US20230227552A1 - Anti-tcr antibody molecules and uses thereof - Google Patents

Anti-tcr antibody molecules and uses thereof Download PDF

Info

Publication number
US20230227552A1
US20230227552A1 US17/855,332 US202217855332A US2023227552A1 US 20230227552 A1 US20230227552 A1 US 20230227552A1 US 202217855332 A US202217855332 A US 202217855332A US 2023227552 A1 US2023227552 A1 US 2023227552A1
Authority
US
United States
Prior art keywords
sequence
seq
region
tcrβ
tcrβv
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
Application number
US17/855,332
Other languages
English (en)
Inventor
Seng-Lai Tan
Brian Edward Vash
Jonathan Hsu
Dilini Charmain GUNASEKERA
Sangeetha Sagar PALAKURTHI
Andreas Loew
Madan Katragadda
Peter Marek
Gurkan Guntas
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Marengo Therapeutics Inc
Original Assignee
Marengo Therapeutics Inc
Elstar Therapeutics Inc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Marengo Therapeutics Inc, Elstar Therapeutics Inc filed Critical Marengo Therapeutics Inc
Priority to US17/855,332 priority Critical patent/US20230227552A1/en
Assigned to MARENGO THERAPEUTICS, INC. reassignment MARENGO THERAPEUTICS, INC. CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). Assignors: ELSTAR THERAPEUTICS, INC.
Assigned to ELSTAR THERAPEUTICS, INC. reassignment ELSTAR THERAPEUTICS, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: GUNASEKERA, Dilini Charmain, MAREK, PETER, HSU, JONATHAN, GUNTAS, GURKAN, KATRAGADDA, MADAN, VASH, BRIAN EDWARD, LOEW, ANDREAS, PALAKURTHI, Sangeetha Sagar, TAN, Seng-Lai
Priority to US18/341,688 priority patent/US12486326B2/en
Publication of US20230227552A1 publication Critical patent/US20230227552A1/en
Priority to US19/339,740 priority patent/US20260022173A1/en
Pending legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IG], 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 [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IG], 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 [IG], 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2878—Immunoglobulins [IG], 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
    • 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
    • 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
    • A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • 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
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • 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
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)
    • 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
    • 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
    • C07K2317/75—Agonist effect on antigen
    • 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
    • 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
    • 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
    • C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance

