a VL CDR3 having an amino acid sequence of SEQ ID NO:507.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:508, a VH CDR2 having an amino acid sequence of SEQ ID NO:509, and a VH CDR3 having an amino acid sequence of SEQ ID NO:510; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 511, a VL CDR2 having an amino acid sequence of SEQ ID NO: 512, and a VL CDR3 having an amino acid sequence of SEQ ID NO:513.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:514, a VH CDR2 having an amino acid sequence of SEQ ID NO:515, and a VH CDR3 having an amino acid sequence of SEQ ID NO:516; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:517, a VL CDR2 having an amino acid sequence of SEQ ID NO: 518, and a VL CDR3 having an amino acid sequence of SEQ ID NO:519.
  • the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 123.
  • the first binding domain comprises a VL having an amino acid sequence of SEQ ID NO: 124. In some embodiments, the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 123, and a VL having an amino acid sequence of SEQ ID NO: 124. In some embodiments, the first binding domain comprises a heavy chain having an amino acid sequence of SEQ ID NO: 124.
  • the first binding domain comprises a light chain having an amino acid sequence of SEQ ID NO: 126. In some embodiments, the first binding domain comprises a heavy chain having an amino acid sequence of SEQ ID NO: 125, and a light chain having an amino acid sequence of SEQ ID NO: 126. In some embodiments, the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 123. In some embodiments, the first binding domain comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 124.
  • the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 123, and a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 124.
  • the first binding domain comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 125.
  • the first binding domain comprises a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 126.
  • the first binding domain comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 125, and a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 126.
  • the first binding domain that binds to TRGV9 comprises a VH and VL amino acid sequence of VG9SB10SC1087 P19 C03.
  • the first binding domain comprises a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO: 133.
  • the first binding domain comprises a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 134.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO: 133; and (ii) a VL comprising a VL
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 127, a VH CDR2 having an amino acid sequence of SEQ ID NO: 128, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 129, and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 130, a VL CDR2 having an amino acid sequence of SEQ ID NO: 131, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 132.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 520, a VH CDR2 having an amino acid sequence of SEQ ID NO: 521, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 522; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:523, a VL CDR2 having an amino acid sequence of SEQ ID NO: 524, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 525.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 526, a VH CDR2 having an amino acid sequence of SEQ ID NO: 527, and a VH CDR3 having an amino acid sequence of SEQ ID NO:528; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:529, a VL CDR2 having an amino acid sequence of SEQ ID NO:530, and a VL CDR3 having an amino acid sequence of SEQ ID NO:531.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:532, a VH CDR2 having an amino acid sequence of SEQ ID NO:533, and a VH CDR3 having an amino acid sequence of SEQ ID NO:534; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 535, a VL CDR2 having an amino acid sequence of SEQ ID NO:536, and a VL CDR3 having an amino acid sequence of SEQ ID NO:537.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:538, a VH CDR2 having an amino acid sequence of SEQ ID NO:539, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 540; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 541, a VL CDR2 having an amino acid sequence of SEQ ID NO: 542, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 543.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:538, a VH CDR2 having an amino acid sequence of SEQ ID NO:720, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 721; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 541, a VL CDR2 having an amino acid sequence of SEQ ID NO: 542, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 543.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:544, a VH CDR2 having an amino acid sequence of SEQ ID NO:545, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 546; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:547, a VL CDR2 having an amino acid sequence of SEQ ID NO: 548, and a VL CDR3 having an amino acid sequence of SEQ ID NO:549.
  • the first binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:550, a VH CDR2 having an amino acid sequence of SEQ ID NO:551, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 552; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 553, a VL CDR2 having an amino acid sequence of SEQ ID NO: 554, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 555.
  • the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 133.
  • the first binding domain comprises a VL having an amino acid sequence of SEQ ID NO: 134. In some embodiments, the first binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 133, and a VL having an amino acid sequence of SEQ ID NO: 134. In some embodiments, the first binding domain comprises a heavy chain having an amino acid sequence of SEQ ID NO: 135. In some embodiments, the first binding domain comprises a light chain having an amino acid sequence of SEQ ID NO: 136. In some embodiments, the first binding domain comprises a heavy chain having an amino acid sequence of SEQ ID NO: 135, and a light chain having an amino acid sequence of SEQ ID NO: 136.
  • the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 133. In some embodiments, the first binding domain comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 134. In some embodiments, the first binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 133, and a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 134. In some embodiments, the first binding domain comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 135.
  • the first binding domain comprises a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 136. In some embodiments, the first binding domain comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 135, and a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 136.
  • the VH CDR1, VH CDR2 and VH CDR3 amino acid sequences of the first binding domain that binds TRGV9 are according to the Rabat numbering system. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 amino acid sequences of the first binding domain that binds TRGV9 are according to the Chothia numbering system. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 amino acid sequences of the first binding domain that binds TRGV9 are according to the AbM numbering system.
  • the VH CDR1, VH CDR2 and VH CDR3 amino acid sequences of the first binding domain that binds TRGV9 are according to the Contact numbering system. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 amino acid sequences of the first binding domain that binds TRGV9 are according to the IMGT numbering system. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 amino acid sequences of the first binding domain that binds TRGV9 are according to the Exemplary numbering system. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 amino acid sequences of the first binding domain that binds TRGV9 are according to the Rabat numbering system.
  • the VL CDR1, VL CDR2 and VL CDR3 amino acid sequences of the first binding domain that binds TRGV9 are according to the Chothia numbering system. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 amino acid sequences of the first binding domain that binds TRGV9 are according to the AbM numbering system. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 amino acid sequences of the first binding domain that binds TRGV9 are according to the Contact numbering system.
  • the VL CDR1, VL CDR2 and VL CDR3 amino acid sequences of the first binding domain that binds TRGV9 are according to the IMGT numbering system. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 amino acid sequences of the first binding domain that binds TRGV9 are according to the Exemplary numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the first binding domain that binds TRGV9 are according to the Rabat numbering system.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the first binding domain that binds TRGV9 are according to the Chothia numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the first binding domain that binds TRGV9 are according to the AbM numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3,
  • VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the first binding domain that binds TRGV9 are according to the Contact numbering system.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the first binding domain that binds TRGV9 are according to the IMGT numbering system.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the first binding domain that binds TRGV9 are according to the IMGT numbering system.
  • VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the first binding domain that binds TRGV9 are according to the Exemplary numbering system.
  • the first binding domain binds a TRGV9 antigen.
  • the first binding domain binds a TRGV9 epitope. In some embodiments, the first binding domain specifically binds to TRGV9. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the first binding domain form a binding site for an antigen of the TRGV9.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the first binding domain form a binding site for an epitope of the TRGV9.
  • the VH region and the VL region of the first binding domain form a binding site for an antigen of TRGV9.
  • the VH region and the VL region of the first binding domain form a binding site for an epitope of the TRGV9.
  • the heavy chain and the light chain of the first binding domain form a binding site for an antigen of TRGV9.
  • the heavy chain and the light chain of the second binding domain form a binding site for an epitope of TRGV9.
  • the TRGV9 is present on the surface of a cell.
  • the TRGV9 is present on the surface of a T cell.
  • the T cell is a gd T cell.
  • the second target is CD123.
  • the second binding domain that binds CD123 comprises a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO: 15.
  • the second binding domain that binds CD123 comprises a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 16.
  • the second binding domain that binds CD123 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO: 15; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO: 16.
  • the second binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:9, a VH CDR2 having an amino acid sequence of SEQ ID NO: 10, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 11, and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 12, a VL CDR2 having an amino acid sequence of SEQ ID NO: 13, and a VL CDR3 having an amino acid sequence of SEQ ID NO: 14.
  • the second binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:556, a VH CDR2 having an amino acid sequence of SEQ ID NO:557, and a VH CDR3 having an amino acid sequence of SEQ ID NO:558; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:559, a VL CDR2 having an amino acid sequence of SEQ ID NO:560, and a VL CDR3 having an amino acid sequence of SEQ ID NO:561.
  • the second binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:562, a VH CDR2 having an amino acid sequence of SEQ ID NO:563, and a VH CDR3 having an amino acid sequence of SEQ ID NO:564; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:565, a VL CDR2 having an amino acid sequence of SEQ ID NO:566, and a VL CDR3 having an amino acid sequence of SEQ ID NO:567.
  • the second binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:568, a VH CDR2 having an amino acid sequence of SEQ ID NO:569, and a VH CDR3 having an amino acid sequence of SEQ ID NO:570; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:571, a VL CDR2 having an amino acid sequence of SEQ ID NO:572, and a VL CDR3 having an amino acid sequence of SEQ ID NO:573.
  • the second binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:574, a VH CDR2 having an amino acid sequence of SEQ ID NO:575, and a VH CDR3 having an amino acid sequence of SEQ ID NO:576; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:577, a VL CDR2 having an amino acid sequence of SEQ ID NO:578, and a VL CDR3 having an amino acid sequence of SEQ ID NO:579.
  • the second binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO:574, a VH CDR2 having an amino acid sequence of SEQ ID NO:722, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 723; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:577, a VL CDR2 having an amino acid sequence of SEQ ID NO:578, and a VL CDR3 having an amino acid sequence of SEQ ID NO:579.
  • the second binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 580, a VH CDR2 having an amino acid sequence of SEQ ID NO: 581, and a VH CDR3 having an amino acid sequence of SEQ ID NO: 582; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO: 583, a VL CDR2 having an amino acid sequence of SEQ ID NO: 584, and a VL CDR3 having an amino acid sequence of SEQ ID NO:585.
  • the second binding domain comprises: (i) a VH comprising a VH CDR1 having an amino acid sequence of SEQ ID NO: 586, a VH CDR2 having an amino acid sequence of SEQ ID NO: 587, and a VH CDR3 having an amino acid sequence of SEQ ID NO:588; and (ii) a VL comprising a VL CDR1 having an amino acid sequence of SEQ ID NO:589, a VL CDR2 having an amino acid sequence of SEQ ID NO:590, and a VL CDR3 having an amino acid sequence of SEQ ID NO:591.
  • the second binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 15.
  • the second binding domain comprises a VL having an amino acid sequence of SEQ ID NO: 16. In some embodiments, the second binding domain comprises a VH having an amino acid sequence of SEQ ID NO: 15, and a VL having an amino acid sequence of SEQ ID NO: 16. In some embodiments, the second binding domain comprises a heavy chain having an amino acid sequence of SEQ ID NO:25. In some embodiments, the second binding domain comprises a light chain having an amino acid sequence of SEQ ID NO:26. In some embodiments, the second binding domain comprises a heavy chain having an amino acid sequence of SEQ ID NO:25, and a light chain having an amino acid sequence of SEQ ID NO:26. In some embodiments, the second binding domain comprises an amino acid sequence of SEQ ID NO: 18.
  • the second binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 15. In some embodiments, the second binding domain comprises a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 16. In some embodiments, the second binding domain comprises a VH comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 15, and a VL comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 16. In some embodiments, the second binding domain comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:25.
  • the second binding domain comprises a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:26. In some embodiments, the second binding domain comprises a heavy chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:25, and a light chain comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:26. In some embodiments, the second binding domain comprises an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO: 18.
  • the TRGV9xCD123 multispecific antibody can comprise a first binding domain comprising any TRGV9 antibody provided herein.
  • the TRGV9xCD123 multispecific antibody can further comprise a second binding domain comprising any CD 123 antibody, including any CD 123 antibody provided herein.
  • the second target is CD33.
  • the second target is the C2 domain of CD33.
  • the second target is the V domain of CD33.
  • the second binding domain that binds to CD33 comprises a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:43.
  • the second binding domain that binds to CD33 comprises a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:44.
  • the second binding domain that binds to CD33 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:43; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:44.
  • the second binding domain that binds to CD33 has a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, having the amino acid sequence of SEQ ID NOs:37, 38, 39, 40, 41, and 42, respectively.
  • the second binding domain that binds to CD33 has a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, having the amino acid sequence of SEQ ID NOs:592, 593, 594, 595, 596, and 597, respectively.
  • the second binding domain that binds to CD33 has a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, having the amino acid sequence of SEQ ID NOs:598, 599, 600, 601, 602, and 603, respectively.
  • the second binding domain that binds to CD33 has a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, having the amino acid sequence of SEQ ID NOs:604, 605, 606, 607, 608, and 609, respectively.
  • the second binding domain that binds to CD33 has a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, having the amino acid sequence of SEQ ID NOs:610, 611, 612, 613, 614, and 615, respectively.
  • the second binding domain that binds to CD33 has a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, having the amino acid sequence of SEQ ID NOs:616, 617, 618, 619, 620, and 621, respectively.
  • the second binding domain that binds to CD33 has a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, having the amino acid sequence of SEQ ID NOs:622, 623, 624, 625, 626, and 627, respectively.
  • the second binding domain that binds CD33 has a VH having the amino acid sequence of SEQ ID NO:43.
  • the second binding domain that binds CD33 has a VL having the amino acid sequence of SEQ ID NO:44.
  • the second binding domain that binds CD33 has a VH having the amino acid sequence of SEQ ID NO:43, and a VL having the amino acid sequence of SEQ ID NO:44. In certain embodiments, the second binding domain that binds CD33 has a heavy chain having the amino acid sequence of SEQ ID NO:47. In certain embodiments, the second binding domain that binds CD33 has a light chain having the amino acid sequence of SEQ ID NO:48. In some embodiments, the second binding domain that binds CD33 has a heavy chain having the amino acid sequence of SEQ ID NO:47, and a light chain having the amino acid sequence of SEQ ID NO:48.
  • the second binding domain that binds CD33 has an amino acid sequence of SEQ ID NO:45. In certain embodiments, the second binding domain that binds CD33 has a VH having at least 95% sequence identity to an amino acid sequence of SEQ ID NO:43. In certain embodiments, the second binding domain that binds CD33 has a VL having at least 95% sequence identity to an amino acid sequence of SEQ ID NO:44. In some embodiments, the second binding domain that binds CD33 has a VH having at least 95% sequence identity to an amino acid sequence of SEQ ID NO:43, and a VL having at least 95% sequence identity to an amino acid sequence of SEQ ID NO:44.
  • the second binding domain that binds CD33 has a heavy chain having at least 95% sequence identity to an amino acid sequence of SEQ ID NO:47. In certain embodiments, the second binding domain that binds CD33 has a light chain having at least 95% sequence identity to an amino acid sequence of SEQ ID NO:48. In some embodiments, the second binding domain that binds CD33 has a heavy chain having at least 95% sequence identity to an amino acid sequence of SEQ ID NO:47, and a light chain having at least 95% sequence identity to an amino acid sequence of SEQ ID NO:48. In certain embodiments, the second binding domain that binds CD33 has an amino acid sequence having at least 95% sequence identity to an amino acid sequence of SEQ ID NO:45.
  • Additional CD33 antibodies that can be used for the TRGV9 multispecific antibodies provided herein include AMG330 and AMG673 (Amgen; Friedrich et al., 2014), AMV564 (Amphivena; U.S. Pat. No. 9,803,029), IMGN779 (Immunogen; U.S. Pat. No. 9,359,442), BI836858 (Boehringer Ingelheim; Vasu et al., 2016), Actimab (Actinium Pharma), gemtuzumab (Godwin, Gale, & Walter, 2017), and SGN33A (Seattle Genetics).
  • the second binding domain that binds CD33 comprises the VH CDRl-3 and VL CDRl-3 of AMG330. In some embodiments of the multispecific TRGV9 antibodies provided herein, the second binding domain that binds CD33 comprises the VH CDRl-3 and VL CDRl-3 of AMG673. In some embodiments of the multispecific TRGV9 antibodies provided herein, the second binding domain that binds CD33 comprises the VH CDRl-3 and VL CDRl-3 of AMV564. In some embodiments of the multispecific TRGV9 antibodies provided herein, the second binding domain that binds CD33 comprises the VH CDRl-3 and VL CDRl-3 of IMGN779.
  • the second binding domain that binds CD33 comprises the VH CDRl-3 and VL CDRl-3 of BI836858. In some embodiments of the multispecific TRGV9 antibodies provided herein, the second binding domain that binds CD33 comprises the VH CDRl-3 and VL CDRl-3 of Actimab. In some embodiments of the multispecific TRGV9 antibodies provided herein, the second binding domain that binds CD33 comprises the VH CDRl-3 and VL CDRl-3 of gentuzimab. In some embodiments of the multispecific TRGV9 antibodies provided herein, the second binding domain that binds CD33 comprises the VH CDRl-3 and VL CDRl-3 of SGN33A.
  • the TRGV9xCD33 multispecific antibody can comprise a first binding domain comprising any TRGV9 antibody provided herein.
  • the TRGV9xCD33 multispecific antibody can further comprise a second binding domain comprising any CD33 antibody, including any CD33 antibody provided herein.
  • the second target is TRBCl.
  • the second binding domain that binds to TRBCl comprises a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:55.
  • the second binding domain that binds to TRBC1 comprises a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:56.
  • the second binding domain that binds to TRBC1 comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having an amino acid sequence of a VH CDR1, a VH CDR2, and a VH CDR3, respectively, of a VH having an amino acid sequence of SEQ ID NO:55; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having an amino acid sequence of a VL CDR1, a VL CDR2, and a VL CDR3, respectively, of a VL having an amino acid sequence of SEQ ID NO:56.
  • the second binding domain that binds to TRBC1 has a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, having the amino acid sequence of SEQ ID NOs:49, 50, 51, 52, 53 and 54, respectively.
  • the second binding domain that binds to TRBC1 has a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, having the amino acid sequence of SEQ ID NOs:628, 629, 630, 631, 632, and 633, respectively.
  • the second binding domain that binds to TRBC1 has a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, having the amino acid sequence of SEQ ID NOs:634, 635, 636, 637, 638, and 639, respectively.
  • the second binding domain that binds to TRBC1 has a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, having the amino acid sequence of SEQ ID NOs:640, 641, 642, 643, 644, 645, respectively.
  • the second binding domain that binds to TRBC1 has a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, having the amino acid sequence of SEQ ID NOs:646, 647, 648, 649, 650, and 651, respectively.
  • the second binding domain that binds to TRBC1 has a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, having the amino acid sequence of SEQ ID NOs:652, 653, 654, 655, 656, and 657, respectively.
  • the second binding domain that binds to TRBC1 has a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3, having the amino acid sequence of SEQ ID NOs:658, 659, 660, 661, 662, and 633, respectively.
  • the second binding domain that binds TRBC1 has a VH having the amino acid sequence of SEQ ID NO: 55.
  • the second binding domain that binds TRBC1 has a VL having the amino acid sequence of SEQ ID NO:56.
  • the second binding domain that binds TRBC1 has a VH having the amino acid sequence of SEQ ID NO:55, and a VL having the amino acid sequence of SEQ ID NO:56. In certain embodiments, the second binding domain that binds TRBC1 has a heavy chain having the amino acid sequence of SEQ ID NO:58. In certain embodiments, the second binding domain that binds TRBC1 has a light chain having the amino acid sequence of SEQ ID NO: 59. In some embodiments, the second binding domain that binds TRBC1 has a heavy chain having the amino acid sequence of SEQ ID NO: 58, and a light chain having the amino acid sequence of SEQ ID NO:59.
  • the second binding domain that binds TRBC1 has an amino acid sequence of SEQ ID NO:57. In certain embodiments, the second binding domain that binds TRBC1 has a VH having at least 95% sequence identity to an amino acid sequence of SEQ ID NO: 55. In certain embodiments, the second binding domain that binds TRBC1 has a VL having at least 95% sequence identity to an amino acid sequence of SEQ ID NO:56. In some embodiments, the second binding domain that binds TRBC1 has a VH having at least 95% sequence identity to an amino acid sequence of SEQ ID NO:55, and a VL having at least 95% sequence identity to an amino acid sequence of SEQ ID NO:56.
  • the second binding domain that binds TRBC1 has a heavy chain having at least 95% sequence identity to an amino acid sequence of SEQ ID NO: 58. In certain embodiments, the second binding domain that binds TRBC1 has a light chain having at least 95% sequence identity to an amino acid sequence of SEQ ID NO:59. In some embodiments, the second binding domain that binds TRBC1 has a heavy chain having at least 95% sequence identity to an amino acid sequence of SEQ ID NO: 58, and a light chain having at least 95% sequence identity to an amino acid sequence of SEQ ID NO:59. In certain embodiments, the second binding domain that binds TRBC1 has an amino acid sequence having at least 95% sequence identity to an amino acid sequence of SEQ ID NO:57.
  • the TRGV9xTRBCl multispecific antibody can comprise a first binding domain comprising any TRGV9 antibody provided herein.
  • the TRGV9xTRBCl multispecific antibody can further comprise a second binding domain comprising any TRBC1 antibody, including any TRBC1 antibody provided herein.
  • the second target is BCMA.
  • the second binding domain binds to BCMA.
  • the second binding domain that binds BCMA comprises a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of the VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 143.
  • the second binding domain that binds BCMA comprises a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of the VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 144.
  • the second binding domain that binds BCMA comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of the VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 143; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of the VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 144.
  • the second binding domain binds to BCMA.
  • the second binding domain comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of the VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO: 143; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of the VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO: 144.
  • the second binding domain that binds to BCMA has a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NOs:137, 138, 139, 140, 141, and 142, respectively.
  • the second binding domain that binds to BCMA has a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NOs:664, 665, 666, 667, 668, and 669, respectively.
  • the second binding domain that binds to BCMA has a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NOs:670, 671, 672, 673, 674, and 675, respectively.
  • the second binding domain that binds to BCMA has a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL
  • CDR3 having the amino acid sequence of SEQ ID Nos:676, 677, 678, 679, 680, and
  • the second binding domain that binds to BCMA has a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NOs:682, 683, 684, 685, 686, and 687, respectively.
  • the second binding domain that binds to BCMA has a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NOs:688, 689, 690, 691, 692, and 693, respectively.
  • the second binding domain that binds to BCMA has a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NOs:694, 695, 696, 697, 698, and 699, respectively.
  • the second binding domain that binds BCMA has a VH having the amino acid sequence of SEQ ID NO: 143.
  • the second binding domain that binds BCMA has a VL having the amino acid sequence of SEQ ID NO: 144.
  • the second binding domain that binds BCMA has a VH having the amino acid sequence of SEQ ID NO: 143, and a VL having the amino acid sequence of SEQ ID NO: 144. In certain embodiments, the second binding domain that binds BCMA has a heavy chain having the amino acid sequence of SEQ ID NO: 146. In certain embodiments, the second binding domain that binds BCMA has a light chain having the amino acid sequence of SEQ ID NO: 147. In some embodiments, the second binding domain that binds BCMA has a heavy chain having the amino acid sequence of SEQ ID NO: 146, and a light chain having the amino acid sequence of SEQ ID NO: 147.
  • the second binding domain that binds BCMA has an amino acid sequence of SEQ ID NO: 145. In certain embodiments, the second binding domain that binds BCMA has an amino acid sequence of SEQ ID NO: 148. In certain embodiments, the second binding domain that binds BCMA has an amino acid sequence of SEQ ID NO: 149. In certain embodiments, the second binding domain that binds BCMA has a VH having at least 95% sequence identity to an amino acid sequence of SEQ ID NO: 143. In certain embodiments, the second binding domain that binds BCMA has a VL having at least 95% sequence identity to an amino acid sequence of SEQ ID NO: 144.
  • the second binding domain that binds BCMA has a VH having at least 95% sequence identity to an amino acid sequence of SEQ ID NO: 143, and a VL having at least 95% sequence identity to an amino acid sequence of SEQ ID NO: 144.
  • the second binding domain that binds BCMA has a heavy chain having at least 95% sequence identity to an amino acid sequence of SEQ ID NO: 146.
  • the second binding domain that binds BCMA has a light chain having at least 95% sequence identity to an amino acid sequence of SEQ ID NO: 147.
  • the second binding domain that binds BCMA has a heavy chain having at least 95% sequence identity to an amino acid sequence of SEQ ID NO: 146, and a light chain having at least 95% sequence identity to an amino acid sequence of SEQ ID NO: 147. In certain embodiments, the second binding domain that binds BCMA has an amino acid sequence having at least 95% sequence identity to an amino acid sequence of SEQ ID NO: 145. In certain embodiments, the second binding domain that binds BCMA has an amino acid sequence having at least 95% sequence identity to an amino acid sequence of SEQ ID NO: 148. In certain embodiments, the second binding domain that binds BCMA has an amino acid sequence having at least 95% sequence identity to an amino acid sequence of SEQ ID NO: 149.
  • the TRGV9xBCMA multispecific antibody can comprise a first binding domain comprising any TRGV9 antibody provided herein.
  • the TRGV9xBCMA multispecific antibody can further comprise a second binding domain comprising any BCMA antibody, including any BCMA antibody provided herein.
  • the second target is PSMA.
  • the second binding domain binds to PSMA.
  • the second binding domain that binds PSMA comprises a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of the VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO:775.
  • the second binding domain that binds PSMA comprises a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of the VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO:776.
  • the second binding domain that binds PSMA comprises: (i) a VH comprising a VH CDR1, a VH CDR2, and a VH CDR3 having amino acid sequences of the VH CDR1, VH CDR2, and VH CDR3, respectively, of SEQ ID NO:775; and (ii) a VL comprising a VL CDR1, a VL CDR2, and a VL CDR3 having amino acid sequences of the VL CDR1, VL CDR2, and VL CDR3, respectively, of SEQ ID NO:776.
  • the second binding domain that binds to PSMA has a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequence of SEQ ID NOs:783, 784, 785, 786, 787 and 788, respectively.
  • the second binding domain that binds PSMA has a VH having the amino acid sequence of SEQ ID NO:775.
  • the second binding domain that binds PSMA has a VL having the amino acid sequence of SEQ ID NO:776.
  • the second binding domain that binds PSMA has a VH having the amino acid sequence of SEQ ID NO:775, and a VL having the amino acid sequence of SEQ ID NO:776. In certain embodiments, the second binding domain that binds PSMA has a heavy chain having the amino acid sequence of SEQ ID NO:781. In certain embodiments, the second binding domain that binds PSMA has a light chain having the amino acid sequence of SEQ ID NO:782. In some embodiments, the second binding domain that binds PSMA has a heavy chain having the amino acid sequence of SEQ ID NO:781, and a light chain having the amino acid sequence of SEQ ID NO:782.
  • the second binding domain that binds PSMA has a VH having at least 95% sequence identity to an amino acid sequence of SEQ ID NO:775. In certain embodiments, the second binding domain that binds PSMA has a VL having at least 95% sequence identity to an amino acid sequence of SEQ ID NO:776. In some embodiments, the second binding domain that binds PSMA has a VH having at least 95% sequence identity to an amino acid sequence of SEQ ID NO:775, and a VL having at least 95% sequence identity to an amino acid sequence of SEQ ID NO:776. In certain embodiments, the second binding domain that binds PSMA has a heavy chain having at least 95% sequence identity to an amino acid sequence of SEQ ID NO:781.
  • the second binding domain that binds PSMA has a light chain having at least 95% sequence identity to an amino acid sequence of SEQ ID NO:782. In some embodiments, the second binding domain that binds PSMA has a heavy chain having at least 95% sequence identity to an amino acid sequence of SEQ ID NO:781, and a light chain having at least 95% sequence identity to an amino acid sequence of SEQ ID NO:782.
  • the TRGV9xPSMA multispecific antibody can comprise a first binding domain comprising any TRGV9 antibody provided herein.
  • the TRGV9xPSMA multispecific antibody can further comprise a second binding domain comprising any PSMA antibody, including any PSMA antibody provided herein.
  • VH CDR1, VH CDR2 and VH CDR3 amino acid sequences of the second binding domain that binds TRGV9 are according to the
  • the VH CDR1, VH CDR2 and VH CDR3 amino acid sequences of the second binding domain that binds TRGV9 are according to the Chothia numbering system. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 amino acid sequences of the second binding domain that binds TRGV9 are according to the AbM numbering system. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 amino acid sequences of the second binding domain that binds TRGV9 are according to the Contact numbering system.
  • the VH CDR1, VH CDR2 and VH CDR3 amino acid sequences of the second binding domain that binds TRGV9 are according to the IMGT numbering system. In some embodiments, the VH CDR1, VH CDR2 and VH CDR3 amino acid sequences of the second binding domain that binds TRGV9 are according to the Exemplary numbering system. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 amino acid sequences of the second binding domain that binds TRGV9 are according to the Rabat numbering system.
  • the VL CDR1, VL CDR2 and VL CDR3 amino acid sequences of the second binding domain that binds TRGV9 are according to the Chothia numbering system. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 amino acid sequences of the second binding domain that binds TRGV9 are according to the AbM numbering system. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 amino acid sequences of the second binding domain that binds TRGV9 are according to the Contact numbering system.
  • the VL CDR1, VL CDR2 and VL CDR3 amino acid sequences of the second binding domain that binds TRGV9 are according to the IMGT numbering system. In some embodiments, the VL CDR1, VL CDR2 and VL CDR3 amino acid sequences of the second binding domain that binds TRGV9 are according to the Exemplary numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the second binding domain that binds the second target are according to the Rabat numbering system.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the second binding domain that binds the second target are according to the Chothia numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the second binding domain that binds the second target are according to the AbM numbering system. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL
  • VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the second binding domain that binds the second target are according to the Contact numbering system.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the second binding domain that binds the second target are according to the IMGT numbering system.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of the second binding domain that binds the second target are according to the Exemplary numbering system.
  • the multispecific TRGV9 antibody does not comprise L7A5 1 (TRGV9 1). In some embodiments, the multispecific TRGV9 antibody does not comprise L7A5 2 (TRGV9 2). In some embodiments, the multispecific TRGV9 antibody does not comprise L7A5 3 (TRGV9 3). In some embodiments, the multispecific TRGV9 antibody does not comprise L7A5 4 (TRGV9 4). In some embodiments, the multispecific TRGV9 antibody does not comprise a VH CDRl-3 or a VL CDRl-3 of L7A5 1 (TRGV9 1).
  • the multispecific TRGV9 antibody does not comprise a VH CDRl-3 or a VL CDRl-3 of L7A5 2 (TRGV9 2). In some embodiments, the multispecific TRGV9 antibody does not comprise a VH CDRl-3 or a VL CDRl-3 of L7A5 3 (TRGV9 3). In some embodiments, the multispecific TRGV9 antibody does not comprise a VH CDRl-3 or a VL CDRl-3 of L7A5 4 (TRGV9 4). In some embodiments, the multispecific TRGV9 antibody does not comprise a second binding arm that binds CD 123.
  • the second binding domain binds an antigen of the second target. In some embodiments, In some embodiments, the second binding domain binds an 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 an antigen of the second target. In some embodiments, the second binding domain specifically binds an epitope of the second target. In some embodiments, the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the second binding domain form a binding site for an antigen of the second target.
  • the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3 of the second binding domain form a binding site for an epitope of the second target.
  • the VH region and the VL region of the second binding domain form a binding site for an antigen of the second target.
  • the VH region and the VL region of the second binding domain form a binding site for an epitope of the second target.
  • the heavy chain and the light chain of the second binding domain form a binding site for an antigen of the second target.
  • the heavy chain and the light chain of the second binding domain form a binding site for an epitope of the second target.
  • the first binding domain of the multispecific TRGV9 antibody is multivalent. In some embodiments, the first binding domain of the multispecific TRGV9 antibody is capable of binding at least three antigens. In some embodiments, the first binding domain of the multispecific TRGV9 antibody is capable of binding at least four antigens. In some embodiments, the first binding domain of the multispecific TRGV9 antibody is capable of binding at least five antigens. In some embodiments, the second binding domain of the multispecific TRGV9 antibody is multivalent. In some embodiments, the second binding domain of the multispecific TRGV9 antibody is capable of binding at least three antigens. In some embodiments, the second binding domain of the multispecific TRGV9 antibody is capable of binding at least four antigens. In some embodiments, the second binding domain of the multispecific TRGV9 antibody is capable of binding at least five antigens.
  • the second target is expressed by target cell.
  • the second target is on the surface of a target cell.
  • the target cell is an undesired cell.
  • the target cell expressing the second target is killed when the multispecific TRGV9 antibody binds to TRGV9 on the surface of a T cell and the second target.
  • the T cell is a gd T cell.
  • a first heavy chain (HC1) comprises a VH CDRl-3 that binds to TRGV9.
  • a first light chain (LC1) comprises a VL CDRl-3 that binds to TRGV9.
  • the HC1 VH CDRl-3 and the LC1 VL CDRl-3 form a binding site for the TRGV9.
  • the binding site specifically binds TRGV9.
  • a second heavy chain (HC2) comprises a VH CDRl-3 that binds to the second target.
  • a second light chain (LC2) comprises a VL CDRl-3 that binds to the second target.
  • the HC2 VH CDRl-3 and the LC2 VL CDRl-3 form a binding site for the second target.
  • the binding site specifically binds the second target.
  • the TRGV9 is on the surface of a gd T cell.
  • the second target antigen is on the surface of a second target cell.
  • 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 a 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 an erythrocyte. In one embodiment, the target cell is an endothelial cell. In one embodiment, the target cell is an epithelial cell. In one embodiment, the target cell is a pathogen. In one embodiment, the target cell is a blood cell. In one embodiment, the target cell is a myeloid cell.
  • the second binding arm binds a second target.
  • the second target is present on a target cell.
  • the second target is present on the surface of a target cell.
  • the target cell is a cancer cell.
  • the second target is a cancer antigen.
  • the second target is on a cancer cell.
  • the target cell is a cancer cell.
  • the second target is on the surface of a cancer cell.
  • the second target is an antigen on the surface of a cancer cell.
  • the antigen on the surface of the cancer cell is a tumor-specific antigen, a tumor-associated antigen, or a neoantigen.
  • a multispecific antibody comprising: (a) a first binding domain that binds to TRGV9, and (b) a second binding domain that binds to a cancer antigen present on the surface of a cancer cell.
  • the antigen on the surface of the cancer cell is a tumor-specific antigen.
  • the antigen on the surface of the cancer cell is a tumor associated antigen.
  • the antigen on the surface of the cancer cell is a neoantigen.
  • the first binding domain of the bispecific antibody specifically binds TRGV9.
  • the TRGV9 is present on the surface of a gd T cell.
  • the cancer cell is killed when the multispecific antibody binds to the TRGV9 on the surface of the gd T cell and the antigen on the surface of the cancer cell.
  • Bispecific antibodies comprising any of the TRGV9 antibodies provided herein as the first binding domain are contemplated, in certain embodiments.
  • the cancer antigen is CD123. In some embodiments, the cancer antigen is CD33. In some embodiments, the cancer antigen is BCMA. In some embodiments, the cancer antigen is PSMA. The binding of the TRGV9 multispecific antibody to TRGV9 present on the surface of the T cell, and the binding of the cancer antigen present on the surface of the cancer cell can, for example, result in the killing of the cancer cell.
  • the anti-TRGV9 antibodies or antigen binding fragments thereof binds to a first epitope located on TRGV9 and a second epitope of a cancer cell.
  • a bispecific antibody comprising: (a) a first binding domain that binds to a TRGV9 antigen, and (b) a second binding domain that binds to a cancer cell antigen.
  • a bispecific antibody comprising: (a) a first binding domain that specifically binds to a TRGV9 antigen, and (b) a second binding domain that specifically binds to a cancer cell antigen.
  • a bispecific antibody comprising: (a) a first binding domain that binds to a first epitope on a TRGV9 antigen, and (b) a second binding domain that binds to a second epitope on a cancer cell antigen.
  • a bispecific antibody comprising: (a) a first binding domain that specifically binds to a first epitope on a TRGV9 antigen, and (b) a second binding domain that specifically binds to a second epitope on a cancer cell antigen.
  • the antigen is CD123.
  • the antigen is CD33.
  • the antigen is BCMA.
  • the antigen is PSMA.
  • the first epitope is located on TRGV9 and the second epitope is located on the surface of a cancer cell. In some embodiments, the second epitope is located on a cancer cell antigen. In an embodiment of the bispecific antibodies provided herein, the first epitope is located on TRGV9 and the second epitope is located on a tumor. In an embodiment of the bispecific antibodies provided herein, the first epitope is located on TRGV9 and the second epitope is located on a tumor-specific antigen. In an embodiment of the bispecific antibodies provided herein, the first epitope is located on TRGV9 and the second epitope is located on a tumor associated antigen. In an embodiment of the bispecific antibodies provided herein, the first epitope is located on TRGV9 and the second epitope is located on a neoantigen.
  • the cancer cell is a cell of an adrenal cancer, anal cancer, appendix cancer, bile duct cancer, bladder cancer, bone cancer, brain cancer, breast cancer, cervical cancer, colorectal cancer, esophageal cancer, gallbladder cancer, gestational trophoblastic, head and neck cancer, Hodgkin lymphoma, intestinal cancer, kidney cancer, leukemia, liver cancer, lung cancer, melanoma, mesothelioma, multiple myeloma, neuroendocrine tumor, non-Hodgkin lymphoma, oral cancer, ovarian cancer, pancreatic cancer, prostate cancer, sinus cancer, skin cancer, soft tissue sarcoma spinal cancer, stomach cancer, testicular cancer, throat cancer, thyroid cancer, uterine cancer endometrial cancer, vaginal cancer, or vulvar cancer.
  • the cancer is an adrenal cancer, anal cancer, appendix cancer, bile duct cancer, bladder cancer, bone cancer, brain cancer, breast cancer, cervical cancer, colorectal cancer, esophageal cancer, gallbladder cancer, gestational trophoblastic, head and neck cancer, Hodgkin lymphoma, intestinal cancer, kidney cancer, leukemia, liver cancer, lung cancer, melanoma, mesothelioma, multiple myeloma, neuroendocrine tumor, non-Hodgkin lymphoma, oral cancer, ovarian cancer, pancreatic cancer, prostate cancer, sinus cancer, skin cancer, soft tissue sarcoma spinal cancer, stomach cancer, testicular cancer, throat cancer, thyroid cancer, uterine cancer endometrial cancer, vaginal cancer, or vulvar cancer.
  • the cancer is a adrenal cancer. In some embodiments, the cancer is a anal cancer. In some embodiments, the cancer is an appendix cancer. In some embodiments, the cancer is a bile duct cancer. In some embodiments, the cancer is a bladder cancer. In some embodiments, the cancer is a bone cancer. In some embodiments, the cancer is a brain cancer. In some embodiments, the cancer is a breast cancer. In some embodiments, the cancer is a cervical cancer. In some embodiments, the cancer is a colorectal cancer. In some embodiments, the cancer is a esophageal cancer. In some embodiments, the cancer is a gallbladder cancer. In some embodiments, the cancer is a gestational trophoblastic.
  • the cancer is a head and neck cancer. In some embodiments, the cancer is a Hodgkin lymphoma. In some embodiments, the cancer is an intestinal cancer. In some embodiments, the cancer is a kidney cancer. In some embodiments, the cancer is a leukemia. In some embodiments, the cancer is a liver cancer. In some embodiments, the cancer is a lung cancer. In some embodiments, the cancer is a melanoma. In some embodiments, the cancer is a mesothelioma. In some embodiments, the cancer is a multiple myeloma. In some embodiments, the cancer is a neuroendocrine tumor. In some embodiments, the cancer is a non-Hodgkin lymphoma.
  • the cancer is an oral cancer. In some embodiments, the cancer is a ovarian cancer. In some embodiments, the cancer is a pancreatic cancer. In some embodiments, the cancer is a prostate cancer. In some embodiments, the cancer is a sinus cancer. In some embodiments, the cancer is a skin cancer. In some embodiments, the cancer is a soft tissue sarcoma spinal cancer. In some embodiments, the cancer is a stomach cancer. In some embodiments, the cancer is a testicular cancer. In some embodiments, the cancer is a throat cancer. In some embodiments, the cancer is a thyroid cancer. In some embodiments, the cancer is a uterine cancer endometrial cancer. In some embodiments, the cancer is a vaginal cancer. In some embodiments, the cancer is a vulvar cancer.
  • the adrenal cancer is an adrenocortical carcinoma (ACC), adrenal cortex cancer, pheochromocytoma, or neuroblastoma.
  • ACC adrenocortical carcinoma
  • adrenal cortex cancer pheochromocytoma
  • neuroblastoma adrenocortical carcinoma
  • the anal cancer is a squamous cell carcinoma, cloacogenic carcinoma, adenocarcinoma, basal cell carcinoma, or melanoma.
  • the appendix cancer is a neuroendocrine tumor (NET), mucinous adenocarcinoma, goblet cell carcinoid, intestinal-type adenocarcinoma, or signet-ring cell adenocarcinoma.
  • NET neuroendocrine tumor
  • mucinous adenocarcinoma goblet cell carcinoid
  • intestinal-type adenocarcinoma or signet-ring cell adenocarcinoma.
  • the bile duct cancer is an extrahepatic bile duct cancer, adenocarcinomas, hilar bile duct cancer, perihilar bile duct cancer, distal bile duct cancer, or intrahepatic bile duct cancer.
  • the bladder cancer is transitional cell carcinoma (TCC), papillary carcinoma, flat carcinoma, squamous cell carcinoma, adenocarcinoma, small-cell carcinoma, or sarcoma.
  • the bone cancer is a primary bone cancer, sarcoma, osteosarcoma, chondrosarcoma, sarcoma, fibrosarcoma, malignant fibrous histiocytoma, giant cell tumor of bone, chordoma, or metastatic bone cancer.
  • the brain cancer is an astrocytoma, brain stem glioma, glioblastoma, meningioma, ependymoma, oligodendroglioma, mixed glioma, pituitary carcinoma, pituitary adenoma, craniopharyngioma, germ cell tumor, pineal region tumor, medulloblastoma, or primary CNS lymphoma.
  • the breast cancer is a breast adenocarcinoma, invasive breast cancer, noninvasive breast cancer, breast sarcoma, metaplastic carcinoma, adenocystic carcinoma, phyllodes tumor, angiosarcoma, HER2 -positive breast cancer, triple-negative breast cancer, or inflammatory breast cancer.
  • the cervical cancer is a squamous cell carcinoma, or adenocarcinoma.
  • the colorectal cancer is a colorectal adenocarcinoma, primary colorectal lymphoma, gastrointestinal stromal tumor, leiomyosarcoma, carcinoid tumor, mucinous adenocarcinoma, signet ring cell adenocarcinoma, gastrointestinal carcinoid tumor, or melanoma.
  • the esophageal cancer is an adenocarcinoma or squamous cell carcinoma.
  • the gall bladder cancer is an adenocarcinoma, papillary adenocarcinoma, adenosquamous carcinoma, squamous cell carcinoma, small cell carcinoma, or sarcoma.
  • the gestational trophoblastic disease is a hydatidiform mole, gestational trophoblastic neoplasia (GTN), choriocarcinoma, placental -site trophoblastic tumor (PSTT), or epithelioid trophoblastic tumor (ETT).
  • GTN gestational trophoblastic neoplasia
  • PSTT placental -site trophoblastic tumor
  • ETT epithelioid trophoblastic tumor
  • the head and neck cancer is a laryngeal cancer, nasopharyngeal cancer, hypopharyngeal cancer, nasal cavity cancer, paranasal sinus cancer, salivary gland cancer, oral cancer, oropharyngeal cancer, or tonsil cancer.
  • the Hodgkin lymphoma is a classical Hodgkin lymphoma, nodular sclerosis, mixed cellularity, lymphocyte-rich, lymphocyte- depleted, or nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL).
  • the intestinal cancer is a small intestine cancer, small bowel cancer, adenocarcinoma, sarcoma, gastrointestinal stromal tumors, carcinoid tumors, or lymphoma.
  • the kidney cancer is a renal cell carcinoma (RCC), clear cell RCC, papillary RCC, chromophobe RCC, collecting duct RCC, unclassified RCC, transitional cell carcinoma, urothelial cancer, renal pelvis carcinoma, or renal sarcoma.
  • the leukemia is an acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), hairy cell leukemia (HCL), or a myelodysplastic syndrome (MDS).
  • ALL acute lymphocytic leukemia
  • AML acute myeloid leukemia
  • CLL chronic lymphocytic leukemia
  • CML chronic myeloid leukemia
  • HCL hairy cell leukemia
  • MDS myelodysplastic syndrome
  • the leukemia is AML.
  • the liver cancer is a hepatocellular carcinoma (HCC), fibrolamellar HCC, cholangiocarcinoma, angiosarcoma, or liver metastasis.
  • the lung cancer is a small cell lung cancer, small cell carcinoma, combined small cell carcinoma, non-small cell lung cancer, lung adenocarcinoma, squamous cell lung cancer, large-cell undifferentiated carcinoma, pulmonary nodule, metastatic lung cancer, adenosquamous carcinoma, large cell neuroendocrine carcinoma, salivary gland-type lung carcinoma, lung carcinoid, mesothelioma, sarcomatoid carcinoma of the lung, or malignant granular cell lung tumor.
  • the melanoma is a superficial spreading melanoma, nodular melanoma, acral-lentiginous melanoma, lentigo maligna melanoma, amelanotic melanoma, desmoplastic melanoma, ocular melanoma, or metastatic melanoma.
  • the mesothelioma is a pleural mesothelioma, peritoneal mesothelioma, pericardial mesothelioma, or testicular mesothelioma.
  • the multiple myeloma is an active myeloma or smoldering myeloma.
  • the neuroendocrine tumor is a gastrointestinal neuroendocrine tumor, pancreatic neuroendocrine tumor, or lung neuroendocrine tumor.
  • the non-Hodgkin’s lymphoma is an anaplastic large-cell lymphoma, lymphoblastic lymphoma, peripheral T cell lymphoma, follicular lymphoma, cutaneous T cell lymphoma, lymphoplasmacytic lymphoma, marginal zone B-cell lymphoma, MALT lymphoma, small-cell lymphocytic lymphoma, Burkitt lymphoma, chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), precursor T-lymphoblastic leukemia/lymphoma, acute lymphocytic leukemia (ALL), adult T cell lymphoma/leukemia (ATLL), hairy cell leukemia, B-cell lymphomas, diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma, primary central nervous system (CNS) lymphoma, mantle cell lymphoma (MCL),
  • DLBCL diffuse large B
  • the cancer is multiple myeloma (MM).
  • the cancer is chronic lymphocytic leukemia.
  • the cancer is acute B-lymphoblastic leukemia.
  • the cancer is non-Hodgkin lymphoma (NHL).
  • the cancer is Hodgkin lymphoma.
  • the oral cancer is a squamous cell carcinoma, verrucous carcinoma, minor salivary gland carcinomas, lymphoma, benign oral cavity tumor, eosinophilic granuloma, fibroma, granular cell tumor, karatoacanthoma, leiomyoma, osteochondroma, lipoma, schwannoma, neurofibroma, papilloma, condyloma acuminatum, verruciform xanthoma, pyogenic granuloma, rhabdomyoma, odontogenic tumors, leukoplakia, erythroplakia, squamous cell lip cancer, basal cell lip cancer, mouth cancer, gum cancer, or tongue cancer.