Definitions

  • CD3e CD3 epsilon subunit of the T cell receptor (TCR).
  • TCR T cell receptor
  • Such non-physiological massive activation of T cells by these anti-CD3e mAbs can result in the production of proinflammatory cytokines such as IFN-gamma, IL-1-beta, IL-6, IL-10 and TNF-alpha, causing a “cytokine storm” known as the cytokine release syndrome (CRS), which is also associated with neurotoxicity (NT).
  • CRS cytokine release syndrome
  • NT neurotoxicity
  • a multispecific molecule optionally a bispecific molecule, comprising a first moiety, optionally a first immune cell engager, comprising an antibody molecule which binds, optionally specifically binds, to a T cell receptor beta variable region (TCR ⁇ V) (“anti-TCR ⁇ V antibody molecule”), wherein binding of the first moiety to the TCR ⁇ V region results in a cytokine profile that differs from a cytokine profile of a T cell engager that binds to a receptor or molecule other than a TCR ⁇ V region (“a non-TCR ⁇ V-binding T cell engager”).
  • TCR ⁇ V T cell receptor beta variable region
  • the multispecific molecule as provided herein comprises a second moiety which comprises one or more of: a tumor-targeting moiety, a cytokine molecule, a stromal modifying moiety, or an anti-TCR ⁇ V antibody molecule other than the first moiety.
  • the first moiety comprising the anti-TCR ⁇ V antibody molecule comprises an Fc region comprising a variant, optionally an Fc variant described in Table 21, optionally an Asn297Ala (N297A) mutation or a Leu234Ala/Leu235Ala (LALA) mutation.
  • the non-TCR ⁇ V-binding T cell engager comprises an antibody that binds to a CD3 molecule, optionally CD3 epsilon (CD3e) molecule; or a TCR alpha (TCR ⁇ ) molecule.
  • the cytokine profile of the first moiety comprises, one, two, three, four, five, six, seven, or all of the following:
  • a delay optionally at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more hours delay, in increased level, optionally expression level, and/or activity of IL-2;
  • a delay optionally at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 hours delay, in increased level, optionally expression level, and/or activity of IFNg; or
  • binding of the first moiety to the TCR ⁇ V region results in reduced cytokine storm, optionally reduced cytokine release syndrome (CRS), as measured by an assay of Example 3, optionally relative to the cytokine storm induced by the non-TCR ⁇ V-binding T cell engager.
  • CRS cytokine release syndrome
  • binding of the first moiety to the TCR ⁇ V region results in one, two, three or all of:
  • (xii) expansion optionally at least about 1.1-10 fold expansion, optionally at least about 1.1, 1.2, 1.3, 1.4, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 fold expansion, of a population of T cells having a memory-like phenotype, optionally wherein (ix)-(xii) are relative to the non-TCR ⁇ V-binding T cell engager.
  • the population of T cells having a memory-like phenotype comprises CD45RA+ CCR7 ⁇ T cells, optionally CD4+ and/or CD8+ T cells.
  • the first moiety binds to one or more of a TCR ⁇ V subfamily chosen from:
  • TCR ⁇ V6 subfamily comprising, optionally one or more of TCR ⁇ V6-4*01, TCR ⁇ V6-4*02, TCR ⁇ V6-9*01, TCR ⁇ V6-8*01, TCR ⁇ V6-5*01, TCR ⁇ V6-6*02, TCR ⁇ V6-6*01, TCR ⁇ V6-2*01, TCR ⁇ V6-3*01 or TCR ⁇ V6-1*01;
  • TCR ⁇ V10 subfamily comprising, optionally one or more of TCR ⁇ V10-1*01, TCR ⁇ V10-1*02, TCR ⁇ V10-3*01 or TCR ⁇ V10-2*01;
  • TCR ⁇ V5 subfamily comprising, optionally one or more of TCR ⁇ V5-6*01, TCR ⁇ V5-4*01, TCR ⁇ V5-1*01 or TCR ⁇ V5-8*01;
  • TCR ⁇ V12 subfamily comprising, optionally one or more of TCR ⁇ V12-4*01, TCR ⁇ V12-3*01, or TCR ⁇ V12-5*01;
  • TCR ⁇ V4 subfamily comprising, optionally one or more of TCR ⁇ V4-1, TCR ⁇ V4-2 or TCR ⁇ V4-3;
  • TCR ⁇ V11 subfamily comprising, optionally TCR ⁇ V11-2.
  • the anti-TCR ⁇ V antibody molecule is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl
  • (v) competes for binding, and/or binds the same epitope, with an anti-TCR ⁇ V antibody molecule as described herein, optionally a second anti-TCR ⁇ V antibody molecule, wherein the second anti-TCR ⁇ V antibody molecule comprises an antigen binding domain comprising a heavy chain complementarity determining region 1 (HC CDR1), a heavy chain complementarity determining region 2 (HC CDR2) and/or a heavy chain complementarity determining region 3 (HC CDR3) of SEQ ID NO: 1 or SEQ ID NO: 9; and/or a light chain complementarity determining region 1 (LC CDR1), a light chain complementarity determining region 2 (LC CDR2), and/or a light chain complementarity determining region 3 (LC CDR3) of SEQ ID NO: 2, SEQ ID NO: 10 or SEQ ID NO: 11.
  • HC CDR1 heavy chain complementarity determining region 1
  • HC CDR2 heavy chain complementarity determining region 2
  • HC CDR3
  • the anti-TCR ⁇ V antibody molecule comprises an antigen binding domain comprising:
  • the anti-TCR ⁇ V antibody molecule binds the same or different TCR ⁇ V subfamily members.
  • the multispecific molecule as provided herein comprises an antibody molecule chosen from a bispecific antibody molecule, a bivalent antibody molecule, or a biparatopic antibody molecule.
  • the multispecific molecule as provided herein comprises a bispecific antibody molecule that binds to two different TCR ⁇ V subfamily members.
  • the anti-TCR ⁇ V antibody molecule binds:
  • TCR ⁇ V6 subfamily member one or more of a TCR ⁇ V6 subfamily member and one or more of a TCR ⁇ V10 subfamily member;
  • TCR ⁇ V6 subfamily member one or more of a TCR ⁇ V6 subfamily member and one or more of a TCR ⁇ V5 subfamily member;
  • TCR ⁇ V6 subfamily member one or more of a TCR ⁇ V6 subfamily member and one or more of a TCR ⁇ V12 subfamily member;
  • TCR ⁇ V10 subfamily member one or more of a TCR ⁇ V5 subfamily member
  • TCR ⁇ V10 subfamily member one or more of a TCR ⁇ V10 subfamily member and one or more of a TCR ⁇ V12 subfamily member;
  • TCR ⁇ V5 subfamily member one or more of a TCR ⁇ V5 subfamily member and one or more of a TCR ⁇ V12 subfamily member.
  • a multispecific molecule optionally a bispecific molecule, comprising the anti-TCR ⁇ V antibody molecule as provided herein.
  • an antibody molecule which binds, optionally specifically binds, to a T cell receptor beta variable chain (TCR ⁇ V) region, wherein the anti-TCR ⁇ V antibody molecule comprises an antigen binding domain comprising:
  • VL light chain variable region
  • LC CDR1 light chain complementarity determining region 1
  • LC CDR2 light chain complementarity determining region 2
  • LC CDR3 light chain complementarity determining region 3
  • FR framework region having at least 95% identity with one, two, three, or all of, optionally four, a non-murine germline framework 1 (FR1), a non-murine germline framework region 2 (FR2), a non-murine germline framework region 3 (FR3), and a non-murine germline framework region 4 (FR4); and/or
  • VH heavy chain variable region
  • HC CDR1 heavy chain complementarity determining region 1
  • HC CDR2 heavy chain complementarity determining region 2
  • HC CDR3 heavy chain complementarity determining region 3
  • FR framework region having at least 95% identity with one, two, three, or all of, optionally four, a non-murine germline framework 1 (FR1), a non-murine germline framework region 2 (FR2), a non-murine germline framework region 3 (FR3), and a non-murine germline framework region 4 (FR4).
  • FR1 non-murine germline framework 1
  • FR2 non-murine germline framework region 2
  • FR3 non-murine germline framework region 3
  • FR4 non-murine germline framework region 4
  • the VL comprises an amino acid sequence having a consensus sequence of SEQ ID NO: 230.
  • the VH comprises an amino acid sequence having a consensus sequence of SEQ ID NO: 231.
  • the anti-TCR ⁇ V antibody molecule as provided herein binds to TCR ⁇ V6, optionally one or more of TCR ⁇ V6-4*01, TCR ⁇ V6-4*02, TCR ⁇ V6-9*01, TCR ⁇ V6-8*01, TCR ⁇ V6-5*01, TCR ⁇ V6-6*02, TCR ⁇ V6-6*01, TCR ⁇ V6-2*01, TCR ⁇ V6-3*01 or TCR ⁇ V6-1*01, or a variant thereof.
  • the anti-TCR ⁇ V antibody molecule comprises an antigen binding domain comprising:
  • the anti-TCR ⁇ V antibody molecule comprises an antigen binding domain comprising a light chain variable region (VL) comprising one, two or all, optionally three, of a LC CDR1, a LC CDR2 and a LC CDR3 of SEQ ID NO: 2, SEQ ID NO: 10 or SEQ ID NO: 11, or an amino acid sequence listed in Table 1.
  • VL light chain variable region
  • the anti-TCR ⁇ V antibody molecule comprises an antigen binding domain comprising a heavy chain variable region (VH) comprising one, two or all, optionally three, of a HC CDR1, a HC CDR2 and a HC CDR3 of SEQ ID NO:1 or SEQ ID NO: 9, or an amino acid sequence listed in Table 1.
  • VH heavy chain variable region
  • the anti-TCR ⁇ V antibody molecule comprises an antigen binding domain comprising:
  • a VL comprising: a LC CDR1 amino acid sequence of SEQ ID NO: 6 or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, optionally substitutions, additions or deletions thereof, a LC CDR2 amino acid sequence of SEQ ID NO:7 or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, optionally substitutions, additions or deletions thereof, and/or a LC CDR3 amino acid sequence of SEQ ID NO:8 or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, optionally substitutions, additions or deletions thereof; and/or
  • a VH comprising: a HC CDR1 amino acid sequence of SEQ ID NO: 3 or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, optionally substitutions, additions or deletions thereof, a HC CDR2 amino acid sequence of SEQ ID NO:4 or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, optionally substitutions, additions or deletions thereof, and/or a HC CDR3 amino acid sequence of SEQ ID NO:5 or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, optionally substitutions, additions or deletions thereof.
  • the anti-TCR ⁇ V antibody molecule comprises an antigen binding domain comprising:
  • VH variable heavy chain
  • VL variable light chain
  • the anti-TCR ⁇ V antibody molecule comprises an antigen binding domain comprising:
  • the anti-TCR ⁇ V antibody molecule comprises an antigen binding domain comprising:
  • the anti-TCR ⁇ V antibody molecule comprises a heavy chain comprising a framework region, optionally framework region 3 (FR3), comprising one or both of:
  • Threonine at position 73 optionally a substitution at position 73 according to Kabat numbering, optionally a Glutamic Acid to Threonine substitution;
  • substitution is relative to a human germline heavy chain framework region sequence.
  • the anti-TCR ⁇ V antibody molecule comprises a light chain comprising a framework region, optionally framework region 1 (FR1), comprising a Phenyalanine at position 10, optionally a substitution at position 10 according to Kabat numbering, optionally a Serine to Phenyalanine substitution, wherein the substitution is relative to a human germline light chain framework region sequence.
  • FR1 framework region 1
  • the anti-TCR ⁇ V antibody molecule comprises a light chain comprising a framework region, optionally framework region 2 (FR2), comprising one or both of:
  • a Histidine at position 36 optionally a substitution at position 36 according to Kabat numbering, optionally a Tyrosine to Histidine substitution;
  • substitution is relative to a human germline light chain framework region sequence.
  • the anti-TCR ⁇ V antibody molecule comprises a light chain comprising a framework region, optionally framework region 3 (FR3), comprising a Phenyalanine at position 87, optionally a substitution at position 87 according to Kabat numbering, optionally a Tyrosine to Phenyalanine substitution, wherein the substitution is relative to a human germline light chain framework region sequence.
  • FR3 framework region 3
  • an antibody molecule which binds, optionally specifically binds, to a T cell receptor beta variable chain (TCR ⁇ V) region, wherein the anti-TCR ⁇ V antibody molecule comprises an antigen binding domain comprising:
  • VL light chain variable region
  • LC CDR1 light chain complementarity determining region 1
  • LC CDR2 light chain complementarity determining region 2
  • LC CDR3 light chain complementarity determining region 3
  • VH heavy chain variable region
  • HC CDR1 heavy chain complementarity determining region 1
  • HC CDR2 heavy chain complementarity determining region 2
  • HC CDR3 heavy chain complementarity determining region 3
  • FR1 framework region 1
  • FR2 framework region 2
  • FR3 framework region 3
  • FR4 framework region 4
  • the anti-TCR ⁇ V antibody molecule as provided herein binds to TCR ⁇ V12, optionally TCR ⁇ V12-4*01, TCR ⁇ V12-3*01, or TCR ⁇ V12-5*01, or a variant thereof.
  • the anti-TCR ⁇ V antibody molecule comprises an antigen binding domain comprising:
  • the anti-TCR ⁇ V antibody molecule comprises an antigen binding domain comprising a light chain variable region (VL) comprising one, two or all, optionally three, of a LC CDR1, a LC CDR2 and a LC CDR3 of SEQ ID NO: 2, SEQ ID NO: 10 or SEQ ID NO: 11, or an amino acid sequence listed in Table 1.
  • VL light chain variable region
  • the anti-TCR ⁇ V antibody molecule comprises an antigen binding domain comprising a heavy chain variable region (VH) comprising one, two or all, optionally three, of a HC CDR1, a HC CDR2 and a HC CDR3 of a humanized Antibody B-H listed in Table 2.
  • VH heavy chain variable region
  • the anti-TCR ⁇ V antibody molecule comprises an antigen binding domain comprising a light chain variable region (VL) comprising one, two or all, optionally three, of a LC CDR1, a LC CDR2 and a LC CDR3 of a humanized Antibody B-H listed in Table 2.
  • VL light chain variable region
  • the anti-TCR ⁇ V antibody molecule comprises:
  • VH sequence of a humanized Antibody B-H listed in Table 2 or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity to a VH of a humanized Antibody B-H listed in Table 2;
  • VL sequence of a humanized Antibody B-H listed in Table 2 or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity to a VL of a humanized Antibody B-H listed in Table 2.
  • the anti-TCR ⁇ V antibody molecule comprises a framework region (FR) having at least 95% identity with one of: a FR1, a FR2, a FR3, and a FR4 of a humanized B-H LC of Table 2.
  • FR framework region
  • the anti-TCR ⁇ V antibody molecule comprises a framework region (FR) having at least 95% identity with any two of: a FR1, a FR2, a FR3, and a FR4 of a humanized B-H LC of Table 2.
  • FR framework region
  • the anti-TCR ⁇ V antibody molecule comprises a framework region (FR) having at least 95% identity with any three of: a FR1, a FR2, a FR3, and a FR4 of a humanized B-H LC of Table 2.
  • FR framework region
  • the anti-TCR ⁇ V antibody molecule comprises a framework region (FR) having at least 95% identity with all of: a FR1, a FR2, a FR3, and a FR4 of a humanized B-H LC of Table 2.
  • FR framework region
  • the anti-TCR ⁇ V antibody molecule comprises a framework region (FR) having at least 95% identity with one of: a FR1, a FR2, a FR3, and a FR4 of a humanized B-H HC of Table 2.
  • FR framework region
  • the anti-TCR ⁇ V antibody molecule comprises a framework region (FR) having at least 95% identity with any two of: a FR1, a FR2, a FR3, and a FR4 of a humanized B-H HC of Table 2.
  • FR framework region
  • the anti-TCR ⁇ V antibody molecule comprises a framework region (FR) having at least 95% identity with any three of: a FR1, a FR2, a FR3, and a FR4 of a humanized B-H HC of Table 2.
  • FR framework region
  • the anti-TCR ⁇ V antibody molecule comprises a framework region (FR) having at least 95% identity with all of: a FR1, a FR2, a FR3, and a FR4 of a humanized B-H HC of Table 2.
  • FR framework region
  • binding of the anti-TCR ⁇ V antibody molecule to the TCR ⁇ V region results in a cytokine profile that differs from a cytokine profile of a T cell engager that binds to a receptor or molecule other than a TCR ⁇ V region (“a non-TCR ⁇ V-binding T cell engager”).
  • the non-TCR ⁇ V-binding T cell engager comprises an antibody that binds to a CD3 molecule, optionally CD3 epsilon (CD3e) molecule; or a TCR alpha (TCR ⁇ ) molecule.
  • the cytokine profile of the first moiety comprises, one, two, three, four, five, six, seven, or all of the following:
  • a delay optionally at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more hours delay, in increased level, optionally expression level, and/or activity of IL-2;
  • a delay optionally at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 hours delay, in increased level, optionally expression level, and/or activity of IFNg; or
  • binding of the anti-TCR ⁇ V antibody molecule to the TCR ⁇ V region results in reduced cytokine storm, optionally reduced cytokine release syndrome (CRS), as measured by an assay of Example 3, optionally relative to the cytokine storm induced by the non-TCR ⁇ V-binding T cell engager.
  • CRS cytokine release syndrome
  • binding of the anti-TCR ⁇ V antibody molecule to the TCR ⁇ V region results in one, two, three or all of:
  • (xii) expansion optionally at least about 1.1-10 fold expansion, optionally at least about 1.1, 1.2, 1.3, 1.4, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 fold expansion, of a population of T cells having a memory-like phenotype
  • the population of T cells having a memory-like phenotype comprises CD45RA+ CCR7 ⁇ T cells, optionally CD4+ and/or CD8+ T cells.
  • binding of the anti-TCR ⁇ V antibody molecule to a TCR ⁇ V region results in a reduction of at least 2, 5, 10, 20, 50, 100, or 200 fold, or at least 2-200 fold, optionally 5-150, 10-100, 20-50 fold, in the expression level and or activity of IL-10 as measured by an assay of Example 3.
  • binding of the anti-TCR ⁇ V antibody molecule to a TCR ⁇ V region results in a reduction of at least 2, 5, 10, 20, 50, 100, 200, 300, 400, 500, 600, 700, 800, 900, or 1000 fold, or at least 2-1000 fold, optionally 5-900, 10-800, 20-700, 50-600, 100-500, or 200-400 fold, in the expression level and or activity of IL-6 as measured by an assay of Example 3.
  • binding of the anti-TCR ⁇ V antibody molecule to a TCR ⁇ V region results in a reduction of at least 2, 5, 10, 20, 50, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, or 2000 fold, or at least 2-2000 fold, optionally 5-1000, 10-900, 20-800, 50-700, 100-600, 200-500, or 300-400 fold, in the expression level and or activity of TNF ⁇ as measured by an assay of Example 3.
  • binding of the anti-TCR ⁇ V antibody molecule to a TCR ⁇ V region results in an increase of at least 2, 5, 10, 20, 50, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, or 2000 fold, or at least 2-2000 fold, optionally 5-1000, 10-900, 20-800, 50-700, 100-600, 200-500, or 300-400 fold, in the expression level and or activity of IL-2 as measured by an assay of Example 3.
  • the anti-TCR ⁇ V antibody molecule comprises an antigen binding domain comprising a single chain Fv (scFv) or a Fab.
  • the anti-TCR ⁇ V antibody molecule binds to a conformational or a linear epitope on the T cell.
  • the anti-TCR ⁇ V antibody molecule is a full antibody, optionally an antibody that includes at least one, and preferably two, complete heavy chains, and at least one, and preferably two, complete light chains, or an antigen-binding fragment, optionally a Fab, F(ab′)2, Fv, a single chain Fv fragment, a single domain antibody, a diabody (dAb), a bivalent antibody, or bispecific antibody or fragment thereof, a single domain variant thereof, or a camelid antibody.
  • the anti-TCR ⁇ V antibody molecule comprises one or more heavy chain constant regions chosen from IgG1, IgG2, IgG3, IgGA1, IgGA2, IgG4, IgJ, IgM, IgD, or IgE, or a fragment thereof, optionally as described in Table 3.
  • the anti-TCR ⁇ V antibody molecule comprises a heavy chain constant region of an IgM or a fragment thereof, optionally wherein the IgM heavy chain constant region comprises the sequence of SEQ ID NO: 73, or a sequence with at least 85%, 90%, 95%, or 99% sequence identity thereto.
  • the anti-TCR ⁇ V antibody molecule comprises a heavy chain constant region of an IgJ or a fragment thereof, optionally wherein the IgJ heavy chain constant region comprises the sequence of SEQ ID NO: 76 or a sequence with at least 85%, 90%, 95%, or 99% sequence identity thereto.
  • the anti-TCR ⁇ V antibody molecule comprises a heavy chain constant region of an IgGA1, or a fragment thereof, optionally wherein the IgGA1 heavy chain constant region comprises the sequence of SEQ ID NO: 74, or a sequence with at least 85%, 90%, 95%, or 99% sequence identity thereto.
  • the anti-TCR ⁇ V antibody molecule comprises a heavy chain constant region of an IgGA2, or a fragment thereof, optionally wherein the IgGA2 heavy chain constant region comprises a sequence listed in Table 3, optionally SEQ ID NO: 75, or a sequence with at least 85%, 90%, 95%, or 99% sequence identity thereto.
  • the anti-TCR ⁇ V antibody molecule comprises a light chain constant region chosen from the light chain constant regions of kappa or lambda, or a fragment thereof, optionally as described in Table 3.
  • the anti-TCR ⁇ V antibody molecule comprises a light chain constant region of a kappa chain, or a fragment thereof, optionally wherein the kappa chain constant region comprises the sequence of SEQ ID NO: 39, or a sequence with at least 85%, 90%, 95%, or 99% sequence identity thereto.
  • the anti-TCR ⁇ V antibody molecule comprises:
  • one or more heavy chain constant regions comprising a heavy chain constant region chosen from IgG1, IgG2, IgG3, IgGA1, IgGA2, IgG4, IgJ, IgM, IgD, or IgE, or a fragment thereof, optionally as described in Table 3; and
  • a light chain constant region comprising a light chain constant region chosen from the light chain constant regions of kappa or lambda, or a fragment thereof, optionally as described in Table 3.
  • the anti-TCR ⁇ V antibody molecule comprises:
  • an IgM heavy chain constant region or a fragment thereof comprising the sequence of SEQ ID NO: 73, or a sequence with at least 85%, 90%, 95%, or 99% sequence identity thereto;
  • an IgGA1 heavy chain constant region or a fragment thereof comprising the sequence of SEQ ID NO: 74, or a sequence with at least 85%, 90%, 95%, or 99% sequence identity thereto; or
  • an IgGA2 heavy chain constant region or a fragment thereof comprising the sequence of SEQ ID NO: 75, or a sequence with at least 85%, 90%, 95%, or 99% sequence identity thereto;
  • the anti-TCR ⁇ V antibody molecule further comprises an IgJ heavy chain constant region or a fragment thereof, wherein the IgJ heavy chain constant region comprises the sequence of SEQ ID NO: 76 or a sequence with at least 85%, 90%, 95%, or 99% sequence identity thereto.
  • the second moiety is a tumor-targeting moiety.
  • the second moiety is a cytokine molecule.
  • the second moiety is a stromal modifying moiety.
  • the second moiety is an anti-TCR ⁇ V antibody molecule other than the first moiety.
  • the first and/or second moiety binds to and activates an immune cell, optionally an effector cell.
  • the first and/or second moiety binds to, but does not activate an immune cell, optionally an effector cell.
  • the second moiety is chosen from an NK cell engager, a T cell engager other than an anti-TCR ⁇ V antibody molecule, a B cell engager, a dendritic cell engager, or a macrophage cell engager, or a combination thereof.
  • the tumor-targeting moiety comprises an antibody molecule, optionally Fab or scFv, a receptor molecule, optionally a receptor, a receptor fragment or functional variant thereof, or a ligand molecule, optionally a ligand, a ligand fragment or functional variant thereof, or a combination thereof, that binds to a cancer antigen.
  • the tumor-targeting moiety binds to a cancer antigen present on a cancer, optionally a hematological cancer, a solid tumor, a metastatic cancer, soft tissue tumor, metastatic lesion, or a combination thereof.
  • the cancer antigen is a tumor antigen or stromal antigen, or a hematological antigen.
  • the cancer antigen is chosen from: BCMA, CD19, CD20, CD22, FcRH5, PDL1, CD47, gangloside 2 (GD2), prostate stem cell antigen (PSCA), prostate specific membrane antigen (PMSA), prostate-specific antigen (PSA), carcinoembryonic antigen (CEA), Ron Kinase, c-Met, Immature laminin receptor, TAG-72, BING-4, Calcium-activated chloride channel 2, Cyclin-B1, 9D7, Ep-CAM, EphA3, Her2/neu, Telomerase, SAP-1, Survivin, NY-ESO-1/LAGE-1, PRAME, SSX-2, Melan-A/MART-1, Gp100/pme117, Tyrosinase, TRP-1/-2, MC1R, ⁇ -catenin, BRCA1/2, CDK4, CML66, Fibronectin, p53, Ras, TGF-B receptor, AFP, ETA, MAGE, MUC-1, CA
  • the tumor-targeting moiety is a BCMA targeting moiety or a FcRH5 targeting moiety.
  • the cancer is a solid tumor including but not limited to: pancreatic, optionally pancreatic adenocarcinoma, cancer, breast cancer, colorectal cancer, lung cancer, optionally small or non-small cell lung cancer, skin cancer, ovarian cancer, or liver cancer.
  • the cancer is a hematological cancer including, but not limited to: a B-cell or T cell malignancy, optionally Hodgkin's lymphoma, Non-Hodgkin's lymphoma, optionally B cell lymphoma, diffuse large B cell lymphoma, follicular lymphoma, chronic lymphocytic leukemia, mantle cell lymphoma, marginal zone B-cell lymphoma, Burkitt lymphoma, lymphoplasmacytic lymphoma, hairy cell leukemia, acute myeloid leukemia (AML), chronic myeloid leukemia, myelodysplastic syndrome, multiple myeloma, and acute lymphocytic leukemia.
  • a B-cell or T cell malignancy optionally Hodgkin's lymphoma, Non-Hodgkin's lymphoma, optionally B cell lymphoma, diffuse large B cell lymphoma, follicular lymphoma, chronic lymphocytic
  • the cytokine molecule is chosen from interleukin-2 (IL-2), interleukin-7 (IL-7), interleukin-12 (IL-12), interleukin-15 (IL-15), interleukin-18 (IL-18), interleukin-21 (IL-21), or interferon gamma, or a fragment, variant or combination thereof.
  • IL-2 interleukin-2
  • IL-7 interleukin-7
  • IL-12 interleukin-12
  • IL-15 interleukin-15
  • IL-18 interleukin-18
  • interleukin-21 interferon gamma
  • the cytokine molecule is a monomer or a dimer.
  • the cytokine molecule further comprises a receptor dimerizing domain, optionally an IL15Ralpha dimerizing domain.
  • the cytokine molecule, optionally IL-15) and the receptor dimerizing domain, optionally an IL15Ralpha dimerizing domain are not covalently linked, optionally are non-covalently associated.
  • the multispecific molecule as provided herein further comprises an immunoglobulin constant region, optionally Fc region, chosen from the heavy chain constant regions of IgG1, IgG2, IgG3, IgGA1, IgGA2, IgG4, IgJ, IgM, IgD, or IgE, or a fragment thereof, optionally wherein, the heavy chain constant region comprises the heavy chain constant region of human IgG1, IgG2 or IgG4.
  • an immunoglobulin constant region optionally Fc region, chosen from the heavy chain constant regions of IgG1, IgG2, IgG3, IgGA1, IgGA2, IgG4, IgJ, IgM, IgD, or IgE, or a fragment thereof, optionally wherein, the heavy chain constant region comprises the heavy chain constant region of human IgG1, IgG2 or IgG4.
  • the immunoglobulin constant region is linked, optionally covalently linked to, one or more of tumor-targeting moiety, the cytokine molecule, or the stromal modifying moiety.
  • an interface of a first and second immunoglobulin chain constant regions, optionally Fc region, is altered, optionally mutated, to increase or decrease dimerization, optionally relative to a non-engineered interface.
  • the dimerization of the immunoglobulin chain constant region, optionally Fc region is enhanced by providing an Fc interface of a first and a second Fc region with one or more of: a paired cavity-protuberance (“knob-in-a hole”), an electrostatic interaction, or a strand-exchange, such that a greater ratio of heteromultimer:homomultimer forms, optionally relative to a non-engineered interface.
  • Fc interface of a first and a second Fc region with one or more of: a paired cavity-protuberance (“knob-in-a hole”), an electrostatic interaction, or a strand-exchange, such that a greater ratio of heteromultimer:homomultimer forms, optionally relative to a non-engineered interface.
  • the multispecific molecule as provided herein further comprises a linker, optionally a linker described herein, optionally wherein the linker is selected from: a cleavable linker, a non-cleavable linker, a peptide linker, a flexible linker, a rigid linker, a helical linker, or a non-helical linker.
  • a linker optionally a linker described herein, optionally wherein the linker is selected from: a cleavable linker, a non-cleavable linker, a peptide linker, a flexible linker, a rigid linker, a helical linker, or a non-helical linker.
  • an isolated nucleic acid molecule comprising a nucleotide sequence encoding the anti-TCR ⁇ V antibody molecule as provided herein, or a nucleotide sequence having at least 75%, 80%, 85%, 90%, 95%, or 99% identity thereto.
  • nucleic acid molecule comprising a nucleotide sequence encoding the multispecific molecule as provided herein, or a nucleotide sequence having at least 75%, 80%, 85%, 90%, 95%, or 99% identity thereto.
  • a vector optionally an expression vector, comprising one or more of the nucleic acid molecules as provided herein.
  • a cell optionally host cell, comprising the nucleic acid molecule as provided herein, or the vector as provided herein.
  • provided herein is a method of making, optionally producing or manufacturing, the anti-TCR ⁇ V antibody molecule as provided herein, or the multispecific molecule as provided herein, comprising culturing the host cell as provided herein, under suitable conditions, optionally conditions suitable expression of the anti-TCR ⁇ V antibody molecule or the multispecific molecule.
  • a pharmaceutical composition comprising the anti-TCR ⁇ V antibody molecule as provided herein, or the multispecific molecule as provided herein, and a pharmaceutically acceptable carrier, excipient, or stabilizer.
  • a method of modulating, optionally enhancing, an immune response in a subject comprising administering to the subject an effective amount of an antibody molecule which binds, optionally specifically binds, to a T cell receptor beta variable region (TCR ⁇ V) (“anti-TCR ⁇ V antibody molecule”).
  • TCR ⁇ V T cell receptor beta variable region
  • provided herein is a method of modulating, optionally enhancing, an immune response in a subject comprising administering to the subject an effective amount of the multispecific molecule as provided herein.
  • the method comprises expanding, optionally increasing the number of, an immune cell population in the subject.
  • a method of expanding, optionally increasing the number of, an immune cell population comprising, contacting the immune cell population with an effective amount of an antibody molecule which binds, optionally specifically binds, to a T cell receptor beta variable region (TCR ⁇ V) (“anti-TCR ⁇ V antibody molecule”).
  • TCR ⁇ V T cell receptor beta variable region
  • provided herein is a method of expanding, optionally increasing the number of, an immune cell population comprising, contacting the immune cell population with an effective amount of the multispecific molecule as provided herein.
  • the expansion occurs in vivo or ex vivo, optionally in vitro.
  • the immune cell population comprises a TCR ⁇ V expressing cell, optionally a TCR ⁇ V+ cell.
  • the TCR ⁇ V expressing cell is a T cell, optionally a CD8+ T cell, a CD3+ T cell or a CD4+ T cell.
  • the immune cell population comprises a T cell, optionally a CD4 T cell, a CD8 T cell, optionally an effector T cell, a T cell having a memory-like phenotype or a memory T cell, optionally a memory effector T cell, optionally TEM cell, optionally TEMRA cell, or a tumor infiltrating lymphocyte (TIL).
  • TIL tumor infiltrating lymphocyte
  • the immune cell population comprises a T cell, a Natural Killer cell, a B cell, or a myeloid cell.
  • the immune cell population is obtained from a healthy subject.
  • the immune cell population is obtained from a subject, optionally from an apheresis sample from the subject, having a disease, optionally a cancer, optionally as described herein, optionally wherein the immune cell population comprises a tumor infiltrating lymphocyte (TIL).
  • TIL tumor infiltrating lymphocyte
  • the method results in an expansion of at least 1.1-10 fold, optionally at least 1.1, 1.2, 1.3, 1.4, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 fold expansion.
  • the method as provided herein further comprises contacting the population of cells with an agent that promotes, optionally increases, immune cell expansion.
  • the method as provided herein further comprises contacting the population of cells with an immune checkpoint inhibitor, optionally a PD-1 inhibitor.
  • the method as provided herein further comprises contacting the population of cells with a 4-1BB (CD127) agonist, optionally an anti-4-1BB antibody.
  • a 4-1BB CD127
  • an anti-4-1BB antibody optionally an anti-4-1BB antibody.
  • the method as provided herein further comprises contacting the population of cells with a non-dividing population of cells, optionally feeder cells, optionally irradiated allogenic human PBMCs.
  • the population of cells is expanded in an appropriate media, optionally media described herein, that includes one or more cytokines, optionally IL-2, IL-7, IL-15, or a combination thereof.
  • the population of cells is expanded for a period of at least about 4 hours, 6 hours, 10 hours, 12 hours, 15 hours, 18 hours, 20 hours, or 22 hours, or for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 1, 6 17, 18, 19, 20 or 21 days, or for at least about 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks or 8 weeks.
  • expansion of the population of immune cells is compared to expansion of a similar population of cells with an antibody that binds to: a CD3 molecule, optionally CD3 epsilon (CD3e) molecule; or a TCR alpha (TCR ⁇ ) molecule.
  • a CD3 molecule optionally CD3 epsilon (CD3e) molecule
  • CD3e CD3 epsilon
  • TCR ⁇ TCR alpha
  • expansion of the population of immune cells is compared to expansion of a similar population of cells not contacted with the anti-TCR ⁇ V antibody molecule, or multispecific molecule comprising the anti-TCR ⁇ V antibody molecule.
  • expansion of the population of T cells having a memory-like phenotype, optionally CD45RA+ CCR7 ⁇ cells, optionally memory effector T cells, optionally TEM cells, optionally TEMRA cells, is compared to expansion of a similar population of cells with an antibody that binds to: a CD3 molecule, optionally CD3 epsilon (CD3e) molecule; or a TCR alpha (TCR ⁇ ) molecule.
  • CD3 molecule optionally CD3 epsilon (CD3e) molecule
  • TCR ⁇ TCR alpha
  • the population of expanded T cells having a memory-like phenotype, optionally effector memory cells comprises cells which:
  • (iii) have a detectable level of CD95, optionally express CD95, optionally a population of CD45RA+, CCR7 ⁇ , CD95+ T cells, optionally wherein the T cells comprise CD3+, CD4+ or CD8+ T cells.
  • the method results in expansion of, optionally selective or preferential expansion of, T cells expressing a T cell receptor (TCR) comprising a TCR alpha and/or TCR beta molecule, optionally TCR alpha-beta T cells ( ⁇ T cells).
  • TCR T cell receptor
  • the method results in expansion of ⁇ T cells over expansion of T cells expressing a TCR comprising a TCR gamma and/or TCR delta molecule, optionally TCR gamma-delta T cells ( ⁇ T cells).
  • a method of treating a disease, optionally cancer, in a subject comprising administering to the subject an effective amount of an antibody molecule which binds, optionally specifically binds, to a T cell receptor beta variable region (TCR ⁇ V) (“anti-TCR ⁇ V antibody molecule”), thereby treating the cancer.
  • TCR ⁇ V T cell receptor beta variable region
  • composition comprising an antibody molecule which binds, optionally specifically binds, to a T cell receptor beta variable region (TCR ⁇ V) (“anti-TCR ⁇ V antibody molecule”), for use in treating a disease, optionally cancer, in a subject.
  • TCR ⁇ V T cell receptor beta variable region
  • composition comprising an antibody molecule which binds, optionally specifically binds, to a T cell receptor beta variable region (TCR ⁇ V) (“anti-TCR ⁇ V antibody molecule”), for use in the manufacture of a medicament for treating a disease, optionally cancer, in a subject.
  • TCR ⁇ V T cell receptor beta variable region
  • provided herein is a method of treating a disease, optionally cancer, in a subject comprising administering to the subject an effective amount of the multispecific molecule as provided herein, thereby treating the cancer.
  • composition comprising the multispecific molecule as provided herein, for use in treating a disease, optionally cancer, in a subject.
  • composition comprising the multispecific molecule as provided herein, for use in the manufacture of a medicament for treating a disease, optionally cancer, in a subject.
  • CRS cytokine release syndrome
  • NT neurotoxicity
  • CRS cytokine release syndrome
  • NT neurotoxicity
  • a therapy optionally treatment
  • a T cell in a subject having a disease optionally cancer
  • administering an effective amount of:
  • TCR ⁇ V antibody molecule an antibody molecule which binds, optionally specifically binds, to a T cell receptor beta variable region (TCR ⁇ V) (“anti-TCR ⁇ V antibody molecule”); and
  • the therapy optionally a tumor targeting therapy, optionally an antibody that binds to a cancer antigen, optionally as described herein, thereby targeting the therapy to the T cell in the subject.
  • a therapy optionally treatment
  • a T cell in a subject having a disease optionally cancer
  • administering an effective amount of:
  • the therapy optionally a tumor targeting therapy, optionally an antibody that binds to a cancer antigen, optionally as described herein, thereby targeting the therapy to the T cell in the subject.
  • the method results in: reduced cytokine release syndrome (CRS), optionally lesser duration of CRS or no CRS, or a reduced severity of CRS, optionally absence of severe CRS, optionally CRS grade 4 or 5, compared to administration of (ii) alone.
  • CRS cytokine release syndrome
  • the anti-TCR ⁇ V antibody or the multispecific molecule is administered concurrently with or after the administration of the treatment associated with CRS.
  • a method of treating a subject having a cancer comprising:
  • acquiring a value of the status of a TCR ⁇ V subfamily for the subject wherein said value comprises a measure of the presence of, optionally level or activity of, a TCR ⁇ V molecule in a sample from the subject, and
  • TCR ⁇ V T cell receptor beta variable region
  • a method of treating a subject having a cancer comprising:
  • acquiring a value of the status of a TCR ⁇ V subfamily for the subject wherein said value comprises a measure of the presence of, optionally level or activity of, a TCR ⁇ V molecule in a sample from the subject, and
  • a method of treating a subject having a cancer comprising administering an effective amount of an antibody molecule which binds, optionally specifically binds, to a T cell receptor beta variable region (TCR ⁇ V) (“anti-TCR ⁇ V antibody molecule”) to the subject, wherein the subject has a higher, optionally increased, level or activity of one or more TCR ⁇ V subfamilies, optionally as described herein, compared to a reference level or activity of one or more TCR ⁇ V subfamilies, optionally in a healthy subject, optionally a subject not having a cancer.
  • TCR ⁇ V T cell receptor beta variable region
  • a method of treating a subject having a cancer comprising administering an effective amount of the multispecific molecule as provided herein to the subject, wherein the subject has a higher, optionally increased, level or activity of one or more TCR ⁇ V subfamilies, optionally as described herein, compared to a reference level or activity of one or more TCR ⁇ V subfamilies, optionally in a healthy subject, optionally a subject not having a cancer.
  • a method of expanding a population of immune effector cells from a subject having a cancer comprising:
  • the method as provided herein further comprises administering the population of immune effector cells contacted with the anti-TCR ⁇ V antibody molecule to the subject.
  • a method of expanding a population of immune effector cells from a subject having a cancer comprising:
  • the method as provided herein further comprises administering the population of immune effector cells contacted with the multispecific molecule to the subject.
  • the method as provided herein comprises measuring T cell function, optionally cytotoxic activity, cytokine secretion, or degranulation, in the population of immune effector cells, optionally compared to a reference population, optionally an otherwise similar population not contacted with the anti-TCR ⁇ V antibody molecule or a population of immune effector cells obtained from a healthy subject, optionally a subject that does not have a cancer.
  • the biological sample comprising the population of immune effector cells is contacted with an anti-TCR ⁇ V antibody molecule or a multispecific molecule that binds to the one or more TCR ⁇ V subfamilies, optionally the same TCR ⁇ V subfamily, identified as being higher, optionally increased, in the biological sample.
  • the biological sample comprising the population of immune effector cells is contacted with an anti-TCR ⁇ V antibody molecule or a multispecific molecule that does not bind to the one or more TCR ⁇ V subfamilies, optionally a different TCR ⁇ V subfamily, identified as being higher, optionally increased, in the biological sample.
  • the cancer is a solid tumor including but not limited to: melanoma, pancreatic, optionally pancreatic adenocarcinoma, cancer, breast cancer, colorectal cancer (CRC), lung cancer, optionally small or non-small cell lung cancer, skin cancer, ovarian cancer, or liver cancer.
  • melanoma pancreatic
  • pancreatic adenocarcinoma cancer
  • breast cancer colorectal cancer (CRC)
  • lung cancer optionally small or non-small cell lung cancer
  • skin cancer skin cancer
  • ovarian cancer or liver cancer.
  • the cancer is a hematological cancer including, but not limited to: a B-cell or T cell malignancy, optionally Hodgkin's lymphoma, Non-Hodgkin's lymphoma, optionally B cell lymphoma, diffuse large B cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukemia (B-CLL), mantle cell lymphoma, marginal zone B-cell lymphoma, Burkitt lymphoma, lymphoplasmacytic lymphoma, or hairy cell leukemia, acute myeloid leukemia (AML), chronic myeloid leukemia, myelodysplastic syndrome, multiple myeloma, and acute lymphocytic leukemia.
  • a B-cell or T cell malignancy optionally Hodgkin's lymphoma, Non-Hodgkin's lymphoma, optionally B cell lymphoma, diffuse large B cell lymphoma (DLBCL),
  • the cancer is B-CLL and the TCR ⁇ V molecule comprises:
  • TCR ⁇ V6 subfamily comprising, optionally TCR ⁇ V6-4*01, TCR ⁇ V6-4*02, TCR ⁇ V6-9*01, TCR ⁇ V6-8*01, TCR ⁇ V6-5*01, TCR ⁇ V6-6*02, TCR ⁇ V6-6*01, TCR ⁇ V6-2*01, TCR ⁇ V6-3*01 or TCR ⁇ V6-1*01;
  • TCR ⁇ V5 subfamily comprising TCR ⁇ V5-6*01, TCR ⁇ V5-4*01, or TCR ⁇ V5-8*01;
  • TCR ⁇ V3 subfamily comprising TCR ⁇ V3-1*01;
  • TCR ⁇ V2 subfamily comprising TCR ⁇ V2*01;
  • TCR ⁇ V19 subfamily comprising TCR ⁇ V19*01, or TCR ⁇ V19*02.
  • the cancer is melanoma and the TCR ⁇ V molecule comprises the TCR ⁇ V6 subfamily comprising, optionally TCR ⁇ V6-4*01, TCR ⁇ V6-4*02, TCR ⁇ V6-9*01, TCR ⁇ V6-8*01, TCR ⁇ V6-5*01, TCR ⁇ V6-6*02, TCR ⁇ V6-6*01, TCR ⁇ V6-2*01, TCR ⁇ V6-3*01 or TCR ⁇ V6-1*01.
  • the cancer is DLBCL and the TCR ⁇ V molecule comprises:
  • TCR ⁇ V13 subfamily comprising TCR ⁇ V13*01;
  • TCR ⁇ V3 subfamily comprising TCR ⁇ V3-1*01;
  • the cancer is CRC and the TCR ⁇ V molecule comprises:
  • TCR ⁇ V19 subfamily comprising TCR ⁇ V19*01, or TCR ⁇ V19*02
  • TCR ⁇ V12 subfamily comprising TCR ⁇ V12-4*01, TCR ⁇ V12-3*01, or TCR ⁇ V12-5*01
  • TCR ⁇ V16 subfamily comprising TCR ⁇ V16*01