  • the ovarian cancer is a ovarian epithelial cancer, mucinous epithelial ovarian cancer, endometrioid epithelial ovarian cancer, clear cell epithelial ovarian cancer, undifferentiated epithelial ovarian cancer, ovarian low malignant potential tumors, primary peritoneal carcinoma, fallopian tube cancer, germ cell tumors, teratoma, dysgerminoma ovarian germ cell cancer, endodermal sinus tumor, sex cord-stromal tumors, sex cord-gonadal stromal tumor, ovarian stromal tumor, granulosa cell tumor, granulosa-theca tumor, Sertoli-Leydig tumor, ovarian sarcoma, ovarian carcinosarcoma, ovarian adenosarcoma, ovarian leiomyosarcoma, ovarian fibrosarcoma, Krukenberg tumor, or ovarian cyst.
  • the pancreatic cancer is a pancreatic exocrine gland cancer, pancreatic endocrine gland cancer, or pancreatic adenocarcinoma, islet cell tumor, or neuroendocrine tumor.
  • the prostate cancer is a prostate adenocarcinoma, prostate sarcoma, transitional cell carcinoma, small cell carcinoma, or neuroendocrine tumor.
  • the sinus cancer is a squamous cell carcinoma, mucosa cell carcinoma, adenoid cystic cell carcinoma, acinic cell carcinoma, sinonasal undifferentiated carcinoma, nasal cavity cancer, paranasal sinus cancer, maxillary sinus cancer, ethmoid sinus cancer, or nasopharynx cancer.
  • the skin cancer is a basal cell carcinoma, squamous cell carcinoma, melanoma, Merkel cell carcinoma, Kaposi sarcoma (KS), actinic keratosis, skin lymphoma, or keratoacanthoma.
  • basal cell carcinoma squamous cell carcinoma, melanoma, Merkel cell carcinoma, Kaposi sarcoma (KS), actinic keratosis, skin lymphoma, or keratoacanthoma.
  • the soft tissue cancer is an angiosarcoma , dermatofibrosarcoma, epithelioid sarcoma, Ewing’s sarcoma, fibrosarcoma, gastrointestinal stromal tumors (GISTs), Kaposi sarcoma, leiomyosarcoma, liposarcoma, dedifferentiated liposarcoma (DL), myxoid/round cell liposarcoma (MRCL), well-differentiated liposarcoma (WDL), malignant fibrous histiocytoma, neurofibrosarcoma, rhabdomyosarcoma (RMS), or synovial sarcoma.
  • GISTs gastrointestinal stromal tumors
  • Kaposi sarcoma leiomyosarcoma, liposarcoma, dedifferentiated liposarcoma (DL), myxoid/round cell liposarcoma (MRCL), well-differentiated liposar
  • the spinal cancer is a spinal metastatic tumor.
  • the stomach cancer is a stomach adenocarcinoma, stomach lymphoma, gastrointestinal stromal tumors, carcinoid tumor, gastric carcinoid tumors, Type I ECL-cell carcinoid, Type II ECL-cell carcinoid, or Type III ECL-cell carcinoid.
  • the testicular cancer is a seminoma, non-seminoma, embryonal carcinoma, yolk sac carcinoma, choriocarcinoma, teratoma, gonadal stromal tumor, leydig cell tumor, or sertoli cell tumor.
  • the throat cancer is a squamous cell carcinoma, adenocarcinoma, sarcoma, laryngeal cancer, pharyngeal cancer, nasopharynx cancer, oropharynx cancer, hypopharynx cancer, laryngeal cancer, laryngeal squamous cell carcinoma, laryngeal adenocarcinoma, lymphoepithelioma, spindle cell carcinoma, verrucous cancer, undifferentiated carcinoma, or lymph node cancer.
  • the thyroid cancer is a papillary carcinoma, follicular carcinoma, Hiirthle cell carcinoma, medullary thyroid carcinoma, or anaplastic carcinoma.
  • the uterine cancer is an endometrial cancer, endometrial adenocarcinoma, endometroid carcinoma, serous adenocarcinoma, adenosquamous carcinoma, uterine carcinosarcoma, uterine sarcoma, uterine leiomyosarcoma, endometrial stromal sarcoma, or undifferentiated sarcoma.
  • the vaginal cancer is a squamous cell carcinoma, adenocarcinoma, melanoma, or sarcoma.
  • the vulvar cancer is a squamous cell carcinoma or adenocarcinoma.
  • the cancer is a solid cancer. In one embodiment, the cancer is a solid tumor. In one embodiment, the cancer is a liquid cancer. In one embodiment, the cancer is a liquid tumor. In some embodiments, the cancer is a hematologic malignancy. In cersin embodiments, the cancer is benign. In some embodiments, the cancer is malignant. Im some embodiments, the cancer is metastatic.
  • the second epitope is located on a cancer antigen.
  • the cancer antigen is angiopoietin, BCMA, CD 19, CD20, CD22, CD25 (IL2-R), CD30, CD33, CD37, CD38, CD52, CD56, CD123 (IL- 3R), cMET, DLL/Notch, EGFR, EpCAM, FGF, FGF-R, GD2, HER2, Mesothelin, Nectin-4, prostatic acid phosphatase (PAP), PDGFRa, prostate-specific antigen (PSA), PSA3, prostate-specific membrane antigen (PSMA), RANKL, SLAMF7, STEAPl, T cell receptor gamma alternate reading frame protein (TARP), TROP2, VEGF, or VEGF-R.
  • PAP prostatic acid phosphatase
  • PDGFRa prostate-specific antigen
  • PSA prostate-specific antigen
  • PSMA prostate-specific membrane antigen
  • RANKL SLAMF7
  • the cancer antigen is angiopoietin. In some embodiments, the cancer antigen is BCMA. In some embodiments, the cancer antigen is CD 19. In some embodiments, the cancer antigen is CD20. In some embodiments, the cancer antigen is CD22. In some embodiments, the cancer antigen is CD25 (IL2-R). In some embodiments, the cancer antigen is CD30. In some embodiments, the cancer antigen is CD33. In some embodiments, the cancer antigen is CD37. In some embodiments, the cancer antigen is CD38. In some embodiments, the cancer antigen is CD52. In some embodiments, the cancer antigen is CD56. In some embodiments, the cancer antigen is CD123 (IL-3R).
  • the cancer antigen is cMET. In some embodiments, the cancer antigen is DLL/Notch. In some embodiments, the cancer antigen is EGFR. In some embodiments, the cancer antigen is EpCAM. In some embodiments, the cancer antigen is FGF. In some embodiments, the cancer antigen is FGF-R. In some embodiments, the cancer antigen is GD2. In some embodiments, the cancer antigen is HER2. In some embodiments, the cancer antigen is Mesothelin. In some embodiments, the cancer antigen is Nectin-4. In some embodiments, the cancer antigen is PAP. In some embodiments, the cancer antigen is PDGFRa. In some embodiments, the cancer antigen is PSA.
  • the cancer antigen is PS A3. In some embodiments, the cancer antigen is PSCA. In some embodiments, the cancer antigen is PSMA. In some embodiments, the cancer antigen is RANKL. In some embodiments, the cancer antigen is SLAMF7. In some embodiments, the cancer antigen is STEAP1. In some embodiments, the cancer antigen is TARP. In some embodiments, the cancer antigen is TROP2. In some embodiments, the cancer antigen is VEGF. In some embodiments, the cancer antigen is VEGF-R.
  • the cancer antigen is CEA, immature laminin receptor, TAG-72, HPV E6, HPV E7, BING-4, calcium-activated chloride channel 2, cyclin-Bl, 9D7, EpCAM, EphA3, Her2/neu, tel om erase, mesothelin, SAP-1, surviving, a B AGE family antigen, CAGE family antigen, GAGE family antigen, MAGE family antigen, SAGE family antigen, XAGE family antigen, NY-ESO- 1/LAGE-l, PRAME, SSX-2, Melan-A, MART-1, GplOO, pmell7, tyrosinase, TRP- 1, TRP-2, P.
  • the cancer antigen is CEA. In some embodiments, the cancer antigen is immature laminin receptor. In some embodiments, the cancer antigen is TAG-72. In some embodiments, the cancer antigen is HPV E6. In some embodiments, the cancer antigen is HPV E7. In some embodiments, the cancer antigen is BING-4. In some embodiments, the cancer antigen is calcium-activated chloride channel 2. In some embodiments, the cancer antigen is cyclin-Bl.
  • the cancer antigen is 9D7. In some embodiments, the cancer antigen is EpCAM. In some embodiments, the cancer antigen is EphA3. In some embodiments, the cancer antigen is Her2/neu. In some embodiments, the cancer antigen is telomerase. In some embodiments, the cancer antigen is mesothelin. In some embodiments, the cancer antigen is SAP-1. In some embodiments, the cancer antigen is surviving. In some embodiments, the cancer antigen is a BAGE family antigen. In some embodiments, the cancer antigen is CAGE family antigen. In some embodiments, the cancer antigen is GAGE family antigen. In some embodiments, the cancer antigen is MAGE family antigen.
  • the cancer antigen is SAGE family antigen. In some embodiments, the cancer antigen is XAGE family antigen. In some embodiments, the cancer antigen is NY-ESO-l/LAGE-1. In some embodiments, the cancer antigen is PRAME. In some embodiments, the cancer antigen is SSX-2. In some embodiments, the cancer antigen is Melan-A. In some embodiments, the cancer antigen is MART-1. In some embodiments, the cancer antigen is GplOO. In some embodiments, the cancer antigen is pmell7. In some embodiments, the cancer antigen is tyrosinase. In some embodiments, the cancer antigen is TRP-1. In some embodiments, the cancer antigen is TRP-2.
  • the cancer antigen is P. polypeptide. In some embodiments, the cancer antigen is MC1R. In some embodiments, the cancer antigen is prostate-specific antigen. In some embodiments, the cancer antigen is b-catenin. In some embodiments, the cancer antigen is BRCA1. In some embodiments, the cancer antigen is BRCA2. In some embodiments, the cancer antigen is CDK4. In some embodiments, the cancer antigen is CML66. In some embodiments, the cancer antigen is fibronectin. In some embodiments, the cancer antigen is MART -2. In some embodiments, the cancer antigen is p53. In some embodiments, the cancer antigen is Ras. In some embodiments, the cancer antigen is TGF-PRII. In some embodiments, the cancer antigen is MUC1.
  • the binding of the TRGV9 bispecific antibody to TRGV9 present on the surface of the gd T cell, and the binding of the tumor associated antigen present on the surface of the cancer cell can, for example, result in the killing of the cancer cell.
  • the first epitope is located on TRGV9 and the second epitope is located on CD123.
  • the first epitope is located on TRGV9 and the second epitope is located on PD-1, PD-L1, CTLA-4, EGFR, HER-2, CD 19, CD20, CD3 and/or other cancer associated immune suppressors or surface antigens.
  • the second binding arm binds a second target.
  • the second target is present on a target cell.
  • the second target is present on the surface of a target cell.
  • the target cell is a T cell.
  • the second target is a T cell antigen.
  • a multispecific TRGV9 antibody provided herein comprises: (a) a first binding domain that binds to TRGV9, and (b) a second binding domain that binds to a T cell antigen present on the surface of a T cell.
  • the first binding domain of the multispecific TRGV9 antibody specifically binds TRGV9.
  • the TRGV9 is present on the surface of a gd T cell.
  • the T cell is killed when the multispecific antibody binds to the TRGV9 on the surface of the gd T cell and the antigen on the surface of the T cell.
  • the multispecific TRGV9 antibody is a bispecific TRGV9 antibody. Bispecific antibodies comprising any of the TRGV9 antibodies provided herein as the first binding domain are contemplated.
  • the TRGV9 antibody binds to a first epitope located on TRGV9 and a second epitope of a T cell.
  • a bispecific antibody comprising: (a) a first binding domain that binds to a TRGV9 antigen, and (b) a second binding domain that binds to a T cell antigen. In some embodiments, provided herein is a bispecific antibody comprising: (a) a first binding domain that specifically binds to a TRGV9 antigen, and (b) a second binding domain that specifically binds to a T cell antigen.
  • a bispecific antibody comprising: (a) a first binding domain that binds to a first epitope on a TRGV9 antigen, and (b) a second binding domain that binds to a second epitope on a T cell antigen.
  • a bispecific antibody comprising: (a) a first binding domain that specifically binds to a first epitope on a TRGV9 antigen, and (b) a second binding domain that specifically binds to a second epitope on a T cell antigen.
  • the first epitope is located on TRGV9 and the second epitope is located on the surface of a T cell.
  • the second epitope is located on a T cell antigen.
  • the T cell antigen is not a TRGV9 antigen.
  • the T cell antigen is a C
  • the T cell antigen is a CD3 antigen. In some embodiments, the T cell antigen is a CD4 antigen. In some embodiments, the T cell antigen is a CD8 antigen. In some embodiments, the T cell antigen is a CD 13 antigen. In some embodiments, the T cell antigen is a CD 16 antigen. In some embodiments, the T cell antigen is a CD 17 antigen. In some embodiments, the T cell antigen is a CD 18 antigen. In some embodiments, the T cell antigen is a CD 19 antigen. In some embodiments, the T cell antigen is a CD20 antigen. In some embodiments, the T cell antigen is a CD21 antigen.
  • the T cell antigen is a CD23 antigen. In some embodiments, the T cell antigen is a CD25 antigen. In some embodiments, the T cell antigen is a CD26 antigen. In some embodiments, the T cell antigen is a CD27 antigen. In some embodiments, the T cell antigen is a CD28 antigen. In some embodiments, the T cell antigen is a CD29 antigen. In some embodiments, the T cell antigen is a CD30 antigen. In some embodiments, the T cell antigen is a CD31 antigen. In some embodiments, the T cell antigen is a CD32b antigen. In some embodiments, the T cell antigen is a CD35 antigen.
  • the T cell antigen is a CD37 antigen. In some embodiments, the T cell antigen is a CD38 antigen. In some embodiments, the T cell antigen is a CD39 antigen. In some embodiments, the T cell antigen is a CD43 antigen. In some embodiments, the T cell antigen is a CD44 antigen. In some embodiments, the T cell antigen is a CD45 antigen. In some embodiments, the T cell antigen is a CD45RA antigen. In some embodiments, the T cell antigen is a CD45RB antigen. In some embodiments, the T cell antigen is a CD45RC antigen. In some embodiments, the T cell antigen is a CD45RO antigen.
  • the T cell antigen is a CD46 antigen. In some embodiments, the T cell antigen is a CD47 antigen. In some embodiments, the T cell antigen is a CD48 antigen. In some embodiments, the T cell antigen is a CD49 antigen. In some embodiments, the T cell antigen is a CD49b antigen. In some embodiments, the T cell antigen is a CD49c antigen. In some embodiments, the T cell antigen is a CD49d antigen. In some embodiments, the T cell antigen is a CD49e antigen. In some embodiments, the T cell antigen is a CD49f antigen. In some embodiments, the T cell antigen is a CD50 antigen.
  • the T cell antigen is a CD52 antigen. In some embodiments, the T cell antigen is a CD53 antigen. In some embodiments, the T cell antigen is a CD54 antigen. In some embodiments, the T cell antigen is a CD55 antigen. In some embodiments, the T cell antigen is a CD56 antigen. In some embodiments, the T cell antigen is a CD57 antigen. In some embodiments, the T cell antigen is a CD58 antigen. In some embodiments, the T cell antigen is a CD59 antigen. In some embodiments, the T cell antigen is a CD60a antigen. In some embodiments, the T cell antigen is a CD62L antigen.
  • the T cell antigen is a CD63 antigen. In some embodiments, the T cell antigen is a CD68 antigen. In some embodiments, the T cell antigen is a CD69 antigen. In some embodiments, the T cell antigen is a CD70 antigen. In some embodiments, the T cell antigen is a CD71 antigen. In some embodiments, the T cell antigen is a CD73 antigen. In some embodiments, the T cell antigen is a CD74 antigen. In some embodiments, the T cell antigen is a CD75S antigen. In some embodiments, the T cell antigen is a CD80 antigen. In some embodiments, the T cell antigen is a CD81 antigen.
  • the T cell antigen is a CD82 antigen. In some embodiments, the T cell antigen is a CD84 antigen. In some embodiments, the T cell antigen is a CD85A antigen. In some embodiments, the T cell antigen is a CD85J antigen. In some embodiments, the T cell antigen is a CD86 antigen. In some embodiments, the T cell antigen is a CD87 antigen. In some embodiments, the T cell antigen is a CD92 antigen. In some embodiments, the T cell antigen is a CD94 antigen. In some embodiments, the T cell antigen is a CD95 antigen. In some embodiments, the T cell antigen is a CD96 antigen.
  • the T cell antigen is a CD97 antigen. In some embodiments, the T cell antigen is a CD98 antigen. In some embodiments, the T cell antigen is a CD99 antigen. In some embodiments, the T cell antigen is a CD99R antigen. In some embodiments, the T cell antigen is a CD 100 antigen. In some embodiments, the T cell antigen is a CD101 antigen. In some embodiments, the T cell antigen is a CD 102 antigen. In some embodiments, the T cell antigen is a CD 103 antigen. In some embodiments, the T cell antigen is a CD 107a antigen. In some embodiments, the T cell antigen is a CD 107b antigen.
  • the T cell antigen is a CD 108 antigen. In some embodiments, the T cell antigen is a CD 109 antigen. In some embodiments, the T cell antigen is a CD119 antigen. In some embodiments, the T cell antigen is a CD120a antigen. In some embodiments, the T cell antigen is a CD120b antigen. In some embodiments, the T cell antigen is a CD121a antigen. In some embodiments, the T cell antigen is a CD121b antigen. In some embodiments, the T cell antigen is a CD122 antigen. In some embodiments, the T cell antigen is a CD124 antigen. In some embodiments, the T cell antigen is a CD 126 antigen.
  • the T cell antigen is a CD127 antigen. In some embodiments, the T cell antigen is a CD128 antigen. In some embodiments, the T cell antigen is a CD129 antigen. In some embodiments, the T cell antigen is a CD130 antigen. In some embodiments, the T cell antigen is a CD 132 antigen. In some embodiments, the T cell antigen is a CD134 antigen. In some embodiments, the T cell antigen is a CD137 antigen. In some embodiments, the T cell antigen is a CD 146 antigen. In some embodiments, the T cell antigen is a CD147 antigen. In some embodiments, the T cell antigen is a CD 148 antigen.
  • the T cell antigen is a CD 150 antigen. In some embodiments, the T cell antigen is a CD152 antigen. In some embodiments, the T cell antigen is a CD 153 antigen. In some embodiments, the T cell antigen is a CD 154 antigen. In some embodiments, the T cell antigen is a CD 156b antigen. In some embodiments, the T cell antigen is a CD158a antigen. In some embodiments, the T cell antigen is a CD158M antigen. In some embodiments, the T cell antigen is a CD158b2 antigen. In some embodiments, the T cell antigen is a CD158el/e2 antigen.
  • the T cell antigen is a CD158f antigen. In some embodiments, the T cell antigen is a CD158g antigen. In some embodiments, the T cell antigen is a CD158h antigen. In some embodiments, the T cell antigen is a CD158h antigen. In some embodiments, the T cell antigen is a CD158i antigen. In some embodiments, the T cell antigen is a CD158j antigen. In some embodiments, the T cell antigen is a CD158k antigen. In some embodiments, the T cell antigen is a CD 159a antigen. In some embodiments, the T cell antigen is a CD 160 antigen. In some embodiments, the T cell antigen is a CD161 antigen. In some embodiments, the T cell antigen is a CD158f antigen. In some embodiments, the T cell antigen is a CD158g antigen. In some embodiments, the T cell antigen is a CD158h antigen. In some embodiments, the T cell antigen is
  • T cell antigen is a CD 162 antigen. In some embodiments, the T cell antigen is a CD 164 antigen. In some embodiments, the T cell antigen is a CD172g antigen. In some embodiments, the T cell antigen is a CD 178 antigen. In some embodiments, the T cell antigen is a CD181 antigen. In some embodiments, the T cell antigen is a CD 182 antigen. In some embodiments, the T cell antigen is a CD 183 antigen. In some embodiments, the T cell antigen is a CD184 antigen. In some embodiments, the T cell antigen is a CD 185 antigen. In some embodiments, the T cell antigen is a CD 186 antigen.
  • the T cell antigen is a CD191 antigen. In some embodiments, the T cell antigen is a CD 192 antigen. In some embodiments, the T cell antigen is a CD 193 antigen. In some embodiments, the T cell antigen is a CD 194 antigen. In some embodiments, the T cell antigen is a CD 195 antigen. In some embodiments, the T cell antigen is a CD 196 antigen. In some embodiments, the T cell antigen is a CD 197 antigen. In some embodiments, the T cell antigen is a CDwl98 antigen. In some embodiments, the T cell antigen is a CDwl99 antigen. In some embodiments, the T cell antigen is a CD205 antigen.
  • the T cell antigen is a CD210a antigen. In some embodiments, the T cell antigen is a CDw210b antigen. In some embodiments, the T cell antigen is a CD212 antigen. In some embodiments, the T cell antigen is a CD215 antigen. In some embodiments, the T cell antigen is a CD217 antigen. In some embodiments, the T cell antigen is a CD218a antigen. In some embodiments, the T cell antigen is a CD218b antigen. In some embodiments, the T cell antigen is a CD220 antigen. In some embodiments, the T cell antigen is a CD221 antigen. In some embodiments, the T cell antigen is a CD222 antigen.
  • the T cell antigen is a CD223 antigen. In some embodiments, the T cell antigen is a CD224 antigen. In some embodiments, the T cell antigen is a CD225 antigen. In some embodiments, the T cell antigen is a CD226 antigen. In some embodiments, the T cell antigen is a CD227 antigen. In some embodiments, the T cell antigen is a CD229 antigen. In some embodiments, the T cell antigen is a CD230 antigen. In some embodiments, the T cell antigen is a CD231 antigen. In some embodiments, the T cell antigen is a CD244 antigen. In some embodiments, the T cell antigen is a CD245 antigen.
  • the T cell antigen is a CD246 antigen. In some embodiments, the T cell antigen is a CD247 antigen. In some embodiments, the T cell antigen is a CD253 antigen. In some embodiments, the T cell antigen is a CD254 antigen. In some embodiments, the T cell antigen is a CD255 antigen. In some embodiments, the T cell antigen is a CD256 antigen. In some embodiments, the T cell antigen is a CD257 antigen. In some embodiments, the T cell antigen is a CD258 antigen. In some embodiments, the T cell antigen is a CD259 antigen. In some embodiments, the T cell antigen is a CD260 antigen.
  • the T cell antigen is a CD261 antigen. In some embodiments, the T cell antigen is a CD262 antigen. In some embodiments, the T cell antigen is a CD263 antigen. In some embodiments, the T cell antigen is a CD264 antigen. In some embodiments, the T cell antigen is a CD267 antigen. In some embodiments, the T cell antigen is a CD268 antigen. In some embodiments, the T cell antigen is a CD270 antigen. In some embodiments, the T cell antigen is a CD272 antigen. In some embodiments, the T cell antigen is a CD273 antigen. In some embodiments, the T cell antigen is a CD274 antigen.
  • the T cell antigen is a CD275 antigen. In some embodiments, the T cell antigen is a CD277 antigen. In some embodiments, the T cell antigen is a CD278 antigen. In some embodiments, the T cell antigen is a CD279 antigen. In some embodiments, the T cell antigen is a CD283 antigen. In some embodiments, the T cell antigen is a CD288 antigen. In some embodiments, the T cell antigen is a CD289 antigen. In some embodiments, the T cell antigen is a CD290 antigen. In some embodiments, the T cell antigen is a CD294 antigen. In some embodiments, the T cell antigen is a CD295 antigen.
  • the T cell antigen is a CD296 antigen. In some embodiments, the T cell antigen is a CD298 antigen. In some embodiments, the T cell antigen is a CD300a antigen. In some embodiments, the T cell antigen is a CD300c antigen. In some embodiments, the T cell antigen is a CD300e antigen. In some embodiments, the T cell antigen is a CD305 antigen. In some embodiments, the T cell antigen is a CD306 antigen. In some embodiments, the T cell antigen is a CD307c antigen. In some embodiments, the T cell antigen is a CD314 antigen. In some embodiments, the T cell antigen is a CD316 antigen.
  • the T cell antigen is a CD317 antigen. In some embodiments, the T cell antigen is a CD319 antigen. In some embodiments, the T cell antigen is a CD321 antigen. In some embodiments, the T cell antigen is a CD328 antigen. In some embodiments, the T cell antigen is a CD351 antigen. In some embodiments, the T cell antigen is a CD352 antigen. In some embodiments, the T cell antigen is a CD352 antigen. In some embodiments, the T cell antigen is a CD354 antigen. In some embodiments, the T cell antigen is a CD355 antigen. In some embodiments, the T cell antigen is a CD357 antigen.
  • the T cell antigen is a CD358 antigen. In some embodiments, the T cell antigen is a CD359 antigen. In some embodiments, the T cell antigen is a CD360 antigen. In some embodiments, the T cell antigen is a CD361 antigen. In some embodiments, the T cell antigen is a CD362 antigen. In some embodiments, the T cell antigen is a CD363 antigen.
  • the second binding arm binds a second target.
  • the second target is present on a target cell.
  • the second target is present on the surface of a target cell.
  • the target cell is a B cell.
  • the second target is a B cell antigen.
  • a multispecific TRGV9 antibody provided herein comprises: (a) a first binding domain that binds to TRGV9, and (b) a second binding domain that binds to a B cell antigen present on the surface of a B cell.
  • the first binding domain of the multispecific TRGV9 antibody specifically binds TRGV9.
  • the TRGV9 is present on the surface of a gd T cell.
  • the B cell is killed when the multispecific antibody binds to the TRGV9 on the surface of the gd T cell and the antigen on the surface of the B cell.
  • the multispecific TRGV9 antibody is a bispecific TRGV9 antibody. Bispecific antibodies comprising any of the TRGV9 antibodies provided herein as the first binding domain are contemplated.
  • the TRGV9 antibody binds to a first epitope located on TRGV9 and a second epitope of a B cell.
  • a bispecific antibody comprising: (a) a first binding domain that binds to a TRGV9 antigen, and (b) a second binding domain that binds to a B cell antigen. In some embodiments, provided herein is a bispecific antibody comprising: (a) a first binding domain that specifically binds to a TRGV9 antigen, and (b) a second binding domain that specifically binds to a B cell antigen.
  • a bispecific antibody comprising: (a) a first binding domain that binds to a first epitope on a TRGV9 antigen, and (b) a second binding domain that binds to a second epitope on a B cell antigen.
  • a bispecific antibody comprising: (a) a first binding domain that specifically binds to a first epitope on a TRGV9 antigen, and (b) a second binding domain that specifically binds to a second epitope on a B cell antigen.
  • the first epitope is located on TRGV9 and the second epitope is located on the surface of a B cell.
  • the second epitope is located on a B cell antigen.
  • the B cell antigen is a CD la, CD lb, CDlc, CD Id, CD2, CD5, CD6, CD9, CD 11 a, CD l ib, CD 11c, CD 17, CD 18, CD 19, CD20, CD21, CD22, CD23, CD24, CD25, CD26, CD27, CD29, CD30, CD31, CD32a, CD32b, CD35, CD37, CD38, CD39, CD40, CD45, CD45RA, CD45RB, CD45RC, CD45RO, CD46, CD47, CD48, CD49b, CD49c, CD49d, CD50, CD52, CD53, CD54, CD55, CD58, CD60a, CD62L, CD63, CD68, CD69, CD70, CD72, CD73, CD74, CD75, CD75S, CD77, CD79a, CD79b, CD80, CD81, CD82, CD
  • the B cell antigen is a CDla antigen. In some embodiments, the B cell antigen is a CD lb antigen. In some embodiments, the B cell antigen is a CDlc antigen. In some embodiments, the B cell antigen is a CD Id antigen. In some embodiments, the B cell antigen is a CD2 antigen. In some embodiments, the B cell antigen is a CD5 antigen. In some embodiments, the B cell antigen is a CD6 antigen. In some embodiments, the B cell antigen is a CD9 antigen. In some embodiments, the B cell antigen is a CD1 la antigen. In some embodiments, the B cell antigen is a CD1 lb antigen.
  • the B cell antigen is a CD1 lc antigen. In some embodiments, the B cell antigen is a CD 17 antigen. In some embodiments, the B cell antigen is a CD 18 antigen. In some embodiments, the B cell antigen is a CD 19 antigen. In some embodiments, the B cell antigen is a CD20 antigen. In some embodiments, the B cell antigen is a CD21 antigen. In some embodiments, the B cell antigen is a CD22 antigen. In some embodiments, the B cell antigen is a CD23 antigen. In some embodiments, the B cell antigen is a CD24 antigen. In some embodiments, the B cell antigen is a CD25 antigen.
  • the B cell antigen is a CD26 antigen. In some embodiments, the B cell antigen is a CD27 antigen. In some embodiments, the B cell antigen is a CD29 antigen. In some embodiments, the B cell antigen is a CD30 antigen. In some embodiments, the B cell antigen is a CD31 antigen. In some embodiments, the B cell antigen is a CD32a antigen. In some embodiments, the B cell antigen is a CD32b antigen. In some embodiments, the B cell antigen is a CD35 antigen. In some embodiments, the B cell antigen is a CD37 antigen. In some embodiments, the B cell antigen is a CD38 antigen.
  • the B cell antigen is a CD39 antigen. In some embodiments, the B cell antigen is a CD40 antigen. In some embodiments, the B cell antigen is a CD45 antigen. In some embodiments, the B cell antigen is a CD45RA antigen. In some embodiments, the B cell antigen is a CD45RB antigen. In some embodiments, the B cell antigen is a CD45RC antigen. In some embodiments, the B cell antigen is a CD45RO antigen. In some embodiments, the B cell antigen is a CD46 antigen. In some embodiments, the B cell antigen is a CD47 antigen. In some embodiments, the B cell antigen is a CD48 antigen.
  • the B cell antigen is a CD49b antigen. In some embodiments, the B cell antigen is a CD49c antigen. In some embodiments, the B cell antigen is a CD49d antigen. In some embodiments, the B cell antigen is a CD50 antigen. In some embodiments, the B cell antigen is a CD52 antigen. In some embodiments, the B cell antigen is a CD53 antigen. In some embodiments, the B cell antigen is a CD54 antigen. In some embodiments, the B cell antigen is a CD55 antigen. In some embodiments, the B cell antigen is a CD58 antigen. In some embodiments, the B cell antigen is a CD60a antigen.
  • the B cell antigen is a CD62L antigen. In some embodiments, the B cell antigen is a CD63 antigen. In some embodiments, the B cell antigen is a CD68 antigen. In some embodiments, the B cell antigen is a CD69 antigen. In some embodiments, the B cell antigen is a CD70 antigen. In some embodiments, the B cell antigen is a CD72 antigen. In some embodiments, the B cell antigen is a CD73 antigen. In some embodiments, the B cell antigen is a CD74 antigen. In some embodiments, the B cell antigen is a CD75 antigen. In some embodiments, the B cell antigen is a CD75S antigen.
  • the B cell antigen is a CD77 antigen. In some embodiments, the B cell antigen is a CD79a antigen. In some embodiments, the B cell antigen is a CD79b antigen. In some embodiments, the B cell antigen is a CD80 antigen. In some embodiments, the B cell antigen is a CD81 antigen. In some embodiments, the B cell antigen is a CD82 antigen. In some embodiments, the B cell antigen is a CD83 antigen. In some embodiments, the B cell antigen is a CD84 antigen. In some embodiments, the B cell antigen is a CD85E antigen. In some embodiments, the B cell antigen is a CD85I antigen.
  • the B cell antigen is a CD85J antigen. In some embodiments, the B cell antigen is a CD86 antigen. In some embodiments, the B cell antigen is a CD92 antigen. In some embodiments, the B cell antigen is a CD95 antigen. In some embodiments, the B cell antigen is a CD97 antigen. In some embodiments, the B cell antigen is a CD98 antigen. In some embodiments, the B cell antigen is a CD99 antigen. In some embodiments, the B cell antigen is a CD 100 antigen. In some embodiments, the B cell antigen is a CD 102 antigen. In some embodiments, the B cell antigen is a CD 108 antigen.
  • the B cell antigen is a CD119 antigen. In some embodiments, the B cell antigen is a CD120a antigen. In some embodiments, the B cell antigen is a CD120b antigen. In some embodiments, the B cell antigen is a CD121b antigen. In some embodiments, the B cell antigen is a CD122 antigen. In some embodiments, the B cell antigen is a CD124 antigen. In some embodiments, the B cell antigen is a CD125 antigen. In some embodiments, the B cell antigen is a CD126 antigen. In some embodiments, the B cell antigen is a CD130 antigen. In some embodiments, the B cell antigen is a CD132 antigen.
  • the B cell antigen is a CD137 antigen. In some embodiments, the B cell antigen is a CD138 antigen. In some embodiments, the B cell antigen is a CD139 antigen. In some embodiments, the B cell antigen is a CD147 antigen. In some embodiments, the B cell antigen is a CD148 antigen. In some embodiments, the B cell antigen is a CD 150 antigen. In some embodiments, the B cell antigen is a CD 152 antigen. In some embodiments, the B cell antigen is a CD 162 antigen. In some embodiments, the B cell antigen is a CD 164 antigen. In some embodiments, the B cell antigen is a CD 166 antigen.
  • the B cell antigen is a CD167a antigen. In some embodiments, the B cell antigen is a CD170 antigen. In some embodiments, the B cell antigen is a CD171 antigen. In some embodiments, the B cell antigen is a CD175 antigen. In some embodiments, the B cell antigen is a CD175s antigen. In some embodiments, the B cell antigen is a CD180 antigen. In some embodiments, the B cell antigen is a CD 184 antigen. In some embodiments, the B cell antigen is a CD 185 antigen. In some embodiments, the B cell antigen is a CD 192 antigen. In some embodiments, the B cell antigen is a CD 196 antigen.
  • the B cell antigen is a CD 197 antigen. In some embodiments, the B cell antigen is a CD200 antigen. In some embodiments, the B cell antigen is a CD205 antigen. In some embodiments, the B cell antigen is a CD201a antigen. In some embodiments, the B cell antigen is a CDw210b antigen. In some embodiments, the B cell antigen is a CD212 antigen. In some embodiments, the B cell antigen is a CD213al antigen. In some embodiments, the B cell antigen is a CD213a2 antigen. In some embodiments, the B cell antigen is a CD 215 antigen. In some embodiments, the B cell antigen is a CD217 antigen.
  • the B cell antigen is a CD218a antigen. In some embodiments, the B cell antigen is a CD218b antigen. In some embodiments, the B cell antigen is a CD220 antigen. In some embodiments, the B cell antigen is a CD221 antigen. In some embodiments, the B cell antigen is a CD222 antigen. In some embodiments, the B cell antigen is a CD224 antigen. In some embodiments, the B cell antigen is a CD225 antigen. In some embodiments, the B cell antigen is a CD226 antigen. In some embodiments, the B cell antigen is a CD227 antigen. In some embodiments, the B cell antigen is a CD229 antigen.
  • the B cell antigen is a CD230 antigen. In some embodiments, the B cell antigen is a CD232 antigen. In some embodiments, the B cell antigen is a CD252 antigen. In some embodiments, the B cell antigen is a CD252 antigen. In some embodiments, the B cell antigen is a CD254 antigen. In some embodiments, the B cell antigen is a CD255 antigen. In some embodiments, the B cell antigen is a CD256 antigen. In some embodiments, the B cell antigen is a CD257 CD258 antigen. In some embodiments, the B cell antigen is a CD259 antigen. In some embodiments, the B cell antigen is a CD260 antigen.
  • the B cell antigen is a CD261 antigen. In some embodiments, the B cell antigen is a CD262 antigen. In some embodiments, the B cell antigen is a CD263 antigen. In some embodiments, the B cell antigen is a CD264 antigen. In some embodiments, the B cell antigen is a CD267-270 antigen. In some embodiments, the B cell antigen is a CD272 antigen. In some embodiments, the B cell antigen is a CD274 antigen. In some embodiments, the B cell antigen is a CD275 antigen. In some embodiments, the B cell antigen is a CD277 antigen. In some embodiments, the B cell antigen is a CD279 antigen.
  • the B cell antigen is a CD283 antigen. In some embodiments, the B cell antigen is a CD289 antigen. In some embodiments, the B cell antigen is a CD290 antigen. In some embodiments, the B cell antigen is a CD295 antigen. In some embodiments, the B cell antigen is a CD298 antigen. In some embodiments, the B cell antigen is a CD300 antigen. In some embodiments, the B cell antigen is a CD300c antigen. In some embodiments, the B cell antigen is a CD305 antigen. In some embodiments, the B cell antigen is a CD306 antigen. In some embodiments, the B cell antigen is a CD307a antigen.
  • the B cell antigen is a CD307b antigen. In some embodiments, the B cell antigen is a CD307c antigen. In some embodiments, the B cell antigen is a CD307d antigen. In some embodiments, the B cell antigen is a CD307e antigen. In some embodiments, the B cell antigen is a CD314 antigen. In some embodiments, the B cell antigen is a CD215 antigen. In some embodiments, the B cell antigen is a CD316 antigen. In some embodiments, the B cell antigen is a CD317 antigen. In some embodiments, the B cell antigen is a CD319 antigen.
  • the B cell antigen is a CD321 antigen. In some embodiments, the B cell antigen is a CD327 antigen. In some embodiments, the B cell antigen is a CD328 antigen. In some embodiments, the B cell antigen is a CD329 antigen. In some embodiments, the B cell antigen is a CD338 antigen. In some embodiments, the B cell antigen is a CD351 antigen. In some embodiments, the B cell antigen is a CD352 antigen. In some embodiments, the B cell antigen is a CD353 antigen. In some embodiments, the B cell antigen is a CD354 antigen. In some embodiments, the B cell antigen is a CD355 antigen.
  • the B cell antigen is a CD356 antigen. In some embodiments, the B cell antigen is a CD357 antigen. In some embodiments, the B cell antigen is a CD358 antigen. In some embodiments, the B cell antigen is a CD360 antigen. In some embodiments, the B cell antigen is a CD361 antigen. In some embodiments, the B cell antigen is a CD362 antigen. In some embodiments, the B cell antigen is a CD363 antigen.
  • the second binding arm binds a second target.
  • the second target is present on a target cell.
  • the second target is present on the surface of a target cell.
  • the target cell is a dendritic cell.
  • the second target is a dendritic cell antigen.
  • a multispecific TRGV9 antibody provided herein comprises: (a) a first binding domain that binds to TRGV9, and (b) a second binding domain that binds to a dendritic cell antigen present on the surface of a dendritic cell.
  • the first binding domain of the multispecific TRGV9 antibody specifically binds TRGV9.
  • the TRGV9 is present on the surface of a gd T cell.
  • the dendritic cell is killed when the multispecific antibody binds to the TRGV9 on the surface of the gd T cell and the antigen on the surface of the dendritic cell.
  • the multispecific TRGV9 antibody is a bispecific TRGV9 antibody. Bispecific antibodies comprising any of the TRGV9 antibodies provided herein as the first binding domain are contemplated.
  • the TRGV9 antibody binds to a first epitope located on TRGV9 and a second epitope of a dendritic cell.
  • a bispecific antibody comprising: (a) a first binding domain that binds to a TRGV9 antigen, and (b) a second binding domain that binds to a dendritic cell antigen. In some embodiments, provided herein is a bispecific antibody comprising: (a) a first binding domain that specifically binds to a TRGV9 antigen, and (b) a second binding domain that specifically binds to a dendritic cell antigen.
  • a bispecific antibody comprising: (a) a first binding domain that binds to a first epitope on a TRGV9 antigen, and (b) a second binding domain that binds to a second epitope on a dendritic cell antigen.
  • a bispecific antibody comprising: (a) a first binding domain that specifically binds to a first epitope on a TRGV9 antigen, and (b) a second binding domain that specifically binds to a second epitope on a dendritic cell antigen.
  • the first epitope is located on TRGV9 and the second epitope is located on the surface of a dendritic cell. In some embodiments, the second epitope is located on a dendritic cell antigen.
  • the dendritic cell antigen is a C CD Id CDl CDllb CDll CD16 CD17 CD18 CD19 CD21 CD23 CD29 CD301, CD302, CD303, CD304, CD305, CD312, CD317, CD319, CD320, CD328, CD352, CD354, CD357, or CD361 antigen.
  • the dendritic cell antigen is a CD la antigen.
  • the dendritic cell antigen is a CD lb antigen.
  • the dendritic cell antigen is a CDlc antigen.
  • the dendritic cell antigen is a CD Id antigen.
  • the dendritic cell antigen is a CDle antigen. In some embodiments, the dendritic cell antigen is a CD1 lb antigen. In some embodiments, the dendritic cell antigen is a CD1 lc antigen. In some embodiments, the dendritic cell antigen is a CD 16 antigen. In some embodiments, the dendritic cell antigen is a CD 17 antigen. In some embodiments, the dendritic cell antigen is a CD 18 antigen. In some embodiments, the dendritic cell antigen is a CD 19 antigen. In some embodiments, the dendritic cell antigen is a CD21 antigen.
  • the dendritic cell antigen is a CD23 antigen. In some embodiments, the dendritic cell antigen is a CD29 antigen. In some embodiments, the dendritic cell antigen is a CD33 antigen. In some embodiments, the dendritic cell antigen is a CD35 antigen. In some embodiments, the dendritic cell antigen is a CD36 antigen. In some embodiments, the dendritic cell antigen is a CD38 antigen. In some embodiments, the dendritic cell antigen is a CD39 antigen. In some embodiments, the dendritic cell antigen is a CD40 antigen. In some embodiments, the dendritic cell antigen is a CD45 antigen.
  • the dendritic cell antigen is a CD45RA antigen. In some embodiments, the dendritic cell antigen is a CD45RB antigen. In some embodiments, the dendritic cell antigen is a CD45RC antigen. In some embodiments, the dendritic cell antigen is a CD45RO antigen. In some embodiments, the dendritic cell antigen is a CD48 antigen. In some embodiments, the dendritic cell antigen is a CD49d antigen. In some embodiments, the dendritic cell antigen is a CD49e antigen. In some embodiments, the dendritic cell antigen is a CD58 antigen.
  • the dendritic cell antigen is a CD64a antigen. In some embodiments, the dendritic cell antigen is a CD68 antigen. In some embodiments, the dendritic cell antigen is a CD73 antigen. In some embodiments, the dendritic cell antigen is a CD74 antigen. In some embodiments, the dendritic cell antigen is a CD80 antigen. In some embodiments, the dendritic cell antigen is a CD81 antigen. In some embodiments, the dendritic cell antigen is a CD83 antigen. In some embodiments, the dendritic cell antigen is a CD84 antigen. In some embodiments, the dendritic cell antigen is a
  • the dendritic cell antigen is a CD85D antigen. In some embodiments, the dendritic cell antigen is a CD85E antigen. In some embodiments, the dendritic cell antigen is a CD85G antigen. In some embodiments, the dendritic cell antigen is a CD85J antigen. In some embodiments, the dendritic cell antigen is a CD86 antigen. In some embodiments, the dendritic cell antigen is a CD88 antigen. In some embodiments, the dendritic cell antigen is a CD97 antigen. In some embodiments, the dendritic cell antigen is a CD101 antigen.
  • the dendritic cell antigen is a CD116 antigen. In some embodiments, the dendritic cell antigen is a CD120a antigen. In some embodiments, the dendritic cell antigen is a CD120b antigen. In some embodiments, the dendritic cell antigen is a CD123 antigen. In some embodiments, the dendritic cell antigen is a CD139 antigen. In some embodiments, the dendritic cell antigen is a CD148 antigen. In some embodiments, the dendritic cell antigen is a CD 150 antigen. In some embodiments, the dendritic cell antigen is a CD 156b antigen.
  • the dendritic cell antigen is a CD 157 antigen. In some embodiments, the dendritic cell antigen is a CD 167 antigen. In some embodiments, the dendritic cell antigen is a CD 168 antigen. In some embodiments, the dendritic cell antigen is a CD 169 antigen. In some embodiments, the dendritic cell antigen is a CD 170 antigen. In some embodiments, the dendritic cell antigen is a CD171 antigen. In some embodiments, the dendritic cell antigen is a CD 172a antigen. In some embodiments, the dendritic cell antigen is a CD 172b antigen.
  • the dendritic cell antigen is a CD 180 antigen. In some embodiments, the dendritic cell antigen is a CD 184 antigen. In some embodiments, the dendritic cell antigen is a CD 185 antigen. In some embodiments, the dendritic cell antigen is a CD 193 antigen. In some embodiments, the dendritic cell antigen is a CD 196 antigen. In some embodiments, the dendritic cell antigen is a CD 197 antigen. In some embodiments, the dendritic cell antigen is a CD200 antigen. In some embodiments, the dendritic cell antigen is a CD205 antigen.
  • the dendritic cell antigen is a CD206 antigen. In some embodiments, the dendritic cell antigen is a CD207 antigen. In some embodiments, the dendritic cell antigen is a CD208 antigen. In some embodiments, the dendritic cell antigen is a CD209 antigen. In some embodiments, the dendritic cell antigen is a CDw210b antigen. In some embodiments, the dendritic cell antigen is a CD213al antigen. In some embodiments, the dendritic cell antigen is a CD217 antigen. In some embodiments, the dendritic cell antigen is a CD218a antigen.
  • the dendritic cell antigen is a CD218b antigen. In some embodiments, the dendritic cell antigen is a CD220 antigen. In some embodiments, the dendritic cell antigen is a CD221 antigen. In some embodiments, the dendritic cell antigen is a CD222 antigen. In some embodiments, the dendritic cell antigen is a CD227 antigen. In some embodiments, the dendritic cell antigen is a CD229 antigen. In some embodiments, the dendritic cell antigen is a CD230 antigen. In some embodiments, the dendritic cell antigen is a CD232 antigen.
  • the dendritic cell antigen is a CD244 antigen. In some embodiments, the dendritic cell antigen is a CD252 antigen. In some embodiments, the dendritic cell antigen is a CD256 antigen. In some embodiments, the dendritic cell antigen is a CD257 antigen. In some embodiments, the dendritic cell antigen is a CD258 antigen. In some embodiments, the dendritic cell antigen is a CD265 antigen. In some embodiments, the dendritic cell antigen is a CD270 antigen. In some embodiments, the dendritic cell antigen is a CD271 antigen.
  • the dendritic cell antigen is a CD272 antigen. In some embodiments, the dendritic cell antigen is a CD273 antigen. In some embodiments, the dendritic cell antigen is a CD274 antigen. In some embodiments, the dendritic cell antigen is a CD275 antigen. In some embodiments, the dendritic cell antigen is a CD276 antigen. In some embodiments, the dendritic cell antigen is a CD277 antigen. In some embodiments, the dendritic cell antigen is a CD283 antigen. In some embodiments, the dendritic cell antigen is a CD286 antigen.
  • the dendritic cell antigen is a CD288 antigen. In some embodiments, the dendritic cell antigen is a CD289 antigen. In some embodiments, the dendritic cell antigen is a CD290 antigen. In some embodiments, the dendritic cell antigen is a CD295 antigen. In some embodiments, the dendritic cell antigen is a CD298 antigen. In some embodiments, the dendritic cell antigen is a CD300a antigen. In some embodiments, the dendritic cell antigen is a CD300c antigen. In some embodiments, the dendritic cell antigen is a CD300e antigen.