  • the tumor comprises an antigen, optionally a tumor antigen, optionally a tumor associated antigen or a neoantigen; and/or the one or more TCR ⁇ V subfamilies recognize, optionally bind to, the tumor antigen.
  • the sample comprises a blood sample, optionally a peripheral blood sample, a biopsy, optionally a tumor biopsy, or a bone marrow sample.
  • the sample comprises a biological sample comprising immune cells, optionally TCRBV expressing cells, optionally TCRBV+ cells, T cells, or NK cells.
  • the T cells comprise a CD4 T cell, a CD8 T cell, optionally an effector T cell or a memory T cell, optionally a memory effector T cell, optionally TEM cell, optionally TEMRA cell, or a tumor infiltrating lymphocyte (TIL).
  • TIL tumor infiltrating lymphocyte
  • the method results in an expansion, optionally in vivo or ex vivo expansion, of at least 1.1-1000 fold, optionally 1.1-10, 10-100, 100-200, 200-300, 300-400, 400-500, 500-600, 600-700, 700-800, 800-900, or 900-1000 fold expansion of an immune effector cell population comprising a TCRVB expressing immune effector cell, optionally T cell.
  • the population of cells is expanded in an appropriate media, optionally media described herein, that includes one or more cytokines, optionally IL-2, IL-7, IL-15, or a combination thereof.
  • the population of cells is expanded for a period of at least about 4 hours, 6 hours, 10 hours, 12 hours, 15 hours, 18 hours, 20 hours, or 22 hours, or for at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 1, 6 17, 18, 19, 20 or 21 days, or for at least about 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks or 8 weeks.
  • expansion of the population of immune cells is compared to expansion of a similar population of cells with an antibody that binds to: a CD3 molecule, optionally CD3 epsilon (CD3e) molecule; or a TCR alpha (TCR ⁇ ) molecule.
  • a CD3 molecule optionally CD3 epsilon (CD3e) molecule
  • CD3e CD3 epsilon
  • TCR ⁇ TCR alpha
  • expansion of the population of immune cells is compared to expansion of a similar population of cells not contacted with the anti-TCR ⁇ V antibody molecule.
  • expansion of the population of T cells having a memory-like phenotype is compared to expansion of a similar population of cells with an antibody that binds to: a CD3 molecule, optionally CD3 epsilon (CD3e) molecule; or a TCR alpha (TCR ⁇ ) molecule.
  • CD3 molecule optionally CD3 epsilon (CD3e) molecule
  • TCR ⁇ TCR alpha
  • the population of expanded T cells having a memory-like phenotype, optionally effector memory cells comprises cells which:
  • (iii) have a detectable level of CD95, optionally express CD95, optionally a population of CD45RA+, CCR7 ⁇ , CD95+ T cells, optionally wherein the T cells comprise CD3+, CD4+ or CD8+ T cells.
  • the method results in expansion of, optionally selective or preferential expansion of, T cells expressing a T cell receptor (TCR) comprising a TCR alpha and/or TCR beta molecule, optionally TCR alpha-beta T cells ( ⁇ T cells).
  • TCR T cell receptor
  • the method results in expansion of ⁇ T cells over expansion of T cells expressing a TCR comprising a TCR gamma and/or TCR delta molecule, optionally TCR gamma-delta T cells ( ⁇ T cells).
  • the anti-TCR ⁇ V antibody molecule comprises an antigen binding domain comprising a light chain variable region (VL) comprising one, two or all of a LC CDR1, a LC CDR2 and a LC CDR3 of a VL disclosed in Tables 1, 2, 10, 11, 12 or 13, optionally SEQ ID NO: 1314, SEQ ID NO: 2, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 16, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29 or SEQ ID NO:30
  • VL light chain variable region
  • the anti-TCR ⁇ V antibody molecule comprises an antigen binding domain comprising a heavy chain variable region (VH) comprising one, two or all of a HC CDR1, a HC CDR2 and a HC CDR3 of a VH disclosed in Tables 1, 2, 10, 11, 12 or 13, optionally SEQ ID NO: 1312, SEQ ID NO:1, SEQ ID NO: 9, SEQ ID NO: 15, SEQ ID NO: 23, SEQ ID NO: 24 or SEQ ID NO: 25.
  • VH heavy chain variable region
  • the anti-TCR ⁇ V antibody molecule comprises an antigen binding domain comprising:
  • a VL comprising: a LC CDR1 amino acid sequence of SEQ ID NO: 20 or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, optionally substitutions, additions or deletions thereof, a LC CDR2 amino acid sequence of SEQ ID NO:21 or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, optionally substitutions, additions or deletions thereof, and/or a LC CDR3 amino acid sequence of SEQ ID NO:22 or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, optionally substitutions, additions or deletions thereof; and/or
  • a VH comprising: a HC CDR1 amino acid sequence of SEQ ID NO: 17 or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, optionally substitutions, additions or deletions thereof, a HC CDR2 amino acid sequence of SEQ ID NO:18 or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, optionally substitutions, additions or deletions thereof, and/or a HC CDR3 amino acid sequence of SEQ ID NO:19 or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, optionally substitutions, additions or deletions thereof.
  • the anti-TCR ⁇ V antibody molecule comprises an antigen binding domain comprising:
  • VH variable heavy chain
  • VL variable light chain
  • the anti-TCR ⁇ V antibody molecule comprises an antigen binding domain comprising
  • a VL comprising: a LC CDR1 amino acid sequence of SEQ ID NO: 6 or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, optionally substitutions, additions or deletions thereof, a LC CDR2 amino acid sequence of SEQ ID NO:7 or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, optionally substitutions, additions or deletions thereof, and/or a LC CDR3 amino acid sequence of SEQ ID NO: 8 or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, optionally substitutions, additions or deletions thereof; and/or
  • a VH comprising: a HC CDR1 amino acid sequence of SEQ ID NO: 3 or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, optionally substitutions, additions or deletions thereof, a HC CDR2 amino acid sequence of SEQ ID NO:4 or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, optionally substitutions, additions or deletions thereof, and/or a HC CDR3 amino acid sequence of SEQ ID NO:5 or an amino acid sequence with not more than 1, 2, 3 or 4 modifications, optionally substitutions, additions or deletions thereof.
  • the anti-TCR ⁇ V antibody molecule comprises an antigen binding domain comprising:
  • variable heavy chain of SEQ ID NO: 1 or SEQ ID NO: 9 or SEQ ID NO: 1312, or a sequence having at least about 85%, 90%, 95%, or 99% sequence identity thereto
  • VL variable light chain
  • the anti-TCR ⁇ V antibody molecule comprises a light chain comprising a framework region, optionally framework region 1 (FR1), comprising one, two or all, optionally three, of:
  • an Aspartic Acid at position 1 optionally a substitution at position 1 according to Kabat numbering, optionally a Alanine to Aspartic Acid substitution; or
  • an Asparagine at position 2 optionally a substitution at position 2 according to Kabat numbering, optionally a Isoleucine to Asparagine, a Serine to Asparagine, or a Tyrosine to Asparagine substitution; or
  • the anti-TCR ⁇ V antibody molecule comprises a light chain comprising a framework region, optionally framework region 3 (FR3), comprising one, two or all, optionally three, of:
  • a Glycine at position 66 optionally a substitution at position 66 according to Kabat numbering, optionally a Lysine to Glycine, or a Serine to Glycine substitution; or
  • a Tyrosine at position 71 optionally a substitution at position 71 according to Kabat numbering, optionally a Phenylalanine to Tyrosine, or Alanine to Tyrosine substitution, wherein the substitution is relative to a human germline light chain framework region sequence.
  • binding of the anti-TCR ⁇ V antibody molecule to the TCR ⁇ V region results in a cytokine profile that differs from a cytokine profile of a T cell engager that binds to a receptor or molecule other than a TCR ⁇ V region (“a non-TCR ⁇ V-binding T cell engager”).
  • the non-TCR ⁇ V-binding T cell engager comprises an antibody that binds to a CD3 molecule, optionally CD3 epsilon (CD3e) molecule; or a TCR alpha (TCR ⁇ ) molecule.
  • the cytokine profile of the first moiety comprises, one, two, three, four, five, six, seven, or all of the following:
  • a delay optionally at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more hours delay, in increased level, optionally expression level, and/or activity of IL-2;
  • a delay optionally at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 hours delay, in increased level, optionally expression level, and/or activity of IFNg; or
  • binding of the anti-TCR ⁇ V antibody molecule to the TCR ⁇ V region results in reduced cytokine storm, optionally reduced cytokine release syndrome (CRS), as measured by an assay of Example 3, optionally relative to the cytokine storm induced by the non-TCR ⁇ V-binding T cell engager.
  • CRS cytokine release syndrome
  • binding of the anti-TCR ⁇ V antibody molecule to the TCR ⁇ V region results in one, two, three or all of:
  • (xii) expansion optionally at least about 1.1-10 fold expansion, optionally at least about 1.1, 1.2, 1.3, 1.4, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, or 10 fold expansion, of a population of T cells having a memory-like phenotype
  • the anti-TCR ⁇ V antibody molecule binds to an outward facing region, optionally epitope, on a TCR ⁇ V protein, optionally as depicted by the circled area in FIG. 24 A .
  • the outward facing region on the TCR ⁇ V protein comprises a structurally conserved region of TCR ⁇ V, optionally a region of TCR ⁇ V having a similar structure across one or more TCR ⁇ V subfamilies.
  • the method further comprises administering, optionally sequentially, simultaneously or concurrently, a second agent, optionally therapeutic agent, optionally as described herein.
  • the second agent optionally therapeutic agent, comprises a chemotherapeutic agent, a biologic agent, hormonal therapy, radiation, or surgery.
  • the disease is a cancer, optionally a solid tumor or a hematological cancer, or a metastatic lesion.
  • the cancer antigen is BCMA or FcRH5.
  • FIGS. 1 A- 1 B shows the alignment of the Antibody A source mouse VH and VL framework 1, CDR 1, framework 2, CDR 2, framework 3, CDR3, and framework 4 regions with their respective humanized sequences. Kabat CDRs are shown in bold, Chothia CDRs are shown in italics, and combined CDRs are shown in boxes. The framework positions that were back mutated are double underlined.
  • FIG. 1 A shows VH sequences for murine Antibody A (SEQ ID NO: 1) and humanized Antibody A-H (SEQ ID NO: 9).
  • FIG. 1 B shows VL sequences for murine Antibody A (SEQ ID NO: 2) and humanized Antibody A-H (SEQ ID NO: 10 and SEQ ID NO: 11).
  • FIGS. 2 A- 2 B shows the alignment of the Antibody B source mouse VH and VL framework 1, CDR 1, framework 2, CDR 2, framework 3, CDR3, and framework 4 regions with their respective humanized sequences. Kabat CDRs are shown in bold, Chothia CDRs are shown in italics, and combined CDRs are shown in boxes. The framework positions that were back mutated are double underlined.
  • FIG. 2 A shows the VH sequence for murine Antibody B (SEQ ID NO: 15) and humanized VH sequences B-H.1A to B-H.1C (SEQ ID NOs: 23-25).
  • FIG. 2 B shows the VL sequence for murine Antibody B (SEQ ID NO: 16) and humanized VL sequences B-H.1D to B-H.1H (SEQ ID NOs: 26-30).
  • FIG. 3 depicts the phylogenetic tree of TCRBV gene family and subfamilies with corresponding antibodies mapped.
  • Subfamily identities are as follows: Subfamily A: TCR ⁇ V6; Subfamily B: TCR ⁇ V10; Subfamily C: TCR ⁇ V12; Subfamily D: TCR ⁇ V5; Subfamily E: TCR ⁇ V7; Subfamily F: TCR ⁇ V11; Subfamily G: TCR ⁇ V14; Subfamily H: TCR ⁇ V16; Subfamily I:TCR ⁇ V18; Subfamily J:TCR ⁇ V9; Subfamily K: TCR ⁇ V13; Subfamily L: TCR ⁇ V4; Subfamily M:TCR ⁇ V3; Subfamily N:TCR ⁇ V2; Subfamily O:TCR ⁇ V15; Subfamily P: TCR ⁇ V30; Subfamily Q: TCR ⁇ V19; Subfamily R:TCR ⁇ V27; Subfamily S:TCR ⁇ V28; Subfamily T: TCR ⁇ V24; Subfamily U: TCR ⁇ V20; Subfamily V: T
  • FIGS. 4 A- 4 C show human CD3+ T cells activated by anti-TCR V1313.1 antibody (A-H.1) for 6-days.
  • Human CD3+ T cells were isolated using magnetic-bead separation (negative selection) and activated with immobilized (plate-coated) anti-TCR V ⁇ 13.1 (A-H.1) or anti-CD3E (OKT3) antibodies at 100 nM for 6 days.
  • FIG. 4 A shows two scatter plots (left: activated with OKT3; and right: activated with A-H.1) of expanded T cells assessed for TCR V ⁇ 13.1 surface expression using anti-TCR V ⁇ 13.1 (A-H.1) followed by a secondary fluorochrome—conjugated antibody for flow cytometry analysis.
  • FIG. 1 shows two scatter plots (left: activated with OKT3; and right: activated with A-H.1) of expanded T cells assessed for TCR V ⁇ 13.1 surface expression using anti-TCR V ⁇ 13.1 (A-H.1) followed by a secondary flu
  • FIG. 4 B shows percentage (%) of TCR V ⁇ 13.1 positive T cells activated by anti-TCR V ⁇ 13.1 (A-H.1) or anti-CD3e (OKT3) plotted against total T cells (CD3+).
  • FIG. 4 C shows relative cell count acquired by counting the number of events in each T cell subset gate (CD3 or TCR V1313.1) for 20 seconds at a constant rate of 60 ⁇ l/min. Data shown as mean value from 3 donors.
  • FIGS. 5 A- 5 B show cytolytic activity of human CD3+ T cells activated by anti-TCR V1313.1 antibody (A-H.1) against transformed cell line RPMI 8226.
  • FIG. 5 A depicts target cell lysis of human CD3+ T cells activated with A-H.1 or OKT3.
  • Human CD3+ T cells were isolated using magnetic-bead separation (negative selection) and activated with immobilized (plate-coated) A-H.1 or OKT3 at the indicated concentrations for 4 days prior to co-culture with RPMI 8226 cells at a (E:T) ratio of 5:1 for 2 days.
  • FIGS. 6 A- 6 B show IFNg production by human PBMCs activated with the indicated antibodies.
  • Human PBMCs were isolated from whole blood from the indicated number of donors, followed by solid-phase (plate-coated) stimulation with the indicated antibodies at 100 Nm. Supernatant was collected on Days 1, 2, 3, 5, or 6.
  • FIG. 6 A is a graph comparing the production of IFNg in human PBMCs activated with the antibodies indicated activated with anti-TCR V ⁇ 13.1 antibodies (A-H.1 or A-H.2) or anti-CD3e antibodies (OKT3 or SP34-2) on Day 1, 2, 3, 5, or 6 post-activation.
  • FIG. 6 B shows IFNg production in human PBMCs activated with the antibodies indicated activated with the indicated anti-TCR V ⁇ 13.1 antibodies or anti-CD3e antibody (OKT3) on Day 1, 2, 3, 5, or 6 post-activation.
  • FIGS. 7 A- 7 B show IL-2 production by human PBMCs activated with the indicated antibodies.
  • a similar experimental setup as described for FIGS. 6 A- 6 B was used.
  • FIGS. 8 A- 8 B show IL-6 production by human PBMCs activated with the indicated antibodies.
  • a similar experimental setup as described for FIGS. 6 A- 6 B was used.
  • FIGS. 9 A- 9 B show TNF-alpha production by human PBMCs activated with the indicated antibodies.
  • a similar experimental setup as described for FIGS. 6 A- 6 B was used.
  • FIGS. 10 A- 10 B show IL-1beta production by human PBMCs activated with the indicated antibodies. A similar experimental setup as described for FIGS. 6 A- 6 B was used.
  • FIGS. 11 A- 11 B are graphs showing delayed kinetics of IFNg secretion in human PMBCs activated by anti-TCR V ⁇ 13.1 antibody A-H.1 when compared to PBMCs activated by anti-CD3e antibody OKT3.
  • FIG. 11 A shows IFNg secretion data from 4 donors.
  • FIG. 12 depicts increased CD8+ TSCM and Temra T cell subsets in human PBMCs activated by anti-TCR V ⁇ 13.1 antibodies (A-H.1 or A-H.2) compared to PBMCs activated by anti-CD3e antibodies (OKT3 or SP34-2).
  • FIGS. 13 A- 13 F show characterization of an anti-TCRVb antibody.
  • FIG. 13 A is a graph depicting proliferation of T cells activated with anti-CD3 (OKT3) antibody or anti-TCRVb antibody.
  • FIG. 13 B shows selective expansion of CD45RA+ effector memory CD8+ and CD4+ T cells (TEMRA) cells with anti-TCRVb antibodies.
  • FIG. 13 C is a graph showing IFN-g secretion by PBMCs stimulated with an anti-TCRVb antibody, or anti-CD3 antibodies.
  • FIG. 13 D shows target cell lysis by T cells stimulated with an anti-TCRVb antibody, or anti-CD3 antibodies. Cells were stimulated for 4 days followed by 2 days incubation with multiple myeloma target cells for assessment of cell killing.
  • FIG. 13 E is a graph showing perforin secretion by T cells stimulated with an anti-TCRVb antibody, or an anti-CD3 antibody. Perforin was analyzed by FACS staining in TCRVB-positive and TCRVB-negative T cells in PBMCs after 5 days of stimulation with 100 ng/ml plate-bound antibody.
  • FIG. 13 F is a graph showing Granzyme B by T cells stimulated with an anti-TCRVb antibody, or an anti-CD3 antibody. Granzyme B was analyzed by FACS staining in TCRVB-positive and TCRVB-negative T cells in PBMCs after 5 days of stimulation with 100 ng/ml plate-bound antibody.
  • FIGS. 14 A- 14 B show production of IL-2 and IL-15 and expansion of human NK cells by stimulation of PBMCs with anti-TCRVb antibody for 6 days at a dose of 100 nM.
  • FIG. 14 A shows secretion of IL-2 or IL-15 in T cells stimulated with an anti-TCRVb antibody, or anti-CD3 antibodies.
  • FIG. 14 B depicts flow cytometry dot plots showing NKp46 staining vs CD56 antibody staining in cells stimulated with an anti-TCRVb antibody or an anti-CD3 antibody or a control sample.
  • FIGS. 15 A- 15 C show secretion of cytokines in PBMCs stimulated with an anti-TCRVb antibody, or anti-CD3 antibodies.
  • FIG. 15 A IL-6;
  • FIG. 15 B IL-10;
  • FIG. 15 C TNF ⁇
  • FIGS. 16 A- 16 B show killing of MM cells by dual targeting BCMA-TCRvb antibody molecules.
  • FIG. 16 A shows in vitro killing by one of the following dual-targeting antibody molecules: BCMA-TCRVb (Molecule I), BCMA-CD3, or Control-TCRVb; or an isotype control.
  • FIG. 16 B shows in vivo killing of MM cells by a dual-targeting BCM-TCRVb antibody (Molecule I).
  • FIG. 17 shows lysis of MM target cells with a dual targeting antibody (Molecule E) which recognized FcRH5 on one arm and TCRVb on the other arm.
  • FIGS. 18 A- 18 B demonstrate cytokine production from human PBMCs activated by anti-TCR V ⁇ 8a antibodies (B-H.1) when compared to those activated by anti-CD3 ⁇ antibodies (OKT3 or SP34-2).
  • FIG. 18 A shows that human PBMCs activated by anti-TCR V ⁇ 8a antibodies (B-H.1) produce similar or reduced levels of IFN ⁇ .
  • FIGS. 19 A- 19 C demonstrate cytokine production from human PBMCs activated by anti-TCR V ⁇ 8a antibodies (B-H.1).
  • Human PBMCs activated by anti-TCR V ⁇ 8a antibodies (B-H.1) do not significantly produce IL-6 ( FIG. 19 A ), IL 1b ( FIG. 19 B ), and less TNF ⁇ ( FIG. 19 C ), when compared to PBMCs activated by anti-CD3 ⁇ antibodies (OKT3 or SP34-2).
  • FIGS. 20 A- 20 E demonstrate cytokine production from human PBMCs activated by anti-TCR ⁇ V Antibody D antibody compared to control anti-CD3e antibody (OKT3).
  • FIG. 20 A shows that human PBMCs activated by anti-TCR ⁇ V Antibody D antibody produce similar or reduced levels of IFN ⁇ .
  • FIG. 20 B shows human PBMCs activated by anti-TCR ⁇ V Antibody D antibody produce higher levels of IL-2 when compared to those activated by anti-CD3 ⁇ antibodies (OKT3).
  • FIGS. 21 A- 21 B demonstrate cytokine production from human PBMCs activated by anti-TCR V ⁇ 5 antibody (Antibody E).
  • FIG. 21 A shows that human PBMCs activated by anti-TCR V ⁇ 5 antibody produce similar or reduced levels of IFN ⁇ compared to PBMCS activated by anti-CD3 ⁇ antibodies (OKT3 or SP34-2).
  • FIGS. 22 A- 22 D demonstrate cytokine production from human PBMCs activated by an anti-TCR V ⁇ 5 antibody (Antibody E).
  • Human PBMCs activated by anti-TCR V ⁇ 5 antibody do not significantly produce IL-1beta ( FIG. 22 A ), IL-6, ( FIG. 22 B ), TNFalpha ( FIG. 22 C ), or IL-10 ( FIG. 22 D ) as compared to PBMCs activated by anti-CD3 ⁇ antibodies (OKT3 or SP34-2).
  • FIGS. 23 A- 23 F demonstrate cytokine production from human PBMCs activated by a dual targeting (bispecific molecule) comprising an anti-TCR ⁇ V binding moiety and a BCMA binding moiety.
  • FIG. 23 A shows that human PBMCs activated by the bispecific molecule produce similar or reduced levels of IFN ⁇ as PBMCS activated by anti-CD3 ⁇ antibodies (OKT3).
  • FIG. 23 B shows human PBMCs activated by the bispecific molecule produce higher levels of IL-2 when compared to PBMCs activated by anti-CD3 ⁇ antibodies (OKT3).
  • FIGS. 24 A- 24 B show the structure and sequence of eight TCR ⁇ V proteins from seven different subfamilies: TCR ⁇ V6 subfamily (TCR ⁇ V6-5 and TCR ⁇ V6-4 are shown), TCR ⁇ V28 subfamily, TCR ⁇ V19 subfamily, TCR ⁇ V9 subfamily, TCR ⁇ V5 subfamily, TCR ⁇ V20 subfamily and TCR ⁇ V12 subfamily.
  • FIG. 24 A shows the structural alignment of the different TCR ⁇ V proteins.
  • the circled area represents the outward facing region comprising the proposed binding site for the anti-TCR ⁇ V antibodies disclosed herein.
  • FIG. 24 B shows the amino acid sequence alignment of the proteins shown in FIG. 24 A (SEQ ID NOS: 3449-3456, respectively, in order of appearance).
  • the various TCR ⁇ V proteins (from 7 different TCR ⁇ V subfamilies) have diverse sequences but share a conserved (similar) structure and function.
  • FIG. 25 A IFN ⁇ ; FIG. 25 B , IL-2; FIG. 25 C , IL-1 ⁇ ; FIG. 25 D , IL-6; FIG. 25 E , IL-10; FIG. 25 F , IL-4; FIG. 25 G , TNF ⁇ ; FIG. 2511 , IL-12p70; FIG. 251 , IL-13; FIG. 25 J , IL-8.
  • FIG. 26 A Eotaxin
  • FIG. 26 B Eotaxin-3
  • FIG. 26 C IL-8 (HA)
  • FIG. 26 D IP-10
  • FIG. 26 E MCP-1
  • FIG. 26 F MCP-4
  • FIG. 26 G MDC
  • FIG. 2611 MIP-1a.
  • FIG. 27 A MIP-1B
  • FIG. 27 B TARC
  • FIG. 27 C GM-CSF
  • FIG. 27 D IL-12-23p40
  • FIG. 27 E IL-15
  • FIG. 27 F IL-16
  • FIG. 27 G IL-17a
  • FIG. 2711 , IL-1a
  • FIG. 271 , IL-5
  • FIG. 27 K TNF- ⁇
  • FIG. 27 L VEGF.
  • FIG. 28 is a graph depicting mean tumor volume in NOD/SCID/IL-2R ⁇ null (NSG) mice engrafted with Raji-luc cells at days 10 to 28.
  • the Star denotes PBMC implantation.
  • Open triangles denote antibody treatment with the indicated antibodies.
  • FIGS. 29 A- 29 B depicting Mean tumor burden (Total Flux) in NOD/SCID/IL-2R ⁇ null (NSG) mice engrafted with cancer cells and treated with the indicated antibody.
  • NSG mice were implanted with PBMCs on Day 1 followed by injection with cancer cells on Day 7 (Raji-luc in FIG. 29 A ; K562-Luc control in FIG. 29 B ).
  • Antibody treatment with the indicated antibodies began on Day 16.
  • FIG. 29 A shows mean tumor burden at days 16 to 37 in NOD/SCID/IL-2R ⁇ null (NSG) mice engrafted with Raji-luc cells.
  • FIG. 29 B shows mean tumor burden (Total Flux) at days 16 to 30 in animals engrafted with K562-luc cells.
  • FIG. 30 is a graph depicting Mean tumor burden (Total Flux) mean tumor volume in NOD/SCID/IL-2R ⁇ null (NSG) mice engrafted with RPMI-8226 cells.
  • the RPMI-8226 cells were engrafted on Day 1.
  • PBMCs were implanted into the mice and antibody treatment began on Day 17.
  • FIGS. 31 A- 31 B are graphs showing % target cell lysis at different antibody concentrations.
  • FIG. 31 A shows data generated using anti-TCR V ⁇ 13.1/anti-CD19 (Molecule F), anti-CD3/anti-CD19, and anti-TCR V1313.1 (A-H.1).
  • FIG. 31 B shows data generated using anti-TCR V1313.1/anti-BCMA (Molecule G), anti-CD3/anti-BCMA, and anti-TCR V1313.1 (A-H.1).
  • FIGS. 32 A- 32 F are graphs showing cytokine secretion stimulated by anti-TCR V ⁇ /anti-BCMA (Molecule H) or anti-CD3 (OKT3) at Days 1, 2, 3, and 5.
  • Cytokines examined include: IFN ⁇ ( FIG. 32 A ), IL-2 ( FIG. 32 B ), IL-10 ( FIG. 32 C ), IL-6 ( FIG. 32 D ), IL-10 ( FIG. 32 E ), and TNF ⁇ ( FIG. 32 F ).
  • FIGS. 33 A- 33 F are graphs showing cytokine secretion stimulated by anti-TRBC1 (Antibody F) or anti-CD3 (OKT3) at Days 2 and 5.
  • Cytokines examined include: IFN ⁇ ( FIG. 33 A ), IL-2 ( FIG. 33 B ), IL-10 ( FIG. 33 C ), IL-6 ( FIG. 33 D ), IL-10 ( FIG. 33 E ), and TNF ⁇ ( FIG. 33 F ).
  • FIG. 34 is a FACS plot showing the expansion of TCRvb 6-5+ T cells over 8 days using anti-TCRvb 6-5 v1.
  • FIG. 35 is a bar graph showing the expansion of TCRvb 6-5+CD4+ T cells and TCRvb 6-5+CD8+ T cells over 8 days using the anti-CD3c antibody OKT3 (100 nM).
  • FIG. 36 is a bar graph showing the expansion of TCRvb 6-5+CD4+ T cells and TCRvb 6-5+CD8+ T cells over 8 days using the anti-TCRvb 6-5 v1 antibody (100 nM).
  • FIG. 37 is a FACS plot showing the showing the expansion of TCRvb 6-5+ T cells over 8 days using anti-TCRvb 6-5 v1 or the anti-CD3 ⁇ antibody OKT3.
  • FIG. 38 A is a bar graph showing the percentage of TCR ⁇ V 6-5+ T cells in PBMC cultures after 8 days of culture with the indicated antibody. Data for 5 replicates are shown.
  • FIG. 38 B is a bar graph showing the percentage of TCR ⁇ V 6-5+ T cells in purified T cell cultures after 8 days of culture with the indicated antibody. Data for 5 replicates are shown.
  • FIG. 39 A is a bar graph showing the relative count of TCR ⁇ V 6-5+ T cells in PBMC culture after 8 days of culture with the indicated antibody.
  • FIG. 39 B is a bar graph showing the relative count of TCR ⁇ V 6-5+ T cells in PBMC culture after 8 days of culture with the indicated antibody.
  • FIG. 40 A is a bar graph showing the relative count of TCR ⁇ V 6-5+ T cells in a purified T cell culture after 8 days of culture with the indicated antibody.
  • FIG. 40 B is a bar graph showing the relative count of TCR ⁇ V 6-5+ T cells in a purified T cell culture after 8 days of culture with the indicated antibody.
  • FIG. 41 is a line graph showing the total CD3+ T cell count (fold increase) after 8 days of T cell culture with either the anti-CD3 ⁇ antibody OKT3 or the anti-TCRvb 6-5 v1 antibody.
  • FIG. 42 is a series of line graphs showing the kinetics of target cells by TCR ⁇ V 6-5 v1 activated T cells or anti-CD3 ⁇ (OKT3) activated T cells.
  • T cells from three different donors were utilized (donor 6769, donor 9880, donor 5411).
  • FIG. 43 A is a scatter plot showing the percent of target cell lysis by T cells by TCR ⁇ V 6-5 v1 activated T cells or anti-CD3 ⁇ (OKT3) activated T cells without T cell pre activation. The data is presented at day 6 of co-culture between target cells and effector T cells.
  • FIG. 43 B is a scatter plot showing the percent of target cell lysis by T cells by TCR ⁇ V 6-5 v1 activated T cells or anti-CD3 ⁇ (OKT3) activated T cells with 4 days of T cell pre activation. The data is presented at day 2 of co-culture between target cells and effector T cells (after 4 days of T cell pre-activation).
  • FIG. 44 is a scatter plot showing the percent of target cell lysis by T cells by TCR ⁇ V 6-5 v1 activated T cells or anti-CD3 ⁇ (OKT3) activated T cells with 4 days of T cell pre activation. The data is presented at day 2 of co-culture between target cells and effector T cells (after 4 days of T cell pre-activation).
  • FIG. 45 is a bar graph showing target cell lysis by T cells by TCR ⁇ V 6-5 v1 activated T cells or anti-CD3 ⁇ (OKT3) activated T cells (100 nM each antibody). The data includes seven replicates of each experimental condition.
  • FIG. 46 is a series of FACS plots that show the cell surface expression of CD3 ⁇ on CD4+ TCR ⁇ V 6-5 ⁇ or CD4+ TCR ⁇ V 6-5 + T cells activated with either SP34-2 (anti-CD3 ⁇ antibody) or anti-TCR ⁇ V 6-5 v1 (anti-TCR ⁇ V 6-5 antibody) at days 0, 1, 2, 4, 6, or 8 post antibody activation.
  • FIG. 47 is a series of FACS plots that show the cell surface expression of CD3 ⁇ on CD8+ TCR ⁇ V 6-5 ⁇ or CD8+ TCR ⁇ V 6-5 + T cells activated with either SP34-2 (anti-CD3 ⁇ antibody) or anti-TCR ⁇ V 6-5 v1 (anti-TCR ⁇ V 6-5 antibody) at days 0, 1, 2, 4, 6, or 8 post antibody activation.
  • FIG. 48 is a series of FACS plots that show the cell surface expression of TCR ⁇ V on CD4+ TCR ⁇ V 6-5 ⁇ or CD4+ TCR ⁇ V 6-5 + T cells activated with either SP34-2 (anti-CD3 ⁇ antibody) or anti-TCR ⁇ V 6-5 v1 (anti-TCR ⁇ V 6-5 antibody) at days 0, 1, 2, 4, 6, or 8 post antibody activation.
  • FIG. 49 is a series of FACS plots that show the cell surface expression of TCR ⁇ V on CD8+ TCR ⁇ V 6-5 ⁇ or CD8+ TCR ⁇ V 6-5 + T cells activated with either SP34-2 (anti-CD3 ⁇ antibody) or anti-TCR ⁇ V 6-5 v1 (anti-TCR ⁇ V 6-5 antibody) at days 0, 1, 2, 4, 6, or 8 post antibody activation.
  • FIG. 50 A shows FACS plot of TCR ⁇ V 6-5 + cynomolgus T cell expansion either unstimulated (left) or stimulated with anti-TCR ⁇ V 6-5 v1 (right) 7 days post activation of cynomolgus PBMCs.
  • PBMCs from Donor DW8N fresh PBMC sample, male, age 8, weight 7.9 kgs
  • FIG. 50 B shows FACS plot of TCR ⁇ V 6-5 + cynomolgus T cell expansion either unstimulated (left) or stimulated with anti-TCR ⁇ V 6-5 v1 (right) 7 days post activation of cynomolgus PBMCs.
  • PBMCs from Donor G709 cryopreserved sample, male, age 6, weight 4.7 kgs
  • FIG. 51 shows FACS plot and corresponding microscopy images of TCR ⁇ V 6-5 + cynomolgus T cell expansion either unstimulated (left), stimulated with SP34-2 (anti-CD3 ⁇ antibody) (middle); or stimulated with anti-TCR ⁇ V 6-5 v1 (right) post activation of cryopreserved donor DW8N cynomolgus PBMCs.
  • the microscopy images show the cell cluster formation (indicated by circles).
  • FIG. 52 shows a schematic of FACS plot showing the FACS gating/staining of PBMCs prior ⁇ T cell purification.
  • FIG. 53 shows a schematic of FACS plot showing the FACS gating/staining of purified ⁇ T cell population.
  • FIG. 54 show activation of purified ⁇ T cell population with anti-CD3 ⁇ antibody (SP34-2) (left) or anti-TCR ⁇ V antibody (anti-TCR ⁇ V 6-5 v1) (right).
  • FIG. 55 A shows the release of IFN ⁇ from purified ⁇ T cell populations activated with anti-CD3£ antibody (SP34-2), anti-TCR ⁇ V antibody (anti-TCR ⁇ V 6-5 v1), or unstimulated.
  • FIG. 55 B shows the release of TNF ⁇ from purified ⁇ T cell populations activated with anti-CD3 ⁇ antibody (SP34-2), anti-TCR ⁇ V antibody (anti-TCR ⁇ V 6-5 v1), or unstimulated.
  • FIG. 55 C shows the release of IL-2 from purified ⁇ T cell populations activated with anti-CD3 ⁇ antibody (SP34-2), anti-TCR ⁇ V antibody (anti-TCR ⁇ V 6-5 v1), or unstimulated.
  • FIG. 55 C shows the release of IL-2 from purified ⁇ T cell populations activated with anti-CD3 ⁇ antibody (SP34-2), anti-TCR ⁇ V antibody (anti-TCR ⁇ V 6-5 v1), or unstimulated.
  • FIG. 55 D shows the release of IL-17A from purified ⁇ T cell populations activated with anti-CD3 ⁇ antibody (SP34-2), anti-TCR ⁇ V antibody (anti-TCR ⁇ V 6-5 v1), or unstimulated.
  • FIG. 55 E shows the release of IL-1 ⁇ from purified yS T cell populations activated with anti-CD3 ⁇ antibody (SP34-2), anti-TCR ⁇ V antibody (anti-TCR ⁇ V 6-5 v1), or unstimulated.
  • FIG. 55 F shows the release of IL-10 from purified ⁇ T cell populations activated with anti-CD3 ⁇ antibody (SP34-2), anti-TCR ⁇ V antibody (anti-TCR ⁇ V 6-5 v1), or unstimulated.
  • FIG. 55 G shows the release of IL-6 from purified ⁇ T cell populations activated with anti-CD3 ⁇ antibody (SP34-2), anti-TCR ⁇ V antibody (anti-TCR ⁇ V 6-5 v1), or unstimulated.
  • FIG. 55 H shows the release of IL-10 from purified ⁇ T cell populations activated with anti-CD3£ antibody (SP34-2), anti-TCR ⁇ V antibody (anti-TCR ⁇ V 6-5 v1), or unstimulated.
  • FIG. 56 shows the relative representations of all TCR alpha V segments (TRAV group of genes) and their variants (top), all TCR beta V segment 6-5 variants (TRBV6-5 gene) (bottom left), and all TCR beta V segments and variants excluding 6-5 (bottom right).
  • FIG. 57 A is a FACS plot showing phenotypic markers of CD4+ T cells expanded with anti-TCR ⁇ V antibody (anti-TCR ⁇ V 6-5 v1). Defined phenotypes include TEMRA (top left), Na ⁇ ve/TSCM (top right), TEM (bottom left), and TCM (bottom right).
  • FIG. 57 B is a FACS plot showing phenotypic markers of CD4+ T cells expanded with anti-CD3 ⁇ antibody (OKT3). Defined phenotypes include TEMRA (top left), Na ⁇ ve/TSCM (top right), TEM (bottom left), and TCM (bottom right).
  • FIG. 58 A is a FACS plot showing phenotypic markers of CD8+ T cells expanded with anti-TCR ⁇ V antibody (anti-TCR ⁇ V 6-5 v1). Defined phenotypes include TEMRA (top left), Na ⁇ ve/TSCM (top right), TEM (bottom left), and TCM (bottom right).
  • FIG. 58 B is a FACS plot showing phenotypic markers of CD8+ T cells expanded with anti-CD3 ⁇ antibody (OKT3). Defined phenotypes include TEMRA (top left), Na ⁇ ve/TSCM (top right), TEM (bottom left), and TCM (bottom right).
  • FIG. 59 A is a bar graph showing the percentage of PD1 expressing CD4+ T cells from T cell cultures activated with anti-TCR ⁇ V antibody (anti-TCR ⁇ V 6-5 v1), anti-CD3 ⁇ antibody (OKT3), or unstimulated.
  • FIG. 59 B is a bar graph showing the percentage of PD1 expressing CD8+ T cells from T cell cultures activated with anti-TCR ⁇ V antibody (anti-TCR ⁇ V 6-5 v1), anti-CD3 ⁇ antibody (OKT3), or unstimulated.
  • FIG. 60 A is a bar graph showing the expression of Ki-67 by CD4+ T cells from T cell cultures activated with anti-TCR ⁇ V antibody (anti-TCR ⁇ V 6-5 v1), anti-CD3 ⁇ antibody (OKT3), or unstimulated.
  • FIG. 60 B is a bar graph showing the expression of Ki-67 by CD8+ T cells from T cell cultures activated with anti-TCR ⁇ V antibody (anti-TCR ⁇ V 6-5 v1), anti-CD3 ⁇ antibody (OKT3), or unstimulated.
  • FIG. 61 A is a FACS plot showing the percentage of TEMRA-like CD8+ T cells activated using anti-TCR ⁇ V antibody (anti-TCR ⁇ V 6-5 v1) that express CD57 (18.7%).
  • FIG. 61 B is a FACS plot showing the percentage of TEM-like CD8+ T cells activated using anti-CD3 ⁇ antibody (OKT3) that express CD57 (46.8%) and the percentage of TCM-like CD8+ T cells activated using anti-CD3 ⁇ antibody (OKT3) that express CD57 (18.9%).
  • FIG. 62 shows a series of FACS plots showing the expression of expression of CD27 and by CD4+(top) or CD8+(bottom) T cells from T cell cultures activated with anti-TCR ⁇ V antibody (anti-TCR ⁇ V 6-5 v1), anti-CD3 ⁇ antibody (OKT3), or unstimulated.
  • FIG. 63 shows a series of FACS plots showing the expression of expression of OX40, 41BB, and ICOS by CD4+(top) or CD8+(bottom) T cells from T cell cultures activated with anti-TCR ⁇ V antibody (anti-TCR ⁇ V 6-5 v1), anti-CD3 ⁇ antibody (OKT3), or unstimulated.
  • FIG. 64 shows a series of FACS plots showing the percentage of CD3+(CD4 gated) TCR ⁇ V 6-5+ T cells 1, 2, 3, 4, 5, 6, and 8 days port activation with BCMA and the anti-TCR antibody anti-TCR V ⁇ 6-5 v1.
  • FIG. 65 A shows a series of FACS plots showing the percentage of CD4+ T cells expanded using isotype control (IgG1 N297A), anti-TCR ⁇ V (anti-TCR V ⁇ 6-5 v1), or anti-CD3 ⁇ (OKT3) antibodies on day 0 post activation.
  • FIG. 65 B shows a series of FACS plots showing the percentage of CD4+ T cells expanded using isotype control (IgG1 N297A), anti-TCR ⁇ V (anti-TCR V ⁇ 6-5 v1), or anti-CD3 ⁇ (OKT3) antibodies on day 1 post activation.
  • FIG. 65 C shows a series of FACS plots showing the percentage of CD4+ T cells expanded using isotype control (IgG1 N297A), anti-TCR ⁇ V (anti-TCR V ⁇ 6-5 v1), or anti-CD3 ⁇ (OKT3) antibodies on day 2 post activation.
  • FIG. 65 D shows a series of FACS plots showing the percentage of CD4+ T cells expanded using isotype control (IgG1 N297A), anti-TCR ⁇ V (anti-TCR V ⁇ 6-5 v1), or anti-CD3 ⁇ (OKT3) antibodies on day 3 post activation.
  • FIG. 65 E shows a series of FACS plots showing the percentage of CD4+ T cells expanded using isotype control (IgG1 N297A), anti-TCR ⁇ V (anti-TCR V ⁇ 6-5 v1), or anti-CD3 ⁇ (OKT3) antibodies on day 4 post activation.
  • FIG. 65 F shows a series of FACS plots showing the percentage of CD4+ T cells expanded using isotype control (IgG1 N297A), anti-TCR ⁇ V (anti-TCR V ⁇ 6-5 v1), or anti-CD3 ⁇ (OKT3) antibodies on day 5 post activation.
  • FIG. 65 G shows a series of FACS plots showing the percentage of CD4+ T cells expanded using isotype control (IgG1 N297A), anti-TCR ⁇ V (anti-TCR V ⁇ 6-5 v1), or anti-CD3 ⁇ (OKT3) antibodies on day 6 post activation.
  • FIG. 65 H shows a series of FACS plots showing the percentage of CD4+ T cells expanded using isotype control (IgG1 N297A), anti-TCR ⁇ V (anti-TCR V ⁇ 6-5 v1), or anti-CD3 ⁇ (OKT3) antibodies on day 8 post activation.
  • FIG. 66 A is a bar graph showing ATP production from glycolysis of T cell cultures activated with the indicated antibodies.
  • FIG. 66 B is a bar graph showing ATP production from oxidative phosphorylation of T cell cultures activated with the indicated antibodies.
  • FIG. 67 is a line graph showing the oxygen consumption rate (OCR) of T cells from about 0 to 75 minutes activated with the indicated antibody.
  • OCR oxygen consumption rate
  • FIG. 68 A shows the oxygen consumption rate (OCR) of T cells activated with the indicated antibody during basal respiration.
  • FIG. 68 B shows the oxygen consumption rate (OCR) of T cells activated with the indicated antibody during maximal respiration.
  • FIG. 68 C shows the oxygen consumption rate (OCR) of T cells activated with the indicated antibody during spare respiratory capacity.
  • FIG. 68 D is a line graph indicates the areas of basal respiration and maximal respiration as shown in FIG. 68 A and FIG. 68 B , respectively.
  • FIG. 69 A is a bar graph showing ATP production from glycolysis of T cell cultures activated with anti-TCR ⁇ V 6-5 v1 and re-stimulated with the indicated antibody.
  • FIG. 69 B is a bar graph showing ATP production from oxidative phosphorylation of T cell cultures activated with anti-TCR ⁇ V 6-5 v1 and re-stimulated with the indicated antibody.
  • FIGS. 70 A- 70 G are graphs showing expression of IFNg ( FIG. 70 A ), TNF ⁇ ( FIG. 70 E ), IL-1a ( FIG. 70 B ), IL-1b ( FIG. 70 C ), IL-6 ( FIG. 70 D ), IL-10 ( FIG. 70 F ), IL-17A ( FIG. 70 G ) (CRS and neurotoxicity associated cytokines) with BHM1710 (anti TCRVB), a reduced affinity anti CD3 antibody (TB) and the SP34 anti CD3e antibody.
  • FIG. 71 is a FACS plot showing the percentage of NK cells expanded from T cell cultures activated with the indicated antibody.
  • FIG. 72 is a bar graph showing the number of NK cells expanded from T cell cultures activated with the indicated antibody.
  • FIG. 73 shows a series of FACS plots showing NK cell proliferation induced by T cell cultures activated with the indicated antibody.
  • FIG. 74 is a schematic showing an assay described in Example for determining NK cell mediated lysis of target K562 cells.
  • FIG. 75 is a bar graph showing the percent target cell lysis mediated by NK cells activated by PBMCs activated with the indicated antibody.
  • FIG. 76 shows a series of FACS plots showing the proliferation of NK cells from PBMC cultures activated/expanded with the indicated antibody (isotype control or OKT3).
  • PBMCs from three donors (D1, D2, and D3) were analyzed.
  • FIG. 77 shows a series of FACS plots showing the proliferation of NK cells from PBMC cultures activated/expanded with the indicated antibody (anti-TCR ⁇ 12-3/4 v1 or anti-TCRv ⁇ 12-3/4 v2).
  • PBMCs from three donors (D1, D2, and D3) were analyzed.
  • FIG. 78 shows a series of FACS plots showing the proliferation of NK cells from PBMC cultures activated/expanded with the indicated antibody (anti-TCR ⁇ 12-3/4 v3 or SP34-2).
  • PBMCs from three donors (D1, D2, and D3) were analyzed.
  • FIG. 79 is a bar graph showing the level of secreted IFN ⁇ by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, OKT3, or SP34) and cultured with said antibody for the indicated number of days (1, 3, or 5).
  • FIG. 80 is a bar graph showing the level of secreted IL-2 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, OKT3, or SP34) and cultured with said antibody for the indicated number of days (1, 3, or 5).
  • FIG. 81 is a bar graph showing the level of secreted IL-15 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, OKT3, or SP34) and cultured with said antibody for the indicated number of days (1, 3, or 5).
  • FIG. 82 is a bar graph showing the level of secreted IL-1 ⁇ by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, OKT3, or SP34) and cultured with said antibody for the indicated number of days (1, 3, or 5).
  • FIG. 83 is a bar graph showing the level of secreted IL-6 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, OKT3, or SP34) and cultured with said antibody for the indicated number of days (1, 3, or 5).
  • FIG. 84 is a bar graph showing the level of secreted IL-10 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, OKT3, or SP34) and cultured with said antibody for the indicated number of days (1, 3, or 5).
  • FIG. 85 is a bar graph showing the level of the indicated cytokine secreted by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 or SP34). The data includes use of 17 individual PBMC donors.
  • FIG. 86 A is a bar graph showing the level of secreted IFN ⁇ by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 or OKT3) and cultured with said antibody for the indicated number of days (1, 2, 3, 5, or 6).
  • FIG. 86 B is a bar graph showing the level of secreted IL-1 ⁇ by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 or OKT3) and cultured with said antibody for the indicated number of days (1, 2, 3, 5, or 6).
  • FIG. 86 C is a bar graph showing the level of secreted IL-4 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 or OKT3) and cultured with said antibody for the indicated number of days (1, 2, 3, 5, or 6).
  • FIG. 86 D is a bar graph showing the level of secreted IL-6 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 or OKT3) and cultured with said antibody for the indicated number of days (1, 2, 3, 5, or 6).
  • FIG. 86 C is a bar graph showing the level of secreted IL-4 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 or OKT3) and cultured with said antibody for the indicated number of days (1, 2, 3, 5, or 6).
  • FIG. 86 E is a bar graph showing the level of secreted IL-10 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 or OKT3) and cultured with said antibody for the indicated number of days (1, 2, 3, 5, or 6).
  • FIG. 86 F is a bar graph showing the level of secreted TNF ⁇ by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 or OKT3) and cultured with said antibody for the indicated number of days (1, 2, 3, 5, or 6).
  • FIG. 86 E is a bar graph showing the level of secreted IL-10 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 or OKT3) and cultured with said antibody for the indicated number of days (1, 2, 3, 5, or 6).
  • 86 G is a bar graph showing the level of secreted IL-2 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 or OKT3) and cultured with said antibody for the indicated number of days (1, 2, 3, 5, or 6).
  • FIG. 87 A is a bar graph showing the level of secreted IFN ⁇ by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, anti-TCR ⁇ V 6-5 v1, OKT3, SP34-2, or isotype control) and cultured with said antibody for the indicated number of days (1, 2, 3, 5, or 6).
  • FIG. 87 B is a bar graph showing the level of secreted IL-1 ⁇ by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, anti-TCR ⁇ V 6-5 v1, OKT3, SP34-2, or isotype control) and cultured with said antibody for the indicated number of days (1, 2, 3, 5, or 6).
  • FIG. 87 A is a bar graph showing the level of secreted IFN ⁇ by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, anti-TCR ⁇ V 6-5 v1, OKT3, SP34-2, or isotype control
  • FIG. 87 C is a bar graph showing the level of secreted IL-4 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, anti-TCR ⁇ V 6-5 v1, OKT3, SP34-2, or isotype control) and cultured with said antibody for the indicated number of days (1, 2, 3, 5, or 6).
  • FIG. 87 D is a bar graph showing the level of secreted IL-6 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, anti-TCR ⁇ V 6-5 v1, OKT3, SP34-2, or isotype control) and cultured with said antibody for the indicated number of days (1, 2, 3, 5, or 6).
  • FIG. 87 D is a bar graph showing the level of secreted IL-6 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, anti-TCR ⁇ V 6-5 v1, OKT3, SP34-2, or isotype control)
  • FIG. 87 E is a bar graph showing the level of secreted IL-10 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, anti-TCR ⁇ V 6-5 v1, OKT3, SP34-2, or isotype control) and cultured with said antibody for the indicated number of days (1, 2, 3, 5, or 6).