  • the dendritic cell antigen is a CD301 antigen. In some embodiments, the dendritic cell antigen is a CD302 antigen. In some embodiments, the dendritic cell antigen is a CD303 antigen. In some embodiments, the dendritic cell antigen is a CD304 antigen. In some embodiments, the dendritic cell antigen is a CD305 antigen. In some embodiments, the dendritic cell antigen is a CD312 antigen. In some embodiments, the dendritic cell antigen is a CD317 antigen. In some embodiments, the dendritic cell antigen is a CD319 antigen.
  • the dendritic cell antigen is a CD320 antigen. In some embodiments, the dendritic cell antigen is a CD328 antigen. In some embodiments, the dendritic cell antigen is a CD352 antigen. In some embodiments, the dendritic cell antigen is a CD354 antigen. In some embodiments, the dendritic cell antigen is a CD357 antigen. In some embodiments, the dendritic cell antigen is a CD361 antigen.
  • the second binding arm binds a second target.
  • the second target is present on a target cell.
  • the second target is present on the surface of a target cell.
  • the target cell is a NK cell.
  • the second target is a NK cell antigen.
  • a multispecific TRGV9 antibody provided herein comprises: (a) a first binding domain that binds to TRGV9, and (b) a second binding domain that binds to a NK cell antigen present on the surface of a NK cell.
  • the first binding domain of the multispecific TRGV9 antibody specifically binds TRGV9.
  • the TRGV9 is present on the surface of a gd T cell.
  • the NK cell is killed when the multispecific antibody binds to the TRGV9 on the surface of the gd T cell and the antigen on the surface of the NK cell.
  • the multispecific TRGV9 antibody is a bispecific TRGV9 antibody. Bispecific antibodies comprising any of the TRGV9 antibodies provided herein as the first binding domain are contemplated.
  • the TRGV9 antibody binds to a first epitope located on TRGV9 and a second epitope of a NK cell.
  • a bispecific antibody comprising: (a) a first binding domain that binds to a TRGV9 antigen, and (b) a second binding domain that binds to a NK cell antigen. In some embodiments, provided herein is a bispecific antibody comprising: (a) a first binding domain that specifically binds to a TRGV9 antigen, and (b) a second binding domain that specifically binds to a NK cell antigen.
  • a bispecific antibody comprising: (a) a first binding domain that binds to a first epitope on a TRGV9 antigen, and (b) a second binding domain that binds to a second epitope on a NK cell antigen.
  • a bispecific antibody comprising: (a) a first binding domain that specifically binds to a first epitope on a TRGV9 antigen, and (b) a second binding domain that specifically binds to a second epitope on a NK cell antigen.
  • the first epitope is located on TRGV9 and the second epitope is located on the surface of a NK cell.
  • the second epitope is located on a NK cell antigen.
  • the NK cell antigen is a CD2, CD7, CD8a, CD 10, , or CD363 antigen.
  • the NK cell antigen is a CD2 antigen.
  • the NK cell antigen is a CD7 antigen.
  • the NK cell antigen is a CD8a antigen.
  • the NK cell antigen is a CD 10 antigen.
  • the NK cell antigen is a CD1 la antigen.
  • the NK cell antigen is a CD1 lb antigen.
  • the NK cell antigen is a CD1 lc antigen.
  • the NK cell antigen is a CDwl2 antigen. In some embodiments, the NK cell antigen is a CD 16 antigen. In some embodiments, the NK cell antigen is a CD 18 antigen. In some embodiments, the NK cell antigen is a CD25 antigen. In some embodiments, the NK cell antigen is a CD26 antigen. In some embodiments, the NK cell antigen is a CD27 antigen. In some embodiments, the NK cell antigen is a CD29 antigen. In some embodiments, the NK cell antigen is a CD30 antigen. In some embodiments, the NK cell antigen is a CD31 antigen.
  • the NK cell antigen is a CD32c antigen. In some embodiments, the NK cell antigen is a CD38 antigen. In some embodiments, the NK cell antigen is a CD39 antigen. In some embodiments, the NK cell antigen is a CD43 antigen. In some embodiments, the NK cell antigen is a CD44 antigen. In some embodiments, the NK cell antigen is a CD45 antigen. In some embodiments, the NK cell antigen is a CD45RA antigen. In some embodiments, the NK cell antigen is a CD45RB antigen. In some embodiments, the NK cell antigen is a CD45RC antigen.
  • the NK cell antigen is a CD45RO antigen. In some embodiments, the NK cell antigen is a CD46 antigen. In some embodiments, the NK cell antigen is a CD47 antigen. In some embodiments, the NK cell antigen is a CD48 antigen. In some embodiments, the NK cell antigen is a CD49a antigen. In some embodiments, the NK cell antigen is a CD49b antigen. In some embodiments, the NK cell antigen is a CD49d antigen. In some embodiments, the NK cell antigen is a CD49e antigen. In some embodiments, the NK cell antigen is a CD50 antigen.
  • the NK cell antigen is a CD52 antigen. In some embodiments, the NK cell antigen is a CD53 antigen. In some embodiments, the NK cell antigen is a CD55 antigen. In some embodiments, the NK cell antigen is a CD56 antigen. In some embodiments, the NK cell antigen is a CD7 antigen. In some embodiments, the NK cell antigen is a CD58 antigen. In some embodiments, the NK cell antigen is a CD59 antigen. In some embodiments, the NK cell antigen is a CD62L antigen. In some embodiments, the NK cell antigen is a CD63 antigen. In some embodiments, the NK cell antigen is a CD69 antigen.
  • the NK cell antigen is a CD81 antigen. In some embodiments, the NK cell antigen is a CD82 antigen. In some embodiments, the NK cell antigen is a CD84 antigen. In some embodiments, the NK cell antigen is a CD85C antigen. In some embodiments, the NK cell antigen is a CD85E antigen. In some embodiments, the NK cell antigen is a CD85J antigen. In some embodiments, the NK cell antigen is a CD87 antigen. In some embodiments, the NK cell antigen is a CD94 antigen. In some embodiments, the NK cell antigen is a CD95 antigen.
  • the NK cell antigen is a CD96 antigen. In some embodiments, the NK cell antigen is a CD97 antigen. In some embodiments, the NK cell antigen is a CD98 antigen. In some embodiments, the NK cell antigen is a CD99 antigen. In some embodiments, the NK cell antigen is a CD99R antigen. In some embodiments, the NK cell antigen is a CD 100 antigen. In some embodiments, the NK cell antigen is a CD119 antigen. In some embodiments, the NK cell antigen is a CD120a antigen. In some embodiments, the NK cell antigen is a CD120b antigen.
  • the NK cell antigen is a CD122 antigen. In some embodiments, the NK cell antigen is a CD130 antigen. In some embodiments, the NK cell antigen is a CD132 antigen. In some embodiments, the NK cell antigen is a CD147 antigen. In some embodiments, the NK cell antigen is a CD148 antigen. In some embodiments, the NK cell antigen is a CD 158a antigen. In some embodiments, the NK cell antigen is a CD158M antigen. In some embodiments, the NK cell antigen is a CD158b2 antigen. In some embodiments, the NK cell antigen is a CD158d antigen.
  • the NK cell antigen is a CD158el/e2 antigen. In some embodiments, the NK cell antigen is a CD158f antigen. In some embodiments, the NK cell antigen is a CD158g antigen. In some embodiments, the NK cell antigen is a CD158h antigen. In some embodiments, the NK cell antigen is a CD158i antigen. In some embodiments, the NK cell antigen is a CD158j antigen. In some embodiments, the NK cell antigen is a CD158k antigen. In some embodiments, the NK cell antigen is a CD 159a antigen. In some embodiments, the NK cell antigen is a CD 159c antigen.
  • the NK cell antigen is a CD 160 antigen. In some embodiments, the NK cell antigen is a CD161 antigen. In some embodiments, the NK cell antigen is a CD172g antigen. In some embodiments, the NK cell antigen is a CD 178 antigen. In some embodiments, the NK cell antigen is a CD 183 antigen. In some embodiments, the NK cell antigen is a CD185 antigen. In some embodiments, the NK cell antigen is a CDw210b antigen. In some embodiments, the NK cell antigen is a CD212 antigen. In some embodiments, the NK cell antigen is a CD217 antigen.
  • the NK cell antigen is a CD218a antigen. In some embodiments, the NK cell antigen is a CD218b antigen. In some embodiments, the NK cell antigen is a CD220 antigen. In some embodiments, the NK cell antigen is a CD221 antigen. In some embodiments, the NK cell antigen is a CD222 antigen. In some embodiments, the NK cell antigen is a CD223 antigen. In some embodiments, the NK cell antigen is a CD225 antigen. In some embodiments, the NK cell antigen is a CD226 antigen. In some embodiments, the NK cell antigen is a CD229 antigen.
  • the NK cell antigen is a CD230 antigen. In some embodiments, the NK cell antigen is a CD232 antigen. In some embodiments, the NK cell antigen is a CD244 antigen. In some embodiments, the NK cell antigen is a CD247 antigen. In some embodiments, the NK cell antigen is a CD257 antigen. In some embodiments, the NK cell antigen is a CD261 antigen. In some embodiments, the NK cell antigen is a CD262 antigen. In some embodiments, the NK cell antigen is a CD263 antigen. In some embodiments, the NK cell antigen is a CD264 antigen.
  • the NK cell antigen is a CD270 antigen. In some embodiments, the NK cell antigen is a CD277 antigen. In some embodiments, the NK cell antigen is a CD280 antigen. In some embodiments, the NK cell antigen is a CD295 antigen.
  • the NK cell antigen is a CD298 antigen. In some embodiments, the NK cell antigen is a CD305 antigen. In some embodiments, the NK cell antigen is a CD314 antigen. In some embodiments, the NK cell antigen is a CD316 antigen. In some embodiments, the NK cell antigen is a CD317 antigen. In some embodiments, the NK cell antigen is a CD319 antigen. In some embodiments, the NK cell antigen is a CD321 antigen. In some embodiments, the NK cell antigen is a CD328 antigen. In some embodiments, the NK cell antigen is a CD329 antigen.
  • the NK cell antigen is a CD335 antigen. In some embodiments, the NK cell antigen is a CD336 antigen. In some embodiments, the NK cell antigen is a CD337 antigen. In some embodiments, the NK cell antigen is a CD352 antigen. In some embodiments, the NK cell antigen is a CD354 antigen. In some embodiments, the NK cell antigen is a CD355 antigen. In some embodiments, the NK cell antigen is a CD357 antigen. In some embodiments, the NK cell antigen is a CD360 antigen. In some embodiments, the NK cell antigen is a CD361 antigen. In some embodiments, the NK cell antigen is a CD363 antigen.
  • the second binding arm binds a second target.
  • the second target is present on a target cell.
  • the second target is present on the surface of a target cell.
  • the target cell is a stem cell.
  • the second target is a stem cell antigen.
  • the target cell is a stem cell precursor.
  • the second target is a stem cell precursor antigen.
  • a multispecific TRGV9 antibody provided herein comprises: (a) a first binding domain that binds to TRGV9, and (b) a second binding domain that binds to a stem cell or stem cell precursor antigen present on the surface of a stem cell or stem cell precursor.
  • the first binding domain of the multispecific TRGV9 antibody specifically binds TRGV9.
  • the TRGV9 is present on the surface of a gd T cell.
  • the stem cell or stem cell precursor is killed when the multispecific antibody binds to the TRGV9 on the surface of the gd T cell and the antigen on the surface of the stem cell or stem cell precursor.
  • the multispecific TRGV9 antibody is a bispecific TRGV9 antibody.
  • Bispecific antibodies comprising any of the TRGV9 antibodies provided herein as the first binding domain are contemplated.
  • the TRGV9 antibody binds to a first epitope located on TRGV9 and a second epitope of a stem cell or stem cell precursor.
  • a bispecific antibody comprising: (a) a first binding domain that binds to a TRGV9 antigen, and (b) a second binding domain that binds to a stem cell or stem cell precursor antigen.
  • a bispecific antibody comprising: (a) a first binding domain that specifically binds to a TRGV9 antigen, and (b) a second binding domain that specifically binds to a stem cell or stem cell precursor antigen.
  • a bispecific antibody comprising: (a) a first binding domain that binds to a first epitope on a TRGV9 antigen, and (b) a second binding domain that binds to a second epitope on a stem cell or stem cell precursor antigen.
  • a bispecific antibody comprising: (a) a first binding domain that specifically binds to a first epitope on a TRGV9 antigen, and (b) a second binding domain that specifically binds to a second epitope on a stem cell or stem cell precursor antigen.
  • the first epitope is located on TRGV9 and the second epitope is located on the surface of a stem cell or stem cell precursor.
  • the second epitope is located on a stem cell or stem cell precursor antigen.
  • the stem cell or stem cell precursor antigen is a
  • the stem cell or stem cell precursor antigen is a CD8a antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CDwl2 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD 13 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD 15 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD 19 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD21 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD22 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD29 antigen.
  • the stem cell or stem cell precursor antigen is a CD30 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD33 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD34 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD36 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD38 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD40 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD41 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD42a antigen.
  • the stem cell or stem cell precursor antigen is a CD42b antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD42c antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD42d antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD43 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD45 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD45RA antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD45RB antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD45RC antigen.
  • the stem cell or stem cell precursor antigen is a CD45RO antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD48 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD49b antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD49d antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD49e antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD49f antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD50 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD53 antigen.
  • the stem cell or stem cell precursor antigen is a CD55 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD64a antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD68 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD71 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD72 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD73 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD81 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD82 antigen.
  • the stem cell or stem cell precursor antigen is a CD85A antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD85K antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD90 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD99 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD 104 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD 105 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD 109 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD110 antigen.
  • the stem cell or stem cell precursor antigen is a CD111 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD112 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD114 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD115 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD117 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD123 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD 124 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD126 antigen.
  • the stem cell or stem cell precursor antigen is a CD 127 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD130 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD131 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD133 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD135 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD138 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD151 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD 157 antigen.
  • the stem cell or stem cell precursor antigen is a CD 162 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD 164 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD 168 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD 172a antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD 173 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD 174 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD 175 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD 175s antigen.
  • the stem cell or stem cell precursor antigen is a CD 176 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD 183 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD191 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD200 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD201 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD205 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD217 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD220 antigen.
  • the stem cell or stem cell precursor antigen is a CD221 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD222 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD224 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD225 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD226 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD227 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD228 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD229 antigen.
  • the stem cell or stem cell precursor antigen is a CD230 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD235a antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD235b antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD236 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD236R antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD238 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD240 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD242 antigen.
  • the stem cell or stem cell precursor antigen is a CD243 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD277 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD292 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CDw293 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD295 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD298 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD309 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD318 antigen.
  • the stem cell or stem cell precursor antigen is a CD324 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD325 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD338 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD344 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD349 antigen. In some embodiments, the stem cell or stem cell precursor antigen is a CD350 antigen.
  • the second binding arm binds a second target.
  • the second target is present on a target cell.
  • the second target is present on the surface of a target cell.
  • the target cell is a monocyte.
  • the second target is a monocyte antigen.
  • the target cell is a macrophage.
  • the second target is a macrophage antigen.
  • a multispecific TRGV9 antibody provided herein comprises: (a) a first binding domain that binds to TRGV9, and (b) a second binding domain that binds to a macrophage or monocyte antigen present on the surface of a macrophage or monocyte.
  • the first binding domain of the multispecific TRGV9 antibody specifically binds TRGV9.
  • the TRGV9 is present on the surface of a gd T cell.
  • the macrophage or monocyte is killed when the multispecific antibody binds to the TRGV9 on the surface of the gd T cell and the antigen on the surface of the macrophage or monocyte.
  • the multispecific TRGV9 antibody is a bispecific TRGV9 antibody.
  • Bispecific antibodies comprising any of the TRGV9 antibodies provided herein as the first binding domain are contemplated.
  • the TRGV9 antibody binds to a first epitope located on TRGV9 and a second epitope of a macrophage or monocyte.
  • a bispecific antibody comprising: (a) a first binding domain that binds to a TRGV9 antigen, and (b) a second binding domain that binds to a macrophage or monocyte antigen.
  • a bispecific antibody comprising: (a) a first binding domain that specifically binds to a TRGV9 antigen, and (b) a second binding domain that specifically binds to a macrophage or monocyte antigen.
  • a bispecific antibody comprising: (a) a first binding domain that binds to a first epitope on a TRGV9 antigen, and (b) a second binding domain that binds to a second epitope on a macrophage or monocyte antigen.
  • a bispecific antibody comprising: (a) a first binding domain that specifically binds to a first epitope on a TRGV9 antigen, and (b) a second binding domain that specifically binds to a second epitope on a macrophage or monocyte antigen.
  • the first epitope is located on TRGV9 and the second epitope is located on the surface of a macrophage or monocyte.
  • the second epitope is located on a macrophage or monocyte antigen.
  • the macrophage or monocyte antigen is a CD la, CDlb, CDlc, CD4, CD9, CDl la, CDl lb, CDl lc, CDl ld, CDwl2, CD13, CD14, CD 15, CD 16, CD 17, CD18, CD23, CD25, CD26, CD29, CD30, CD31, CD32a, CD32b, CD32c, CD33, CD35, CD36, CD37, CD38, CD39, CD40, CD44, CD45, CD45RA, CD45RB, CD45RC, CD45RO, CD46, CD47, CD48, CD49a, CD49b, CD49c, CD49d, CD49e, CD49f, CD50, CD51, CD52, CD53, CD54, CD55, CD58, CD59, CD60a, CD61, CD63, CD64a, CD65, CD66, CD68, CD69, CD72, CD74, CD75, CD75S, CD80, CD81, CD82
  • the macrophage or monocyte antigen is a CD la antigen.
  • the macrophage or monocyte antigen is a CDlb antigen.
  • the macrophage or monocyte antigen is a CDlc antigen.
  • the macrophage or monocyte antigen is a CD4 antigen.
  • the macrophage or monocyte antigen is a CD9 antigen. In some embodiments, the macrophage or monocyte antigen is a CD1 la antigen. In some embodiments, the macrophage or monocyte antigen is a CD1 lb antigen. In some embodiments, the macrophage or monocyte antigen is a CD1 lc antigen. In some embodiments, the macrophage or monocyte antigen is a CD1 Id antigen. In some embodiments, the macrophage or monocyte antigen is a CDwl2 antigen. In some embodiments, the macrophage or monocyte antigen is a CD 13 antigen. In some embodiments, the macrophage or monocyte antigen is a CD14 antigen.
  • the macrophage or monocyte antigen is a CD 15 antigen. In some embodiments, the macrophage or monocyte antigen is a CD 16 antigen. In some embodiments, the macrophage or monocyte antigen is a CD 17 antigen. In some embodiments, the macrophage or monocyte antigen is a CD 18 antigen. In some embodiments, the macrophage or monocyte antigen is a CD23 antigen. In some embodiments, the macrophage or monocyte antigen is a CD25 antigen. In some embodiments, the macrophage or monocyte antigen is a CD26 antigen. In some embodiments, the macrophage or monocyte antigen is a CD29 antigen.
  • the macrophage or monocyte antigen is a CD30 antigen. In some embodiments, the macrophage or monocyte antigen is a CD31 antigen. In some embodiments, the macrophage or monocyte antigen is a CD32a antigen. In some embodiments, the macrophage or monocyte antigen is a CD32b antigen. In some embodiments, the macrophage or monocyte antigen is a CD32c antigen. In some embodiments, the macrophage or monocyte antigen is a CD33 antigen. In some embodiments, the macrophage or monocyte antigen is a CD35 antigen. In some embodiments, the macrophage or monocyte antigen is a CD36 antigen.
  • the macrophage or monocyte antigen is a CD37 antigen. In some embodiments, the macrophage or monocyte antigen is a CD38 antigen. In some embodiments, the macrophage or monocyte antigen is a CD39 antigen. In some embodiments, the macrophage or monocyte antigen is a CD40 antigen. In some embodiments, the macrophage or monocyte antigen is a CD44 antigen. In some embodiments, the macrophage or monocyte antigen is a CD45 antigen. In some embodiments, the macrophage or monocyte antigen is a CD45RA antigen. In some embodiments, the macrophage or monocyte antigen is a CD45RB antigen.
  • the macrophage or monocyte antigen is a CD45RC antigen. In some embodiments, the macrophage or monocyte antigen is a CD45RO antigen. In some embodiments, the macrophage or monocyte antigen is a CD46 antigen. In some embodiments, the macrophage or monocyte antigen is a CD47 antigen. In some embodiments, the macrophage or monocyte antigen is a CD48 antigen. In some embodiments, the macrophage or monocyte antigen is a CD49a antigen. In some embodiments, the macrophage or monocyte antigen is a CD49b antigen. In some embodiments, the macrophage or monocyte antigen is a CD49c antigen.
  • the macrophage or monocyte antigen is a CD49d antigen. In some embodiments, the macrophage or monocyte antigen is a CD49e antigen. In some embodiments, the macrophage or monocyte antigen is a CD49f antigen. In some embodiments, the macrophage or monocyte antigen is a CD50 antigen. In some embodiments, the macrophage or monocyte antigen is a CD51 antigen. In some embodiments, the macrophage or monocyte antigen is a CD52 antigen. In some embodiments, the macrophage or monocyte antigen is a CD53 antigen. In some embodiments, the macrophage or monocyte antigen is a CD54 antigen.
  • the macrophage or monocyte antigen is a CD55 antigen. In some embodiments, the macrophage or monocyte antigen is a CD58 antigen. In some embodiments, the macrophage or monocyte antigen is a CD59 antigen. In some embodiments, the macrophage or monocyte antigen is a CD60a antigen. In some embodiments, the macrophage or monocyte antigen is a CD61 antigen. In some embodiments, the macrophage or monocyte antigen is a CD63 antigen. In some embodiments, the macrophage or monocyte antigen is a CD64a antigen. In some embodiments, the macrophage or monocyte antigen is a CD65 antigen.
  • the macrophage or monocyte antigen is a CD66 antigen. In some embodiments, the macrophage or monocyte antigen is a CD68 antigen. In some embodiments, the macrophage or monocyte antigen is a CD69 antigen. In some embodiments, the macrophage or monocyte antigen is a CD72 antigen. In some embodiments, the macrophage or monocyte antigen is a CD74 antigen. In some embodiments, the macrophage or monocyte antigen is a CD75 antigen. In some embodiments, the macrophage or monocyte antigen is a CD75S antigen. In some embodiments, the macrophage or monocyte antigen is a CD80 antigen.
  • the macrophage or monocyte antigen is a CD81 antigen. In some embodiments, the macrophage or monocyte antigen is a CD82 antigen. In some embodiments, the macrophage or monocyte antigen is a CD84 antigen. In some embodiments, the macrophage or monocyte antigen is a CD85A antigen. In some embodiments, the macrophage or monocyte antigen is a CD85C antigen. In some embodiments, the macrophage or monocyte antigen is a CD85D antigen. In some embodiments, the macrophage or monocyte antigen is a CD85E antigen. In some embodiments, the macrophage or monocyte antigen is a CD85F antigen.
  • the macrophage or monocyte antigen is a CD85G antigen. In some embodiments, the macrophage or monocyte antigen is a CD85I antigen. In some embodiments, the macrophage or monocyte antigen is a CD85J antigen. In some embodiments, the macrophage or monocyte antigen is a CD85K antigen. In some embodiments, the macrophage or monocyte antigen is a CD86 antigen. In some embodiments, the macrophage or monocyte antigen is a CD87 antigen. In some embodiments, the macrophage or monocyte antigen is a CD88 antigen. In some embodiments, the macrophage or monocyte antigen is a CD89 antigen.