  • FIG. 87 F is a bar graph showing the level of secreted TNF ⁇ by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, anti-TCR ⁇ V 6-5 v1, OKT3, SP34-2, or isotype control) and cultured with said antibody for the indicated number of days (1, 2, 3, 5, or 6).
  • FIG. 87 E is a bar graph showing the level of secreted IL-10 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, anti-TCR ⁇ V 6-5 v1, OKT3, SP34-2, or isotype control)
  • 87 G is a bar graph showing the level of secreted IL-2 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, anti-TCR ⁇ V 6-5 v1, OKT3, SP34-2, or isotype control) and cultured with said antibody for the indicated number of days (1, 2, 3, 5, or 6).
  • FIG. 88 A is a bar graph showing the level of secreted IFN ⁇ by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, anti-TCR ⁇ V 6-5 v1, OKT3, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 88 B is a bar graph showing the level of secreted IL-1 ⁇ by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, anti-TCR ⁇ V 6-5 v1, OKT3, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 88 A is a bar graph showing the level of secreted IFN ⁇ by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, anti-TCR ⁇ V 6-5 v1, OKT3, or SP34-2) and cultured with said antibody for the indicated number
  • FIG. 88 C is a bar graph showing the level of secreted IL-4 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, anti-TCR ⁇ V 6-5 v1, OKT3, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 88 D is a bar graph showing the level of secreted IL-6 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, anti-TCR ⁇ V 6-5 v1, OKT3, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 88 E is a bar graph showing the level of secreted IL-10 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, anti-TCR ⁇ V 6-5 v1, OKT3, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 88 F is a bar graph showing the level of secreted TNF ⁇ by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, anti-TCR ⁇ V 6-5 v1, OKT3, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 88 E is a bar graph showing the level of secreted IL-10 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, anti-TCR ⁇ V 6-5 v1, OKT3, or SP34-2) and cultured with said antibody for the indicated number of
  • 88 G is a bar graph showing the level of secreted IL-2 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, anti-TCR ⁇ V 6-5 v1, OKT3, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 89 A is a bar graph showing the level of secreted IL-17A by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, OKT3, or SP34-2) and cultured with said antibody for the indicated number of days (2, 5, or 7).
  • FIG. 89 B is a bar graph showing the level of secreted IL-17A by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, OKT3, or SP34-2) and cultured with said antibody for the indicated number of days (2, 5, or 8).
  • FIG. 89 A is a bar graph showing the level of secreted IL-17A by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, OKT3, or SP34-2) and cultured with said antibody for the indicated number of days (2, 5, or 8).
  • FIG. 89 C is a bar graph showing the level of secreted IL-17A by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1, OKT3, or SP34-2) and cultured with said antibody for the indicated number of days (2, 5, or 7).
  • FIG. 89 D is a bar graph showing the level of secreted IL-17A by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 or SP34-2) and cultured with said antibody for the indicated number of days (1, 3, 5, or 7).
  • FIG. 90 A is a bar graph showing the level of secreted IFN ⁇ by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 90 A is a bar graph showing the level of secreted IFN ⁇ by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 90 A is a bar graph showing the level of secreted IFN ⁇ by T cells activated/expanded with the indicated antibody (
  • 90 B is a bar graph showing the level of secreted IL-1 ⁇ by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 1 isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2
  • 90 C is a bar graph showing the level of secreted IL-4 by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 1 isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2
  • 90 D is a bar graph showing the level of secreted IL-6 by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 1 isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2
  • 90 E is a bar graph showing the level of secreted IL-10 by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 90 F is a bar graph showing the level of secreted TNF ⁇ by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 90 F is a bar graph showing the level of secreted TNF ⁇ by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 90 F is a bar graph showing the level of secreted TNF ⁇ by T cells activated/expanded with the indicated antibody (
  • 90 G is a bar graph showing the level of secreted IL-2 by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 1 isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2
  • 90 H is a bar graph showing the level of secreted IL-12p70 by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 1 isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2
  • 90 I is a bar graph showing the level of secreted IL-13 by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 1 is a bar graph showing the level of secreted IL-13 by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • 90 J is a bar graph showing the level of secreted IL-8 by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 1 is a bar graph showing the level of secreted IL-8 by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • 90 K is a bar graph showing the level of secreted exotaxin by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 1 is a bar graph showing the level of secreted exotaxin by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • 90 L is a bar graph showing the level of secreted exotoxin-3 by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • 90 M is a bar graph showing the level of secreted IL-8 by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 1 isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2
  • 90 N is a bar graph showing the level of secreted IP-10 by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 1 isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2
  • FIG. 90 O is a bar graph showing the level of secreted MCP-1 by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 90 O is a bar graph showing the level of secreted MCP-1 by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • 90 P is a bar graph showing the level of secreted MCP-4 by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 1 isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2
  • 90 Q is a bar graph showing the level of secreted MDC by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 1 isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2
  • FIG. 90 R is a bar graph showing the level of secreted MIP-1a by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • 90 S is a bar graph showing the level of secreted MIP-1b by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 1 isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2
  • T is a bar graph showing the level of secreted TARC by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 1 isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2
  • 90 U is a bar graph showing the level of secreted GMCSF by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 1 is a bar graph showing the level of secreted GMCSF by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • 90 V is a bar graph showing the level of secreted IL-12-23p40 by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • 90 W is a bar graph showing the level of secreted IL-15 by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 1 is a bar graph showing the level of secreted IL-15 by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • 90 X is a bar graph showing the level of secreted IL-16 by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 1 is a bar graph showing the level of secreted IL-16 by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • 90 Y is a bar graph showing the level of secreted IL-17a by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 1 isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2
  • 90 Z is a bar graph showing the level of secreted IL-1a by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 1 isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2
  • 90 AA is a bar graph showing the level of secreted IL-5 by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 1 is a bar graph showing the level of secreted IL-5 by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • 90 BB is a bar graph showing the level of secreted IL-7 by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 1 isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2
  • 90 CC is a bar graph showing the level of secreted TNF- ⁇ by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 1 isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2
  • 90 DD is a bar graph showing the level of secreted VEGF by T cells activated/expanded with the indicated antibody (isotype control; anti-TCR ⁇ V 6-5 v1 with anti-BCMA antibody; anti-TCR ⁇ V 6-5 v1; anti-TCR ⁇ V 123/4 v1, or SP34-2) and cultured with said antibody for the indicated number of days (1, 2, 3, 4, 5, 6, or 8).
  • FIG. 91 shows a graphical representation of the relation of sequences between different TCRVB clonotype subfamilies.
  • FIG. 92 A is a bar graph showing the percentage of cytokine release from PBMCs activated/expanded for eight days using the indicated antibody (anti-TCR ⁇ V 12-3/4 v1 or SP34-2).
  • FIG. 92 B is a bar graph showing the percentage of cytokine release from PBMCs activated/expanded for eight days using the indicated antibody (anti-TCR ⁇ V 5 or SP34-2).
  • FIG. 92 C is a bar graph showing the percentage of cytokine release from PBMCs activated/expanded for eight days using the indicated antibody (anti-TCR ⁇ V 10 or SP34-2).
  • FIG. 93 A a bar graph showing the level of secreted IFN ⁇ by T cells activated/expanded with the indicated antibody for the indicated number of days (3 or 6).
  • FIG. 93 B a bar graph showing the level of secreted IL-10 by T cells activated/expanded with the indicated antibody for the indicated number of days (3 or 6).
  • FIG. 93 C a bar graph showing the level of secreted IL-17A by T cells activated/expanded with the indicated antibody for the indicated number of days (3 or 6).
  • FIG. 93 D a bar graph showing the level of secreted IL-1 ⁇ by T cells activated/expanded with the indicated antibody for the indicated number of days (3 or 6).
  • FIG. 93 E a bar graph showing the level of secreted IL-1 ⁇ by T cells activated/expanded with the indicated antibody for the indicated number of days (3 or 6).
  • FIG. 93 F a bar graph showing the level of secreted IL-6 by T cells activated/expanded with the indicated antibody for the indicated number of days (3 or 6).
  • FIG. 93 G a bar graph showing the level of secreted TNF ⁇ by T cells activated/expanded with the indicated antibody for the indicated number of days (3 or 6).
  • FIG. 93 H a bar graph showing the level of secreted IL-2 by T cells activated/expanded with the indicated antibody for the indicated number of days (3 or 6).
  • FIG. 94 is a bar graph summarizing data from FACS analysis of PBMCs activated/expanded for 6 days using the indicated anti-TCRV ⁇ antibody.
  • FIG. 95 A a bar graph showing the level of secreted IFN ⁇ by T cells activated/expanded with the indicated antibody for the indicated number of days (1, 3, 5, or 7).
  • FIG. 95 B a bar graph showing the level of secreted IL-10 by T cells activated/expanded with the indicated antibody for the indicated number of days (1, 3, 5, or 7).
  • FIG. 95 C a bar graph showing the level of secreted IL-17A by T cells activated/expanded with the indicated antibody for the indicated number of days (1, 3, 5, or 7).
  • FIG. 95 D a bar graph showing the level of secreted IL-1 ⁇ by T cells activated/expanded with the indicated antibody for the indicated number of days (1, 3, 5, or 7).
  • FIG. 95 E a bar graph showing the level of secreted IL-1 ⁇ by T cells activated/expanded with the indicated antibody for the indicated number of days (1, 3, 5, or 7).
  • FIG. 95 F a bar graph showing the level of secreted IL-6 by T cells activated/expanded with the indicated antibody for the indicated number of days (1, 3, 5, or 7).
  • FIG. 95 G a bar graph showing the level of secreted IL-4 by T cells activated/expanded with the indicated antibody for the indicated number of days (1, 3, 5, or 7).
  • FIG. 95 H a bar graph showing the level of secreted IL-2 by T cells activated/expanded with the indicated antibody for the indicated number of days (1, 3, 5, or 7).
  • FIG. 96 is a bar graph summarizing data from FACS analysis of PBMCs activated/expanded for 7 days using the indicated anti-TCRV ⁇ antibody.
  • FIG. 97 A is a bar graph showing the level of secreted IFN ⁇ by T cells activated/expanded with the indicated antibody for the indicated number of days (3 or 6).
  • FIG. 97 B a bar graph showing the level of secreted IL-10 by T cells activated/expanded with the indicated antibody for the indicated number of days (3 or 6).
  • FIG. 97 C a bar graph showing the level of secreted IL-17A by T cells activated/expanded with the indicated antibody for the indicated number of days (3 or 6).
  • FIG. 97 D a bar graph showing the level of secreted IL-1a by T cells activated/expanded with the indicated antibody for the indicated number of days (3 or 6).
  • FIG. 97 E a bar graph showing the level of secreted IL-10 ⁇ by T cells activated/expanded with the indicated antibody for the indicated number of days (3 or 6).
  • FIG. 97 F a bar graph showing the level of secreted IL-6 by T cells activated/expanded with the indicated antibody for the indicated number of days (3 or 6).
  • FIG. 97 G a bar graph showing the level of secreted IL-4 by T cells activated/expanded with the indicated antibody for the indicated number of days (3 or 6).
  • FIG. 97 H a bar graph showing the level of secreted TNF ⁇ by T cells activated/expanded with the indicated antibody for the indicated number of days (3 or 6).
  • FIG. 97 I a bar graph showing the level of secreted IL-2 by T cells activated/expanded with the indicated antibody for the indicated number of days (3 or 6).
  • FIG. 98 A is a bar graph showing the level of secreted IFN- ⁇ by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 (plate coated), anti-CD3 ⁇ (plate coated), anti-TCR ⁇ V 6-5 v1 (in solution), or anti-CD3 ⁇ (in solution) and cultured with said antibody for the indicated number of days (1, 3, 5, or 7).
  • FIG. 98 A is a bar graph showing the level of secreted IFN- ⁇ by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 (plate coated), anti-CD3 ⁇ (plate coated), anti-TCR ⁇ V 6-5 v1 (in solution), or anti-CD3 ⁇ (in solution) and cultured with said antibody for the indicated number of days (1, 3, 5, or 7).
  • FIG. 98 A is a bar graph showing the level of secreted IFN- ⁇ by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V
  • 98 B is a bar graph showing the level of secreted IFN- ⁇ by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 (plate coated), anti-CD3 ⁇ (plate coated), anti-TCR ⁇ V 6-5 v1 (in solution), or anti-CD3 ⁇ (in solution) and cultured with said antibody for the indicated number of days (1, 3, 5, or 7).
  • FIG. 1 shows the level of secreted IFN- ⁇ by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 (plate coated), anti-CD3 ⁇ (plate coated), anti-TCR ⁇ V 6-5 v1 (in solution), or anti-CD3 ⁇ (in solution) and cultured with said antibody for the indicated number of days (1, 3, 5, or 7).
  • 98 C is a bar graph showing the level of secreted IL-1b by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 (plate coated), anti-CD3 ⁇ (plate coated), anti-TCR ⁇ V 6-5 v1 (in solution), or anti-CD3 ⁇ (in solution) and cultured with said antibody for the indicated number of days (1, 3, 5, or 7).
  • FIG. 1 shows the level of secreted IL-1b by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 (plate coated), anti-CD3 ⁇ (plate coated), anti-TCR ⁇ V 6-5 v1 (in solution), or anti-CD3 ⁇ (in solution) and cultured with said antibody for the indicated number of days (1, 3, 5, or 7).
  • 98 D is a bar graph showing the level of secreted IL-6 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 (plate coated), anti-CD3 ⁇ (plate coated), anti-TCR ⁇ V 6-5 v1 (in solution), or anti-CD3 ⁇ (in solution) and cultured with said antibody for the indicated number of days (1, 3, 5, or 7).
  • FIG. 1 shows the level of secreted IL-6 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 (plate coated), anti-CD3 ⁇ (plate coated), anti-TCR ⁇ V 6-5 v1 (in solution), or anti-CD3 ⁇ (in solution) and cultured with said antibody for the indicated number of days (1, 3, 5, or 7).
  • 98 E is a bar graph showing the level of secreted IL-10 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 (plate coated), anti-CD3 ⁇ (plate coated), anti-TCR ⁇ V 6-5 v1 (in solution), or anti-CD3 ⁇ (in solution) and cultured with said antibody for the indicated number of days (1, 3, 5, or 7).
  • FIG. 1 shows the level of secreted IL-10 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 (plate coated), anti-CD3 ⁇ (plate coated), anti-TCR ⁇ V 6-5 v1 (in solution), or anti-CD3 ⁇ (in solution) and cultured with said antibody for the indicated number of days (1, 3, 5, or 7).
  • 98 F is a bar graph showing the level of secreted IL-15 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 (plate coated), anti-CD3 ⁇ (plate coated), anti-TCR ⁇ V 6-5 v1 (in solution), or anti-CD3 (in solution) and cultured with said antibody for the indicated number of days (1, 3, 5, or 7).
  • FIG. 98 G is a bar graph showing the level of secreted IL-17A by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 (plate coated), anti-CD3 ⁇ (plate coated), anti-TCR ⁇ V 6-5 v1 (in solution), or anti-CD3 ⁇ (in solution) and cultured with said antibody for the indicated number of days (1, 3, 5, or 7).
  • FIG. 98 G is a bar graph showing the level of secreted IL-17A by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 (plate coated), anti-CD3 ⁇ (plate coated), anti-TCR ⁇ V 6-5 v1 (in solution), or anti-CD3 ⁇ (in solution) and cultured with said antibody for the indicated number of days (1, 3, 5, or 7).
  • 98 H is a bar graph showing the level of secreted IL-1a by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 (plate coated), anti-CD3 ⁇ (plate coated), anti-TCR ⁇ V 6-5 v1 (in solution), or anti-CD3 ⁇ (in solution) and cultured with said antibody for the indicated number of days (1, 3, 5, or 7).
  • FIG. 1 shows the level of secreted IL-1a by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 (plate coated), anti-CD3 ⁇ (plate coated), anti-TCR ⁇ V 6-5 v1 (in solution), or anti-CD3 ⁇ (in solution) and cultured with said antibody for the indicated number of days (1, 3, 5, or 7).
  • 98 I is a bar graph showing the level of secreted IL-1b by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 (plate coated), anti-CD3 ⁇ (plate coated), anti-TCR ⁇ V 6-5 v1 (in solution), or anti-CD3 ⁇ (in solution) and cultured with said antibody for the indicated number of days (1, 3, 5, or 7).
  • FIG. 1 shows the level of secreted IL-1b by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 (plate coated), anti-CD3 ⁇ (plate coated), anti-TCR ⁇ V 6-5 v1 (in solution), or anti-CD3 ⁇ (in solution) and cultured with said antibody for the indicated number of days (1, 3, 5, or 7).
  • 98 J is a bar graph showing the level of secreted IL-2 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 (plate coated), anti-CD3 ⁇ (plate coated), anti-TCR ⁇ V 6-5 v1 (in solution), or anti-CD3 ⁇ (in solution) and cultured with said antibody for the indicated number of days (1, 3, 5, or 7).
  • FIG. 1 shows the level of secreted IL-2 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 (plate coated), anti-CD3 ⁇ (plate coated), anti-TCR ⁇ V 6-5 v1 (in solution), or anti-CD3 ⁇ (in solution) and cultured with said antibody for the indicated number of days (1, 3, 5, or 7).
  • 98 K is a bar graph showing the level of secreted IL-4 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 (plate coated), anti-CD3 ⁇ (plate coated), anti-TCR ⁇ V 6-5 v1 (in solution), or anti-CD3 ⁇ (in solution) and cultured with said antibody for the indicated number of days (1, 3, 5, or 7).
  • FIG. 1 shows the level of secreted IL-4 by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 (plate coated), anti-CD3 ⁇ (plate coated), anti-TCR ⁇ V 6-5 v1 (in solution), or anti-CD3 ⁇ (in solution) and cultured with said antibody for the indicated number of days (1, 3, 5, or 7).
  • 98 L is a bar graph showing the level of secreted TNF- ⁇ by T cells activated/expanded with the indicated antibody (anti-TCR ⁇ V 6-5 v1 (plate coated), anti-CD3 ⁇ (plate coated), anti-TCR ⁇ V 6-5 v1 (in solution), or anti-CD3 ⁇ (in solution) and cultured with said antibody for the indicated number of days (1, 3, 5, or 7).
  • FIG. 99 is a FACS plot showing the showing the ability of MH3-2 to bind PBMCs from one of two donors when the PBMCs are either preincubated with TM23 or not (MH3-2 Alone).
  • FIG. 100 is a FACS plot showing the ability of MH3-2 to bind PBMCs from one of two donors when the PBMCs are either preincubated with TM23 or not (MH3-2 Alone).
  • FIG. 101 A is a bar graph showing the polyfunctional strength index (PSI) of PBMC CD4+ T cells, CD4+ T cells expanded with anti-CD3 antibody, (CD3 Expanded T cells), and CD4+ T cells expanded with anti-TCRV ⁇ 6-5 antibody (Drug Expanded T cells).
  • the Effector mediators are Granzyme B, IFN ⁇ , MIP-1a, perforin, TNF ⁇ , and TNF ⁇ .
  • the Stimulatory mediators are IL-5.
  • the Chemoattractive mediators are MIP-1b.
  • 101 B is a bar graph showing the polyfunctional strength index (PSI) of PBMC CD8+ T cells, CD8+ T cells expanded with anti-CD3 antibody, (CD3 Expanded T cells), and CD8+ T cells expanded with anti-TCRV ⁇ 6-5 antibody (Drug Expanded T cells).
  • the Effector mediators are Granzyme B, IFN ⁇ , MIP-1a, perforin, and TNF ⁇ .
  • the Chemoattractive mediators are MIP-1b and RANTES.
  • FIGS. 102 A- 102 C show binding of a CD19 ⁇ TCRv ⁇ bispecific molecule to a TCR molecule.
  • FIG. 102 A is a schematic of the bispecific molecule used in this study.
  • FIG. 102 B is a graph showing the binding of a CD19 ⁇ TCRv ⁇ bispecific molecule to soluble TCR.
  • FIG. 102 C is a graph showing binding of a CD19 ⁇ TCRv ⁇ bispecific molecule to TCR expressed on Jurkat cells.
  • FIGS. 103 A- 103 D show the characterization of a murine CD19 ⁇ TCRv ⁇ 13-2/3 (2 ⁇ 2) bispecific molecule.
  • FIG. 103 A is a schematic of the bispecific molecule used in this study.
  • FIG. 103 B is a graph showing the binding kinetics of murine CD19 ⁇ TCRv ⁇ 13-2/3.
  • FIG. 103 C are dot plots showing the expansion of TCRVB+ T cells following a 6 day incubation with murine CD19 ⁇ TCRv ⁇ 13-2/3.
  • FIG. 103 D is a graph showing the relative count of splenic B cells after a 6 day in vitro incubation with murine CD19 ⁇ TCRv ⁇ 13-2/3 bispecific antibody.
  • FIG. 104 are graphs showing the level of B cells in the blood or spleen of animals treated with 0.1 mg per kg or 1 mg per kg of a murine CD19 ⁇ TCRv ⁇ 13-2/3 bispecific antibody.
  • FIGS. 105 A- 105 B are graphs showing the level of NK cells ( FIG. 105 A ) or T cells ( FIG. 105 B ) in the blood or spleen of animals treated with 0.1 mg per kg or 1 mg per kg of a murine CD19 ⁇ TCRv ⁇ 13-2/3 bispecific antibody.
  • FIGS. 106 A- 106 F show expansion of TCRVB+ T cells and lysis of target cells with a CD19 ⁇ TCRv ⁇ bispecific molecule.
  • FIG. 106 A is a schematic of the bispecific molecule used in this study.
  • FIG. 106 B is a graph showing target cell lysis by pre-expanded TCRVB+ T cells or CD3+ expanded pan T cells.
  • FIG. 106 C shows depletion of purified B cells by purified T cells treated with a CD19 ⁇ TCRv ⁇ bispecific molecule.
  • FIG. 106 D shows depletion of purified B cells by purified T cells treated with a CD19 ⁇ CD3 bispecific molecule.
  • FIG. 106 E shows depletion of B cells in a PBMC preparation treated with a CD19 ⁇ TCRv ⁇ bispecific molecule.
  • FIG. 106 F shows depletion of B cells in a PBMC preparation treated with a CD19 ⁇ CD3 bispecific molecule.
  • FIGS. 107 A- 107 B are graphs showing the expression of various cytokines from PBMCs treated with a CD19 ⁇ CD3 bispecific molecule ( FIG. 107 A ) or a CD19 ⁇ TCRVB 6-5 bispecific molecule ( FIG. 107 B ).
  • FIGS. 108 A- 108 C show a CD19 ⁇ TCR ⁇ 6-5 (2 ⁇ 2) pharmacokinetic (PK) profile and dosing strategy.
  • FIG. 108 A is a schematic of the experimental design.
  • FIG. 108 B is a graph showing the concentration of CD19 ⁇ TCR ⁇ 6-5 at the indicated timepoints after treatment.
  • FIG. 108 C shows the detection reagents used to detect CD19 ⁇ TCR ⁇ 6-5.
  • FIG. 109 depicts Table 9 showing the alignment of TCRBV amino acid sequences (SEQ ID NOs: 3457-3516, respectively, in order of appearance).
  • FIGS. 110 A and 110 B show the alignment of affinity matured humanized Antibody A-H VL and VH sequences.
  • FIG. 110 A shows the alignment of affinity matured humanized Antibody A-H VL sequences (SEQ ID NOS 3377-3389, respectively, in order of appearance), and consensus VL sequence SEQ ID NO: 230, and consensus VL sequence SEQ ID NO: 3289.
  • FIG. 110 B shows the alignment of affinity matured humanized Antibody A-H VH sequences (SEQ ID NOS 3390-3436, respectively, in order of appearance), and consensus VH sequence SEQ ID NO: 231 and consensus VH sequence SEQ ID NO: 3290.
  • cytokine storm known as the cytokine release syndrome (CRS) (Shimabukuro-Vornhagen et al., J Immunother Cancer. 2018 Jun. 15; 6(1):56, herein incorporated by reference in its entirety).
  • CRS cytokine release syndrome
  • This invention features molecules targeting the TCR ⁇ V chain of TCR and methods thereof. Without wishing to be bound by theory, such molecules are capable of binding, activating, and/or expanding only a subset of T cells, avoiding or reducing CRS and/or NT and minimizing potential immunosuppressive effects of anti-CD3 mAbs.
  • TCR is a disulfide-linked membrane-anchored heterodimeric protein normally consisting of the highly variable alpha ( ⁇ ) and beta ( ⁇ ) chains expressed as part of a complex with the invariant CD3 chain molecules.
  • TCR on ⁇ T cells is formed by a heterodimer of one alpha chain and one beta chain.
  • Each alpha or beta chain consists of a constant domain and a highly variable domain classified as the Immunoglobulin superfamily (IgSF) fold.
  • the TCR ⁇ V chains can be further classified into 30 subfamilies (TRBV1-30). Despite their high structural and functional homology, the amino acid sequence homology in the TRBV genes is very low.
  • TCRs formed between alpha and beta chains of highly diverse sequences show a remarkable structural homology ( FIGS. 24 A and 24 B ) and elicit a similar function, e.g., activation of T cells.
  • anti-TCR ⁇ V antibody molecules disclosed herein which despite having low sequence similarity (e.g., low sequence identity among the different antibody molecules that recognize different TCR ⁇ V subfamilies), recognize a structurally conserved, yet sequence-wise variable, region, e.g., domain, on the TCR ⁇ V protein (as denoted by the circled area in FIG. 24 A ) and have a similar function (e.g., activation of T cells and a similar cytokine profile as described herein).
  • sequence similarity e.g., low sequence identity among the different antibody molecules that recognize different TCR ⁇ V subfamilies
  • a structurally conserved, yet sequence-wise variable, region e.g., domain
  • the anti-TCR ⁇ V antibody molecules disclosed herein share a structure-function relationship.
  • the anti-TCR ⁇ V antibody molecules disclosed herein bind to an outward facing epitope of a TCR ⁇ V protein when it is in a complex with a TCRalpha protein, e.g., as denoted by the circled area in FIG. 24 A .
  • the anti-TCR ⁇ V antibody molecules disclosed herein recognize (e.g., bind to), a domain (e.g., an epitope) on the TCR ⁇ V protein that is: (1) structurally conserved among different TCR ⁇ V subfamilies; and (2) has minimal sequence identity among the different TCR ⁇ V subfamilies.
  • TCR ⁇ V proteins from the different TCRBV subfamilies share minimal sequence similarity.
  • FIG. 24 A-B TCR ⁇ V proteins which have minimal sequence similarity, share a similar 3D conformation and structure.
  • the anti-TCR ⁇ V antibody molecules disclosed herein do not recognize, e.g., bind to, an interface of a TCR ⁇ V:TCRalpha complex.
  • the anti-TCR ⁇ V antibody molecules disclosed herein do not recognize, e.g., bind to, a constant region of a TCR ⁇ V protein.
  • the anti-TCR ⁇ V antibody molecules disclosed herein do not recognize, e.g., bind to, one or more (e.g., all) of a complementarity determining region (e.g., CDR1, CDR2 and/or CDR3) of a TCR ⁇ V protein.
  • a complementarity determining region e.g., CDR1, CDR2 and/or CDR3
  • TCR ⁇ V beta subunit of TCR
  • the anti-TCR ⁇ V antibody molecules disclosed herein result in lesser or no production of cytokines associated with CRS, e.g., IL-6, IL-1beta, IL-10 and TNF alpha; and enhanced and/or delayed production of IL-2 and IFNg.
  • the anti-TCR ⁇ V antibodies disclosed herein have a cytokine profile, e.g., as described herein, which differs from a cytokine profile of a T cell engager that binds to a receptor or molecule other than a TCR ⁇ V region (“a non-TCR ⁇ V-binding T cell engager”).
  • the anti-TCR ⁇ V antibodies disclosed herein result in expansion of TCR ⁇ V+ T cells, e.g., a subset of memory effector T cells known as TEMRA.
  • TEMRA cells can promote tumor cell lysis but not CRS.
  • compositions comprising anti-TCR ⁇ V antibody molecules of the present disclosure can be used, e.g., to: (1) activate and redirect T cells to promote tumor cell lysis for cancer immunotherapy; and/or (2) expand TCR ⁇ V+ T cells.
  • compositions comprising anti-TCR ⁇ V antibody molecules as disclosed herein limit the harmful side-effects of CRS and/or NT, e.g., CRS and/or NT associated with anti-CD3e targeting.
  • the anti-TCR ⁇ V antibody molecule does not bind to TCR ⁇ V12, or binds to TCR ⁇ V12 with an affinity and/or binding specificity that is less than (e.g., less than about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or about 2-, 5-, or 10-fold) the affinity and/or binding specificity of the 16G8 murine antibody or a humanized version thereof as described in U.S. Pat. No. 5,861,155.
  • the anti-TCR ⁇ V antibody molecule binds to TCR ⁇ V12 with an affinity and/or binding specificity that is greater than (e.g., greater than about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or about 2-, 5-, or 10-fold) the affinity and/or binding specificity of the 16G8 murine antibody or a humanized version thereof as described in U.S. Pat. No. 5,861,155.
  • the anti-TCR ⁇ V antibody molecule binds to a TCR ⁇ V region other than TCR ⁇ V12 (e.g., TCR ⁇ V region as described herein, e.g., TCR ⁇ V6 subfamily (e.g., TCR ⁇ V6-5*01) with an affinity and/or binding specificity that is greater than (e.g., greater than about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or about 2-, 5-, or 10-fold) the affinity and/or binding specificity of the 16G8 murine antibody or a humanized version thereof as described in U.S. Pat. No. 5,861,155.
  • TCR ⁇ V region as described herein, e.g., TCR ⁇ V6 subfamily (e.g., TCR ⁇ V6-5*01) with an affinity and/or binding specificity that is greater than (e.g., greater than about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or about 2-, 5-, or 10-fold) the affinity and
  • the anti-TCR ⁇ V antibody molecule does not comprise the CDRs of the Antibody B murine antibody.
  • the anti-TCR ⁇ V antibody molecule does not bind to TCR ⁇ V5-5*01 or TCR ⁇ V5-1*01, or binds to TCR ⁇ V5-5*01 or TCR ⁇ V5-1*01 with an affinity and/or binding specificity that is less than (e.g., less than about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or about 2-, 5-, or 10-fold) the affinity and/or binding specificity of the TM23 murine antibody or a humanized version thereof as described in U.S. Pat. No. 5,861,155.
  • the anti-TCR ⁇ V antibody molecule binds to TCR ⁇ V5-5*01 or TCR ⁇ V5-1*01 with an affinity and/or binding specificity that is greater than (e.g., greater than about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or about 2-, 5-, or 10-fold) the affinity and/or binding specificity of the TM23 murine antibody or a humanized version thereof as described in U.S. Pat. No. 5,861,155.
  • the anti-TCR ⁇ V antibody molecule binds to a TCR ⁇ V region other than TCR ⁇ V5-5*01 or TCR ⁇ V5-1*01 (e.g., TCR ⁇ V region as described herein, e.g., TCR ⁇ V6 subfamily (e.g., TCR ⁇ V6-5*01) with an affinity and/or binding specificity that is greater than (e.g., greater than about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or about 2-, 5-, or 10-fold) the affinity and/or binding specificity of the TM23 murine antibody or a humanized version thereof as described in U.S. Pat. No. 5,861,155.
  • the anti-TCR ⁇ V antibody molecule does not comprise the CDRs of the TM23 murine antibody.
  • anti-TCR ⁇ V antibody molecules multispecific or multifunctional molecules (e.g., multispecific or multifunctional antibody molecules) that comprise anti-TCR ⁇ V antibody molecules, nucleic acids encoding the same, methods of producing the aforesaid molecules, pharmaceutical compositions comprising aforesaid molecules, and methods of treating a disease or disorder, e.g., cancer, using the aforesaid molecules.
  • the antibody molecules and pharmaceutical compositions disclosed herein can be used (alone or in combination with other agents or therapeutic modalities) to treat, prevent and/or diagnose disorders and conditions, e.g., cancer, e.g., as described herein.
  • an element means one element or more than one element.
  • acquire or “acquiring” as the terms are used herein, refer to obtaining possession of a physical entity (e.g., a sample, a polypeptide, a nucleic acid, or a sequence), or a value, e.g., a numerical value, by “directly acquiring” or “indirectly acquiring” the physical entity or value.
  • Directly acquiring means performing a process (e.g., performing a synthetic or analytical method) to obtain the physical entity or value.
  • Indirectly acquiring refers to receiving the physical entity or value from another party or source (e.g., a third party laboratory that directly acquired the physical entity or value).
  • Directly acquiring a physical entity includes performing a process that includes a physical change in a physical substance, e.g., a starting material.
  • Directly acquiring a value includes performing a process that includes a physical change in a sample or another substance, e.g., performing an analytical process which includes a physical change in a substance, e.g., a sample.
  • T cell receptor beta variable chain refers to an extracellular region of the T cell receptor beta chain which comprises the antigen recognition domain of the T cell receptor.
  • TCR ⁇ V includes isoforms, mammalian, e.g., human TCR ⁇ V, species homologs of human and analogs comprising at least one common epitope with TCR ⁇ V.
  • Human TCR ⁇ V comprises a gene family comprising subfamilies including, but not limited to: a TCR ⁇ V6 subfamily, a TCR ⁇ V10 subfamily, a TCR ⁇ V12 subfamily, a TCR ⁇ V5 subfamily, a TCR ⁇ V7 subfamily, a TCR ⁇ V11 subfamily, a TCR ⁇ V14 subfamily, a TCR ⁇ V16 subfamily, a TCR ⁇ V18 subfamily, a TCR ⁇ V9 subfamily, a TCR ⁇ V13 subfamily, a TCR ⁇ V4 subfamily, a TCR ⁇ V3 subfamily, a TCR ⁇ V2 subfamily, a TCR ⁇ V15 subfamily, a TCR ⁇ V30 subfamily, a TCR ⁇ V19 subfamily, a TCR ⁇ V27 subfamily, a TCR ⁇ V28 subfamily, a TCR ⁇ V24 subfamily, a TCR ⁇ V20 subfamily, TCR ⁇ V25 subfamily, a TCR ⁇ V29 subfamily, a T
  • the TCR ⁇ V6 subfamily comprises: TCR ⁇ V6-4*01, TCR ⁇ V6-4*02, TCR ⁇ V6-9*01, TCR ⁇ V6-8*01, TCR ⁇ V6-5*01, TCR ⁇ V6-6*02, TCR ⁇ V6-6*01, TCR ⁇ V6-2*01, TCR ⁇ V6-3*01 or TCR ⁇ V6-1*01.
  • TCR ⁇ V comprises TCR ⁇ V6-5*01, or a variant thereof, e.g., a variant having 85%, 90%, 95%, 99% or more identity the naturally-occurring sequence.
  • TCR ⁇ V6-5*01 is also known as TRBV65; TCRBV6S5; TCRBV13S1, or TCR ⁇ V13.1.
  • the amino acid sequence of TCR ⁇ V6-5*01 e.g., human TCR ⁇ V6-5*01, is known in that art, e.g., as provided by IMGT ID L36092.
  • TCR ⁇ V6-5*01 is encoded by the nucleic acid sequence of SEQ ID NO: 43, or a sequence having 85%, 90%, 95%, 99% or more identity thereof.
  • TCR ⁇ V6-5*01 comprises the amino acid sequence of SEQ ID NO: 44, or a sequence having 85%, 90%, 95%, 99% or more identity thereof.
  • human-like antibody molecule refers to a humanized antibody molecule, human antibody molecule or an antibody molecule having at least 95% identity with a non-murine germline framework region, e.g., FR1, FR2, FR3 and/or FR4.
  • the human-like antibody molecule comprises a framework region having at least 95% identity to a human germline framework region, e.g., a FR1, FR2, FR3 and/or FR4 of a human germline framework region.
  • the human-like antibody molecule is a recombinant antibody.
  • the human-like antibody molecule is a humanized antibody molecule.
  • the human-like antibody molecule is human antibody molecule. In some embodiments, the human-like antibody molecule is a phage display or a yeast display antibody molecule. In some embodiments, the human-like antibody molecule is a chimeric antibody molecule. In some embodiments, the human-like antibody molecule is a CDR grafted antibody molecule.
  • cytokine profile refers to the level and/or activity of on one or more cytokines or chemokines, e.g., as described herein.
  • a cytokine profile comprises the level and/or activity of a naturally occurring cytokine, a fragment or a variant thereof.
  • a cytokine profile comprises the level and/or activity of one or more cytokines and/or one or more chemokines (e.g., as described herein).
  • a cytokine profile comprises the level and/or activity of a naturally occurring cytokine, a fragment or a variant thereof.
  • a cytokine profile comprises the level and/or activity of a naturally occurring chemokine, a fragment or a variant thereof.
  • a cytokine profile comprises the level and/or activity of one or more of: IL-2 (e.g., full length, a variant, or a fragment thereof); IL-1beta (e.g., full length, a variant, or a fragment thereof); IL-6 (e.g., full length, a variant, or a fragment thereof); TNF ⁇ (e.g., full length, a variant, or a fragment thereof); IFNg (e.g., full length, a variant, or a fragment thereof) IL-10 (e.g., full length, a variant, or a fragment thereof); IL-4 (e.g., full length, a variant, or a fragment thereof); TNF alpha (e.g., full length, a variant, or a fragment thereof); IL-12p70 (e.g., full length, full length, a
  • a cytokine in a cytokine profile can be modulated, e.g., increased or decreased, by an anti-TCRBV antibody molecule described herein.
  • the cytokine profile includes cytokines associated with a cytokine storm or cytokine release syndrome (CRS), e.g., IL-6, IL-1beta, TNFalpha and IL-10.
  • CRS cytokine storm or cytokine release syndrome
  • variant refers to a polypeptide that has a substantially identical amino acid sequence to the naturally-occurring sequence, or are encoded by a substantially identical nucleotide sequence.
  • the variant is a functional variant.
  • a TCR ⁇ V variant can bind to TCR ⁇ and form a TCR ⁇ : ⁇ complex.
  • the term “functional variant” refers to a polypeptide that has a substantially identical amino acid sequence to the naturally-occurring sequence, or are encoded by a substantially identical nucleotide sequence, and are capable of having one or more activities of the naturally-occurring sequence.
  • a “multifunctional” or a “multispecific” molecule refers to molecule, e.g., a polypeptide, that has two or more functionalities, e.g., two or more binding specificities.
  • the functionalities can include one or more immune cell engagers, one or more tumor binding molecules, one or more cytokine molecules, one or more stromal modifiers, and other moieties described herein.
  • the multispecific molecule is a multispecific antibody molecule, e.g., a bispecific antibody molecule.
  • the multispecific molecule includes an anti-TCRVb antibody molecule as described herein.
  • the multifunctional molecule includes an immune cell engager.
  • An immune cell engager refers to one or more binding specificities that bind and/or activate an immune cell, e.g., a cell involved in an immune response.
  • the immune cell is chosen from a T cell, an NK cell, a B cell, a dendritic cell, and/or the macrophage cell.
  • the immune cell engager can be an antibody molecule, a receptor molecule (e.g., a full length receptor, receptor fragment, or fusion thereof (e.g., a receptor-Fc fusion)), or a ligand molecule (e.g., a full length ligand, ligand fragment, or fusion thereof (e.g., a ligand-Fc fusion)) that binds to the immune cell antigen (e.g., the T cell, the NK cell antigen, the B cell antigen, the dendritic cell antigen, and/or the macrophage cell antigen).
  • the immune cell engager specifically binds to the target immune cell, e.g., binds preferentially to the target immune cell.
  • the immune cell engager when it is an antibody molecule, it binds to an immune cell antigen (e.g., a T cell antigen, an NK cell antigen, a B cell antigen, a dendritic cell antigen, and/or a macrophage cell antigen) with a dissociation constant of less than about 10 nM.
  • an immune cell antigen e.g., a T cell antigen, an NK cell antigen, a B cell antigen, a dendritic cell antigen, and/or a macrophage cell antigen
  • the multifunctional molecule includes a cytokine molecule.
  • a “cytokine molecule” refers to full length, a fragment or a variant of a cytokine; a cytokine further comprising a receptor domain, e.g., a cytokine receptor dimerizing domain; or an agonist of a cytokine receptor, e.g., an antibody molecule (e.g., an agonistic antibody) to a cytokine receptor, that elicits at least one activity of a naturally-occurring cytokine.
  • the cytokine molecule is chosen from interleukin-2 (IL-2), interleukin-7 (IL-7), interleukin-12 (IL-12), interleukin-10 (IL-10), interleukin-15 (IL-15), interleukin-18 (IL-18), interleukin-21 (IL-21), or interferon gamma, or a fragment or variant thereof, or a combination of any of the aforesaid cytokines.
  • the cytokine molecule can be a monomer or a dimer.
  • the cytokine molecule can further include a cytokine receptor dimerizing domain.
  • the cytokine molecule is an agonist of a cytokine receptor, e.g., an antibody molecule (e.g., an agonistic antibody) to a cytokine receptor chosen from an IL-15Ra or IL-21R.
  • a cytokine receptor e.g., an antibody molecule (e.g., an agonistic antibody) to a cytokine receptor chosen from an IL-15Ra or IL-21R.
  • the term “molecule” as used in, e.g., antibody molecule, cytokine molecule, receptor molecule, includes full-length, naturally-occurring molecules, as well as variants, e.g., functional variants (e.g., truncations, fragments, mutated (e.g., substantially similar sequences) or derivatized form thereof), so long as at least one function and/or activity of the unmodified (e.g., naturally-occurring) molecule remains.
  • the multifunctional molecule includes a stromal modifying moiety.
  • a “stromal modifying moiety,” as used herein refers to an agent, e.g., a protein (e.g., an enzyme), that is capable of altering, e.g., degrading a component of, the stroma.
  • the component of the stroma is chosen from, e.g., an ECM component, e.g., a glycosaminoglycan, e.g., hyaluronan (also known as hyaluronic acid or HA), chondroitin sulfate, chondroitin, dermatan sulfate, heparin sulfate, heparin, entactin, tenascin, aggrecan and keratin sulfate; or an extracellular protein, e.g., collagen, laminin, elastin, fibrinogen, fibronectin, and vitronectin.
  • ECM component e.g., a glycosaminoglycan, e.g., hyaluronan (also known as hyaluronic acid or HA), chondroitin sulfate, chondroitin, dermatan sulfate, heparin sulfate,
  • the articles “a” and “an” refer to one or more than one, e.g., to at least one, of the grammatical object of the article.
  • the use of the words “a” or “an” when used in conjunction with the term “comprising” herein may mean “one,” but it is also consistent with the meaning of “one or more,” “at least one,” and “one or more than one.”
  • “about” and “approximately” generally mean an acceptable degree of error for the quantity measured given the nature or precision of the measurements. Exemplary degrees of error are within 20 percent (%), typically, within 10%, and more typically, within 5% of a given range of values.
  • Antibody molecule refers to a protein, e.g., an immunoglobulin chain or fragment thereof, comprising at least one immunoglobulin variable domain structure and/or sequence.
  • An antibody molecule encompasses antibodies (e.g., full-length antibodies) and antibody fragments.
  • an antibody molecule comprises an antigen binding or functional fragment of a full length antibody, or a full length immunoglobulin chain.
  • a full-length antibody is an immunoglobulin (Ig) molecule (e.g., an IgG antibody) that is naturally occurring or formed by normal immunoglobulin gene fragment recombinatorial processes).
  • an antibody molecule refers to an immunologically active, antigen-binding portion of an immunoglobulin molecule, such as an antibody fragment.
  • An antibody fragment e.g., functional fragment, is a portion of an antibody, e.g., Fab, Fab′, F(ab′)2, F(ab) 2 , variable fragment (Fv), domain antibody (dAb), or single chain variable fragment (scFv).
  • a functional antibody fragment binds to the same antigen as that recognized by the intact (e.g., full-length) antibody.
  • antibody fragment or “functional fragment” also include isolated fragments consisting of the variable regions, such as the “Fv” fragments consisting of the variable regions of the heavy and light chains or recombinant single chain polypeptide molecules in which light and heavy variable regions are connected by a peptide linker (“scFv proteins”).
  • an antibody fragment does not include portions of antibodies without antigen binding activity, such as Fc fragments or single amino acid residues.
  • Exemplary antibody molecules include full length antibodies and antibody fragments, e.g., dAb (domain antibody), single chain, Fab, Fab′, and F(ab′)2 fragments, and single chain variable fragments (scFvs).
  • the antibody molecule is an antibody mimetic.
  • the antibody molecule is, or comprises, an antibody-like framework or scaffold, such as, fibronectins, ankyrin repeats (e.g., designed ankyrin repeat proteins (DARPins)), avimers, affibody affinity ligands, anticalins, or affilin molecules.
  • an antibody-like framework or scaffold such as, fibronectins, ankyrin repeats (e.g., designed ankyrin repeat proteins (DARPins)), avimers, affibody affinity ligands, anticalins, or affilin molecules.
  • an “immunoglobulin variable domain sequence” refers to an amino acid sequence which can form the structure of an immunoglobulin variable domain.
  • the sequence may include all or part of the amino acid sequence of a naturally-occurring variable domain.
  • the sequence may or may not include one, two, or more N- or C-terminal amino acids, or may include other alterations that are compatible with formation of the protein structure.
  • an antibody molecule is monospecific, e.g., it comprises binding specificity for a single epitope.
  • an antibody molecule is multispecific, e.g., it comprises a plurality of immunoglobulin variable domain sequences, where a first immunoglobulin variable domain sequence has binding specificity for a first epitope and a second immunoglobulin variable domain sequence has binding specificity for a second epitope.
  • an antibody molecule is a bispecific antibody molecule. “Bispecific antibody molecule” as used herein refers to an antibody molecule that has specificity for more than one (e.g., two, three, four, or more) epitope and/or antigen.
  • Antigen refers to a molecule that can provoke an immune response, e.g., involving activation of certain immune cells and/or antibody generation. Any macromolecule, including almost all proteins or peptides, can be an antigen. Antigens can also be derived from genomic recombinant or DNA. For example, any DNA comprising a nucleotide sequence or a partial nucleotide sequence that encodes a protein capable of eliciting an immune response encodes an “antigen.” In embodiments, an antigen does not need to be encoded solely by a full length nucleotide sequence of a gene, nor does an antigen need to be encoded by a gene at all.
  • an antigen can be synthesized or can be derived from a biological sample, e.g., a tissue sample, a tumor sample, a cell, or a fluid with other biological components.
  • a biological sample e.g., a tissue sample, a tumor sample, a cell, or a fluid with other biological components.
  • a tumor antigen or interchangeably, a “cancer antigen” includes any molecule present on, or associated with, a cancer, e.g., a cancer cell or a tumor microenvironment that can provoke an immune response.
  • an “immune cell antigen” includes any molecule present on, or associated with, an immune cell that can provoke an immune response.
  • the “antigen-binding site,” or “binding portion” of an antibody molecule refers to the part of an antibody molecule, e.g., an immunoglobulin (Ig) molecule, that participates in antigen binding.
  • the antigen binding site is formed by amino acid residues of the variable (V) regions of the heavy (H) and light (L) chains.
  • V variable regions of the heavy and light chains
  • hypervariable regions Three highly divergent stretches within the variable regions of the heavy and light chains, referred to as hypervariable regions, are disposed between more conserved flanking stretches called “framework regions,” (FRs).
  • FRs are amino acid sequences that are naturally found between, and adjacent to, hypervariable regions in immunoglobulins.
  • the three hypervariable regions of a light chain and the three hypervariable regions of a heavy chain are disposed relative to each other in three dimensional space to form an antigen-binding surface, which is complementary to the three-dimensional surface of a bound antigen.
  • the three hypervariable regions of each of the heavy and light chains are referred to as “complementarity-determining regions,” or “CDRs.”
  • the framework region and CDRs have been defined and described, e.g., in Kabat, E. A., et al. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, U.S. Department of Health and Human Services, NIH Publication No. 91-3242, and Chothia, C. et al.
  • variable chain e.g., variable heavy chain and variable light chain
  • cancer as used herein can encompass all types of oncogenic processes and/or cancerous growths.
  • cancer includes primary tumors as well as metastatic tissues or malignantly transformed cells, tissues, or organs.
  • cancer encompasses all histopathologies and stages, e.g., stages of invasiveness/severity, of a cancer.
  • cancer includes relapsed and/or resistant cancer.
  • cancer and tumor can be used interchangeably. For example, both terms encompass solid and liquid tumors.
  • cancer or tumor includes premalignant, as well as malignant cancers and tumors.
  • an “immune cell” refers to any of various cells that function in the immune system, e.g., to protect against agents of infection and foreign matter.
  • this term includes leukocytes, e.g., neutrophils, eosinophils, basophils, lymphocytes, and monocytes.
  • leukocytes include phagocytes (e.g., macrophages, neutrophils, and dendritic cells), mast cells, eosinophils, basophils, and natural killer cells.
  • phagocytes e.g., macrophages, neutrophils, and dendritic cells
  • mast cells e.g., eosinophils, basophils, and natural killer cells.
  • Innate leukocytes identify and eliminate pathogens, either by attacking larger pathogens through contact or by engulfing and then killing microorganisms, and are mediators in the activation of an adaptive immune response.
  • lymphocytes The cells of the adaptive immune system are special types of leukocytes, called lymphocytes.
  • B cells and T cells are important types of lymphocytes and are derived from hematopoietic stem cells in the bone marrow. B cells are involved in the humoral immune response, whereas T cells are involved in cell-mediated immune response.
  • immune cell includes immune effector cells.
  • Immuno effector cell refers to a cell that is involved in an immune response, e.g., in the promotion of an immune effector response.
  • immune effector cells include, but are not limited to, T cells, e.g., alpha/beta T cells and gamma/delta T cells, B cells, natural killer (NK) cells, natural killer T (NK T) cells, and mast cells.
  • effector function refers to a specialized function of a cell. Effector function of a T cell, for example, may be cytolytic activity or helper activity including the secretion of cytokines.
  • compositions and methods of the present invention encompass polypeptides and nucleic acids having the sequences specified, or sequences substantially identical or similar thereto, e.g., sequences at least 80%, 85%, 90%, 95% identical or higher to the sequence specified.
  • substantially identical is used herein to refer to a first amino acid that contains a sufficient or minimum number of amino acid residues that are i) identical to, or ii) conservative substitutions of aligned amino acid residues in a second amino acid sequence such that the first and second amino acid sequences can have a common structural domain and/or common functional activity.
  • amino acid sequences that contain a common structural domain having at least about 80%, 85%, 90%. 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identity to a reference sequence, e.g., a sequence provided herein.
  • nucleotide sequence in the context of nucleotide sequence, the term “substantially identical” is used herein to refer to a first nucleic acid sequence that contains a sufficient or minimum number of nucleotides that are identical to aligned nucleotides in a second nucleic acid sequence such that the first and second nucleotide sequences encode a polypeptide having common functional activity, or encode a common structural polypeptide domain or a common functional polypeptide activity.
  • variant refers to a polypeptide that has a substantially identical amino acid sequence to a reference amino acid sequence, or is encoded by a substantially identical nucleotide sequence. In some embodiments, the variant is a functional variant.
  • the term “functional variant” refers to a polypeptide that has a substantially identical amino acid sequence to a reference amino acid sequence, or is encoded by a substantially identical nucleotide sequence, and is capable of having one or more activities of the reference amino acid sequence.
  • the sequences are aligned for optimal comparison purposes (e.g., gaps can be introduced in one or both of a first and a second amino acid or nucleic acid sequence for optimal alignment and non-homologous sequences can be disregarded for comparison purposes).
  • the length of a reference sequence aligned for comparison purposes is at least 30%, preferably at least 40%, more preferably at least 50%, 60%, and even more preferably at least 70%, 80%, 90%, 100% of the length of the reference sequence.
  • the amino acid residues or nucleotides at corresponding amino acid positions or nucleotide positions are then compared.
  • amino acid or nucleic acid “identity” is equivalent to amino acid or nucleic acid “homology”.
  • the percent identity between the two sequences is a function of the number of identical positions shared by the sequences, taking into account the number of gaps, and the length of each gap, which need to be introduced for optimal alignment of the two sequences.
  • the comparison of sequences and determination of percent identity between two sequences can be accomplished using a mathematical algorithm.
  • the percent identity between two amino acid sequences is determined using the Needleman and Wunsch ((1970) J Mol. Biol. 48:444-453) algorithm which has been incorporated into the GAP program in the GCG software package (available at http://www.gcg.com), using either a Blossum 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5, or 6.
  • the percent identity between two nucleotide sequences is determined using the GAP program in the GCG software package (available at http://www.gcg.com), using a NWSgapdna.CMP matrix and a gap weight of 40, 50, 60, 70, or 80 and a length weight of 1, 2, 3, 4, 5, or 6.
  • a particularly preferred set of parameters are a Blossum 62 scoring matrix with a gap penalty of 12, a gap extend penalty of 4, and a frameshift gap penalty of 5.
  • the percent identity between two amino acid or nucleotide sequences can be determined using the algorithm of E. Meyers and W. Miller ((1989) CABIOS, 4:11-17) which has been incorporated into the ALIGN program (version 2.0), using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4.
  • nucleic acid and protein sequences described herein can be used as a “query sequence” to perform a search against public databases to, for example, identify other family members or related sequences.
  • Such searches can be performed using the NBLAST and)(BLAST programs (version 2.0) of Altschul, et al. (1990) J Mol. Biol. 215:403-10.
  • Gapped BLAST can be utilized as described in Altschul et al., (1997) Nucleic Acids Res. 25:3389-3402.
  • the default parameters of the respective programs e.g., XBLAST and NBLAST
  • molecules of the present invention may have additional conservative or non-essential amino acid substitutions, which do not have a substantial effect on their functions.
  • amino acid is intended to embrace all molecules, whether natural or synthetic, which include both an amino functionality and an acid functionality and capable of being included in a polymer of naturally-occurring amino acids.
  • exemplary amino acids include naturally-occurring amino acids; analogs, derivatives and congeners thereof; amino acid analogs having variant side chains; and all stereoisomers of any of any of the foregoing.
  • amino acid includes both the D- or L-optical isomers and peptidomimetics.
  • a “conservative amino acid substitution” is one in which the amino acid residue is replaced with an amino acid residue having a similar side chain.
  • Families of amino acid residues having similar side chains have been defined in the art. These families include amino acids with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine).
  • polypeptide “peptide” and “protein” (if single chain) are used interchangeably herein to refer to polymers of amino acids of any length.
  • the polymer may be linear or branched, it may comprise modified amino acids, and it may be interrupted by non-amino acids.
  • the terms also encompass an amino acid polymer that has been modified; for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation, such as conjugation with a labeling component.
  • the polypeptide can be isolated from natural sources, can be a produced by recombinant techniques from a eukaryotic or prokaryotic host, or can be a product of synthetic procedures.
  • nucleic acid refers to a polymeric form of nucleotides of any length, either deoxyribonucleotides or ribonucleotides, or analogs thereof.
  • the polynucleotide may be either single-stranded or double-stranded, and if single-stranded may be the coding strand or non-coding (antisense) strand.
  • a polynucleotide may comprise modified nucleotides, such as methylated nucleotides and nucleotide analogs.
  • the sequence of nucleotides may be interrupted by non-nucleotide components.
  • a polynucleotide may be further modified after polymerization, such as by conjugation with a labeling component.
  • the nucleic acid may be a recombinant polynucleotide, or a polynucleotide of genomic, cDNA, semisynthetic, or synthetic origin which either does not occur in nature or is linked to another polynucleotide in a non-natural arrangement.
  • isolated refers to material that is removed from its original or native environment (e.g., the natural environment if it is naturally occurring).
  • a naturally-occurring polynucleotide or polypeptide present in a living animal is not isolated, but the same polynucleotide or polypeptide, separated by human intervention from some or all of the co-existing materials in the natural system, is isolated.
  • Such polynucleotides could be part of a vector and/or such polynucleotides or polypeptides could be part of a composition, and still be isolated in that such vector or composition is not part of the environment in which it is found in nature.
  • TCR Human T Cell Receptor
  • T cell receptors can be found on the surface of T cells.
  • TCRs recognize antigens, e.g., peptides, presented on, e.g., bound to, major histocompatibility complex (MHC) molecules on the surface of cells, e.g., antigen-presenting cells.
  • MHC major histocompatibility complex
  • TCRs are heterodimeric molecules and can comprise an alpha chain, a beta chain, a gamma chain or a delta chain. TCRs comprising an alpha chain and a beta chain are also referred to as TCR ⁇ .
  • the TCR beta chain consists of the following regions (also known as segments): variable (V), diversity (D), joining (J) and constant (C) (see Mayer G. and Nyland J.
  • TCR alpha chain consists of V, J and C regions.
  • the rearrangement of the T-cell receptor (TCR) through somatic recombination of V (variable), D (diversity), J (joining), and C (constant) regions is a defining event in the development and maturation of a T cell. TCR gene rearrangement takes place in the thymus.
  • TCRs can comprise a receptor complex, known as the TCR complex, which comprises a TCR heterodimer comprising of an alpha chain and a beta chain, and dimeric signaling molecules, e.g., CD3 co-receptors, e.g., CD3 ⁇ / ⁇ , and/or CD3 ⁇ / ⁇ .
  • TCR complex which comprises a TCR heterodimer comprising of an alpha chain and a beta chain, and dimeric signaling molecules, e.g., CD3 co-receptors, e.g., CD3 ⁇ / ⁇ , and/or CD3 ⁇ / ⁇ .
  • the TCR V beta repertoire varies between individuals and populations because of, e.g., 7 frequently occurring inactivating polymorphisms in functional gene segments and a large insertion/deletion-related polymorphism encompassing 2 V beta gene segments.
  • TCR beta V human TCR beta V chain
  • TCR ⁇ V human TCR beta V chain
  • a TCR ⁇ V gene family also referred to as a group
  • TCR ⁇ V subfamily also referred to as a subgroup
  • TCR beta V families and subfamilies are known in the art, e.g., as described in Yassai et al., (2009) Immunogenetics 61(7)pp:493-502; Wei S. and Concannon P. (1994) Human Immunology 41(3) pp: 201-206.
  • the antibodies described herein can be recombinant antibodies, e.g., recombinant non-murine antibodies, e.g., recombinant human or humanized antibodies.
  • TCRBV TCRVB, TRBV, TCR ⁇ V, TCRV ⁇ or TRW are used interchangeably herein and refer to a TCR beta V chain, e.g., as described herein.
  • the disclosure provides an anti-TCR ⁇ V antibody molecule that binds to human TCR ⁇ V, e.g., a TCR ⁇ V family, e.g., gene family or a variant thereof.
  • a TCRBV gene family comprises one or more subfamilies, e.g., as described herein, e.g., in FIG. 3 , Table 8A or Table 8B.
  • the TCR ⁇ V gene family comprises: a TCR ⁇ V6 subfamily, a TCR ⁇ V10 subfamily, a TCR ⁇ V12 subfamily, a TCR ⁇ V5 subfamily, a TCR ⁇ V7 subfamily, a TCR ⁇ V11 subfamily, a TCR ⁇ V14 subfamily, a TCR ⁇ V16 subfamily, a TCR ⁇ V18 subfamily, a TCR ⁇ V9 subfamily, a TCR ⁇ V13 subfamily, a TCR ⁇ V4 subfamily, a TCR ⁇ V3 subfamily, a TCR ⁇ V2 subfamily, a TCR ⁇ V15 subfamily, a TCR ⁇ V30 subfamily, a TCR ⁇ V19 subfamily, a TCR ⁇ V27 subfamily, a TCR ⁇ V28 subfamily, a TCR ⁇ V24 subfamily, a TCR ⁇ V20 subfamily, TCR ⁇ V25 subfamily, a TCR ⁇ V29 subfamily, a TCR ⁇ V1 subfamily, a TCR ⁇ V6
  • TCR ⁇ V6 subfamily is also known as TCR ⁇ V13.1.
  • the TCR ⁇ V6 subfamily comprises: TCR ⁇ V6-4*01, TCR ⁇ V6-4*02, TCR ⁇ V6-9*01, TCR ⁇ V6-8*01, TCR ⁇ V6-5*01, TCR ⁇ V6-6*02, TCR ⁇ V6-6*01, TCR ⁇ V6-2*01, TCR ⁇ V6-3*01 or TCR ⁇ V6-1*01, or a variant thereof.
  • TCR ⁇ V6 comprises TCR ⁇ V6-4*01, or a variant thereof.
  • TCR ⁇ V6 comprises TCR ⁇ V6-4*02, or a variant thereof.
  • TCR ⁇ V6 comprises TCR ⁇ V6-9*01, or a variant thereof. In some embodiments, TCR ⁇ V6 comprises TCR ⁇ V6-8*01, or a variant thereof. In some embodiments, TCR ⁇ V6 comprises TCR ⁇ V6-5*01, or a variant thereof. In some embodiments, TCR ⁇ V6 comprises TCR ⁇ V6-6*02, or a variant thereof. In some embodiments, TCR ⁇ V6 comprises TCR ⁇ V6-6*01, or a variant thereof. In some embodiments, TCR ⁇ V6 comprises TCR ⁇ V6-2*01, or a variant thereof. In some embodiments, TCR ⁇ V6 comprises TCR ⁇ V6-3 *01, or a variant thereof. In some embodiments, TCR ⁇ V6 comprises TCR ⁇ V6-1*01, or a variant thereof.
  • TCR ⁇ V6 comprises TCR ⁇ V6-5*01, or a variant thereof.
  • TCR ⁇ V6, e.g., TCR ⁇ V6-5*01 is recognized, e.g., bound, by SEQ ID NO: 1 and/or SEQ ID NO: 2.
  • TCR ⁇ V6, e.g., TCR ⁇ V6-5*01 is recognized, e.g., bound, by SEQ ID NO: 9 and/or SEQ ID NO: 10.
  • TCR ⁇ V6 is recognized, e.g., bound, by SEQ ID NO: 9 and/or SEQ ID NO: 11.
  • TCR ⁇ V10 subfamily is also known as TCR ⁇ V12.
  • the TCR ⁇ V10 subfamily comprises: TCR ⁇ V10-1*01, TCR ⁇ V10-1*02, TCR ⁇ V10-3*01 or TCR ⁇ V10-2*01, or a variant thereof.
  • TCR ⁇ V12 subfamily is also known as TCR ⁇ V8.1.
  • the TCR ⁇ V12 subfamily comprises: TCR ⁇ V12-4*01, TCR ⁇ V12-3*01, or TCR ⁇ V12-5*01, or a variant thereof.
  • TCR ⁇ V12 is recognized, e.g., bound, by SEQ ID NO: 15 and/or SEQ ID NO: 16.
  • TCR ⁇ V12 is recognized, e.g., bound, by any one of SEQ ID NOs 23-25, and/or any one of SEQ ID NO: 26-30:
  • the TCR ⁇ V5 subfamily is chosen from: TCR ⁇ V5-5*01, TCR ⁇ V5-6*01, TCR ⁇ V5-4*01, TCR ⁇ V5-8*01, TCR ⁇ V5-1*01, or a variant thereof.
  • the TCR ⁇ V7 subfamily comprises TCR ⁇ V7-7*01, TCR ⁇ V7-6*01, TCR ⁇ V7-8*02, TCR ⁇ V7-4*01, TCR ⁇ V7-2*02, TCR ⁇ V7-2*03, TCR ⁇ V7-2*01, TCR ⁇ V7-3 *01, TCR ⁇ V7-9*03, or TCR ⁇ V7-9*01, or a variant thereof.
  • the TCR ⁇ V11 subfamily comprises: TCR ⁇ V11-1*01, TCR ⁇ V11-2*01 or TCR ⁇ V11-3*01, or a variant thereof.
  • the TCR ⁇ V14 subfamily comprises TCR ⁇ V14*01, or a variant thereof.
  • the TCR ⁇ V16 subfamily comprises TCR ⁇ V16*01, or a variant thereof.
  • the TCR ⁇ V18 subfamily comprises TCR ⁇ V18*01, or a variant thereof.
  • the TCR ⁇ V9 subfamily comprises TCR ⁇ V9*01 or TCR ⁇ V9*02, or a variant thereof.
  • the TCR ⁇ V13 subfamily comprises TCR ⁇ V13*01, or a variant thereof.
  • the TCR ⁇ V4 subfamily comprises TCR ⁇ V4-2*01, TCR ⁇ V4-3*01, or TCR ⁇ V4-1*01, or a variant thereof.
  • the TCR ⁇ V3 subfamily comprises TCR ⁇ V3-1*01, or a variant thereof.
  • the TCR ⁇ V2 subfamily comprises TCR ⁇ V2*01, or a variant thereof.
  • the TCR ⁇ V15 subfamily comprises TCR ⁇ V15*01, or a variant thereof.
  • the TCR ⁇ V30 subfamily comprises TCR ⁇ V30*01, or TCR ⁇ V30*02, or a variant thereof.
  • the TCR ⁇ V19 subfamily comprises TCR ⁇ V19*01, or TCR ⁇ V19*02, or a variant thereof.
  • the TCR ⁇ V27 subfamily comprises TCR ⁇ V27*01, or a variant thereof.
  • the TCR ⁇ V28 subfamily comprises TCR ⁇ V28*01, or a variant thereof.
  • the TCR ⁇ V24 subfamily comprises TCR ⁇ V24-1*01, or a variant thereof.
  • the TCR ⁇ V20 subfamily comprises TCR ⁇ V20-1*01, or TCR ⁇ V20-1*02, or a variant thereof.
  • the TCR ⁇ V25 subfamily comprises TCR ⁇ V25-1*01, or a variant thereof.
  • the TCR ⁇ V29 subfamily comprises TCR ⁇ V29-1*01, or a variant thereof.
  • TCR ⁇ V6 TCR ⁇ V6-4*01, TCR ⁇ V6-4*02, TCR ⁇ V6-9*01, TCR ⁇ V6-8*01 also referred to as: TCR ⁇ V6-5*01, TCR ⁇ V6-6*02, TCR ⁇ V6-6*01, TCR ⁇ V6-2*01, TCR VB 13.1 TCR ⁇ V6-3*01 or TCR ⁇ V6-1*01.
  • TCR ⁇ V10 TCR ⁇ V10-1*01, TCR ⁇ V10-1*02, TCR ⁇ V10-3*01 or TCR ⁇ V10- also referred to as: 2*01 TCR ⁇ V12 C TCR ⁇ V12 TCR ⁇ V12-4*01, TCR ⁇ V12-3*01, or TCR ⁇ V12-5*01 Also referred to as: TCR ⁇ V8.1 D TCR ⁇ V5 TCR ⁇ V5-5*01, TCR ⁇ V5-6*01, TCR ⁇ V5-4*01, TCR ⁇ V5-8*01, TCR ⁇ V5-1*01
  • TCR ⁇ V subfamilies and/or subfamily members can be expressed at different levels in individuals, e.g., healthy individuals, as disclosed in Kitaura K. et al (2016), BMC Immunology vol 17: 38, the entire contents of which are hereby incorporated by reference.
  • TCR ⁇ V6-5 is represented in approximately 3-6% healthy donors.
  • TCR ⁇ V is present in about 3-6% of tumor infiltrating T cells irrespective of tumor type (see Li B. et al., Nature Genetics, 2016, vol:48(7):725-32 the entire contents of which are hereby incorporated by references). Li et al., also disclose that TCR ⁇ V6-5 is present at a high frequency in tumor cells.
  • Exemplary amino acid sequences for TCR ⁇ V subfamily members can be found on the ImMunoGeneTics Information System website: www.imgt.org, or in a similar resource.
  • TCRBV amino acid sequences in Table 9 underscores the diversity of TCR sequences.
  • TRBV sequences from different subfamilies are considerably different from each other.
  • anti-TCR ⁇ V antibody molecules disclosed herein which despite having low sequence similarity (e.g., low sequence identity among the different antibody molecules that recognize different TCR ⁇ V subfamilies), recognize a structurally conserved region, e.g., domain, on the TCR ⁇ V protein (e.g., as denoted by the circled area in FIG. 24 A ) and have a similar function (e.g., a similar cytokine profile).
  • the anti-TCR ⁇ V antibody molecules disclosed herein share a structure-function relationship.
  • the anti-TCR ⁇ V antibody molecules disclosed herein bind to an outward facing epitope of a TCR ⁇ V protein when it is in a complex with a TCRalpha protein, e.g., as described by the circled area in FIG. 24 A .
  • the anti-TCR ⁇ V antibody molecules disclosed herein recognize (e.g., bind to), a structurally conserved domain on the TCR ⁇ V protein (e.g., as denoted by the circled area in FIG. 24 A ).
  • the anti-TCR ⁇ V antibody molecules disclosed herein do not recognize, e.g., bind to, an interface of a TCR ⁇ V:TCRalpha complex.
  • the anti-TCR ⁇ V antibody molecules disclosed herein do not recognize, e.g., bind to, a constant region of a TCR ⁇ V protein.
  • An exemplary antibody that binds to a constant region of a TCRBV region is JOVI. 1 as described in Viney et al., ( Hybridoma. 1992 December; 11(6):701-13).
  • the anti-TCR ⁇ V antibody molecules disclosed herein do not recognize, e.g., bind to, one or more (e.g., all) of a complementarity determining region (e.g., CDR1, CDR2 and/or CDR3) of a TCR ⁇ V protein.
  • a complementarity determining region e.g., CDR1, CDR2 and/or CDR3
  • the anti-TCR ⁇ V antibody molecules disclosed herein binds (e.g., specifically binds) to a TCR ⁇ V region. In some embodiments, binding of anti-TCR ⁇ V antibody molecules disclosed herein results in a cytokine profile that differs from a cytokine profile of a T cell engager that binds to a receptor or molecule other than a TCR ⁇ V region (“a non-TCR ⁇ V-binding T cell engager”). In some embodiments, the non-TCR ⁇ V-binding T cell engager comprises an antibody that binds to a CD3 molecule (e.g., CD3 epsilon (CD3e) molecule); or a TCR alpha (TCR ⁇ ) molecule. In some embodiments, the non-TCR ⁇ V-binding T cell engager is an OKT3 antibody or an SP34-2 antibody.
  • a CD3 molecule e.g., CD3 epsilon (CD3e) molecule
  • TCR ⁇ TCR
  • the disclosure provides an anti-TCR ⁇ V antibody molecule that binds to human TCR ⁇ V, e.g., a TCR ⁇ V gene family, e.g., one or more of a TCR ⁇ V subfamily, e.g., as described herein, e.g., in FIG. 3 , Table 8A, or Table 8B.
  • a TCR ⁇ V gene family e.g., one or more of a TCR ⁇ V subfamily, e.g., as described herein, e.g., in FIG. 3 , Table 8A, or Table 8B.
  • the anti-TCR ⁇ V antibody molecule binds to one or more TCR ⁇ V subfamilies chosen from: a TCR ⁇ V6 subfamily, a TCR ⁇ V10 subfamily, a TCR ⁇ V12 subfamily, a TCR ⁇ V5 subfamily, a TCR ⁇ V7 subfamily, a TCR ⁇ V11 subfamily, a TCR ⁇ V14 subfamily, a TCR ⁇ V16 subfamily, a TCR ⁇ V18 subfamily, a TCR ⁇ V9 subfamily, a TCR ⁇ V13 subfamily, a TCR ⁇ V4 subfamily, a TCR ⁇ V3 subfamily, a TCR ⁇ V2 subfamily, a TCR ⁇ V15 subfamily, a TCR ⁇ V30 subfamily, a TCR ⁇ V19 subfamily, a TCR ⁇ V27 subfamily, a TCR ⁇ V28 subfamily, a TCR ⁇ V24 subfamily, a TCR ⁇ V20 subfamily, TCR ⁇ V25 subfamily, a TCR
  • the anti-TCR ⁇ V antibody molecule binds to a TCR ⁇ V6 subfamily comprising: TCR ⁇ V6-4*01, TCR ⁇ V6-4*02, TCR ⁇ V6-9*01, TCR ⁇ V6-8*01, TCR ⁇ V6-5*01, TCR ⁇ V6-6*02, TCR ⁇ V6-6*01, TCR ⁇ V6-2*01, TCR ⁇ V6-3*01 or TCR ⁇ V6-1*01, or a variant thereof.
  • the TCR ⁇ V6 subfamily comprises TCR ⁇ V6-5*01, or a variant thereof.
  • TCR ⁇ V6 comprises TCR ⁇ V6-4*01, or a variant thereof.
  • TCR ⁇ V6 comprises TCR ⁇ V6-4*02, or a variant thereof. In some embodiments, TCR ⁇ V6 comprises TCR ⁇ V6-9*01, or a variant thereof. In some embodiments, TCR ⁇ V6 comprises TCR ⁇ V6-8*01, or a variant thereof. In some embodiments, TCR ⁇ V6 comprises TCR ⁇ V6-5*01, or a variant thereof. In some embodiments, TCR ⁇ V6 comprises TCR ⁇ V6-6*02, or a variant thereof. In some embodiments, TCR ⁇ V6 comprises TCR ⁇ V6-6*01, or a variant thereof. In some embodiments, TCR ⁇ V6 comprises TCR ⁇ V6-2*01, or a variant thereof. In some embodiments, TCR ⁇ V6 comprises TCR ⁇ V6-3 *01, or a variant thereof. In some embodiments, TCR ⁇ V6 comprises TCR ⁇ V6-1*01, or a variant thereof.
  • the anti-TCR ⁇ V antibody molecule binds to a TCR ⁇ V10 subfamily comprising: TCR ⁇ V10-1*01, TCR ⁇ V10-1*02, TCR ⁇ V10-3*01 or TCR ⁇ V10-2*01, or a variant thereof.
  • the anti-TCR ⁇ V antibody molecule binds to a TCR ⁇ V12 subfamily comprising: TCR ⁇ V12-4*01, TCR ⁇ V12-3*01 or TCR ⁇ V12-5*01, or a variant thereof.
  • the anti-TCR ⁇ V antibody molecule binds to a TCR ⁇ V5 subfamily comprising: TCR ⁇ V5-5*01, TCR ⁇ V5-6*01, TCR ⁇ V5-4*01, TCR ⁇ V5-8*01, TCR ⁇ V5-1*01, or a variant thereof.
  • Exemplary anti-TCR ⁇ V antibody molecules and the corresponding TCR ⁇ V subfamily recognized by said anti-TCR ⁇ V antibody molecules is disclosed in Table 10A.
  • TRBV TRBV TRBV Reagents monoclonal antibodies gene name allele name Clone name and Specificity Company product Isotype TRBV2 TRBV2*01 IsMMU 546 (TRBV2) Serotec V BETA 22 Mouse TRBV2*02 Coulter Vbeta22 IgG1 TRBV2*03 TRBV3-1 TRBV3-1*01 FIN9 (TRBV3-1) Serotec Vbeta9 Mouse AMKB1-2 (TRBV3-1) Coulter Vbeta9 IgG2a TRBV3-1*02 BD Biosciences Vbeta9 Mouse IgG1 TRBV4-1 TRBV4-1*01 ZOE (TRBV4-1, TRBV4-2, Serotec V BETA 7 Mouse TRBV4-3) Coulter Vbeta7 IgG2a TRBV4-1*02 3G5 (TRBV4-1) Pierce EndogenV beta 7.1 Mouse IgG2b TRBV4-2 TRBV4-2*01 ZOE (TRBV4-1) Pierce EndogenV beta 7.1 Mouse
  • the anti-TCR ⁇ V antibody molecule does not bind to TCR ⁇ V12, or binds to TCR ⁇ V12 with an affinity and/or binding specificity that is less than (e.g., less than about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or about 2-, 5-, or 10-fold) the affinity and/or binding specificity of the 16G8 murine antibody or a humanized version thereof as described in U.S. Pat. No. 5,861,155.
  • the anti-TCR ⁇ V antibody molecule binds to TCR ⁇ V12 with an affinity and/or binding specificity that is greater than (e.g., greater than about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or about 2-, 5-, or 10-fold) the affinity and/or binding specificity of the 16G8 murine antibody or a humanized version thereof as described in U.S. Pat. No. 5,861,155.
  • the anti-TCR ⁇ V antibody molecule binds to a TCR ⁇ V region other than TCR ⁇ V12 (e.g., TCR ⁇ V region as described herein, e.g., TCR ⁇ V6 subfamily (e.g., TCR ⁇ V6-5*01) with an affinity and/or binding specificity that is greater than (e.g., greater than about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or about 2-, 5-, or 10-fold) the affinity and/or binding specificity of the 16G8 murine antibody or a humanized version thereof as described in U.S. Pat. No. 5,861,155.
  • TCR ⁇ V region as described herein, e.g., TCR ⁇ V6 subfamily (e.g., TCR ⁇ V6-5*01) with an affinity and/or binding specificity that is greater than (e.g., greater than about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or about 2-, 5-, or 10-fold) the affinity and
  • the anti-TCR ⁇ V antibody molecule does not bind to TCR ⁇ V5-5*01 or TCR ⁇ V5-1*01, or binds to TCR ⁇ V5-5*01 or TCR ⁇ V5-1*01 with an affinity and/or binding specificity that is less than (e.g., less than about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or about 2-, 5-, or 10-fold) the affinity and/or binding specificity of the TM23 murine antibody or a humanized version thereof as described in U.S. Pat. No. 5,861,155.
  • the anti-TCR ⁇ V antibody molecule binds to TCR ⁇ V5-5*01 or TCR ⁇ V5-1*01 with an affinity and/or binding specificity that is greater than (e.g., greater than about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or about 2-, 5-, or 10-fold) the affinity and/or binding specificity of the TM23 murine antibody or a humanized version thereof as described in U.S. Pat. No. 5,861,155.
  • the anti-TCR ⁇ V antibody molecule binds to a TCR ⁇ V region other than TCR ⁇ V5-5*01 or TCR ⁇ V5-1*01 (e.g., TCR ⁇ V region as described herein, e.g., TCR ⁇ V6 subfamily (e.g., TCR ⁇ V6-5*01) with an affinity and/or binding specificity that is greater than (e.g., greater than about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or about 2-, 5-, or 10-fold) the affinity and/or binding specificity of the TM23 murine antibody or a humanized version thereof as described in U.S. Pat. No. 5,861,155.
  • the disclosure provides an anti-TCR ⁇ V antibody molecule that binds to human TCR ⁇ V6, e.g., a TCR ⁇ V6 subfamily comprising: TCR ⁇ V6-4*01, TCR ⁇ V6-4*02, TCR ⁇ V6-9*01, TCR ⁇ V6-8*01, TCR ⁇ V6-5*01, TCR ⁇ V6-6*02, TCR ⁇ V6-6*01, TCR ⁇ V6-2*01, TCR ⁇ V6-3*01 or TCR ⁇ V6-1*01.
  • the TCR ⁇ V6 subfamily comprises TCR ⁇ V6-5*01 or a variant thereof.
  • TCR ⁇ V6 comprises TCR ⁇ V6-4*01, or a variant thereof.
  • TCR ⁇ V6 comprises TCR ⁇ V6-4*02, or a variant thereof. In some embodiments, TCR ⁇ V6 comprises TCR ⁇ V6-9*01, or a variant thereof. In some embodiments, TCR ⁇ V6 comprises TCR ⁇ V6-8*01, or a variant thereof. In some embodiments, TCR ⁇ V6 comprises TCR ⁇ V6-5*01, or a variant thereof. In some embodiments, TCR ⁇ V6 comprises TCR ⁇ V6-6*02, or a variant thereof. In some embodiments, TCR ⁇ V6 comprises TCR ⁇ V6-6*01, or a variant thereof. In some embodiments, TCR ⁇ V6 comprises TCR ⁇ V6-2*01, or a variant thereof. In some embodiments, TCR ⁇ V6 comprises TCR ⁇ V6-3 *01, or a variant thereof. In some embodiments, TCR ⁇ V6 comprises TCR ⁇ V6-1*01, or a variant thereof.
  • TCR ⁇ V6-5*01 is encoded by the nucleic acid sequence of SEQ ID NO: 43, or a sequence having 85%, 90%, 95%, 99% or more identity thereof.
  • TCR ⁇ V6-5*01 comprises the amino acid sequence of SEQ ID NO: 44, or an amino acid sequence having 85%, 90%, 95%, 99% or more identity thereof.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V6 (e.g., anti-TC ⁇ V6-5*01) antibody molecule
  • is a non-murine antibody molecule e.g., a human or humanized antibody molecule.
  • the anti-TCR ⁇ V antibody molecule, e.g., anti-TC ⁇ V6 (e.g., anti-TC ⁇ V6-5*01) antibody molecule is a human antibody molecule.
  • the anti-TCR ⁇ V antibody molecule, e.g., anti-TC ⁇ V6 (e.g., anti-TC ⁇ V6-5*01) antibody molecule is a humanized antibody molecule.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V6 (e.g., anti-TC ⁇ V6-5*01) antibody molecule, is isolated or recombinant.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V6 (e.g., anti-TC ⁇ V6-5*01) antibody molecule
  • an antibody described herein e.g., an antibody chosen from any one of A-H.1 to A-H.85, e.g., A-H.1, A-H.2 or A-
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V6 (e.g., anti-TC ⁇ V6-5*01) antibody molecule
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V6 (e.g., anti-TC ⁇ V6-5*01) antibody molecule
  • the anti-TCR ⁇ V antibody molecule comprises a heavy chain variable region (VH) having a consensus sequence of SEQ ID NO: 231 or 3290.
  • VH heavy chain variable region
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V6 (e.g., anti-TC ⁇ V6-5*01) antibody molecule
  • the anti-TCR ⁇ V antibody molecule comprises a light chain variable region (VL) having a consensus sequence of SEQ ID NO: 230 or 3289.
  • VL light chain variable region
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V6 (e.g., anti-TC ⁇ V6-5*01) antibody molecule
  • the anti-TCR ⁇ V antibody molecule, e.g., anti-TC ⁇ V6 (e.g., anti-TC ⁇ V6-5*01) antibody molecule includes a heavy chain constant region for an IgG1, e.g., a human IgG1.
  • the heavy chain constant region comprises an amino sequence set forth in Table 3, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) thereto.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V6 (e.g., anti-TC ⁇ V6-5*01) antibody molecule
  • the anti-TCR ⁇ V antibody molecule includes a kappa light chain constant region, e.g., a human kappa light chain constant region.
  • the light chain constant region comprises an amino sequence set forth in Table 3, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) thereto.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V6 (e.g., anti-TC ⁇ V6-5*01) antibody molecule
  • the anti-TCR ⁇ V antibody molecule includes at least one, two, or three complementarity determining regions (CDRs) from a heavy chain variable region (VH) of an antibody described herein, e.g., an antibody chosen from any one of A-H.1 to A-H.85, e.g., A-H.1, A-H.2 or A-H.68, or an antibody described in Table 1, or encoded by a nucleotide sequence in Table 1, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences.
  • VH heavy chain variable region
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule, includes at least one, two, or three CDRs (or collectively all of the CDRs) from a heavy chain variable region comprising an amino acid sequence shown in Table 1, or encoded by a nucleotide sequence shown in Table 1.
  • one or more of the CDRs (or collectively all of the CDRs) have one, two, three, four, five, six or more changes, e.g., amino acid substitutions or deletions, relative to the amino acid sequence shown in Table 1, or encoded by a nucleotide sequence shown in Table 1.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule
  • the anti-TCR ⁇ V antibody molecule includes at least one, two, or three complementarity determining regions (CDRs) from a light chain variable region of an antibody described herein, e.g., an antibody chosen from any one of A-H.1 to A-H.85, e.g., A-H.1, A-H.2 or A-H.68, or an antibody described in Table 1, or encoded by a nucleotide sequence in Table 1, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences.
  • CDRs complementarity determining regions
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule, includes at least one, two, or three CDRs (or collectively all of the CDRs) from a light chain variable region comprising an amino acid sequence shown in Table 1, or encoded by a nucleotide sequence shown in Table 1.
  • one or more of the CDRs (or collectively all of the CDRs) have one, two, three, four, five, six or more changes, e.g., amino acid substitutions or deletions, relative to the amino acid sequence shown in Table 1, or encoded by a nucleotide sequence shown in Table 1.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule, includes at least one, two, three, four, five or six CDRs (or collectively all of the CDRs) from a heavy and light chain variable region comprising an amino acid sequence shown in Table 1, or encoded by a nucleotide sequence shown in Table 1.
  • one or more of the CDRs (or collectively all of the CDRs) have one, two, three, four, five, six or more changes, e.g., amino acid substitutions or deletions, relative to the amino acid sequence shown in Table 1, or encoded by a nucleotide sequence shown in Table 1.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule, molecule includes all six CDRs from an antibody described herein, e.g., an antibody chosen from any one of A-H.1 to A-H.85, e.g., A-H.1, A-H.2 or A-H.68, or an antibody described in Table 1, or encoded by a nucleotide sequence in Table 1, or closely related CDRs, e.g., CDRs which are identical or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions).
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule, may include
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule includes at least one, two, or three CDRs according to Kabat et al.
  • an antibody described herein e.g., an antibody chosen from any one of A-H.1 to A-H.85, e.g., A-H.1, A-H.2 or A-H.68, or an antibody described in Table 1, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences; or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to one, two, or three CDRs according to Kabat et al. shown in Table 1.
  • an antibody chosen from any one of A-H.1 to A-H.85 e.g., A-H.1, A-H.2 or A-H.68, or an antibody described in Table 1
  • a sequence substantially identical e.g., at least 80%,
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule includes at least one, two, or three CDRs according to Kabat et al.
  • an antibody described herein e.g., an antibody chosen from any one of A-H.1 to A-H.85, e.g., A-H.1, A-H.2 or A-H.68, or an antibody described in Table 1, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences; or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to one, two, or three CDRs according to Kabat et al. shown in Table 1.
  • an antibody chosen from any one of A-H.1 to A-H.85 e.g., A-H.1, A-H.2 or A-H.68, or an antibody described in Table 1
  • a sequence substantially identical e.g., at least 80%,
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule, includes at least one, two, three, four, five, or six CDRs according to Kabat et al.
  • an antibody described herein e.g., an antibody chosen from any one of A-H.1 to A-H.85, e.g., A-H.1, A-H.2 or A-H.68, or an antibody described in Table 1, or encoded by a nucleotide sequence in Table 1; or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences; or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to one, two, three, four, five, or six CDRs according to Kabat et al. shown in Table 1.
  • an antibody chosen from any one of A-H.1 to A-H.85 e.g., A-H.1, A-H.2 or A-H.68, or an antibody
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule, includes all six CDRs according to Kabat et al.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-T
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule
  • the anti-TCR ⁇ V antibody molecule includes at least one, two, or three hypervariable loops that have the same canonical structures as the corresponding hypervariable loop of an antibody described herein, e.g., an antibody chosen from chosen from any one of A-H.1 to A-H.85, e.g., A-H.1, A-H.2 or A-H.68, e.g., the same canonical structures as at least loop 1 and/or loop 2 of the heavy and/or light chain variable domains of an antibody described herein.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule includes at least one, two, or three CDRs according to Chothia et al.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule includes at least one, two, or three CDRs according to Chothia et al.
  • an antibody described herein e.g., an antibody chosen from any one of A-H.1 to A-H.85, e.g., A-H.1, A-H.2 or A-H.68, or an antibody described in Table 1, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences; or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to one, two, or three CDRs according to Chothia et al. shown in Table 1.
  • an antibody chosen from any one of A-H.1 to A-H.85 e.g., A-H.1, A-H.2 or A-H.68, or an antibody described in Table 1
  • a sequence substantially identical e.g., at least 80%
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule, includes at least one, two, three, four, five, or six CDRs according to Chothia et al.
  • an antibody described herein e.g., an antibody chosen from any one of A-H.1 to A-H.85, e.g., A-H.1, A-H.2 or A-H.68, or an antibody described in Table 1, or encoded by the nucleotide sequence in Table 1; or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences; or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to one, two, three, four, five, or six CDRs according to Chothia et al. shown in Table 1.