  • the macrophage or monocyte antigen is a CD91 antigen. In some embodiments, the macrophage or monocyte antigen is a CD92 antigen. In some embodiments, the macrophage or monocyte antigen is a CD93 antigen. In some embodiments, the macrophage or monocyte antigen is a CD95 antigen. In some embodiments, the macrophage or monocyte antigen is a CD97 antigen. In some embodiments, the macrophage or monocyte antigen is a CD98 antigen. In some embodiments, the macrophage or monocyte antigen is a CD99 antigen. In some embodiments, the macrophage or monocyte antigen is a CD99R antigen.
  • the macrophage or monocyte antigen is a CD 100 antigen. In some embodiments, the macrophage or monocyte antigen is a CD101 antigen. In some embodiments, the macrophage or monocyte antigen is a CD 102 antigen. In some embodiments, the macrophage or monocyte antigen is a CD 105 antigen. In some embodiments, the macrophage or monocyte antigen is a CD111 antigen. In some embodiments, the macrophage or monocyte antigen is a CD112 antigen. In some embodiments, the macrophage or monocyte antigen is a CD114 antigen. In some embodiments, the macrophage or monocyte antigen is a CD115 antigen.
  • the macrophage or monocyte antigen is a CD116 antigen. In some embodiments, the macrophage or monocyte antigen is a CD119 antigen. In some embodiments, the macrophage or monocyte antigen is a CD120a antigen. In some embodiments, the macrophage or monocyte antigen is a CD120b antigen. In some embodiments, the macrophage or monocyte antigen is a CD121b antigen. In some embodiments, the macrophage or monocyte antigen is a CD122 antigen. In some embodiments, the macrophage or monocyte antigen is a CD124 antigen. In some embodiments, the macrophage or monocyte antigen is a CD127 antigen.
  • the macrophage or monocyte antigen is a CD130 antigen. In some embodiments, the macrophage or monocyte antigen is a CD 131 antigen. In some embodiments, the macrophage or monocyte antigen is a CD 132 antigen. In some embodiments, the macrophage or monocyte antigen is a CD136 antigen. In some embodiments, the macrophage or monocyte antigen is a CD137 antigen. In some embodiments, the macrophage or monocyte antigen is a CD139 antigen. In some embodiments, the macrophage or monocyte antigen is a CD141 antigen. In some embodiments, the macrophage or monocyte antigen is a CD142 antigen.
  • the macrophage or monocyte antigen is a CD143 antigen. In some embodiments, the macrophage or monocyte antigen is a CD147 antigen. In some embodiments, the macrophage or monocyte antigen is a CD148 antigen. In some embodiments, the macrophage or monocyte antigen is a CD 153 antigen. In some embodiments, the macrophage or monocyte antigen is a CD155 antigen. In some embodiments, the macrophage or monocyte antigen is a CD 156a antigen. In some embodiments, the macrophage or monocyte antigen is a CD 156b antigen. In some embodiments, the macrophage or monocyte antigen is a CD 156c antigen.
  • the macrophage or monocyte antigen is a CD 157 antigen. In some embodiments, the macrophage or monocyte antigen is a CD 162 antigen. In some embodiments, the macrophage or monocyte antigen is a CD 163 antigen. In some embodiments, the macrophage or monocyte antigen is a CD 164 antigen. In some embodiments, the macrophage or monocyte antigen is a CD 165 antigen. In some embodiments, the macrophage or monocyte antigen is a CD 166 antigen. In some embodiments, the macrophage or monocyte antigen is a CD 168 antigen. In some embodiments, the macrophage or monocyte antigen is a CD 169 antigen.
  • the macrophage or monocyte antigen is a CD 170 antigen. In some embodiments, the macrophage or monocyte antigen is a CD171 antigen. In some embodiments, the macrophage or monocyte antigen is a CD 172a antigen. In some embodiments, the macrophage or monocyte antigen is a CD 172b antigen. In some embodiments, the macrophage or monocyte antigen is a CD 180 antigen. In some embodiments, the macrophage or monocyte antigen is a CD181 antigen. In some embodiments, the macrophage or monocyte antigen is a CD 182 antigen. In some embodiments, the macrophage or monocyte antigen is a CD 184 antigen.
  • the macrophage or monocyte antigen is a CD 185 antigen. In some embodiments, the macrophage or monocyte antigen is a CD191 antigen. In some embodiments, the macrophage or monocyte antigen is a CD 192 antigen. In some embodiments, the macrophage or monocyte antigen is a CD 194 antigen. In some embodiments, the macrophage or monocyte antigen is a CD 195 antigen. In some embodiments, the macrophage or monocyte antigen is a CDwl98 antigen. In some embodiments, the macrophage or monocyte antigen is a CD24 antigen. In some embodiments, the macrophage or monocyte antigen is a CD205 antigen.
  • the macrophage or monocyte antigen is a CD206 antigen. In some embodiments, the macrophage or monocyte antigen is a CD209 antigen. In some embodiments, the macrophage or monocyte antigen is a CD210a antigen. In some embodiments, the macrophage or monocyte antigen is a CDw210b antigen. In some embodiments, the macrophage or monocyte antigen is a CD213al antigen. In some embodiments, the macrophage or monocyte antigen is a CD213a2 antigen. In some embodiments, the macrophage or monocyte antigen is a CD217 antigen. In some embodiments, the macrophage or monocyte antigen is a CD220 antigen.
  • the macrophage or monocyte antigen is a CD221 antigen. In some embodiments, the macrophage or monocyte antigen is a CD222 antigen. In some embodiments, the macrophage or monocyte antigen is a CD224 antigen. In some embodiments, the macrophage or monocyte antigen is a CD226 antigen. In some embodiments, the macrophage or monocyte antigen is a CD227 antigen. In some embodiments, the macrophage or monocyte antigen is a CD230 antigen. In some embodiments, the macrophage or monocyte antigen is a CD232 antigen. In some embodiments, the macrophage or monocyte antigen is a CD244 antigen.
  • the macrophage or monocyte antigen is a CD252 antigen. In some embodiments, the macrophage or monocyte antigen is a CD256 antigen. In some embodiments, the macrophage or monocyte antigen is a CD257 antigen. In some embodiments, the macrophage or monocyte antigen is a CD258 antigen. In some embodiments, the macrophage or monocyte antigen is a CD261 antigen. In some embodiments, the macrophage or monocyte antigen is a CD262 antigen. In some embodiments, the macrophage or monocyte antigen is a CD263 antigen. In some embodiments, the macrophage or monocyte antigen is a CD264 antigen.
  • the macrophage or monocyte antigen is a CD265 antigen. In some embodiments, the macrophage or monocyte antigen is a CD267 antigen. In some embodiments, the macrophage or monocyte antigen is a CD268 antigen. In some embodiments, the macrophage or monocyte antigen is a CD270 antigen. In some embodiments, the macrophage or monocyte antigen is a CD272 antigen. In some embodiments, the macrophage or monocyte antigen is a CD273 antigen. In some embodiments, the macrophage or monocyte antigen is a CD274 antigen. In some embodiments, the macrophage or monocyte antigen is a CD275 antigen.
  • the macrophage or monocyte antigen is a CD276 antigen. In some embodiments, the macrophage or monocyte antigen is a CD277 antigen. In some embodiments, the macrophage or monocyte antigen is a CD280 antigen. In some embodiments, the macrophage or monocyte antigen is a CD281 antigen. In some embodiments, the macrophage or monocyte antigen is a CD282 antigen. In some embodiments, the macrophage or monocyte antigen is a CD284 antigen. In some embodiments, the macrophage or monocyte antigen is a CD286 antigen. In some embodiments, the macrophage or monocyte antigen is a CD288 antigen.
  • the macrophage or monocyte antigen is a CD289 antigen. In some embodiments, the macrophage or monocyte antigen is a CD295 antigen. In some embodiments, the macrophage or monocyte antigen is a CD297 antigen. In some embodiments, the macrophage or monocyte antigen is a CD298 antigen. In some embodiments, the macrophage or monocyte antigen is a CD300a antigen. In some embodiments, the macrophage or monocyte antigen is a CD300c antigen. In some embodiments, the macrophage or monocyte antigen is a CD300e antigen. In some embodiments, the macrophage or monocyte antigen is a CD301 antigen.
  • the macrophage or monocyte antigen is a CD302 antigen. In some embodiments, the macrophage or monocyte antigen is a CD305 antigen. In some embodiments, the macrophage or monocyte antigen is a CD306 antigen. In some embodiments, the macrophage or monocyte antigen is a CD312 antigen. In some embodiments, the macrophage or monocyte antigen is a CD214 antigen. In some embodiments, the macrophage or monocyte antigen is a CD315 antigen. In some embodiments, the macrophage or monocyte antigen is a CD317 antigen. In some embodiments, the macrophage or monocyte antigen is a CD319 antigen.
  • the macrophage or monocyte antigen is a CD321 antigen. In some embodiments, the macrophage or monocyte antigen is a CD328 antigen. In some embodiments, the macrophage or monocyte antigen is a CD329 antigen. In some embodiments, the macrophage or monocyte antigen is a CD338 antigen. In some embodiments, the macrophage or monocyte antigen is a CD351 antigen. In some embodiments, the macrophage or monocyte antigen is a CD352 antigen. In some embodiments, the macrophage or monocyte antigen is a CD352 antigen. In some embodiments, the macrophage or monocyte antigen is a CD354 antigen.
  • the macrophage or monocyte antigen is a CD357 antigen. In some embodiments, the macrophage or monocyte antigen is a CD358 antigen. In some embodiments, the macrophage or monocyte antigen is a CD360 antigen. In some embodiments, the macrophage or monocyte antigen is a CD361 antigen. In some embodiments, the macrophage or monocyte antigen is a CD362 antigen.
  • the second binding arm binds a second target.
  • the second target is present on a target cell.
  • the second target is present on the surface of a target cell.
  • the target cell is a granulocyte.
  • the second target is a granulocyte antigen.
  • a multispecific TRGV9 antibody provided herein comprises: (a) a first binding domain that binds to TRGV9, and (b) a second binding domain that binds to a granulocyte antigen present on the surface of a granulocyte.
  • the first binding domain of the multispecific TRGV9 antibody specifically binds TRGV9.
  • the TRGV9 is present on the surface of a gd T cell.
  • the granulocyte is killed when the multispecific antibody binds to the TRGV9 on the surface of the gd T cell and the antigen on the surface of the granulocyte.
  • the multispecific TRGV9 antibody is a bispecific TRGV9 antibody. Bispecific antibodies comprising any of the TRGV9 antibodies provided herein as the first binding domain are contemplated.
  • the TRGV9 antibody binds to a first epitope located on TRGV9 and a second epitope of a granulocyte.
  • a bispecific antibody comprising: (a) a first binding domain that binds to a TRGV9 antigen, and (b) a second binding domain that binds to a granulocyte antigen. In some embodiments, provided herein is a bispecific antibody comprising: (a) a first binding domain that specifically binds to a TRGV9 antigen, and (b) a second binding domain that specifically binds to a granulocyte antigen.
  • a bispecific antibody comprising: (a) a first binding domain that binds to a first epitope on a TRGV9 antigen, and (b) a second binding domain that binds to a second epitope on a granulocyte antigen.
  • a bispecific antibody comprising: (a) a first binding domain that specifically binds to a first epitope on a TRGV9 antigen, and (b) a second binding domain that specifically binds to a second epitope on a granulocyte antigen.
  • the first epitope is located on TRGV9 and the second epitope is located on the surface of a granulocyte. In some embodiments, the second epitope is located on a granulocyte antigen.
  • the granulocyte antigen is a la, , or CD362 antigen. In some embodiments, the granulocyte antigen is a CD4 antigen. In some embodiments, the granulocyte antigen is a CD9 antigen. In some embodiments, the granulocyte antigen is a CD1 la antigen. In some embodiments, the granulocyte antigen is a CD1 lb antigen. In some embodiments, the granulocyte antigen is a CD1 lc antigen. In some embodiments, the granulocyte antigen is a CDwl2 antigen. In some embodiments, the granulocyte antigen is a CD13 antigen.
  • the granulocyte antigen is a CD14 antigen. In some embodiments, the granulocyte antigen is a CD 15 antigen. In some embodiments, the granulocyte antigen is a CD 16 antigen. In some embodiments, the granulocyte antigen is a CD 16b antigen. In some embodiments, the granulocyte antigen is a
  • the granulocyte antigen is a CD 18 antigen. In some embodiments, the granulocyte antigen is a CD23 antigen. In some embodiments, the granulocyte antigen is a CD24 antigen. In some embodiments, the granulocyte antigen is a CD29 antigen. In some embodiments, the granulocyte antigen is a CD31 antigen. In some embodiments, the granulocyte antigen is a CD32a antigen. In some embodiments, the granulocyte antigen is a CD32b antigen. In some embodiments, the granulocyte antigen is a CD32c antigen. In some embodiments, the granulocyte antigen is a CD33 antigen.
  • the granulocyte antigen is a CD35 antigen. In some embodiments, the granulocyte antigen is a CD37 antigen. In some embodiments, the granulocyte antigen is a CD43 antigen. In some embodiments, the granulocyte antigen is a CD44 antigen. In some embodiments, the granulocyte antigen is a CD45 antigen. In some embodiments, the granulocyte antigen is a CD45RB antigen. In some embodiments, the granulocyte antigen is a CD45RO antigen. In some embodiments, the granulocyte antigen is a CD46 antigen. In some embodiments, the granulocyte antigen is a CD47 antigen.
  • the granulocyte antigen is a CD50 antigen. In some embodiments, the granulocyte antigen is a CD53 antigen. In some embodiments, the granulocyte antigen is a CD55 antigen. In some embodiments, the granulocyte antigen is a CD58 antigen. In some embodiments, the granulocyte antigen is a CD59 antigen. In some embodiments, the granulocyte antigen is a CD60a antigen. In some embodiments, the granulocyte antigen is a CD62L antigen. In some embodiments, the granulocyte antigen is a CD63 antigen. In some embodiments, the granulocyte antigen is a CD64a antigen.
  • the granulocyte antigen is a CD65 antigen. In some embodiments, the granulocyte antigen is a CD65s antigen. In some embodiments, the granulocyte antigen is a CD66a antigen. In some embodiments, the granulocyte antigen is a CD66b antigen. In some embodiments, the granulocyte antigen is a CD66c antigen. In some embodiments, the granulocyte antigen is a CD66d antigen. In some embodiments, the granulocyte antigen is a CD68 antigen. In some embodiments, the granulocyte antigen is a CD69 antigen. In some embodiments, the granulocyte antigen is a CD75S antigen.
  • the granulocyte antigen is a CD82 antigen. In some embodiments, the granulocyte antigen is a CD85A antigen. In some embodiments, the granulocyte antigen is a CD85D antigen. In some embodiments, the granulocyte antigen is a CD85K antigen. In some embodiments, the granulocyte antigen is a CD87 antigen.
  • the granulocyte antigen is a CD88 antigen. In some embodiments, the granulocyte antigen is a CD89 antigen. In some embodiments, the granulocyte antigen is a CD92 antigen. In some embodiments, the granulocyte antigen is a CD93 antigen. In some embodiments, the granulocyte antigen is a CD95 antigen. In some embodiments, the granulocyte antigen is a CD97 antigen. In some embodiments, the granulocyte antigen is a CD98 antigen. In some embodiments, the granulocyte antigen is a CD 100 antigen. In some embodiments, the granulocyte antigen is a CD101 antigen.
  • the granulocyte antigen is a CD 107a antigen. In some embodiments, the granulocyte antigen is a CD 107b antigen. In some embodiments, the granulocyte antigen is a CD114 antigen. In some embodiments, the granulocyte antigen is a CD116 antigen. In some embodiments, the granulocyte antigen is a CD119 antigen. In some embodiments, the granulocyte antigen is a CD 120a antigen. In some embodiments, the granulocyte antigen is a CD120b antigen. In some embodiments, the granulocyte antigen is a CD123 antigen. In some embodiments, the granulocyte antigen is a CD125 antigen.
  • the granulocyte antigen is a CD130 antigen. In some embodiments, the granulocyte antigen is a CD131 antigen. In some embodiments, the granulocyte antigen is a CD 132 antigen. In some embodiments, the granulocyte antigen is a CD139 antigen. In some embodiments, the granulocyte antigen is a CD141 antigen. In some embodiments, the granulocyte antigen is a CD147 antigen. In some embodiments, the granulocyte antigen is a CD148 antigen. In some embodiments, the granulocyte antigen is a CD 153 antigen. In some embodiments, the granulocyte antigen is a CD 156a antigen.
  • the granulocyte antigen is a CD 156b antigen. In some embodiments, the granulocyte antigen is a CD 157 antigen. In some embodiments, the granulocyte antigen is a CD 162 antigen. In some embodiments, the granulocyte antigen is a CD 170 antigen. In some embodiments, the granulocyte antigen is a CD171 antigen. In some embodiments, the granulocyte antigen is a CD 172a antigen. In some embodiments, the granulocyte antigen is a CD 177 antigen. In some embodiments, the granulocyte antigen is a CD 178 antigen. In some embodiments, the granulocyte antigen is a CD181 antigen.
  • the granulocyte antigen is a CD 182 antigen. In some embodiments, the granulocyte antigen is a CD 183 antigen. In some embodiments, the granulocyte antigen is a CD 192 antigen. In some embodiments, the granulocyte antigen is a CD 193 antigen. In some embodiments, the granulocyte antigen is a CD 195 antigen.
  • the granulocyte antigen is a CD203c antigen. In some embodiments, the granulocyte antigen is a CD217 antigen. In some embodiments, the granulocyte antigen is a CD218a antigen. In some embodiments, the granulocyte antigen is a CD218b antigen. In some embodiments, the granulocyte antigen is a CD220 antigen. In some embodiments, the granulocyte antigen is a CD221 antigen. In some embodiments, the granulocyte antigen is a CD222 antigen. In some embodiments, the granulocyte antigen is a CD230 antigen. In some embodiments, the granulocyte antigen is a CD232 antigen.
  • the granulocyte antigen is a CD244 antigen. In some embodiments, the granulocyte antigen is a CD256 antigen. In some embodiments, the granulocyte antigen is a CD257 antigen. In some embodiments, the granulocyte antigen is a CD258 antigen. In some embodiments, the granulocyte antigen is a CD261 antigen. In some embodiments, the granulocyte antigen is a CD262 antigen. In some embodiments, the granulocyte antigen is a CD263 antigen. In some embodiments, the granulocyte antigen is a CD264 antigen. In some embodiments, the granulocyte antigen is a CD268 antigen.
  • the granulocyte antigen is a CD270 antigen. In some embodiments, the granulocyte antigen is a CD274 antigen. In some embodiments, the granulocyte antigen is a CD275 antigen. In some embodiments, the granulocyte antigen is a CD281 antigen. In some embodiments, the granulocyte antigen is a CD282 antigen. In some embodiments, the granulocyte antigen is a CD289 antigen. In some embodiments, the granulocyte antigen is a CD290 antigen. In some embodiments, the granulocyte antigen is a CD294 antigen. In some embodiments, the granulocyte antigen is a CD295 antigen.
  • the granulocyte antigen is a CD298 antigen. In some embodiments, the granulocyte antigen is a CD302 antigen. In some embodiments, the granulocyte antigen is a CD305 antigen. In some embodiments, the granulocyte antigen is a CD312 antigen. In some embodiments, the granulocyte antigen is a CD314 antigen. In some embodiments, the granulocyte antigen is a CD321 antigen. In some embodiments, the granulocyte antigen is a CD328 antigen. In some embodiments, the granulocyte antigen is a CD329 antigen. In some embodiments, the granulocyte antigen is a CD352 antigen. In some embodiments, the granulocyte antigen is a CD354 antigen. In some embodiments, the granulocyte antigen is a CD360 antigen. In some embodiments, the granulocyte antigen is a CD362 antigen.
  • the second binding arm binds a second target.
  • the second target is present on a target cell.
  • the second target is present on the surface of a target cell.
  • the target cell is a platelet.
  • the second target is a platelet antigen.
  • a multispecific TRGV9 antibody provided herein comprises: (a) a first binding domain that binds to TRGV9, and (b) a second binding domain that binds to a platelet antigen present on the surface of a platelet.
  • the first binding domain of the multispecific TRGV9 antibody specifically binds TRGV9.
  • the TRGV9 is present on the surface of a gd T cell.
  • the platelet is killed when the multispecific antibody binds to the TRGV9 on the surface of the gd T cell and the antigen on the surface of the platelet.
  • the multispecific TRGV9 antibody is a bispecific TRGV9 antibody. Bispecific antibodies comprising any of the TRGV9 antibodies provided herein as the first binding domain are contemplated.
  • the TRGV9 antibody binds to a first epitope located on TRGV9 and a second epitope of a platelet.
  • a bispecific antibody comprising: (a) a first binding domain that binds to a TRGV9 antigen, and (b) a second binding domain that binds to a platelet antigen. In some embodiments, provided herein is a bispecific antibody comprising: (a) a first binding domain that specifically binds to a TRGV9 antigen, and (b) a second binding domain that specifically binds to a platelet antigen.
  • a bispecific antibody comprising: (a) a first binding domain that binds to a first epitope on a TRGV9 antigen, and (b) a second binding domain that binds to a second epitope on a platelet antigen.
  • a bispecific antibody comprising: (a) a first binding domain that specifically binds to a first epitope on a TRGV9 antigen, and (b) a second binding domain that specifically binds to a second epitope on a platelet antigen.
  • the first epitope is located on TRGV9 and the second epitope is located on the surface of a platelet.
  • the second epitope is located on a platelet antigen.
  • the platelet antigen is a antigen. In some embodiments, the platelet antigen is a CD9 antigen. In some embodiments, the platelet antigen is a CD 17 antigen. In some embodiments, the platelet antigen is a CD 18 antigen. In some embodiments, the platelet antigen is a CD23 antigen. In some embodiments, the platelet antigen is a CD29 antigen. In some embodiments, the platelet antigen is a CD31 antigen. In some embodiments, the platelet antigen is a CD32a antigen. In some embodiments, the platelet antigen is a CD32b antigen. In some embodiments, the platelet antigen is a CD36 antigen.
  • the platelet antigen is a CD41 antigen. In some embodiments, the platelet antigen is a CD42a antigen. In some embodiments, the platelet antigen is a CD42b antigen. In some embodiments, the platelet antigen is a CD42c antigen. In some embodiments, the platelet antigen is a CD42d antigen. In some embodiments, the platelet antigen is a CD43 antigen. In some embodiments, the platelet antigen is a CD46 antigen. In some embodiments, the platelet antigen is a CD47 antigen. In some embodiments, the platelet antigen is a CD62P antigen. In some embodiments, the platelet antigen is a CD63 antigen.
  • the platelet antigen is a CD69 antigen. In some embodiments, the platelet antigen is a CD82 antigen. In some embodiments, the platelet antigen is a CD84 antigen. In some embodiments, the platelet antigen is a CD98 antigen. In some embodiments, the platelet antigen is a CD99 antigen. In some embodiments, the platelet antigen is a CD 107a antigen. In some embodiments, the platelet antigen is a CD 107b antigen. In some embodiments, the platelet antigen is a CD 109 antigen. In some embodiments, the platelet antigen is a CD110 antigen. In some embodiments, the platelet antigen is a CD111 antigen.
  • the platelet antigen is a CD112 antigen. In some embodiments, the platelet antigen is a CD114 antigen. In some embodiments, the platelet antigen is a CD140a antigen. In some embodiments, the platelet antigen is a CD141 antigen. In some embodiments, the platelet antigen is a CD147 antigen. In some embodiments, the platelet antigen is a CD148 antigen. In some embodiments, the platelet antigen is a CD151 antigen. In some embodiments, the platelet antigen is a CD 165 antigen. In some embodiments, the platelet antigen is a CD 194 antigen. In some embodiments, the platelet antigen is a CD226 antigen. In some embodiments, the platelet antigen is a CD295 antigen. In some embodiments, the platelet antigen is a CD298 antigen. In some embodiments, the platelet antigen is a CD321 antigen.