  • an antibody chosen from any one of A-H.1 to A-H.85 e.g., A-H.1, A-H.2 or A-H.68, or an antibody
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule, includes all six CDRs according to Chothia et al.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V antibody molecule, anti-TCR ⁇ V antibody molecule, anti-TCR ⁇ V antibody molecule, anti-TCR ⁇ V antibody molecule, anti-TCR ⁇ V antibody molecule, anti-TCR ⁇ V antibody molecule, anti-TCR ⁇ V antibody molecule, anti-TCR ⁇ V antibody molecule, anti-TCR ⁇ V antibody molecule, anti-TCR ⁇ V antibody molecule, e.g., anti-TCR ⁇ V antibody molecule, e.g., anti-TCR ⁇ V antibody molecule, e.g., anti-TCR ⁇ V antibody molecule, e.g., anti-TCR ⁇ V antibody molecule, anti-TCR ⁇ V antibody molecule, anti-TCR ⁇ V antibody molecule, anti-TCR ⁇ V antibody molecule, anti-TCR ⁇ V antibody molecule, anti-TCR ⁇ V antibody molecule, anti-TCR ⁇ V antibody molecule, anti-TCR ⁇ V antibody molecule, anti-TCR
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule, molecule includes a combination of CDRs or hypervariable loops defined according to Kabat et al., Chothia et al., or as described in Table 1.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule
  • a combined CDR as set out in Table 1 is a CDR that comprises a Kabat CDR and a Chothia CDR.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule, molecule includes a combination of CDRs or hypervariable loops identified as combined CDRs in Table 1.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule, can contain any combination of CDRs or hypervariable loops according the “combined” CDRs are described in Table 1.
  • the antibody molecule is a monospecific antibody molecule, a bispecific antibody molecule, a bivalent antibody molecule, a biparatopic antibody molecule, or an antibody molecule that comprises an antigen binding fragment of an antibody, e.g., a half antibody or antigen binding fragment of a half antibody.
  • the antibody molecule comprises a multispecific molecule, e.g., a bispecific molecule, e.g., as described herein.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule includes:
  • LC CDR1 light chain complementarity determining region 1
  • LC CDR2 light chain complementarity determining region 2
  • LC CDR3 light chain complementarity determining region 3
  • HC CDR1 heavy chain complementarity determining region 1
  • HC CDR2 heavy chain complementarity determining region 2
  • HC CDR3 heavy chain complementarity determining region 3
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule comprises a LC CDR1, LC CDR2, and LC CDR3 of SEQ ID NO: 2, and a HC CDR1, HC CDR2, and HC CDR3 of SEQ ID NO: 1.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule comprises a LC CDR1, LC CDR2, and LC CDR3 of SEQ ID NO: 10, and a HC CDR1, HC CDR2, and HC CDR3 of SEQ ID NO: 9.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule comprises a LC CDR1, LC CDR2, and LC CDR3 of SEQ ID NO: 11, and a HC CDR1, HC CDR2, and HC CDR3 of SEQ ID NO: 9.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule comprises:
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule comprises:
  • VL light chain variable region
  • VH heavy chain variable region
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule comprises:
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule comprises:
  • VL light chain variable region
  • VH heavy chain variable region
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule comprises:
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule comprises:
  • VL light chain variable region
  • VH heavy chain variable region
  • the light or the heavy chain variable framework (e.g., the region encompassing at least FR1, FR2, FR3, and optionally FR4) of the anti-TCR ⁇ V antibody molecule, e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule can be chosen from: (a) a light or heavy chain variable framework including at least 80%, 85%, 87% 90%, 92%, 93%, 95%, 97%, 98%, or 100% of the amino acid residues from a human light or heavy chain variable framework, e.g., a light or heavy chain variable framework residue from a human mature antibody, a human germline sequence, or a human consensus sequence; (b) a light or heavy chain variable framework including from 20% to 80%, 40% to 60%, 60% to 90%, or 70% to 95% of the amino acid residues from a human light or heavy chain variable framework, e.g., a light or heavy chain variable framework residue from a human mature antibody, a
  • the light or heavy chain variable framework region (particularly FR1, FR2 and/or FR3) includes a light or heavy chain variable framework sequence at least 70, 75, 80, 85, 87, 88, 90, 92, 94, 95, 96, 97, 98, 99% identical or identical to the frameworks of a VL or VH segment of a human germline gene.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule, includes one, two, three, or four heavy chain framework regions shown in FIG. 1 A , or a sequence substantially identical thereto.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule, includes one, two, three, or four light chain framework regions shown in FIG. 1 B , or a sequence substantially identical thereto.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule, comprises the light chain framework region 1 of A-H.1 or A-H.2, e.g., as shown in FIG. 1 B .
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule, comprises the light chain framework region 2 of A-H.1 or A-H.2, e.g., as shown in FIG. 1 B .
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule, comprises the light chain framework region 3 of A-H.1 or A-H.2, e.g., as shown in FIG. 1 B .
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule, comprises the light chain framework region 4 of A-H.1 or A-H.2, e.g., as shown in FIG. 1 B .
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule
  • the FR1 comprises a Phenylalanine at position 10, e.g., a Serine to Phenyalanine substitution.
  • the substitution is relative to a human germline light chain framework region sequence.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule
  • FR2 comprises a Histidine at position 36, e.g., a substitution at position 36 according to Kabat numbering, e.g., a Tyrosine to Histidine substitution.
  • FR2 comprises an Alanine at position 46, e.g., a substitution at position 46 according to Kabat numbering, e.g., an Arginine to Alanine substitution.
  • the substitution is relative to a human germline light chain framework region sequence.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule
  • FR3 comprises a Phenyalanine at position 87, e.g., a substitution at position 87 according to Kabat numbering, e.g., a Tyrosine to Phenyalanine substitution.
  • the substitution is relative to a human germline light chain framework region sequence.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule
  • FR1
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule
  • FR2 framework region 2
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule
  • the substitution is relative to a human germline
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule, comprises the heavy chain framework region 1 of A-H.1 or A-H.2, e.g., as shown in FIG. 1 A .
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule, comprises the heavy chain framework region 2 of A-H.1 or A-H.2, e.g., as shown in FIG. 1 A
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule, comprises the heavy chain framework region 3 of A-H.1 or A-H.2, e.g., as shown in FIG. 1 A .
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule, comprises the heavy chain framework region 4 of A-H.1 or A-H.2, e.g., as shown in FIG. 1 A .
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule
  • FR3 comprises a Threonine at position 73, e.g., a substitution at position 73 according to Kabat numbering, e.g., a Glutamic Acid to Threonine substitution.
  • FR3 comprises a Glycine at position 94, e.g., a substitution at position 94 according to Kabat numbering, e.g., an Arginine to Glycine substitution.
  • the substitution is relative to a human germline heavy chain framework region sequence.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule
  • FR3 framework region 3
  • Threonine at position 73 e.g., a substitution at position 73 according to Kabat numbering, e.g., a Glutamic Acid to Threonine substitution
  • a Glycine at position 94 e.g.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule, comprises the heavy chain framework regions 1 ⁇ 4 of A-H.1 or A-H.2, e.g., SEQ ID NO: 9, or as shown in FIGS. 1 A and 1 B .
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule, comprises the light chain framework regions 1 ⁇ 4 of A-H.1, e.g., SEQ ID NO: 10, or as shown in FIGS. 1 A and 1 B .
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule, comprises the light chain framework regions 1 ⁇ 4 of A-H.2, e.g., SEQ ID NO: 11, or as shown in FIGS. 1 A and 1 B .
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule
  • the anti-TCR ⁇ V antibody molecule comprises the heavy chain framework regions 1-4 of A-H.1, e.g., SEQ ID NO: 9; and the light chain framework regions 1 ⁇ 4 of A-H.1, e.g., SEQ ID NO: 10, or as shown in FIGS. 1 A and 1 B .
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V6 (e.g., anti-TC ⁇ V6-5*01) antibody molecule
  • the anti-TCR ⁇ V antibody molecule comprises the heavy chain framework regions 1-4 of A-H.2, e.g., SEQ ID NO: 9; and the light chain framework regions 1 ⁇ 4 of A-H.2, e.g., SEQ ID NO: 11, or as shown in FIGS. 1 A and 1 B .
  • the heavy or light chain variable domain, or both, of the anti-TCR ⁇ V antibody molecule includes an amino acid sequence, which is substantially identical to an amino acid disclosed herein, e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical to a variable region of an antibody described herein, e.g., an antibody chosen from any one of A-H.1 to A-H.85, e.g., A-H.1, A-H.2 or A-H.68, or as described in Table 1, or encoded by the nucleotide sequence in Table 1; or which differs at least 1 or 5 residues, but less than 40, 30, 20, or 10 residues, from a variable region of an antibody described herein.
  • an antibody chosen from any one of A-H.1 to A-H.85 e.g., A-H.1, A-H.2 or A-H.68, or as described in Table 1, or encoded by the nucleotide sequence in Table 1;
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V6 (e.g., anti-TC ⁇ V6-5*01) antibody molecule
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TC ⁇ V6-5*01) antibody molecule includes a VH and/or VL domain encoded by a nucleic acid having a nucleotide sequence as set forth in Table 1, or a sequence substantially identical thereto (e.g., a sequence at least about 85%, 90%, 95%, 99% or more identical thereto, or which differs by no more than 3, 6, 15, 30, or 45 nucleotides from the sequences shown in Table 1.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V6 (e.g., anti-TC ⁇ V6-5*01) antibody molecule, comprises:
  • VH domain comprising the amino acid sequence of SEQ ID NO: 9, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence of SEQ ID NO: 9, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 9; and/or
  • VL domain comprising the amino acid sequence of SEQ ID NO: 10, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence of SEQ ID NO: 10, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 10.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V6 (e.g., anti-TC ⁇ V6-5*01) antibody molecule, comprises:
  • VH domain comprising the amino acid sequence of SEQ ID NO: 9, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence of SEQ ID NO: 9, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 9; and/or
  • VL domain comprising the amino acid sequence of SEQ ID NO: 11, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence of SEQ ID NO: 11, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 11.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V6 (e.g., anti-TC ⁇ V6-5*01) antibody molecule is a full antibody or fragment thereof (e.g., a Fab, F(ab′)2, Fv, or a single chain Fv fragment (scFv)).
  • the anti-TCR ⁇ V antibody molecule, e.g., anti-TC ⁇ V6 (e.g., anti-TC ⁇ V6-5*01) antibody molecule is a monoclonal antibody or an antibody with single specificity.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V6 (e.g., anti-TC ⁇ V6-5*01) antibody molecule
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V6 (e.g., anti-TC ⁇ V6-5*01) antibody molecule, is a humanized antibody molecule.
  • the heavy and light chains of the anti-TCR ⁇ V antibody molecule can be full-length (e.g., an antibody can include at least one, and preferably two, complete heavy chains, and at least one, and preferably two, complete light chains) or can include an antigen-binding fragment (e.g., a Fab, F(ab′)2, Fv, a single chain Fv fragment, a single domain antibody, a diabody (dAb), a bivalent antibody, or bispecific antibody or fragment thereof, a single domain variant thereof, or a camelid antibody).
  • an antibody can include at least one, and preferably two, complete heavy chains, and at least one, and preferably two, complete light chains
  • an antigen-binding fragment e.g., a Fab, F(ab′)2, Fv, a single chain Fv fragment, a single domain antibody, a diabody (dAb), a bivalent antibody, or bispecific antibody or fragment thereof, a single domain variant thereof, or a camelid antibody.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V6 (e.g., anti-TC ⁇ V6-5*01) antibody molecule
  • the anti-TCR ⁇ V antibody molecule is in the form of a multispecific molecule, e.g., a bispecific molecule, e.g., as described herein.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule
  • the Fc region is chosen from the heavy chain constant regions of IgG1, IgG2, IgG3, and IgG4.
  • the Fc region is chosen from the heavy chain constant region of IgG1 or IgG2 (e.g., human IgG1, or IgG2).
  • the heavy chain constant region is human IgG1.
  • the Fc region comprises a Fc region variant, e.g., as described herein.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule
  • the constant region is altered, e.g., mutated, to modify the properties of the anti-TCR ⁇ V antibody molecule, e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule (e.g., to increase or decrease one or more of: Fc receptor binding, antibody glycosylation, the number of cysteine residues, effector cell function, or complement function).
  • anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule
  • Fc receptor binding e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule
  • the constant region is mutated at positions 296 (M to Y), 298 (S to T), 300 (T to E), 477 (H to K) and 478 (N to F) to alter Fc receptor binding (e.g., the mutated positions correspond to positions 132 (M to Y), 134 (S to T), 136 (T to E), 313 (H to K) and 314 (N to F) of SEQ ID NOs: 212 or 214; or positions 135 (M to Y), 137 (S to T), 139 (T to E), 316 (H to K) and 317 (N to F) of SEQ ID NOs: 215, 216, 217 or 218), e.g., relative to human IgG1.
  • the mutated positions correspond to positions 132 (M to Y), 134 (S to T), 136 (T to E), 313 (H to K) and 314 (N to F) of SEQ ID NOs: 212 or 214; or positions 135 (M to Y
  • Antibody A-H.1 comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 3278 and a light chain comprising the amino acid sequence of SEQ ID NO: 72.
  • Antibody A-H.2 comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 3278 and a light chain comprising the amino acid sequence of SEQ ID NO: 3279.
  • Antibody A-H.68 comprises the amino acid sequence of SEQ ID NO: 1337, or a sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereto.
  • Antibody A-H.69 comprises the amino acid sequence of SEQ ID NO: 1500, or a sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereto.
  • the anti-TCR ⁇ V6 is antibody A, e.g., humanized antibody A (antibody A-H), as provided in Table 1.
  • the anti-TCR ⁇ V antibody comprises one or more (e.g., all three) of a LC CDR1, LC CDR2, and LC CDR3 provided in Table 1; and/or one or more (e.g., all three) of a HC CDR1, HC CDR2, and HC CDR3 provided in Table 1, or a sequence with at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereto.
  • antibody A comprises a variable heavy chain (VH) and/or a variable light chain (VL) provided in Table 1, or a sequence with at least 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereto.
  • VH variable heavy chain
  • VL variable light chain
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V6 (e.g., anti-TC ⁇ V6-5*01) antibody molecule comprises a VH of A-H.1, A-H.2, A-H.3, A-H.4, A-H.5, A-H.6, A-H.7, A-H.8, A-H.9, A-H.10, A-H.11, A-H.12, A-H.13, A-H.14, A-H.15, A-H.16, A-H.17, A-H.18, A-H.19, A-H.20, A-H.21, A-H.22, A-H.23, A-H.24, A-H.25, A-H.26, A-H.27, A-H.28, A-H.29, A-H.30, A-H.31, A-H.32, A-H.33, A-H.34, A-H.35
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V6 (e.g., anti-TC ⁇ V6-5*01) antibody molecule comprises a VL of A-H.1, A-H.2, A-H.3, A-H.4, A-H.5, A-H.6, A-H.7, A-H.8, A-H.9, A-H.10, A-H.11, A-H.12, A-H.13, A-H.14, A-H.15, A-H.16, A-H.17, A-H.18, A-H.19, A-H.20, A-H.21, A-H.22, A-H.23, A-H.24, A-H.25, A-H.26, A-H.27, A-H.28, A-H.29, A-H.30, A-H.31, A-H.32, A-H.33, A-H.34, A-H.35
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V6 (e.g., anti-TC ⁇ V6-5*01) antibody molecule comprises a VH of A-H.1, A-H.2, A-H.3, A-H.4, A-H.5, A-H.6, A-H.7, A-H.8, A-H.9, A-H.10, A-H.11, A-H.12, A-H.13, A-H.14, A-H.15, A-H.16, A-H.17, A-H.18, A-H.19, A-H.20, A-H.21, A-H.22, A-H.23, A-H.24, A-H.25, A-H.26, A-H.27, A-H.28, A-H.29, A-H.30, A-H.31, A-H.32, A-H.33, A-H.34, A-H.35
  • the antibody molecules include murine mAb Antibody A, and humanized mAb Antibody A-H Clones A-H.1 to A-H.85.
  • the amino acid the heavy and light chain CDRs, and the amino acid and nucleotide sequences of the heavy and light chain variable regions, and the heavy and light chains are shown.
  • Antibody A (murine), also referred to as H131, TCRVB 6-5 binder SEQ ID NO: 3 HC CDR1 (Combined) GYSFTTYYIH SEQ ID NO: 4 HC CDR2 (Combined) WFFPGSGNIKYNEKFKG SEQ ID NO: 5 HC CDR3 (Combined) SYYSYDVLDY SEQ ID NO: 45 HC CDR1 (Kabat) TYYIH SEQ ID NO: 46 HC CDR2 (Kabat) WFFPGSGNIKYNEKFKG SEQ ID NO: 47 HC CDR3 (Kabat) SYYSYDVLDY SEQ ID NO: 48 HC CDR1 (Chothia) GYSFTTY SEQ ID NO: 49 HC CDR2 (Chothia) FPGSGN SEQ ID NO: 50 HC CDR3 (Chothia) SYYSYDVLDY SEQ ID NO: 1 VH QVQLQQSGPELVKPGTSVKISC
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule comprises a VH and/or a VL of an antibody described in Table 1, or a sequence with at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more identity thereto.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule comprises a VH and a VL of an antibody described in Table 1, or a sequence with at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more identity thereto.
  • an anti-TCRVb antibody disclosed herein has an antigen binding domain having a VL having a consensus sequence of SEQ ID NO: 230, wherein position 30 is G, E, A or D; position 31 is N or D; position 32 is R or K; position 36 is Y or H; and/or position 56 is K or S.
  • an anti-TCRVb antibody disclosed herein has an antigen binding domain having a VH having a consensus sequence of SEQ ID NO: 231, wherein: position 27 is H or T or G or Y; position 28 is D or T or S; position 30 is H or R or D or K or T; position 31 is L or D or K or T or N; position 32 is W or F or T or I or Y or G; position 49 is R or W; position 50 is V or I or F; position 51 is F or S or Y; position 52 is A or P; position 56 is N or S; position 57 is T or V or Y or I; position 58 is K or R; position 97 is G or V; position 99 is Y or I; position 102 is Y or A; and/or position 103 is D or G.
  • the disclosure provides an anti-TCR ⁇ V antibody molecule that binds to human TCR ⁇ V12, e.g., a TCR ⁇ V12 subfamily comprising: TCR ⁇ V12-4*01, TCR ⁇ V12-3*01 or TCR ⁇ V12-5*01.
  • a TCR ⁇ V12 subfamily comprises TCR ⁇ V12-4*01.
  • the TCR ⁇ V12 subfamily comprises TCR ⁇ V12-3*01.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule
  • is a non-murine antibody molecule e.g., a human or humanized antibody molecule.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule is a human antibody molecule.
  • the anti-TCR ⁇ V antibody molecule, e.g., anti-TCR ⁇ V12 antibody molecule is a humanized antibody molecule.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule, is isolated or recombinant.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule, comprises at least one or two heavy chain variable regions from an antibody described herein, e.g., an antibody as described in Table 2, or encoded by a nucleotide sequence in Table 2, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule, comprises at least one or two light chain variable regions from an antibody described herein, e.g., an antibody as described in Table 2, or encoded by a nucleotide sequence in Table 2, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences.
  • the anti-TCR ⁇ V antibody molecule comprises a heavy chain constant region for an IgG4, e.g., a human IgG4.
  • the anti-TCR ⁇ V antibody molecule includes a heavy chain constant region for an IgG1, e.g., a human IgG1.
  • the heavy chain constant region comprises an amino sequence set forth in Table 3, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) thereto.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule
  • the anti-TCR ⁇ V antibody molecule includes a kappa light chain constant region, e.g., a human kappa light chain constant region.
  • the light chain constant region comprises an amino sequence set forth in Table 3, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) thereto.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule
  • the anti-TCR ⁇ V antibody molecule includes at least one, two, or three complementarity determining regions (CDRs) from a heavy chain variable region of an antibody described herein, e.g., an antibody as described in Table 2, or encoded by the nucleotide sequence in Table 2, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences.
  • CDRs complementarity determining regions
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule, includes at least one, two, or three CDRs (or collectively all of the CDRs) from a heavy chain variable region comprising an amino acid sequence shown in Table 2, or encoded by a nucleotide sequence shown in Table 2.
  • one or more of the CDRs (or collectively all of the CDRs) have one, two, three, four, five, six or more changes, e.g., amino acid substitutions or deletions, relative to the amino acid sequence shown in Table 2, or encoded by a nucleotide sequence shown in Table 2.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule
  • the anti-TCR ⁇ V antibody molecule includes at least one, two, or three complementarity determining regions (CDRs) from a light chain variable region of an antibody described herein, e.g., an antibody as described in Table 2, or encoded by the nucleotide sequence in Table 2, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences.
  • CDRs complementarity determining regions
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule, includes at least one, two, or three CDRs (or collectively all of the CDRs) from a light chain variable region comprising an amino acid sequence shown in Table 2, or encoded by a nucleotide sequence shown in Table 2.
  • one or more of the CDRs (or collectively all of the CDRs) have one, two, three, four, five, six or more changes, e.g., amino acid substitutions or deletions, relative to the amino acid sequence shown in Table 2, or encoded by a nucleotide sequence shown in Table 2.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule, includes at least one, two, three, four, five or six CDRs (or collectively all of the CDRs) from a heavy and light chain variable region comprising an amino acid sequence shown in Table 2, or encoded by a nucleotide sequence shown in Table 2.
  • one or more of the CDRs (or collectively all of the CDRs) have one, two, three, four, five, six or more changes, e.g., amino acid substitutions or deletions, relative to the amino acid sequence shown in Table 2, or encoded by a nucleotide sequence shown in Table 2.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule, molecule includes all six CDRs from an antibody described herein, e.g., an antibody as described in Table 2, or encoded by the nucleotide sequence in Table 2, or closely related CDRs, e.g., CDRs which are identical or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions).
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule, may include any CDR described herein.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule includes at least one, two, or three CDRs according to Kabat et al. (e.g., at least one, two, or three CDRs according to the Kabat definition as set out in Table 2) from a heavy chain variable region of an antibody described herein, e.g., an antibody chosen as described in Table 2, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences; or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to one, two, or three CDRs according to Kabat et al. shown in Table 2.
  • a sequence substantially identical e.g., at least 80%, 85%, 90%, 9
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule includes at least one, two, or three CDRs according to Kabat et al. (e.g., at least one, two, or three CDRs according to the Kabat definition as set out in Table 2) from a light chain variable region of an antibody described herein, e.g., an antibody as described in Table 2, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences; or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to one, two, or three CDRs according to Kabat et al. shown in Table 2.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule includes at least one, two, three, four, five, or six CDRs according to Kabat et al. (e.g., at least one, two, three, four, five, or six CDRs according to the Kabat definition as set out in Table 2) from the heavy and light chain variable regions of an antibody described herein, e.g., an antibody as described in Table 2, or encoded by the nucleotide sequence in Table 2; or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences; or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to one, two, three, four, five, or six CDRs according to Kabat
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule includes all six CDRs according to Kabat et al. (e.g., all six CDRs according to the Kabat definition as set out in Table 2) from the heavy and light chain variable regions of an antibody described herein, e.g., an antibody as described in Table 2, or encoded by the nucleotide sequence in Table 2; or encoded by the nucleotide sequence in Table 2; or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences; or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to all six CDRs according to Kabat et al. shown in Table 2.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule includes at least one, two, or three hypervariable loops that have the same canonical structures as the corresponding hypervariable loop of an antibody described herein, e.g., an antibody described in Table 2, e.g., the same canonical structures as at least loop 1 and/or loop 2 of the heavy and/or light chain variable domains of an antibody described herein. See, e.g., Chothia et al., (1992) J. Mol. Biol. 227:799-817; Tomlinson et al., (1992) J. Mol. Biol. 227:776-798 for descriptions of hypervariable loop canonical structures. These structures can be determined by inspection of the tables described in these references.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule includes at least one, two, or three CDRs according to Chothia et al. (e.g., at least one, two, or three CDRs according to the Chothia definition as set out in Table 2) from a heavy chain variable region of an antibody described herein, e.g., an antibody chosen as described in Table 2, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences; or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to one, two, or three CDRs according to Chothia et al. shown in Table 2.
  • Chothia et al. e.g., at least one, two
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule includes at least one, two, or three CDRs according to Chothia et al. (e.g., at least one, two, or three CDRs according to the Chothia definition as set out in Table 2) from a light chain variable region of an antibody described herein, e.g., an antibody as described in Table 2, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences; or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to one, two, or three CDRs according to Chothia et al. shown in Table 2.
  • Chothia et al. e.g., at least one, two,
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule includes at least one, two, three, four, five, or six CDRs according to Chothia et al. (e.g., at least one, two, three, four, five, or six CDRs according to the Chothia definition as set out in Table 2) from the heavy and light chain variable regions of an antibody described herein, e.g., an antibody as described in Table 2, or encoded by the nucleotide sequence in Table 2; or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences; or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to one, two, three, four, five, or six
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule includes all six CDRs according to Chothia et al. (e.g., all six CDRs according to the Chothia definition as set out in Table 2) from the heavy and light chain variable regions of an antibody described herein, e.g., an antibody as described in Table 2, or encoded by the nucleotide sequence in Table 2; or encoded by the nucleotide sequence in Table 2; or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences; or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to all six CDRs according to Chothia et al. shown in Table 2.
  • alterations e.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule includes at least one, two, or three CDRs according to a combined CDR (e.g., at least one, two, or three CDRs according to the combined CDR definition as set out in Table 2) from a heavy chain variable region of an antibody described herein, e.g., an antibody chosen as described in Table 2, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences; or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to one, two, or three CDRs according to combined CDR shown in Table 2.
  • a combined CDR e.g., at least one, two, or three CDRs according to the combined C
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule includes at least one, two, or three CDRs according to a combined CDR (e.g., at least one, two, or three CDRs according to the combined CDR definition as set out in Table 2) from a light chain variable region of an antibody described herein, e.g., an antibody as described in Table 2, or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences; or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to one, two, or three CDRs according to a combined CDR shown in Table 2.
  • a combined CDR e.g., at least one, two, or three CDRs according to the combined
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule includes at least one, two, three, four, five, or six CDRs according to a combined CDR. (e.g., at least one, two, three, four, five, or six CDRs according to the combined CDR definition as set out in Table 2) from the heavy and light chain variable regions of an antibody described herein, e.g., an antibody as described in Table 2, or encoded by the nucleotide sequence in Table 2; or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences; or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to one, two, three, four, five, or six CDR
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule includes all six CDRs according to a combined CDR (e.g., all six CDRs according to the combined CDR definition as set out in Table 2) from the heavy and light chain variable regions of an antibody described herein, e.g., an antibody as described in Table 2, or encoded by the nucleotide sequence in Table 2; or encoded by the nucleotide sequence in Table 2; or a sequence substantially identical (e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical) to any of the aforesaid sequences; or which have at least one amino acid alteration, but not more than two, three or four alterations (e.g., substitutions, deletions, or insertions, e.g., conservative substitutions) relative to all six CDRs according to a combined CDR shown in Table 2.
  • the anti-CDR e.g.,
  • a combined CDR as set out in Table 1 is a CDR that comprises a Kabat CDR and a Chothia CDR.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule, molecule includes a combination of CDRs or hypervariable loops identified as combined CDRs in Table 1.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule, can contain any combination of CDRs or hypervariable loops according the “combined” CDRs are described in Table 1.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule includes a combination of CDRs or hypervariable loops defined according to the Kabat et al. and Chothia et al., or as described in Table 1
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule can contain any combination of CDRs or hypervariable loops according to the Kabat and Chothia definitions.
  • the antibody molecule is a monospecific antibody molecule, a bispecific antibody molecule, a bivalent antibody molecule, a biparatopic antibody molecule, or an antibody molecule that comprises an antigen binding fragment of an antibody, e.g., a half antibody or antigen binding fragment of a half antibody.
  • the antibody molecule comprises a multispecific molecule, e.g., a bispecific molecule, e.g., as described herein.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule includes:
  • LC CDR1 light chain complementarity determining region 1
  • LC CDR2 light chain complementarity determining region 2
  • LC CDR3 light chain complementarity determining region 3
  • HC CDR1 heavy chain complementarity determining region 1
  • HC CDR2 heavy chain complementarity determining region 2
  • HC CDR3 heavy chain complementarity determining region 3
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises:
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises:
  • VL light chain variable region
  • VH heavy chain variable region
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises:
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises:
  • VL light chain variable region
  • VH heavy chain variable region
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises:
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises:
  • VL light chain variable region
  • VH heavy chain variable region
  • the light or the heavy chain variable framework (e.g., the region encompassing at least FR1, FR2, FR3, and optionally FR4) of the anti-TCR ⁇ V antibody molecule, e.g., anti-TCR ⁇ V12 antibody molecule can be chosen from: (a) a light or heavy chain variable framework including at least 80%, 85%, 87% 90%, 92%, 93%, 95%, 97%, 98%, or 100% of the amino acid residues from a human light or heavy chain variable framework, e.g., a light or heavy chain variable framework residue from a human mature antibody, a human germline sequence, or a human consensus sequence; (b) a light or heavy chain variable framework including from 20% to 80%, 40% to 60%, 60% to 90%, or 70% to 95% of the amino acid residues from a human light or heavy chain variable framework, e.g., a light or heavy chain variable framework residue from a human mature antibody, a human germline sequence, or a human consensus sequence; (c) a light or heavy
  • the light or heavy chain variable framework region (particularly FR1, FR2 and/or FR3) includes a light or heavy chain variable framework sequence at least 70, 75, 80, 85, 87, 88, 90, 92, 94, 95, 96, 97, 98, 99% identical or identical to the frameworks of a VL or VH segment of a human germline gene.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule
  • the amino acid sequence of the FR region in the entire variable region e.g., shown in FIGS. 2 A and 2 B , or in SEQ ID NOs: 23-25.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises a light chain variable domain having at least one, two, three, four, five, six, seven, ten, fifteen, twenty or more amino acid changes, e.g., amino acid substitutions or deletions, from an amino acid sequence of an antibody described herein. e.g., the amino acid sequence of the FR region in the entire variable region, e.g., shown in FIGS. 2 A and 2 B , or in SEQ ID NOs: 26-30.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule includes one, two, three, or four heavy chain framework regions shown in FIG. 2 A , or a sequence substantially identical thereto.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule includes one, two, three, or four light chain framework regions shown in FIG. 2 B , or a sequence substantially identical thereto.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises the light chain framework region 1 e.g., as shown in FIG. 2 B .
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises the light chain framework region 2 e.g., as shown in FIG. 2 B .
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises the light chain framework region 3, e.g., as shown in FIG. 2 B .
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises the light chain framework region 4, e.g., as shown in FIG. 2 B .
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises a light chain comprising a framework region, e.g., framework region 1 (FR1), comprising a change, e.g., a substitution (e.g., a conservative substitution) at one or more, e.g., all, position disclosed herein according to Kabat numbering.
  • FR1 comprises an Aspartic Acid at position 1, e.g., a substitution at position 1 according to Kabat numbering, e.g., an Alanine to Aspartic Acid substitution.
  • FR1 comprises an Asparagine at position 2, e.g., a substitution at position 2 according to Kabat numbering, e.g., an Isoleucine to Asparagine substitution, Serine to Asparagine substitution or Tyrosine to Asparagine substitution.
  • FR1 comprises a Leucine at position 4, e.g., a substitution at position 4 according to Kabat numbering, e.g., a Methionine to Leucine substitution.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises a light chain comprising a framework region, e.g., framework region 1 (FR1), comprising a substitution at position 1 according to Kabat numbering, e.g., an Alanine to Aspartic Acid substitution, a substitution at position 2 according to Kabat numbering, e.g., an Isoleucine to Asparagine substitution, Serine to Asparagine substitution or Tyrosine to Asparagine substitution, and a substitution at position 4 according to Kabat numbering, e.g., a Methionine to Leucine substitution.
  • FR1 framework region 1
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises a light chain comprising a framework region, e.g., framework region 1 (FR1), comprising a substitution at position 1 according to Kabat numbering, e.g., an Alanine to Aspartic Acid substitution, and a substitution at position 2 according to Kabat numbering, e.g., an Isoleucine to Asparagine substitution, Serine to Asparagine substitution or Tyrosine to Asparagine substitution.
  • FR1 framework region 1
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises a light chain comprising a framework region, e.g., framework region 1 (FR1), comprising a substitution at position 1 according to Kabat numbering, e.g., an Alanine to Aspartic Acid substitution, and a substitution at position 4 according to Kabat numbering, e.g., a Methionine to Leucine substitution.
  • FR1 framework region 1
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises a light chain comprising a framework region, e.g., framework region 1 (FR1), comprising a substitution at position 2 according to Kabat numbering, e.g., an Isoleucine to Asparagine substitution, Serine to Asparagine substitution or Tyrosine to Asparagine substitution, and a substitution at position 4 according to Kabat numbering, e.g., a Methionine to Leucine substitution.
  • the substitution is relative to a human germline light chain framework region sequence.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises a light chain comprising a framework region, e.g., framework region 3 (FR3), comprising a change, e.g., a substitution (e.g., a conservative substitution) at one or more, e.g., all, position disclosed herein according to Kabat numbering.
  • FR3 comprises a Glycine at position 66, e.g., a substitution at position 66 according to Kabat numbering, e.g., a Lysine to Glycine substitution, or a Serine to Glycine substitution.
  • FR3 comprises an Asparagine at position 69, e.g., a substitution at position 69 according to Kabat numbering, e.g., a Tyrosine to Asparagine substitution.
  • FR3 comprises a Tyrosine at position 71, e.g., a substitution at position 71 according to Kabat numbering, e.g., a Phenylalanine to Tyrosine substitution, or an Alanine to Tyrosine substitution.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises a light chain comprising a framework region, e.g., framework region 3 (FR3), comprising a substitution at position 66 according to Kabat numbering, e.g., a Lysine to Glycine substitution, or a Serine to Glycine substitution, and a substitution at position 69 according to Kabat numbering, e.g., a Tyrosine to Asparagine substitution.
  • FR3 framework region 3
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises a light chain comprising a framework region, e.g., framework region 3 (FR3), comprising a substitution at position 66 according to Kabat numbering, e.g., Lysine to Glycine substitution, or a Serine to Glycine substitution, and a substitution at position 71 according to Kabat numbering, e.g., a Phenylalanine to Tyrosine substitution, or an Alanine to Tyrosine substitution.
  • FR3 framework region 3
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises a light chain comprising a framework region, e.g., framework region 3 (FR3), comprising a substitution at position 69 according to Kabat numbering, e.g., a Tyrosine to Asparagine substitution and a substitution at position 71 according to Kabat numbering, e.g., a Phenylalanine to Tyrosine substitution, or an Alanine to Tyrosine substitution.
  • FR3 framework region 3
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises a light chain comprising a framework region, e.g., framework region 3 (FR3), comprising a substitution at position 66 according to Kabat numbering, e.g., a Lysine to Glycine substitution, or a Serine to Glycine substitution, a substitution at position 69 according to Kabat numbering, e.g., a Tyrosine to Asparagine substitution and a substitution at position 71 according to Kabat numbering, e.g., a Phenylalanine to Tyrosine substitution, or an Alanine to Tyrosine substitution.
  • the substitution is relative to a human germline light chain framework region sequence.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises a light chain comprising: a framework region 1 (FR1) comprising a substitution at position 2 according to Kabat numbering, e.g., a Isoleucine to Asparagine substitution; and a framework region 3 (FR3), comprising a substitution at position 69 according to Kabat numbering, e.g., a Threonine to Asparagine substitution and a substitution at position 71 according to Kabat numbering, e.g., a Phenylalanine to Tyrosine substitution, e.g., as shown in the amino acid sequence of SEQ ID NO: 26.
  • the substitution is relative to a human germline light chain framework region sequence.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises a light chain comprising: (a) a framework region 1 (FR1) comprising a substitution at position 1 according to Kabat numbering, e.g., a Alanine to Aspartic Acid substitution, and a substitution at position 2 according to Kabat numbering, e.g., a Isoleucine to Asparagine substitution; and (b) a framework region 3 (FR3), comprising a substitution at position 69 according to Kabat numbering, e.g., a Threonine to Asparagine substitution and a substitution at position 71 according to Kabat numbering, e.g., a Phenylalanine to Tyrosine substitution, e.g., as shown in the amino acid sequence of SEQ ID NO: 27
  • the substitution is relative to a human germline light chain framework region sequence.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises a light chain comprising: (a) a framework region 1 (FR1) comprising a substitution at position 2 according to Kabat numbering, e.g., a Serine to Asparagine substitution; and a substitution at position 4 according to Kabat numbering, e.g., a Methionine to Leucine substitution; and (b) a framework region 3 (FR3), comprising a substitution at position 69 according to Kabat numbering, e.g., a Threonine to Asparagine substitution and a substitution at position 71 according to Kabat numbering, e.g., a Phenylalanine to Tyrosine substitution, e.g., as shown in the amino acid sequence of SEQ ID NO: 28
  • the substitution is relative to a human germline light chain framework region sequence.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises a light chain comprising: (a) a framework region 1 (FR1) comprising a substitution at position 2 according to Kabat numbering, e.g., a Serine to Asparagine substitution; and (b) a framework region 3 (FR3) comprising a substitution at position 66 according to Kabat numbering, e.g., a Lysine to Glycine substitution; a substitution at position 69 according to Kabat numbering, e.g., a Threonine to Asparagine substitution; and a substitution at position 71 according to Kabat numbering, e.g., a Alanine to Tyrosine substitution, e.g., as shown in the amino acid sequence of SEQ ID NO: 29.
  • the substitution is relative to a human germline light chain framework region sequence.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises a light chain comprising: (a) a framework region 1 (FR1) comprising a substitution at position 2 according to Kabat numbering, e.g., a Tyrosine to Asparagine substitution; and (b) a framework region 3 (FR3) comprising a substitution at position 66 according to Kabat numbering, e.g., a Serine to Glycine substitution; a substitution at position 69 according to Kabat numbering, e.g., a Threonine to Asparagine substitution; and a substitution at position 71 according to Kabat numbering, e.g., a Alanine to Tyrosine substitution, e.g., as shown in the amino acid sequence of SEQ ID NO: 29.
  • the substitution is relative to a human germline light chain framework region sequence.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises a light chain variable domain comprising: (a) a framework region 1 (FR1) comprising a change, e.g., a substitution (e.g., a conservative substitution) at one or more (e.g., all) positions disclosed herein according to Kabat numbering, and (b) a framework region 3 (FR3) comprising a change, e.g., a substitution (e.g., a conservative substitution) at one or more (e.g., all) position disclosed herein according to Kabat numbering.
  • the substitution is relative to a human germline light chain framework region sequence.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises the heavy chain framework region 1, e.g., as shown in FIG. 2 A .
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule comprises the heavy chain framework region 2, e.g., as shown in FIG. 2 A .
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V12 antibody molecule comprises the heavy chain framework region 3, e.g., as shown in FIG. 2 A .
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V12 antibody molecule comprises the heavy chain framework region 4, e.g., as shown in FIG. 2 A .
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V12 antibody molecule comprises the heavy chain framework regions 1-4, e.g., SEQ ID NOS: 20-23, or as shown in FIG. 2 A .
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V12 antibody molecule comprises the light chain framework regions 1-4, e.g., SEQ ID NOs: 26-30, or as shown in FIG. 2 B .
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V12 antibody molecule comprises the heavy chain framework regions 1-4, e.g., SEQ ID NOs: 23-25; and the light chain framework regions 1-4, e.g., SEQ ID NOs: 26-30, or as shown in FIGS. 2 A and 2 B .
  • the heavy or light chain variable domain, or both, of, the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V12 antibody molecule includes an amino acid sequence, which is substantially identical to an amino acid disclosed herein, e.g., at least 80%, 85%, 90%, 92%, 95%, 97%, 98%, 99% or higher identical to a variable region of an antibody described herein, e.g., an antibody as described in Table 2, or encoded by the nucleotide sequence in Table 2; or which differs at least 1 or 5 residues, but less than 40, 30, 20, or 10 residues, from a variable region of an antibody described herein.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V12 antibody molecule comprises at least one, two, three, or four antigen-binding regions, e.g., variable regions, having an amino acid sequence as set forth in Table 2, or a sequence substantially identical thereto (e.g., a sequence at least about 85%, 90%, 95%, 99% or more identical thereto, or which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the sequences shown in Table 2.
  • antigen-binding regions e.g., variable regions, having an amino acid sequence as set forth in Table 2, or a sequence substantially identical thereto (e.g., a sequence at least about 85%, 90%, 95%, 99% or more identical thereto, or which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the sequences shown in Table 2.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V12 antibody molecule includes a VH and/or VL domain encoded by a nucleic acid having a nucleotide sequence as set forth in Table 2, or a sequence substantially identical thereto (e.g., a sequence at least about 85%, 90%, 95%, 99% or more identical thereto, or which differs by no more than 3, 6, 15, 30, or 45 nucleotides from the sequences shown in Table 2.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V12 antibody molecule comprises:
  • VH domain comprising an amino acid sequence chosen from the amino acid sequence of SEQ ID NO: 23, SEQ ID NO:24 or SEQ ID NO:25, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 23, SEQ ID NO:24 or SEQ ID NO:25, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 23, SEQ ID NO:24 or SEQ ID NO:25; and/or
  • a VL domain comprising an amino acid sequence chosen from the amino acid sequence of SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29 or SEQ ID NO: 30, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence of SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29 or SEQ ID NO: 30, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29 or SEQ ID NO: 30.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V12 antibody molecule comprises:
  • VH domain comprising the amino acid sequence of SEQ ID NO: 23, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 23, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 23; and
  • VL domain comprising the amino acid sequence of SEQ ID NO: 26, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 26, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 26.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V12 antibody molecule comprises:
  • VH domain comprising the amino acid sequence of SEQ ID NO: 23, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 23, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 23; and
  • VL domain comprising the amino acid sequence of SEQ ID NO: 27, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 27, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 27.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V12 antibody molecule comprises:
  • VH domain comprising the amino acid sequence of SEQ ID NO: 23, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 23, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 23; and
  • VL domain comprising the amino acid sequence of SEQ ID NO: 28, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 28, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 28.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V12 antibody molecule comprises:
  • VH domain comprising the amino acid sequence of SEQ ID NO: 23, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 23, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 23; and
  • VL domain comprising the amino acid sequence of SEQ ID NO: 29, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 29, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 29.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V12 antibody molecule comprises:
  • VH domain comprising the amino acid sequence of SEQ ID NO: 23, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 23, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 23; and
  • VL domain comprising the amino acid sequence of SEQ ID NO: 30, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 30, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 30.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V12 antibody molecule comprises:
  • VH domain comprising the amino acid sequence of SEQ ID NO: 24 or 25, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 24 or 25, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 24 or 25; and
  • VL domain comprising the amino acid sequence of SEQ ID NO: 26, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 26, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 26.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V12 antibody molecule comprises:
  • VH domain comprising the amino acid sequence of SEQ ID NO: 24 or 25, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 24 or 25, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 24 or 25; and
  • VL domain comprising the amino acid sequence of SEQ ID NO: 27, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 27, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 27.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V12 antibody molecule comprises:
  • VH domain comprising the amino acid sequence of SEQ ID NO: 24 or 25, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 24 or 25, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 24 or 25; and
  • VL domain comprising the amino acid sequence of SEQ ID NO: 28, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 28, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 28.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V12 antibody molecule comprises:
  • VH domain comprising the amino acid sequence of SEQ ID NO: 24 or 25, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 24 or 25, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 24 or 25; and
  • VL domain comprising the amino acid sequence of SEQ ID NO: 29, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 29, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 29.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V12 antibody molecule comprises:
  • VH domain comprising the amino acid sequence of SEQ ID NO: 24 or 25, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 24 or 25, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 24 or 25; and
  • VL domain comprising the amino acid sequence of SEQ ID NO: 30, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 30, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 30.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V12 antibody molecule comprises:
  • VH domain comprising the amino acid sequence of SEQ ID NO: 25 or 23, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 25 or 23, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 25 or 23; and
  • VL domain comprising the amino acid sequence of SEQ ID NO: 26, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 26, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 26.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V12 antibody molecule comprises:
  • VH domain comprising the amino acid sequence of SEQ ID NO: 25 or 23, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 25 or 23, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 25 or 23; and
  • VL domain comprising the amino acid sequence of SEQ ID NO: 27, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 27, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 27.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V12 antibody molecule comprises:
  • VH domain comprising the amino acid sequence of SEQ ID NO: 25 or 23, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 25 or 23, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 25 or 23; and
  • VL domain comprising the amino acid sequence of SEQ ID NO: 28, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 28, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 28.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V12 antibody molecule comprises:
  • VH domain comprising the amino acid sequence of SEQ ID NO: 25 or 23, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 25 or 23, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 25 or 23; and
  • VL domain comprising the amino acid sequence of SEQ ID NO: 29, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 29, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 29.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TC ⁇ V12 antibody molecule comprises:
  • VH domain comprising the amino acid sequence of SEQ ID NO: 25 or 23, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 25 or 23, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 25 or 23; and
  • VL domain comprising the amino acid sequence of SEQ ID NO: 30, an amino acid sequence at least about 85%, 90%, 95%, 99% or more identical to the amino acid sequence SEQ ID NO: 30, or an amino acid sequence which differs by no more than 1, 2, 5, 10, or 15 amino acid residues from the amino acid sequence of SEQ ID NO: 30.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule is a full antibody or fragment thereof (e.g., a Fab, F(ab′)2, Fv, or a single chain Fv fragment (scFv)).
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V6 (e.g., anti-TCR ⁇ V6-5*01) antibody molecule is a monoclonal antibody or an antibody with single specificity.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule
  • the anti-TCR ⁇ V antibody molecule, e.g., anti-TCR ⁇ V12 antibody molecule is a humanized antibody molecule.
  • the heavy and light chains of the anti-TCR ⁇ V antibody molecule can be full-length (e.g., an antibody can include at least one, and preferably two, complete heavy chains, and at least one, and preferably two, complete light chains) or can include an antigen-binding fragment (e.g., a Fab, F(ab′)2, Fv, a single chain Fv fragment, a single domain antibody, a diabody (dAb), a bivalent antibody, or bispecific antibody or fragment thereof, a single domain variant thereof, or a camelid antibody).
  • an antibody can include at least one, and preferably two, complete heavy chains, and at least one, and preferably two, complete light chains
  • an antigen-binding fragment e.g., a Fab, F(ab′)2, Fv, a single chain Fv fragment, a single domain antibody, a diabody (dAb), a bivalent antibody, or bispecific antibody or fragment thereof, a single domain variant thereof, or a camelid antibody.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule is in the form of a multispecific molecule, e.g., a bispecific molecule, e.g., as described herein.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule has a heavy chain constant region (Fc) chosen from, e.g., the heavy chain constant regions of IgG1, IgG2, IgG3, IgG4, IgM, IgA1, IgA2, IgD, and IgE.
  • the Fc region is chosen from the heavy chain constant regions of IgG1, IgG2, IgG3, and IgG4.
  • the Fc region is chosen from the heavy chain constant region of IgG1 or IgG2 (e.g., human IgG1, or IgG2).
  • the heavy chain constant region is human IgG1.
  • the anti-TCR ⁇ V antibody molecule e.g., anti-TCR ⁇ V12 antibody molecule has a light chain constant region chosen from, e.g., the light chain constant regions of kappa or lambda, preferably kappa (e.g., human kappa).
  • the constant region is altered, e.g., mutated, to modify the properties of the anti-TCR ⁇ V antibody molecule, e.g., anti-TCR ⁇ V12 antibody molecule (e.g., to increase or decrease one or more of: Fc receptor binding, antibody glycosylation, the number of cysteine residues, effector cell function, or complement function).
  • the constant region is mutated at positions 296 (M to Y), 298 (S to T), 300 (T to E), 477 (H to K) and 478 (N to F) to alter Fc receptor binding (e.g., the mutated positions correspond to positions 132 (M to Y), 134 (S to T), 136 (T to E), 313 (H to K) and 314 (N to F) of SEQ ID NOs: 212 or 214; or positions 135 (M to Y), 137 (S to T), 139 (T to E), 316 (H to K) and 317 (N to F) of SEQ ID NOs: 215, 216, 217 or 218).
  • the mutated positions correspond to positions 132 (M to Y), 134 (S to T), 136 (T to E), 313 (H to K) and 314 (N to F) of SEQ ID NOs: 212 or 214; or positions 135 (M to Y), 137 (S to T), 139 (T to
  • Antibody B-H.1 comprises a first chain comprising the amino acid sequence of SEQ ID NO: 3280 and a second chain comprising the amino acid sequence of SEQ ID NO: 3281.
  • the anti-TCR ⁇ V12 is antibody B, e.g., humanized antibody B (antibody B-H), as provided in Table 2.
  • the anti-TCR ⁇ V antibody comprises one or more (e.g., all three) of a LC CDR1, LC CDR2, and LC CDR3 provided in Table 2; and/or one or more (e.g., all three) of a HC CDR1, HC CDR2, and HC CDR3 provided in Table 2, or a sequence with at least 95% identity thereto.
  • antibody B comprises a variable heavy chain (VH) and/or a variable light chain (VL) provided in Table 2, or a sequence with at least 95% identity thereto.
  • the anti-TCRVB 12 antibody molecule (e.g., anti-TCRVB 12-3 or anti-TCRVB 12-4 antibody molecule) comprises a VH of B-H.1A, B-H.1B, B-H.1C, B-H.1D, B-H.1E, B-H.1F, B-H.1G, B-H.1H, B-H.1, B-H.2, B-H.3, B-H.4, B-H.5, or B-H.6, or a sequence with at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more identity thereto.
  • the anti-TCRVB 12 antibody molecule (e.g., anti-TCRVB 12-3 or anti-TCRVB 12-4 antibody molecule) comprises a VL of B-H.1A, B-H.1B, B-H.1C, B-H.1D, B-H.1E, B-H.1F, B-H.1G, B-H.1H, B-H.1, B-H.2, B-H.3, B-H.4, B-H.5, or B-H.6, or a sequence with at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more identity thereto.
  • the anti-TCRVB 12 antibody molecule (e.g., anti-TCRVB 12-3 or anti-TCRVB 12-4 antibody molecule) comprises a VH of B-H.1A, B-H.1B, B-H.1C, B-H.1D, B-H.1E, B-H.1F, B-H.1G, B-H.1H, B-H.1, B-H.2, B-H.3, B-H.4, B-H.5, or B-H.6, or a sequence with at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more identity thereto; and a VL of B-H.1A, B-H.1B, B-H.1C, B-H.1D, B-H.1E, B-H.1F, B-H.1G, B-H.1H, B-H.1, B-H.2, B-H.3, B-H.4, B-H.5,
  • TABLE 2 Amino acid and nucleotide sequences for murine and humanized antibody molecules which bind to TCRVB 12, e.g., TCRVB 12-3 or TCRVB 12-4.
  • the antibody molecules include murine mAb Antibody B and humanized mAb Antibody B-H.1 to B-H.6.
  • the amino acid the heavy and light chain CDRs, and the amino acid and nucleotide sequences of the heavy and light chain variable regions, and the heavy and light chains are shown.
  • Antibody B also referred to as 16G8 SEQ ID NO: 17 HC CDR1 (Combined) GFTFSNFGMH SEQ ID NO: 18 HC CDR2 (Combined) YISSGSSTIYYADTLKG SEQ ID NO: 19 HC CDR3 (Combined) RGEGAMDY SEQ ID NO: 57 HC CDR1 (Kabat) NFGMH SEQ ID NO: 58 HC CDR2 (Kabat) YISSGSSTIYYADTLKG SEQ ID NO: 59 HC CDR3 (Kabat) RGEGAMDY SEQ ID NO: 60 HC CDR1 (Chothia) GFTFSNF SEQ ID NO: 61 HC CDR2 (Chothia) SSGSST SEQ ID NO: 62 HC CDR3 (Chothia) RGEGAMDY SEQ ID NO: 15 VH DVQLVESGGGLVQPGGSRKLSCAASGFTFSNFGMH WVRQAPDKGLEWVAYISSGSSTIY
  • the disclosure provides an anti-TCR ⁇ V antibody molecule that binds to human TCR ⁇ V5.
  • the TCR ⁇ V5 subfamily comprises TCR ⁇ V5-5*01, TCR ⁇ V5-6*01, TCR ⁇ V5-4*01, TCR ⁇ V5-8*01, TCR ⁇ V5-1*01, or a variant thereof.
  • anti-TCR ⁇ V5 antibodies of the disclosure are provided in Table 10.
  • the anti-TCR ⁇ V5 is antibody C, e.g., humanized antibody C (antibody C-H), as provided in Table 10.
  • the anti-TCR ⁇ V antibody comprises one or more (e.g., all three) of a LC CDR1, LC CDR2, and LC CDR3 provided in Table 10; and/or one or more (e.g., all three) of a HC CDR1, HC CDR2, and HC CDR3 provided in Table 10, or a sequence with at least 95% identity thereto.
  • antibody C comprises a variable heavy chain (VH) and/or a variable light chain (VL) provided in Table 10, or a sequence with at least 95% identity thereto.
  • TABLE 10 Amino acid sequences for anti TCR ⁇ V5 antibodies
  • Amino acid and nucleotide sequences for murine and humanized antibody molecules which bind to TCRVB 5 e.g., TCRVB 5-5 or TCRVB 5-6).
  • the amino acid the heavy and light chain CDRs, and the amino acid and nucleotide sequences of the heavy and light chain variable regions, and the heavy and light chains are shown.
  • Murine antibody C also referred to as 4H11 SEQ ID NO: 1315 HC CDR1 (Kabat) AYGVN SEQ ID NO: 1316 HC CDR2 (Kabat) MIWGDGNTDYNSALKS SEQ ID NO: 1317 HC CDR3 (Kabat) DRVTATLYAMDY SEQ ID NO: 1318 HC CDR1 (Chothia) GFSLTAY SEQ ID NO: 1319 HC CDR2 (Chothia) WGDGN SEQ ID NO: 1317 HC CDR3 (Chothia) DRVTATLYAMDY SEQ ID NO: 1320 HC CDR1 (Combined) GFSLTAYGVN SEQ ID NO: 1316 HC CDR2 (Combined) MIWGDGNTDYNSALKS SEQ ID NO: 1317 HC CDR3(Combined) DRVTATLYAMDY SEQ ID NO: 1321 LC CDR1 (Kabat) SASQGISNYLN SEQ ID NO: 1322 LC CDR2 (K
  • anti-TCR ⁇ V5 antibodies of the disclosure are provided in Table 11.
  • the anti-TCR ⁇ V5 is antibody E, e.g., humanized antibody E (antibody E-H), as provided in Table 11.
  • the anti-TCR ⁇ V antibody comprises one or more (e.g., all three) of a LC CDR1, LC CDR2, and LC CDR3 provided in Table 11; and/or one or more (e.g., all three) of a HC CDR1, HC CDR2, and HC CDR3 provided in Table 11, or a sequence with at least 95% identity thereto.
  • antibody E comprises a variable heavy chain (VH) and/or a variable light chain (VL) provided in Table 11, or a sequence with at least 95% identity thereto.
  • antibody E comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 3284 and/or a light chain comprising the amino acid sequence of SEQ ID NO: 3285, or a sequence with at least 95% identity thereto.
  • TABLE 11 Amino acid sequences for anti TCR ⁇ V5 antibodies
  • Amino acid and nucleotide sequences for murine and humanized antibody molecules which bind to TCRVB 5 e.g., TCRVB 5-5 or TCRVB 5-6).
  • the amino acid the heavy and light chain CDRs, and the amino acid and nucleotide sequences of the heavy and light chain variable regions, and the heavy and light chains are shown.
  • Murine antibody E also referred to as MH3-2 SEQ ID NO: 1298 HC CDR1 (Kabat) SSWMN SEQ ID NO: 1299 HC CDR2 (Kabat) RIYPGDGDTKYNGKFKG SEQ ID NO: 1300 HC CDR3 (Kabat) RGTGGWYFDV SEQ ID NO: 1302 HC CDR1 (Chothia) GYAFSSS SEQ ID NO: 1303 HC CDR2 (Chothia) YPGDGD SEQ ID NO: 1301 HC CDR3 (Chothia) RGTGGWYFDV SEQ ID NO: 1304 HC CDR1 (Combined) GYAFSSSWMN SEQ ID NO: 1299 HC CDR2 (Combined) RIYPGDGDTKYNGKFKG SEQ ID NO: 1301 HC CDR3 (Combined) RGTGGWYFDV SEQ ID NO: 1305 LC CDR1 (Kabat) RASESVDSSGNSFMH SEQ ID
  • the anti-TCR ⁇ V5 antibody molecule comprises a VH and/or a VL of an antibody described in Table 10, or a sequence with at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more identity thereto.
  • the anti-TCR ⁇ V5 antibody molecule comprises a VH and a VL of an antibody described in Table 10, or a sequence with at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more identity thereto.
  • the anti-TCR ⁇ V5 antibody molecule comprises a VH and/or a VL of an antibody described in Table 11, or a sequence with at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more identity thereto.
  • the anti-TCR ⁇ V5 antibody molecule comprises a VH and a VL of an antibody described in Table 11, or a sequence with at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more identity thereto.
  • the disclosure provides an anti-TCR ⁇ V antibody molecule that binds to a human TCR ⁇ V10 subfamily member.
  • TCR ⁇ V10 subfamily is also known as TCR ⁇ V12.
  • the TCR ⁇ V10 subfamily comprises: TCR ⁇ V10-1*01, TCR ⁇ V10-1*02, TCR ⁇ V10-3*01 or TCR ⁇ V10-2*01, or a variant thereof.
  • anti-TCR ⁇ V10 antibodies of the disclosure are provided in Table 12.
  • the anti-TCR ⁇ V10 is antibody D, e.g., humanized antibody D (antibody D-H), as provided in Table 12.
  • antibody D comprises one or more (e.g., three) light chain CDRs and/or one or more (e.g., three) heavy chain CDRs provided in Table 12, or a sequence with at least 95% identity thereto.
  • antibody D comprises a variable heavy chain (VH) and/or a variable light chain (VL) provided in Table 12, or a sequence with at least 95% identity thereto.
  • TABLE 12 Amino acid sequences for anti TCR ⁇ V10 antibodies
  • Amino acid and nucleotide sequences for murine and humanized antibody molecules which bind to TCRBV 10 e.g., TCRBV 10-1, TCRBV 10-2 or TCRBV 10-3).
  • the amino acid the heavy and light chain CDRs, and the amino acid and nucleotide sequences of the heavy and light chain variable regions, and the heavy and light chains are shown.
  • Murine antibody D also referred to as S511 antibody SEQ ID NO: 1288 HC CDR1 (Kabat) SYGMS SEQ ID NO: 1289 HC CDR2 (Kabat) LISSGGSYTYYTDSVKG SEQ ID NO: 1290 HC CDR3 (Kabat) HGGNFFDY SEQ ID NO: 1291 HC CDR1 (Chothia) GFTFRSY SEQ ID NO: 1292 HC CDR2 (Chothia) SSGGSY SEQ ID NO: 1290 HC CDR3 (Chothia) HGGNFFDY SEQ ID NO: 1293 HC CDR1 (Combined) GFTFRSYGMS SEQ ID NO: 1289 HC CDR2 (Combined) LISSGGSYTYYTDSVKG SEQ ID NO: 1290 HC CDR3 (Combined) HGGNFFDY SEQ ID NO: 1294 LC CDR1 (Kabat) SVSSSVSYMH SEQ ID NO: 1295 LC CDR2 (
  • the anti-TCR ⁇ V10 antibody molecule comprises a VH or a VL of an antibody described in Table 12, or a sequence with at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more identity thereto.
  • the anti-TCR ⁇ V10 antibody molecule comprises a VH and a VL of an antibody described in Table 12, or a sequence with at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more identity thereto.
  • the anti-TCR ⁇ V antibody is a humanized antibody, e.g., as provided in Table 13.
  • the anti-TCR ⁇ V antibody comprises one or more (e.g., all three) of a LC CDR1, LC CDR2, and LC CDR3 provided in Table 13; and/or one or more (e.g., all three) of a HC CDR1, HC CDR2, and HC CDR3 provided in Table 13, or a sequence with at least 95% identity thereto.
  • the anti-TCR ⁇ V antibody comprises a variable heavy chain (VH) and/or a variable light chain (VL) provided in Table 13, or a sequence with at least 95% identity thereto.
  • IMMU 222 binds human TCR ⁇ V 6-5, TCR ⁇ V 6-6, or TCR ⁇ V 6-9 (TCR ⁇ V13.1 per old nomenclature).
  • REA1062 binds human TCR ⁇ V 5-1).
  • JOVI-3 binds human TCR ⁇ V 28 (TCR ⁇ V3.1 per old nomenclature).
  • IMMU546 binds human TCR ⁇ V 2.
  • MPB2D5 (murine), also referred to here as BJ1188, BJ1190 and REA654; or Antibody G Binds to human TCRV ⁇ 20-1
  • SEQ ID NO: 1102 HC CDR1 (Kabat) SAYMH SEQ ID NO: 1103 HC CDR2 (Kabat) RIDPATGKTKYAPKFQA
  • SEQ ID NO: 1104 HC CDR3 (Kabat) SLNWDYGLDY SEQ ID NO: 1105 HC CDR1 (Chothia) GFNIKSA
  • SEQ ID NO: 1106 HC CDR2 (Chothia) DPATGK SEQ ID NO: 1104 HC CDR3 (Chothia) SLNWDYGLDY SEQ ID NO: 3640 HC CDR1 (Combined) GFNIKSAYMH
  • SEQ ID NO: 1103 HC CDR2 (Combined) RIDPATGKTKYAPKFQA
  • an anti-TCRV ⁇ antibody disclosed herein comprises an Fc region, e.g., as described herein.
  • the Fc region is a wildtype Fc region, e.g., a wildtype human Fc region.
  • the Fc region comprises a variant, e.g., an Fc region comprising an addition, substitution, or deletion of at least one amino acid residue in the Fc region which results in, e.g., reduced or ablated affinity for at least one Fc receptor.
  • the Fc region of an antibody interacts with a number of receptors or ligands including Fc Receptors (e.g., Fc ⁇ RI, Fc ⁇ RIIA, Fc ⁇ RIIIA), the complement protein CIq, and other molecules such as proteins A and G.
  • Fc Receptors e.g., Fc ⁇ RI, Fc ⁇ RIIA, Fc ⁇ RIIIA
  • the complement protein CIq e.g., Fc ⁇ RI, Fc ⁇ RIIA, Fc ⁇ RIIIA
  • an anti-TCRV ⁇ antibody comprising a variant Fc region has reduced, e.g., ablated, affinity for an Fc receptor, e.g., an Fc receptor described herein.
  • the reduced affinity is compared to an otherwise similar antibody with a wildtype Fc region.
  • an anti-TCRV ⁇ antibody comprising a variant Fc region has one or more of the following properties: (1) reduced effector function (e.g., reduced ADCC, ADCP and/or CDC); (2) reduced binding to one or more Fc receptors; and/or (3) reduced binding to Clq complement.
  • the reduction in any one, or all of properties (1)-(3) is compared to an otherwise similar antibody with a wildtype Fc region.
  • an anti-TCRV ⁇ antibody comprising a variant Fc region has reduced affinity to a human Fc receptor, e.g., Fc ⁇ R I, Fc ⁇ R II and/or Fc ⁇ R III.
  • the anti-TCRV ⁇ antibody comprising a variant Fc region comprises a human IgG1 region or a human IgG4 region.
  • an anti-TCRV ⁇ antibody comprising a variant Fc region activates and/or expands T cells, e.g., as described herein.
  • an anti-TCRV ⁇ antibody comprising a variant Fc region has a cytokine profile described herein, e.g., a cytokine profile that differs from a cytokine profile of a T cell engager that binds to a receptor or molecule other than a TCR ⁇ V region (“a non-TCR ⁇ V-binding T cell engager”).
  • the non-TCR ⁇ V-binding T cell engager comprises an antibody that binds to a CD3 molecule (e.g., CD3 epsilon (CD3e) molecule); or a TCR alpha (TCR ⁇ ) molecule.
  • a CD3 molecule e.g., CD3 epsilon (CD3e) molecule
  • TCR ⁇ TCR alpha
  • Exemplary Fc region variants are provided in Table 21 and also disclosed in Saunders 0, (2019) Frontiers in Immunology ; vol 10, article 1296, the entire contents of which is hereby incorporated by reference.
  • an anti-TCRV ⁇ antibody disclosed herein comprises any one or all, or any combination of Fc region variants disclosed in Table 21.
  • an anti-TCRV ⁇ antibody disclosed herein comprises any one or all, or any combination of Fc region variants, e.g., mutations, disclosed in Table 21.
  • an anti-TCRV ⁇ antibody disclosed herein comprise an Asn297Ala (N297A) mutation.
  • an anti-TCRV ⁇ antibody disclosed herein comprise a Leu234A1a/Leu235Ala (LALA) mutation.
  • the antibody molecule binds to a cancer antigen, e.g., a tumor antigen or a stromal antigen.
  • the cancer antigen is, e.g., a mammalian, e.g., a human, cancer antigen.
  • the antibody molecule binds to an immune cell antigen, e.g., a mammalian, e.g., a human, immune cell antigen.
  • the antibody molecule binds specifically to an epitope, e.g., linear or conformational epitope, on the cancer antigen or the immune cell antigen.
  • an antibody molecule is a monospecific antibody molecule and binds a single epitope.
  • a monospecific antibody molecule having a plurality of immunoglobulin variable domain sequences, each of which binds the same epitope.
  • an antibody molecule is a multispecific or multifunctional antibody molecule, e.g., it comprises a plurality of immunoglobulin variable domains 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 are on the same antigen, e.g., the same protein (or subunit of a multimeric protein).
  • the first and second epitopes overlap. In an embodiment the first and second epitopes do not overlap.
  • first and second epitopes are on different antigens, e.g., the different proteins (or different subunits of a multimeric protein).
  • a multispecific antibody molecule comprises a third, fourth or fifth immunoglobulin variable domain.
  • a multispecific antibody molecule is a bispecific antibody molecule, a trispecific antibody molecule, or a tetraspecific antibody molecule.
  • a multispecific antibody molecule is a bispecific antibody molecule.
  • a bispecific antibody has specificity for no more than two antigens.
  • a bispecific antibody molecule is characterized by a first immunoglobulin variable domain sequence which has binding specificity for a first epitope and a second immunoglobulin variable domain sequence that has binding specificity for a second epitope.
  • the first and second epitopes are on the same antigen, e.g., the same protein (or subunit of a multimeric protein).
  • the first and second epitopes overlap.
  • the first and second epitopes do not overlap.
  • first and second epitopes are on different antigens, e.g., the different proteins (or different subunits of a multimeric protein).
  • a bispecific antibody molecule 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 molecule comprises a half antibody having binding specificity for a first epitope and a half antibody having binding specificity for a second epitope.
  • a bispecific antibody molecule 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 molecule comprises a scFv or a Fab, or fragment thereof, have binding specificity for a first epitope and a scFv or a Fab, or fragment thereof, have binding specificity for a second epitope.
  • an antibody molecule comprises a diabody, and a single-chain molecule, as well as an antigen-binding fragment of an antibody (e.g., Fab, F(ab′) 2 , and Fv).
  • an antibody molecule can include a heavy (H) chain variable domain sequence (abbreviated herein as VH), and a light (L) chain variable domain sequence (abbreviated herein as VL).
  • VH heavy chain variable domain sequence
  • VL light chain variable domain sequence
  • an antibody molecule comprises or consists of a heavy chain and a light chain (referred to herein as a half antibody.
  • an antibody molecule in another example, includes two heavy (H) chain variable domain sequences and two light (L) chain variable domain sequence, thereby forming two antigen binding sites, such as Fab, Fab′, F(ab′) 2 , Fc, Fd, Fd′, Fv, single chain antibodies (scFv for example), single variable domain antibodies, diabodies (Dab) (bivalent and bispecific), and chimeric (e.g., humanized) antibodies, which may be produced by the modification of whole antibodies or those synthesized de novo using recombinant DNA technologies. These functional antibody fragments retain the ability to selectively bind with their respective antigen or receptor.
  • Antibodies and antibody fragments can be from any class of antibodies including, but not limited to, IgG, IgA, IgM, IgD, and IgE, and from any subclass (e.g., IgG1, IgG2, IgG3, and IgG4) of antibodies.
  • the preparation of antibody molecules can be monoclonal or polyclonal.
  • An antibody molecule can also be a human, humanized, CDR-grafted, or in vitro generated antibody.
  • the antibody can have a heavy chain constant region chosen from, e.g., IgG1, IgG2, IgG3, or IgG4.
  • the antibody can also have a light chain chosen from, e.g., kappa or lambda.
  • immunoglobulin (Ig) is used interchangeably with the term “antibody” herein.
  • antigen-binding fragments of an antibody molecule include: (i) a Fab fragment, a monovalent fragment consisting of the VL, VH, CL and CH1 domains; (ii) a F(ab′)2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region; (iii) a Fd fragment consisting of the VH and CH1 domains; (iv) a Fv fragment consisting of the VL and VH domains of a single arm of an antibody, (v) a diabody (dAb) fragment, which consists of a VH domain; (vi) a camelid or camelized variable domain; (vii) a single chain Fv (scFv), see e.g., Bird et al.
  • a Fab fragment a monovalent fragment consisting of the VL, VH, CL and CH1 domains
  • a F(ab′)2 fragment a bivalent fragment comprising two Fab fragment
  • Antibody molecules include intact molecules as well as functional fragments thereof. Constant regions of the antibody molecules can be altered, e.g., mutated, to modify the properties of the antibody (e.g., to increase or decrease one or more of: Fc receptor binding, antibody glycosylation, the number of cysteine residues, effector cell function, or complement function).
  • Antibody molecules can also be single domain antibodies.
  • Single domain antibodies can include antibodies whose complementary determining regions are part of a single domain polypeptide. Examples include, but are not limited to, heavy chain antibodies, antibodies naturally devoid of light chains, single domain antibodies derived from conventional 4-chain antibodies, engineered antibodies and single domain scaffolds other than those derived from antibodies.
  • Single domain antibodies may be any of the art, or any future single domain antibodies.
  • Single domain antibodies may be derived from any species including, but not limited to mouse, human, camel, llama, fish, shark, goat, rabbit, and bovine.
  • a single domain antibody is a naturally occurring single domain antibody known as heavy chain antibody devoid of light chains. Such single domain antibodies are disclosed in WO 9404678, for example.
  • variable domain derived from a heavy chain antibody naturally devoid of light chain is known herein as a VHH or nanobody to distinguish it from the conventional VH of four chain immunoglobulins.
  • VHH molecule can be derived from antibodies raised in Camelidae species, for example in camel, llama, dromedary, alpaca and guanaco. Other species besides Camelidae may produce heavy chain antibodies naturally devoid of light chain; such VHHs are within the scope of the invention.
  • VH and VL regions can be subdivided into regions of hypervariability, termed “complementarity determining regions” (CDR), interspersed with regions that are more conserved, termed “framework regions” (FR or FW).
  • CDR complementarity determining regions
  • FR framework regions
  • CDR complementarity determining region
  • the precise amino acid sequence boundaries of a given CDR can be determined using any of a number of known schemes, including those described by Kabat et al. (1991), “Sequences of Proteins of Immunological Interest,” 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md. (“Kabat” numbering scheme), Al-Lazikani et al., (1997) JMB 273,927-948 (“Chothia” numbering scheme). As used herein, the CDRs defined according the “Chothia” number scheme are also sometimes referred to as “hypervariable loops.”
  • the CDR amino acid residues in the heavy chain variable domain (VH) are numbered 31-35 (HCDR1), 50-65 (HCDR2), and 95-102 (HCDR3); and the CDR amino acid residues in the light chain variable domain (VL) are numbered 24-34 (LCDR1), 50-56 (LCDR2), and 89-97 (LCDR3).
  • the CDR amino acids in the VH are numbered 26-32 (HCDR1), 52-56 (HCDR2), and 95-102 (HCDR3); and the amino acid residues in VL are numbered 26-32 (LCDR1), 50-52 (LCDR2), and 91-96 (LCDR3).
  • Each VH and VL typically includes three CDRs and four FRs, arranged from amino-terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4.
  • the antibody molecule can be a polyclonal or a monoclonal antibody.
  • monoclonal antibody or “monoclonal antibody composition” as used herein refer to a preparation of antibody molecules of single molecular composition.
  • a monoclonal antibody composition displays a single binding specificity and affinity for a particular epitope.
  • a monoclonal antibody can be made by hybridoma technology or by methods that do not use hybridoma technology (e.g., recombinant methods).
  • the antibody can be recombinantly produced, e.g., produced by phage display or by combinatorial methods, or by yeast display.
  • Phage display and combinatorial methods for generating antibodies are known in the art (as described in, e.g., Ladner et al. U.S. Pat. No. 5,223,409; Kang et al. International Publication No. WO 92/18619; Dower et al. International Publication No. WO 91/17271; Winter et al. International Publication WO 92/20791; Markland et al. International Publication No. WO 92/15679; Breitling et al. International Publication WO 93/01288; McCafferty et al. International Publication No. WO 92/01047; Garrard et al. International Publication No.
  • yeast display method for generating or identifying antibodies is known in the art, e.g., as described in Chao et al. (2006) Nature Protocols 1(2):755-68, the entire contents of which is incorporated by reference herein.
  • the antibody is a fully human antibody (e.g., an antibody made in a mouse which has been genetically engineered to produce an antibody from a human immunoglobulin sequence), or a non-human antibody, e.g., a rodent (mouse or rat), goat, primate (e.g., monkey), camel antibody.
  • a rodent mouse or rat
  • the non-human antibody is a rodent (mouse or rat antibody).
  • Methods of producing rodent antibodies are known in the art.
  • Human monoclonal antibodies can be generated using transgenic mice carrying the human immunoglobulin genes rather than the mouse system. Splenocytes from these transgenic mice immunized with the antigen of interest are used to produce hybridomas that secrete human mAbs with specific affinities for epitopes from a human protein (see, e.g., Wood et al. International Application WO 91/00906, Kucherlapati et al. PCT publication WO 91/10741; Lonberg et al. International Application WO 92/03918; Kay et al. International Application 92/03917; Lonberg, N. et al. 1994 Nature 368:856-859; Green, L. L. et al.
  • An antibody molecule can be one in which the variable region, or a portion thereof, e.g., the CDRs, are generated in a non-human organism, e.g., a rat or mouse. Chimeric, CDR-grafted, and humanized antibodies are within the invention. Antibody molecules generated in a non-human organism, e.g., a rat or mouse, and then modified, e.g., in the variable framework or constant region, to decrease antigenicity in a human are within the invention.
  • An “effectively human” protein is a protein that does substantially not evoke a neutralizing antibody response, e.g., the human anti-murine antibody (HAMA) response.
  • HAMA can be problematic in a number of circumstances, e.g., if the antibody molecule is administered repeatedly, e.g., in treatment of a chronic or recurrent disease condition.
  • a HAMA response can make repeated antibody administration potentially ineffective because of an increased antibody clearance from the serum (see, e.g., Saleh et al., Cancer Immunol. Immunother., 32:180-190 (1990)) and also because of potential allergic reactions (see, e.g., LoBuglio et al., Hybridoma, 5:5117-5123 (1986)).
  • Chimeric antibodies can be produced by recombinant DNA techniques known in the art (see Robinson et al., International Patent Publication PCT/US86/02269; Akira, et al., European Patent Application 184,187; Taniguchi, M., European Patent Application 171,496; Morrison et al., European Patent Application 173,494; Neuberger et al., International Application WO 86/01533; Cabilly et al. U.S. Pat. No. 4,816,567; Cabilly et al., European Patent Application 125,023; Better et al. (1988 Science 240:1041-1043); Liu et al.
  • a humanized or CDR-grafted antibody will have at least one or two but generally all three recipient CDRs (of heavy and or light immuoglobulin chains) replaced with a donor CDR.
  • the antibody may be replaced with at least a portion of a non-human CDR or only some of the CDRs may be replaced with non-human CDRs. It is only necessary to replace the number of CDRs required for binding to the antigen.
  • the donor will be a rodent antibody, e.g., a rat or mouse antibody
  • the recipient will be a human framework or a human consensus framework.
  • the immunoglobulin providing the CDRs is called the “donor” and the immunoglobulin providing the framework is called the “acceptor.”
  • the donor immunoglobulin is a non-human (e.g., rodent).
  • the acceptor framework is a naturally-occurring (e.g., a human) framework or a consensus framework, or a sequence about 85% or higher, preferably 90%, 95%, 99% or higher identical thereto.
  • the term “consensus sequence” refers to the sequence formed from the most frequently occurring amino acids (or nucleotides) in a family of related sequences (See e.g., Winnaker, From Genes to Clones (Verlagsgesellschaft, Weinheim, Germany 1987). In a family of proteins, each position in the consensus sequence is occupied by the amino acid occurring most frequently at that position in the family. If two amino acids occur equally frequently, either can be included in the consensus sequence.
  • a “consensus framework” refers to the framework region in the consensus immunoglobulin sequence.
  • An antibody molecule can be humanized by methods known in the art (see e.g., Morrison, S. L., 1985 , Science 229:1202-1207, by Oi et al., 1986 , BioTechniques 4:214, and by Queen et al. U.S. Pat. Nos. 5,585,089, 5,693,761 and 5,693,762, the contents of all of which are hereby incorporated by reference).