  • the second binding arm binds a second target.
  • the second target is present on a target cell.
  • the second target is present on the surface of a target cell.
  • the target cell is an erythrocyte.
  • the second target is an erythrocyte antigen.
  • a multispecific TRGV9 antibody provided herein comprises: (a) a first binding domain that binds to TRGV9, and (b) a second binding domain that binds to an erythrocyte antigen present on the surface of an erythrocyte.
  • the first binding domain of the multispecific TRGV9 antibody specifically binds TRGV9.
  • the TRGV9 is present on the surface of a gd T cell.
  • the erythrocyte is killed when the multispecific antibody binds to the TRGV9 on the surface of the gd T cell and the antigen on the surface of the erythrocyte.
  • the multispecific TRGV9 antibody is a bispecific TRGV9 antibody. Bispecific antibodies comprising any of the TRGV9 antibodies provided herein as the first binding domain are contemplated.
  • the TRGV9 antibody binds to a first epitope located on TRGV9 and a second epitope of an erythrocyte.
  • a bispecific antibody comprising: (a) a first binding domain that binds to a TRGV9 antigen, and (b) a second binding domain that binds to an erythrocyte antigen. In some embodiments, provided herein is a bispecific antibody comprising: (a) a first binding domain that specifically binds to a TRGV9 antigen, and (b) a second binding domain that specifically binds to an erythrocyte antigen.
  • a bispecific antibody comprising: (a) a first binding domain that binds to a first epitope on a TRGV9 antigen, and (b) a second binding domain that binds to a second epitope on an erythrocyte antigen.
  • a bispecific antibody comprising: (a) a first binding domain that specifically binds to a first epitope on a TRGV9 antigen, and (b) a second binding domain that specifically binds to a second epitope on an erythrocyte antigen.
  • the first epitope is located on TRGV9 and the second epitope is located on the surface of an erythrocyte. In some embodiments, the second epitope is located on an erythrocyte antigen.
  • the erythrocyte antigen is a CD35, CD36, CD44, CD47, CD49e, CD55, CD58, CD59, CD75S, CD99, CD108, CD111, CD139,
  • the erythrocyte antigen is a CD35 antigen. In some embodiments, the erythrocyte antigen is a CD36 antigen. In some embodiments, the erythrocyte antigen is a CD44 antigen. In some embodiments, the erythrocyte antigen is a CD47 antigen. In some embodiments, the erythrocyte antigen is a CD49e antigen. In some embodiments, the erythrocyte antigen is a CD55 antigen. In some embodiments, the erythrocyte antigen is a CD58 antigen. In some embodiments, the erythrocyte antigen is a CD59 antigen.
  • the erythrocyte antigen is a CD75S antigen. In some embodiments, the erythrocyte antigen is a CD99 antigen. In some embodiments, the erythrocyte antigen is a CD 108 antigen. In some embodiments, the erythrocyte antigen is a CD111 antigen. In some embodiments, the erythrocyte antigen is a CD139 antigen. In some embodiments, the erythrocyte antigen is a CD147 antigen.
  • the erythrocyte antigen is a CD 173 antigen. In some embodiments, the erythrocyte antigen is a CD 176 antigen. In some embodiments, the erythrocyte antigen is a CD233 antigen. In some embodiments, the erythrocyte antigen is a CD234 antigen. In some embodiments, the erythrocyte antigen is a CD235a antigen. In some embodiments, the erythrocyte antigen is a CD235b antigen. In some embodiments, the erythrocyte antigen is a CD236 antigen. In some embodiments, the erythrocyte antigen is a CD236R antigen.
  • the erythrocyte antigen is a CD238 antigen. In some embodiments, the erythrocyte antigen is a CD239 antigen. In some embodiments, the erythrocyte antigen is a CD240 antigen. In some embodiments, the erythrocyte antigen is a CD241 antigen.
  • the erythrocyte antigen is a CD242 antigen. In some embodiments, the erythrocyte antigen is a CD324 antigen.
  • the second binding arm binds a second target.
  • the second target is present on a target cell.
  • the second target is present on the surface of a target cell.
  • the target cell is an endothelial cell.
  • the second target is an endothelial cell antigen.
  • a multispecific TRGV9 antibody provided herein comprises: (a) a first binding domain that binds to TRGV9, and (b) a second binding domain that binds to an endothelial cell antigen present on the surface of an endothelial cell.
  • the first binding domain of the multispecific TRGV9 antibody specifically binds TRGV9.
  • the TRGV9 is present on the surface of a gd T cell.
  • the endothelial cell is killed when the multispecific antibody binds to the TRGV9 on the surface of the gd T cell and the antigen on the surface of the endothelial cell.
  • the multispecific TRGV9 antibody is a bispecific TRGV9 antibody. Bispecific antibodies comprising any of the TRGV9 antibodies provided herein as the first binding domain are contemplated.
  • the TRGV9 antibody binds to a first epitope located on TRGV9 and a second epitope of an endothelial cell.
  • a bispecific antibody comprising: (a) a first binding domain that binds to a TRGV9 antigen, and (b) a second binding domain that binds to an endothelial cell antigen. In some embodiments, provided herein is a bispecific antibody comprising: (a) a first binding domain that specifically binds to a TRGV9 antigen, and (b) a second binding domain that specifically binds to an endothelial cell antigen.
  • a bispecific antibody comprising: (a) a first binding domain that binds to a first epitope on a TRGV9 antigen, and (b) a second binding domain that binds to a second epitope on an endothelial cell antigen.
  • a bispecific antibody comprising: (a) a first binding domain that specifically binds to a first epitope on a TRGV9 antigen, and (b) a second binding domain that specifically binds to a second epitope on an endothelial cell antigen.
  • the first epitope is located on TRGV9 and the second epitope is located on the surface of an endothelial cell. In some embodiments, the second epitope is located on an endothelial cell antigen.
  • the endothelial cell antigen is a CD321, CD322, or CD344 antigen. In some embodiments, the endothelial cell antigen is a CD9 antigen. In some embodiments, the endothelial cell antigen is a CD 10 antigen. In some embodiments, the endothelial cell antigen is a CD 13 antigen. In some embodiments, the endothelial cell antigen is a CD 17 antigen. In some embodiments, the endothelial cell antigen is a CD29 antigen. In some embodiments, the endothelial cell antigen is a CD30 antigen. In some embodiments, the endothelial cell antigen is a CD31 antigen.
  • the endothelial cell antigen is a CD32b antigen. In some embodiments, the endothelial cell antigen is a CD34 antigen. In some embodiments, the endothelial cell antigen is a CD36 antigen. In some embodiments, the endothelial cell antigen is a CD39 antigen. In some embodiments, the endothelial cell antigen is a CD40 antigen. In some embodiments, the endothelial cell antigen is a CD44 antigen. In some embodiments, the endothelial cell antigen is a CD46 antigen. In some embodiments, the endothelial cell antigen is a CD47 antigen.
  • the endothelial cell antigen is a CD49b antigen. In some embodiments, the endothelial cell antigen is a CD49c antigen. In some embodiments, the endothelial cell antigen is a CD49d antigen. In some embodiments, the endothelial cell antigen is a CD4e antigen. In some embodiments, the endothelial cell antigen is a CD49f antigen. In some embodiments, the endothelial cell antigen is a CD50 antigen. In some embodiments, the endothelial cell antigen is a CD51 antigen. In some embodiments, the endothelial cell antigen is a CD54 antigen. In some embodiments, the endothelial cell antigen is a CD5 antigen.
  • the endothelial cell antigen is a CD58 antigen. In some embodiments, the endothelial cell antigen is a CD61 antigen. In some embodiments, the endothelial cell antigen is a CD62E antigen. In some embodiments, the endothelial cell antigen is a CD62P antigen. In some embodiments, the endothelial cell antigen is a CD63 antigen. In some embodiments, the endothelial cell antigen is a CD71 antigen. In some embodiments, the endothelial cell antigen is a CD73 antigen. In some embodiments, the endothelial cell antigen is a CD74 antigen.
  • the endothelial cell antigen is a CD75S antigen. In some embodiments, the endothelial cell antigen is a CD77 antigen. In some embodiments, the endothelial cell antigen is a CD81 antigen. In some embodiments, the endothelial cell antigen is a CD82 antigen. In some embodiments, the endothelial cell antigen is a CD86 antigen. In some embodiments, the endothelial cell antigen is a CD87 antigen. In some embodiments, the endothelial cell antigen is a CD88 antigen. In some embodiments, the endothelial cell antigen is a CD90 antigen.
  • the endothelial cell antigen is a CD92 antigen. In some embodiments, the endothelial cell antigen is a CD93 antigen. In some embodiments, the endothelial cell antigen is a CD98 antigen. In some embodiments, the endothelial cell antigen is a CD99 antigen. In some embodiments, the endothelial cell antigen is a CD 102 antigen. In some embodiments, the endothelial cell antigen is a CD 104 antigen. In some embodiments, the endothelial cell antigen is a CD 105 antigen. In some embodiments, the endothelial cell antigen is a CD 106 antigen.
  • the endothelial cell antigen is a CD 107a antigen. In some embodiments, the endothelial cell antigen is a CD 107b antigen. In some embodiments, the endothelial cell antigen is a CD 109 antigen. In some embodiments, the endothelial cell antigen is a CD110 antigen. In some embodiments, the endothelial cell antigen is a CD111 antigen. In some embodiments, the endothelial cell antigen is a CD112 antigen. In some embodiments, the endothelial cell antigen is a CD114 antigen. In some embodiments, the endothelial cell antigen is a CD117 antigen.
  • the endothelial cell antigen is a CD119 antigen. In some embodiments, the endothelial cell antigen is a CD120a antigen. In some embodiments, the endothelial cell antigen is a CD120b antigen. In some embodiments, the endothelial cell antigen is a CD121a antigen. In some embodiments, the endothelial cell antigen is a CD123 antigen. In some embodiments, the endothelial cell antigen is a CD130 antigen. In some embodiments, the endothelial cell antigen is a CD133 antigen. In some embodiments, the endothelial cell antigen is a CD138.
  • the endothelial cell antigen is a CD140a antigen. In some embodiments, the endothelial cell antigen is a CD140b antigen. In some embodiments, the endothelial cell antigen is a CD141 antigen. In some embodiments, the endothelial cell antigen is a CD142 antigen. In some embodiments, the endothelial cell antigen is a CD143 antigen. In some embodiments, the endothelial cell antigen is a CD144 antigen. In some embodiments, the endothelial cell antigen is a CDwl54 antigen. In some embodiments, the endothelial cell antigen is a CD146 antigen.
  • the endothelial cell antigen is a CD147 antigen. In some embodiments, the endothelial cell antigen is a CD 150 antigen. In some embodiments, the endothelial cell antigen is a CD151 antigen. In some embodiments, the endothelial cell antigen is a CD 156b antigen. In some embodiments, the endothelial cell antigen is a CD 157 antigen. In some embodiments, the endothelial cell antigen is a CD 166 antigen. In some embodiments, the endothelial cell antigen is a CD171 antigen. In some embodiments, the endothelial cell antigen is a CD 173 antigen.
  • the endothelial cell antigen is a CD175S antigen. In some embodiments, the endothelial cell antigen is a CD 176 antigen. In some embodiments, the endothelial cell antigen is a CD 178 antigen. In some embodiments, the endothelial cell antigen is a CD 184 antigen. In some embodiments, the endothelial cell antigen is a CD 192 antigen. In some embodiments, the endothelial cell antigen is a CD200 antigen. In some embodiments, the endothelial cell antigen is a CD201 antigen. In some embodiments, the endothelial cell antigen is a CD202b antigen.
  • the endothelial cell antigen is a CD206 antigen. In some embodiments, the endothelial cell antigen is a CD209 antigen. In some embodiments, the endothelial cell antigen is a CD213al antigen. In some embodiments, the endothelial cell antigen is a CD217 antigen. In some embodiments, the endothelial cell antigen is a CD218a antigen. In some embodiments, the endothelial cell antigen is a CD220 antigen. In some embodiments, the endothelial cell antigen is a CD221 antigen. In some embodiments, the endothelial cell antigen is a CD222 antigen.
  • the endothelial cell antigen is a CD224 antigen. In some embodiments, the endothelial cell antigen is a CD225 antigen. In some embodiments, the endothelial cell antigen is a CD228 antigen. In some embodiments, the endothelial cell antigen is a CD230 antigen. In some embodiments, the endothelial cell antigen is a CD234 antigen. In some embodiments, the endothelial cell antigen is a CD239 antigen. In some embodiments, the endothelial cell antigen is a CD242 antigen. In some embodiments, the endothelial cell antigen is a CD246 antigen.
  • the endothelial cell antigen is a CD248 antigen. In some embodiments, the endothelial cell antigen is a CD252 antigen. In some embodiments, the endothelial cell antigen is a CD266 antigen. In some embodiments, the endothelial cell antigen is a CD280. 295 antigen. In some embodiments, the endothelial cell antigen is a CD297 antigen. In some embodiments, the endothelial cell antigen is a CD299 antigen. In some embodiments, the endothelial cell antigen is a CD309 antigen. In some embodiments, the endothelial cell antigen is a CD321 antigen. In some embodiments, the endothelial cell antigen is a CD322 antigen. In some embodiments, the endothelial cell antigen is a CD344 antigen.
  • the second binding arm binds a second target.
  • the second target is present on a target cell.
  • the second target is present on the surface of a target cell.
  • the target cell is an epithelial cell.
  • the second target is an epithelial cell antigen.
  • a multispecific TRGV9 antibody provided herein comprises: (a) a first binding domain that binds to TRGV9, and (b) a second binding domain that binds to an epithelial cell antigen present on the surface of an epithelial cell.
  • the first binding domain of the multispecific TRGV9 antibody specifically binds TRGV9.
  • the TRGV9 is present on the surface of a gd T cell.
  • the epithelial cell is killed when the multispecific antibody binds to the TRGV9 on the surface of the gd T cell and the antigen on the surface of the epithelial cell.
  • the multispecific TRGV9 antibody is a bispecific TRGV9 antibody. Bispecific antibodies comprising any of the TRGV9 antibodies provided herein as the first binding domain are contemplated.
  • the TRGV9 antibody binds to a first epitope located on TRGV9 and a second epitope of an epithelial cell.
  • a bispecific antibody comprising: (a) a first binding domain that binds to a TRGV9 antigen, and (b) a second binding domain that binds to an epithelial cell antigen. In some embodiments, provided herein is a bispecific antibody comprising: (a) a first binding domain that specifically binds to a TRGV9 antigen, and (b) a second binding domain that specifically binds to an epithelial cell antigen.
  • a bispecific antibody comprising: (a) a first binding domain that binds to a first epitope on a TRGV9 antigen, and (b) a second binding domain that binds to a second epitope on an epithelial cell antigen.
  • a bispecific antibody comprising: (a) a first binding domain that specifically binds to a first epitope on a TRGV9 antigen, and (b) a second binding domain that specifically binds to a second epitope on an epithelial cell antigen.
  • the first epitope is located on TRGV9 and the second epitope is located on the surface of an epithelial cell. In some embodiments, the second epitope is located on an epithelial cell antigen.
  • the epithelial cell antigen is a CD 124, CD129, CD133, CD136, CD137, CD138, CD141, CD142, CD143,
  • the epithelial cell antigen is a CD Id antigen. In some embodiments, the epithelial cell antigen is a CD9 antigen.
  • the epithelial cell antigen is a CD 13 antigen. In some embodiments, the epithelial cell antigen is a CD 18 antigen. In some embodiments, the epithelial cell antigen is a CD21 antigen. In some embodiments, the epithelial cell antigen is a CD23 antigen. In some embodiments, the epithelial cell antigen is a CD24 antigen.
  • the epithelial cell antigen is a CD26 antigen. In some embodiments, the epithelial cell antigen is a CD29 antigen. In some embodiments, the epithelial cell antigen is a CD39 antigen. In some embodiments, the epithelial cell antigen is a CD40 antigen. In some embodiments, the epithelial cell antigen is a CD44 antigen. In some embodiments, the epithelial cell antigen is a CD46 antigen.
  • the epithelial cell antigen is a CD47 antigen. In some embodiments, the epithelial cell antigen is a CD49b antigen. In some embodiments, the epithelial cell antigen is a CD49c antigen. In some embodiments, the epithelial cell antigen is a CD49e antigen. In some embodiments, the epithelial cell antigen is a CD49f antigen. In some embodiments, the epithelial cell antigen is a CD52 antigen. In some embodiments, the epithelial cell antigen is a CD55 antigen. In some embodiments, the epithelial cell antigen is a CD58 antigen.
  • the epithelial cell antigen is a CD66a antigen. In some embodiments, the epithelial cell antigen is a CD66c antigen. In some embodiments, the epithelial cell antigen is a CD66e antigen. In some embodiments, the epithelial cell antigen is a CD66f antigen. In some embodiments, the epithelial cell antigen is a CD73 antigen. In some embodiments, the epithelial cell antigen is a CD74 antigen. In some embodiments, the epithelial cell antigen is a CD75S antigen. In some embodiments, the epithelial cell antigen is a CD77 antigen. In some embodiments, the epithelial cell antigen is a CD81 antigen. In some embodiments, the epithelial cell antigen is a CD82 antigen.
  • the epithelial cell antigen is a CD88. 91 antigen. In some embodiments, the epithelial cell antigen is a CD92 antigen. In some embodiments, the epithelial cell antigen is a CD98 antigen. In some embodiments, the epithelial cell antigen is a CD99 antigen. In some embodiments, the epithelial cell antigen is a CD 104 antigen. In some embodiments, the epithelial cell antigen is a CD110 antigen. In some embodiments, the epithelial cell antigen is a CD111 antigen. In some embodiments, the epithelial cell antigen is a CD112 antigen.
  • the epithelial cell antigen is a CD113 antigen. In some embodiments, the epithelial cell antigen is a CD114 antigen. In some embodiments, the epithelial cell antigen is a CD118 antigen. In some embodiments, the epithelial cell antigen is a CD 120a antigen. In some embodiments, the epithelial cell antigen is a CD120b antigen. In some embodiments, the epithelial cell antigen is a CD 124 antigen. In some embodiments, the epithelial cell antigen is a CD129 antigen. In some embodiments, the epithelial cell antigen is a CD133 antigen. In some embodiments, the epithelial cell antigen is a CD136 antigen.
  • the epithelial cell antigen is a CD 137 antigen. In some embodiments, the epithelial cell antigen is a CD138 antigen. In some embodiments, the epithelial cell antigen is a CD141 antigen. In some embodiments, the epithelial cell antigen is a CD142 antigen. In some embodiments, the epithelial cell antigen is a CD143 antigen. In some embodiments, the epithelial cell antigen is a CDwl45 antigen. In some embodiments, the epithelial cell antigen is a CD151 antigen. In some embodiments, the epithelial cell antigen is a CD 164 antigen.
  • the epithelial cell antigen is a CD 165 antigen. In some embodiments, the epithelial cell antigen is a CD 166 antigen. In some embodiments, the epithelial cell antigen is a CD 167a antigen. In some embodiments, the epithelial cell antigen is a CD171 antigen. In some embodiments, the epithelial cell antigen is a CD 174 antigen. In some embodiments, the epithelial cell antigen is a CD175 antigen. In some embodiments, the epithelial cell antigen is a CD175S antigen. In some embodiments, the epithelial cell antigen is a CD 176 antigen.
  • the epithelial cell antigen is a CD 178 antigen. In some embodiments, the epithelial cell antigen is a CD 193 antigen. In some embodiments, the epithelial cell antigen is a CD206 antigen. In some embodiments, the epithelial cell antigen is a CD213a2 antigen. In some embodiments, the epithelial cell antigen is a CD217 antigen. In some embodiments, the epithelial cell antigen is a CD220 antigen. In some embodiments, the epithelial cell antigen is a CD221 antigen. In some embodiments, the epithelial cell antigen is a CD222 antigen.
  • the epithelial cell antigen is a CD224 antigen. In some embodiments, the epithelial cell antigen is a CD227 antigen. In some embodiments, the epithelial cell antigen is a CD230 antigen. In some embodiments, the epithelial cell antigen is a CD234 antigen. In some embodiments, the epithelial cell antigen is a CD239 antigen. In some embodiments, the epithelial cell antigen is a CD249 antigen. In some embodiments, the epithelial cell antigen is a CD286 antigen. In some embodiments, the epithelial cell antigen is a CD295 antigen.
  • the epithelial cell antigen is a CD296 antigen. In some embodiments, the epithelial cell antigen is a CD321 antigen. In some embodiments, the epithelial cell antigen is a CD324 antigen. In some embodiments, the epithelial cell antigen is a CD326 antigen. In some embodiments, the epithelial cell antigen is a CD331 antigen. In some embodiments, the epithelial cell antigen is a CD332 antigen. In some embodiments, the epithelial cell antigen is a CD333 antigen. In some embodiments, the epithelial cell antigen is a CD334 antigen.
  • the epithelial cell antigen is a CD339 antigen. In some embodiments, the epithelial cell antigen is a CD340 antigen. In some embodiments, the epithelial cell antigen is a CD344 antigen. In some embodiments, the epithelial cell antigen is a CD350 antigen.
  • the second binding arm binds a second target.
  • the second target is a pathogen.
  • the second target is present on a target cell.
  • the second target is present on the surface of a target cell.
  • the target cell is a cell comprising a pathogen.
  • the second target is a pathogen antigen.
  • a multispecific TRGV9 antibody provided herein comprises: (a) a first binding domain that binds to TRGV9, and (b) a second binding domain that binds to a pathogen antigen present on the surface of a cell comprising a pathogen.
  • the first binding domain of the multispecific TRGV9 antibody specifically binds TRGV9.
  • the TRGV9 is present on the surface of a gd T cell.
  • the cell comprising the pathogen is killed when the multispecific antibody binds to the TRGV9 on the surface of the gd T cell and the antigen on the surface of the cell.
  • the multispecific TRGV9 antibody is a bispecific TRGV9 antibody. Bispecific antibodies comprising any of the TRGV9 antibodies provided herein as the first binding domain are contemplated.
  • the TRGV9 antibody binds to a first epitope located on TRGV9 and a second epitope of a pathogen.
  • a bispecific antibody comprising: (a) a first binding domain that binds to a TRGV9 antigen, and (b) a second binding domain that binds to a pathogen antigen. In some embodiments, provided herein is a bispecific antibody comprising: (a) a first binding domain that specifically binds to a TRGV9 antigen, and (b) a second binding domain that specifically binds to a pathogen antigen.
  • a bispecific antibody comprising: (a) a first binding domain that binds to a first epitope on a TRGV9 antigen, and (b) a second binding domain that binds to a second epitope on a pathogen antigen.
  • a bispecific antibody comprising: (a) a first binding domain that specifically binds to a first epitope on a TRGV9 antigen, and (b) a second binding domain that specifically binds to a second epitope on a pathogen antigen.
  • the first epitope is located on TRGV9 and the second epitope is located on the surface of a cell comprising a pathogen. In some embodiments, the second epitope is located on a pathogen antigen.
  • the pathogen causes an infectious disease selected from the group consisting of an Acute Flaccid Myelitis (AFM), Anaplasmosis, Anthrax, Babesiosis, Botulism, Brucellosis, Campylobacteriosis, Carbapenem- resistant Infection, Chancroid, Chikungunya Virus Infection, Chlamydia, Ciguatera, Difficile Infection, Perfringens, Coccidioidomycosis fungal infection, coronavirus infection, Covid-19 (SARS-CoV-2), Creutzfeldt-Jacob Disease/transmissible spongiform encephalopathy, Cryptosporidiosis (Crypto), Cyclosporiasis, Dengue 1,2,3 or 4, Diphtheria, E.
  • AMF Acute Flaccid Myelitis
  • Anaplasmosis Anaplasmosis
  • Anthrax Anthrax
  • Babesiosis Botulism
  • Brucellosis Campyloba
  • coli infection/Shiga toxin-producing (STEC), Eastern Equine Encephalitis, Hemorrhagic Fever (Ebola), Ehrlichiosis, Encephalitis, Arboviral or parainfectious, Non-Polio Enterovirus, D68 Enteroviru(EV-D68), Giardiasis, Glanders, Gonococcal Infection, Granuloma inguinale, Haemophilus Influenza disease Type B (Hib or H-flu), Hantavirus Pulmonary Syndrome (HPS), Hemolytic Uremic Syndrome (HUS), Hepatitis A (Hep A), Hepatitis B (Hep B), Hepatitis C (Hep C), Hepatitis D (Hep D), Hepatitis E (Hep E), Herpes, Herpes Zoster (Shingles), Histoplasmosis infection, Human Immunodeficiency Virus/ AIDS (HIV/AIDS), Human Papillomavirus (HPV), Influenza (
  • the infectious disease is Acute Flaccid Myelitis (AFM).
  • the infectious disease is Anaplasmosis.
  • the infectious disease is Anthrax.
  • the infectious disease is Babesiosis.
  • the infectious disease is Botulism.
  • the infectious disease is Brucellosis.
  • the infectious disease is Campylobacteriosis.
  • the infectious disease is Carbapenem-resistant Infection.
  • the infectious disease is Chancroid.
  • the infectious disease is Chikungunya Virus Infection.
  • the infectious disease is Chlamydia.
  • the infectious disease is Ciguatera. In some embodiments, the infectious disease is Difficile Infection. In some embodiments, the infectious disease is Perfringens. In some embodiments, the infectious disease is Coccidioidomycosis fungal infection. In some embodiments, the infectious disease is coronavirus. In some embodiments, the infectious disease is Covid-19 (SARS-CoV-2). In some embodiments, the infectious disease is Creutzfeldt- Jacob Disease/transmissible spongiform encephalopathy. In some embodiments, the infectious disease is Cryptosporidiosis (Crypto). In some embodiments, the infectious disease is Cyclosporiasis. In some embodiments, the infectious disease is Dengue 1,2,3 or 4.
  • the infectious disease is Diphtheria. In some embodiments, the infectious disease is E. coli infection/Shiga toxin-producing (STEC). In some embodiments, the infectious disease is Eastern Equine Encephalitis. In some embodiments, the infectious disease is Hemorrhagic Fever (Ebola). In some embodiments, the infectious disease is Ehrlichiosis. In some embodiments, the infectious disease is Encephalitis. In some embodiments, the infectious disease is Arboviral or parainfectious. In some embodiments, the infectious disease is Non- Polio Enterovirus. In some embodiments, the infectious disease is D68 Enteroviru(EV-D68). In some embodiments, the infectious disease is Giardiasis.
  • the infectious disease is Glanders. In some embodiments, the infectious disease is Gonococcal Infection. In some embodiments, the infectious disease is Granuloma inguinale. In some embodiments, the infectious disease is Haemophilus Influenza disease Type B (Hib or H-flu). In some embodiments, the infectious disease is Hantavirus Pulmonary Syndrome (HPS). In some embodiments, the infectious disease is Hemolytic Uremic Syndrome (HUS). In some embodiments, the infectious disease is Hepatitis A (Hep A). In some embodiments, the infectious disease is Hepatitis B (Hep B). In some embodiments, the infectious disease is Hepatitis C (Hep C).
  • the infectious disease is Hepatitis D (Hep D). In some embodiments, the infectious disease is Hepatitis E (Hep E). In some embodiments, the infectious disease is Herpes. In some embodiments, the infectious disease is Herpes Zoster (Shingles). In some embodiments, the infectious disease is Histoplasmosis infection. In some embodiments, the infectious disease is Human Immunodeficiency Virus/ AIDS (HIV/AIDS). In some embodiments, the infectious disease is Human Papillomavirus (HPV). In some embodiments, the infectious disease is Influenza (Flu). In some embodiments, the infectious disease is Legionellosis (Legionnaires Disease). In some embodiments, the infectious disease is Leprosy (Hansens Disease). In some embodiments, the infectious disease is Leptospirosis. In some embodiments, the infectious disease is Listeriosis (Listeria).
  • the infectious disease is Lyme Disease. In some embodiments, the infectious disease is Lymphogranuloma venereum infection (LGV). In some embodiments, the infectious disease is Malaria. In some embodiments, the infectious disease is Measles. In some embodiments, the infectious disease is Melioidosis. In some embodiments, the infectious disease is Meningitis (Viral). In some embodiments, the infectious disease is Meningococcal Disease (Meningitis (Bacterial)). In some embodiments, the infectious disease is Middle East Respiratory Syndrome Coronavirus (MERS-CoV). In some embodiments, the infectious disease is Mumps. In some embodiments, the infectious disease is Norovirus. In some embodiments, the infectious disease is Pediculosis.
  • the infectious disease is Pelvic Inflammatory Disease (PID). In some embodiments, the infectious disease is Pertussis (Whooping Cough). In some embodiments, the infectious disease is Plague (Bubonic. In some embodiments, the infectious disease is Septicemic. In some embodiments, the infectious disease is Pneumonic). In some embodiments, the infectious disease is Pneumococcal Disease (Pneumonia). In some embodiments, the infectious disease is Poliomyelitis (Polio).
  • PID Pelvic Inflammatory Disease
  • the infectious disease is Pertussis (Whooping Cough). In some embodiments, the infectious disease is Plague (Bubonic. In some embodiments, the infectious disease is Septicemic. In some embodiments, the infectious disease is Pneumonic). In some embodiments, the infectious disease is Pneumococcal Disease (Pneumonia). In some embodiments, the infectious disease is Poliomyelitis (Polio).
  • the infectious disease is Powassan. In some embodiments, the infectious disease is Psittacosis. In some embodiments, the infectious disease is Pthiriasis. In some embodiments, the infectious disease is Pustular Rash diseases (Small pox. In some embodiments, the infectious disease is monkeypox. In some embodiments, the infectious disease is cowpox). In some embodiments, the infectious disease is Q-Fever. In some embodiments, the infectious disease is Rabies. In some embodiments, the infectious disease is Rickettsiosis (Rocky Mountain Spotted Fever). In some embodiments, the infectious disease is Rubella (German Measles).
  • the infectious disease is Salmonellosis gastroenteritis (Salmonella). In some embodiments, the infectious disease is Scabies. In some embodiments, the infectious disease is Scombroid. In some embodiments, the infectious disease is Sepsis. In some embodiments, the infectious disease is Severe Acute Respiratory Syndrome (SARS). In some embodiments, the infectious disease is Shigellosis gastroenteritis (Shigella). In some embodiments, the infectious disease is Smallpox. In some embodiments, the infectious disease is Staphyloccal Infection Methicillin-resistant (MRSA). In some embodiments, the infectious disease is Staphylococcal Food Poisoning Enterotoxin B Poisoning (Staph Food Poisoning).
  • the infectious disease is Saphylococcal Infection Vancomycin Intermediate (VISA). In some embodiments, the infectious disease is Staphylococcal Infection Vancomycin Resistant (VRSA). In some embodiments, the infectious disease is Streptococcal Disease Group A (invasive) (Strep A (invasive). In some embodiments, the infectious disease is Streptococcal Disease. In some embodiments, the infectious disease is Group B (Strep-B). In some embodiments, the infectious disease is Streptococcal Toxic-Shock Syndrome STSS Toxic Shock. In some embodiments, the infectious disease is Syphilis (primary. In some embodiments, the infectious disease is secondary. In some embodiments, the infectious disease is early latent.
  • VRSA Staphylococcal Infection Vancomycin Resistant
  • the infectious disease is Streptococcal Disease Group A (invasive) (Strep A (invasive). In some embodiments, the infectious disease is Streptococcal Disease. In some embodiments, the infectious disease is Group B (Str
  • the infectious disease is late latent. In some embodiments, the infectious disease is congenital). In some embodiments, the infectious disease is Tetanus Infection. In some embodiments, the infectious disease is Trichomoniasis. In some embodiments, the infectious disease is Trichonosis Infection. In some embodiments, the infectious disease is Tuberculosis (TB). In some embodiments, the infectious disease is Tuberculosis Latent (LTBI). In some embodiments, the infectious disease is Tularemia. In some embodiments, the infectious disease is Typhoid Fever Group D. In some embodiments, the infectious disease is Vaginosis. In some embodiments, the infectious disease is Varicella (Chickenpox), Vibrio cholerae (Cholera).
  • the infectious disease is Vibriosis (Vibrio). In some embodiments, the infectious disease is Ebola Virus Hemorrhagic Fever. In some embodiments, the infectious disease is Lasa Virus Hemorrhagic Fever. In some embodiments, the infectious disease is Marburg Virus Hemorrhagic Fever. In some embodiments, the infectious disease is West Nile Virus. In some embodiments, the infectious disease is Yellow Fever. In some embodiments, the infectious disease is Yersenia. In some embodiments, the infectious disease is and Zika Virus Infection.
  • the pathogen is a virus.
  • the virus is a virus of the adenoviridae, arenaviridae, astroviridae, bunyaviridae, caliciviridae, coronaviridae, filoviridae, flaviviridae, hepadnaviridae, hepeviridae, orthomyxoviridae, papillomaviridae, paramyxoviridae, parvoviridae, picomaviridae, polyomaviridae, poxviridae, reoviridae, retroviridae, rhabdoviridae, or togaviridae family.
  • the virus is a virus of the virus is a virus of the adenoviridae family. In some embodiments, the virus is a virus of the arenaviridae family. In some embodiments, the virus is a virus of the astroviridae family. In some embodiments, the virus is a virus of the bunyaviridae family. In some embodiments, the virus is a virus of the caliciviridae family. In some embodiments, the virus is a virus of the coronaviridae family. In some embodiments, the virus is a virus of the filoviridae family. In some embodiments, the virus is a virus of the flaviviridae family.
  • the virus is a virus of the hepadnaviridae family. In some embodiments, the virus is a virus of the hepeviridae family. In some embodiments, the virus is a virus of the orthomyxoviridae family. In some embodiments, the virus is a virus of the papillomaviridae family. In some embodiments, the virus is a virus of the paramyxoviridae family. In some embodiments, the virus is a virus of the parvoviridae family. In some embodiments, the virus is a virus of the picomaviridae family. In some embodiments, the virus is a virus of the polyomaviridae family.
  • the virus is a virus of the poxviridae family. In some embodiments, the virus is a virus of the reoviridae family. In some embodiments, the virus is a virus of the retroviridae family. In some embodiments, the virus is a virus of the rhabdoviridae family. In some embodiments, the virus is a virus of the togaviridae family.
  • the virus is an adenovirus, coronavirus, coxsackievirus, Epstein-Barr virus, hepatitis A virus, hepatitis B virus, hepatitis C virus, herpes simplex virus type 2, cytomegalovirus, human herpes virus type 8, human immunodeficiency virus, influenza virus, measles virus, mumps virus, human papillomavirus, parainfluenza virus, poliovirus, rabies virus, respiratory syncytial virus, rubella virus, or varicella-zoster virus.
  • the virus is an adenovirus.
  • the virus is a coronavirus.
  • the coronavirus virus is Covid-19 (SARS-CoV-2). In some embodiments, the virus is a coxsackievirus. In some embodiments, the virus is a Epstein-Barr virus. In some embodiments, the virus is a hepatitis A virus. In some embodiments, the virus is a hepatitis B virus. In some embodiments, the virus is a hepatitis C virus. In some embodiments, the virus is a herpes simplex virus type 2. In some embodiments, the virus is a cytomegalovirus. In some embodiments, the virus is a human herpes virus type 8. In some embodiments, the virus is a human immunodeficiency virus.
  • the virus is an influenza virus. In some embodiments, the virus is a measles virus. In some embodiments, the virus is a mumps virus. In some embodiments, the virus is a human papillomavirus. In some embodiments, the virus is a parainfluenza virus. In some embodiments, the virus is a poliovirus. In some embodiments, the virus is a rabies virus. In some embodiments, the virus is a respiratory syncytial virus. In some embodiments, the virus is a rubella virus. In some embodiments, the virus is a varicella-zoster virus.
  • the pathogen is a bacteria.
  • the bacteria is a bacteria of a bacillus, bartonella, bordetella, borrelia, brucella, Campylobacter, chlamydia, chlamydophila, Clostridium, corynebacterium, enterococcus, escherichia, francisella, haemophilus, helicobacter, legionella, leptospira, listeria, mycobacterium, mycoplasma, neisseria, pseudomonas, rickettsia, salmonella, shigella, staphylococcus, streptococcus, treponema, ureaplasma, vibrio or yersinia genus.
  • the bacteria is a bacteria of the bacillus genus. In some embodiments, the bacteria is a bacteria of the bartonella genus. In some embodiments, the bacteria is a bacteria of the bordetella genus. In some embodiments, the bacteria is a bacteria of the borrelia genus. In some embodiments, the bacteria is a bacteria of the brucella genus. In some embodiments, the bacteria is a bacteria of the Campylobacter genus. In some embodiments, the bacteria is a bacteria of the chlamydia genus. In some embodiments, the bacteria is a bacteria of the chlamydophila genus.
  • the bacteria is a bacteria of the Clostridium genus. In some embodiments, the bacteria is a bacteria of the corynebacterium genus. In some embodiments, the bacteria is a bacteria of the enterococcus genus. In some embodiments, the bacteria is a bacteria of the escherichia genus. In some embodiments, the bacteria is a bacteria of the francisella genus. In some embodiments, the bacteria is a bacteria of the haemophilus genus. In some embodiments, the bacteria is a bacteria of the helicobacter genus. In some embodiments, the bacteria is a bacteria of the legionella genus.
  • the bacteria is a bacteria of the leptospira genus. In some embodiments, the bacteria is a bacteria of the listeria genus. In some embodiments, the bacteria is a bacteria of the mycobacterium genus. In some embodiments, the bacteria is a bacteria of the mycoplasma genus. In some embodiments, the bacteria is a bacteria of the neisseria genus. In some embodiments, the bacteria is a bacteria of the pseudomonas genus. In some embodiments, the bacteria is a bacteria of the rickettsia genus. In some embodiments, the bacteria is a bacteria of the salmonella genus. In some embodiments, the bacteria is a bacteria of the shigella genus.
  • the bacteria is a bacteria of the staphylococcus genus. In some embodiments, the bacteria is a bacteria of the streptococcus genus. In some embodiments, the bacteria is a bacteria of the treponema genus. In some embodiments, the bacteria is a bacteria of the ureaplasma genus. In some embodiments, the bacteria is a bacteria of the vibrio genus. In some embodiments, the bacteria is a bacteria of the yersinia genus. In some embodiments, the pathogen is a parasite. In some embodiments, the parasite is a protozoa, helminth, or ectoparasite.
  • the protozoa is an entamoeba, giardia, leishmania, balantidium, plasmodium, or Cryptosporidium.
  • the helminth is a trematode, cestode, acanthocephalan, or round worm.
  • the ectoparasite is a arthropod.
  • the first binding domain that binds to TRGV9 is chimeric. In some embodiments, the first binding domain that binds to TRGV9 is human. In some embodiments, the first binding domain that binds to TRGV9 is humanized. In certain embodiments, the first binding domain that binds to TRGV9 is an isolated antibody. In certain embodiments, the first binding domain that binds to TRGV9 is an intact antibody. In some embodiments, the first binding domain that binds to TRGV9 is an IgG antibody. In some embodiments, the first binding domain that binds to TRGV9 is an IgGl antibody. In some embodiments, the first binding domain that binds to TRGV9 is an IgG2 antibody.
  • the first binding domain that binds to TRGV9 is an IgG3 antibody. In some embodiments, the first binding domain that binds to TRGV9 is an IgG4 antibody. In some embodiments, the first binding domain that binds to TRGV9 comprises a kappa light chain. In some embodiments, the first binding domain that binds to TRGV9 comprises a lambda light chain. In some embodiments, the first binding domain that binds to TRGV9 is a monoclonal antibody. In some embodiments, the first binding domain that binds to TRGV9 is multivalent. In some embodiments, the first binding domain that binds to TRGV9 is capable of binding at least three antigens.
  • the first binding domain that binds to TRGV9 is capable of binding at least four antigens. In some embodiments, the first binding domain that binds to TRGV9 is capable of binding at least five antigens. In some embodiments, the first binding domain that binds to TRGV9 is a multispecific antibody. In some embodiments, the first binding domain that binds to TRGV9 is a bispecific antibody. In some embodiments, the first binding domain that binds to TRGV9 is a trispecific antibody. In some embodiments, the first binding domain that binds to TRGV9 is a quadraspecific antibody. In other embodiments, the first binding domain that binds to TRGV9 is an antigen binding fragment.
  • the antigen binding fragment is a functional fragment. In some embodiments, the antigen binding fragment is chimeric. In some embodiments, the antigen binding fragment is human. In some embodiments, a antigen binding fragment is humanized. In certain embodiments, the antigen binding fragment is an isolated antigen binding fragment. [00257] In some embodiments, the second binding domain that binds to the second target is chimeric. In some embodiments, the second binding domain that binds to the second target is human. In some embodiments, the second binding domain that binds to the second target is humanized. In certain embodiments, the second binding domain that binds to the second target is an isolated antibody. In certain embodiments, the second binding domain that binds to the second target is an intact antibody.
  • the second binding domain that binds to the second target is an IgG antibody. In some embodiments, the second binding domain that binds to the second target is an IgGl antibody. In some embodiments, the second binding domain that binds to the second target is an IgG2 antibody. In some embodiments, the second binding domain that binds to the second target is an IgG3 antibody. In some embodiments, the second binding domain that binds to the second target is an IgG4 antibody. In some embodiments, the second binding domain that binds to the second target comprises a kappa light chain. In some embodiments, the second binding domain that binds to the second target comprises a lambda light chain.
  • the second binding domain that binds to the second target is a monoclonal antibody. In some embodiments, the second binding domain that binds to the second target is multivalent. In some embodiments, the second binding domain that binds to the second target is capable of binding at least three antigens. In some embodiments, the second binding domain that binds to the second target is capable of binding at least four antigens. In some embodiments, the second binding domain that binds to the second target is capable of binding at least five antigens other embodiments, the second binding domain that binds to the second target is an antigen binding fragment. In some embodiments, the antigen binding fragment is a functional fragment. In some embodiments, the antigen binding fragment is chimeric.
  • the antigen binding fragment is human. In some embodiments, an antigen binding fragment is humanized. In certain embodiments, the antigen binding fragment is an isolated antigen binding fragment. [00258] In certain embodiments, the multispecific antibody comprises any of the TRGV9 antibodies provided herein. In some embodiments, the multispecific antibody comprises an antigen binding fragment of any of the TRGV9 antibodies provided herein. [00259] In certain embodiments, the multispecific antibody comprises any of the CD 123 antibodies provided herein. In some embodiments, the multispecific antibody comprises an antigen binding fragment of any of the CD123 antibodies provided herein. In other embodiments, the multispecific antibody comprises any of the TRGV9 antibodies provided herein, and any of the CD123 antibodies provided herein.
  • the multispecific antibody comprises any of the TRGV9 antibodies provided herein, and an antigen binding fragment of any of the CD123 antibodies provided herein. In other embodiments, the multispecific antibody comprises an antigen binding fragment any of the TRGV9 antibodies provided herein, and any of the CD 123 antibodies provided herein. In yet other embodiments, the multispecific antibody comprises an antigen binding fragment of any of the TRGV9 antibodies provided herein, and an antigen binding fragment of any of the CD 123 antibodies provided herein.
  • the multispecific antibody comprises any of the CD33 antibodies provided herein. In some embodiments, the multispecific antibody comprises an antigen binding fragment of any of the CD33 antibodies provided herein. In other embodiments, the multispecific antibody comprises any of the TRGV9 antibodies provided herein, and any of the CD33 antibodies provided herein. In some embodiments, the multispecific antibody comprises any of the TRGV9 antibodies provided herein, and an antigen binding fragment of any of the CD33 antibodies provided herein. In other embodiments, the multispecific antibody comprises an antigen binding fragment any of the TRGV9 antibodies provided herein, and any of the CD33 antibodies provided herein. In yet other embodiments, the multispecific antibody comprises an antigen binding fragment of any of the TRGV9 antibodies provided herein, and an antigen binding fragment of any of the CD33 antibodies provided herein.
  • the multispecific antibody comprises any of the TRBC1 antibodies provided herein. In some embodiments, the multispecific antibody comprises an antigen binding fragment of any of the TRBC1 antibodies provided herein. In other embodiments, the multispecific antibody comprises any of the TRGV9 antibodies provided herein, and any of the TRBC1 antibodies provided herein. In some embodiments, the multispecific antibody comprises any of the TRGV9 antibodies provided herein, and an antigen binding fragment of any of the TRBC1 antibodies provided herein.
  • the multispecific antibody comprises an antigen binding fragment any of the TRGV9 antibodies provided herein, and any of the TRBC1 antibodies provided herein. In yet other embodiments, the multispecific antibody comprises an antigen binding fragment of any of the TRGV9 antibodies provided herein, and an antigen binding fragment of any of the TRBC1 antibodies provided herein.
  • the multispecific antibody comprises any of the BCMA antibodies provided herein. In some embodiments, the multispecific antibody comprises an antigen binding fragment of any of the BCMA antibodies provided herein. In other embodiments, the multispecific antibody comprises any of the TRGV9 antibodies provided herein, and any of the BCMA antibodies provided herein. In some embodiments, the multispecific antibody comprises any of the TRGV9 antibodies provided herein, and an antigen binding fragment of any of the BCMA antibodies provided herein. In other embodiments, the multispecific antibody comprises an antigen binding fragment any of the TRGV9 antibodies provided herein, and any of the BCMA antibodies provided herein. In yet other embodiments, the multispecific antibody comprises an antigen binding fragment of any of the TRGV9 antibodies provided herein, and an antigen binding fragment of any of the BCMA antibodies provided herein.
  • the multispecific antibody comprises any of the PSMA antibodies provided herein. In some embodiments, the multispecific antibody comprises an antigen binding fragment of any of the PSMA antibodies provided herein. In other embodiments, the multispecific antibody comprises any of the TRGV9 antibodies provided herein, and any of the PSMA antibodies provided herein. In some embodiments, the multispecific antibody comprises any of the TRGV9 antibodies provided herein, and an antigen binding fragment of any of the PSMA antibodies provided herein. In other embodiments, the multispecific antibody comprises an antigen binding fragment any of the TRGV9 antibodies provided herein, and any of the PSMA antibodies provided herein. In yet other embodiments, the multispecific antibody comprises an antigen binding fragment of any of the TRGV9 antibodies provided herein, and an antigen binding fragment of any of the PSMA antibodies provided herein.

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Abstract

La présente invention concerne des molécules anti-TRGV9 telles que des anticorps anti-TRGV9 ou des fragments de liaison à l'antigène de celles-ci. L'invention concerne également des acides nucléiques codant pour les anticorps, des compositions comprenant les anticorps, des procédés de production des anticorps, et des procédés d'utilisation des anticorps pour le traitement ou la prévention de maladies.
EP21760487.5A 2020-02-27 2021-02-26 Matériels et méthodes de modulation d'une réponse immunitaire Pending EP4110390A1 (fr)

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US202062982525P 2020-02-27 2020-02-27
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PCT/US2020/031749 WO2020227457A1 (fr) 2019-05-08 2020-05-07 Matières et méthodes pour moduler l'immunité médiée par les lymphocytes t
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