Landscapes

  • Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
US17/855,332 2020-01-03 2022-06-30 Anti-tcr antibody molecules and uses thereof Pending US20230227552A1 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
US17/855,332 US20230227552A1 (en) 2020-01-03 2022-06-30 Anti-tcr antibody molecules and uses thereof
US18/341,688 US12486326B2 (en) 2020-01-03 2023-06-26 Anti-TCR antibody molecules and uses thereof
US19/339,740 US20260022173A1 (en) 2020-01-03 2025-09-25 Anti-tcr antibody molecules and uses thereof

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US202062957024P 2020-01-03 2020-01-03
US202063070596P 2020-08-26 2020-08-26
PCT/US2020/067543 WO2021138474A2 (en) 2020-01-03 2020-12-30 Anti-tcr antibody molecules and uses thereof
US17/855,332 US20230227552A1 (en) 2020-01-03 2022-06-30 Anti-tcr antibody molecules and uses thereof

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2020/067543 Continuation WO2021138474A2 (en) 2020-01-03 2020-12-30 Anti-tcr antibody molecules and uses thereof

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US18/341,688 Continuation US12486326B2 (en) 2020-01-03 2023-06-26 Anti-TCR antibody molecules and uses thereof

Publications (1)

Publication Number Publication Date
US20230227552A1 true US20230227552A1 (en) 2023-07-20

Family

ID=76687461

Family Applications (3)

Application Number Title Priority Date Filing Date
US17/855,332 Pending US20230227552A1 (en) 2020-01-03 2022-06-30 Anti-tcr antibody molecules and uses thereof
US18/341,688 Active US12486326B2 (en) 2020-01-03 2023-06-26 Anti-TCR antibody molecules and uses thereof
US19/339,740 Pending US20260022173A1 (en) 2020-01-03 2025-09-25 Anti-tcr antibody molecules and uses thereof

Family Applications After (2)

Application Number Title Priority Date Filing Date
US18/341,688 Active US12486326B2 (en) 2020-01-03 2023-06-26 Anti-TCR antibody molecules and uses thereof
US19/339,740 Pending US20260022173A1 (en) 2020-01-03 2025-09-25 Anti-tcr antibody molecules and uses thereof

Country Status (8)

Country Link
US (3) US20230227552A1 (https=)
EP (1) EP4084823A4 (https=)
JP (2) JP2023509708A (https=)
CN (1) CN116234829A (https=)
AU (1) AU2020416273A1 (https=)
CA (1) CA3166629A1 (https=)
GB (1) GB2609554B (https=)
WO (1) WO2021138474A2 (https=)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024197296A1 (en) 2023-03-23 2024-09-26 Bodhi Bio Llc Compositions and methods for antigen-specific therapy
US12247060B2 (en) 2018-01-09 2025-03-11 Marengo Therapeutics, Inc. Calreticulin binding constructs and engineered T cells for the treatment of diseases
US12286477B2 (en) 2018-07-03 2025-04-29 Marengo Therapeutics, Inc. Anti-TCR antibody molecules and uses thereof
US12358982B2 (en) 2019-02-21 2025-07-15 Marengo Therapeutics, Inc. Multifunctional molecules that bind to T cell related cancer cells and uses thereof
US12384842B2 (en) 2019-02-21 2025-08-12 Marengo Therapeutics, Inc. Antibody molecules that bind to NKP30 and uses thereof
US12486326B2 (en) 2020-01-03 2025-12-02 Marengo Therapeutics, Inc. Anti-TCR antibody molecules and uses thereof

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12152073B2 (en) 2018-03-14 2024-11-26 Marengo Therapeutics, Inc. Multifunctional molecules that bind to calreticulin and uses thereof
JP7590430B2 (ja) * 2019-11-14 2024-11-26 マレンゴ・セラピューティクス，インコーポレーテッド 抗ｔｃｒ抗体分子およびその使用
CA3214757A1 (en) * 2021-04-08 2022-10-13 Andreas Loew Multifuntional molecules binding to tcr and uses thereof
WO2023081412A2 (en) * 2021-11-05 2023-05-11 Marengo Therapeutics, Inc. Immune cell populations and uses thereof
CN118786150A (zh) * 2021-12-22 2024-10-15 马伦戈治疗公司 与tcr结合的多功能分子及其用途
WO2024197082A2 (en) * 2023-03-21 2024-09-26 Marengo Therapeutics, Inc. Tcr targeting molecules and uses thereof
WO2024226532A2 (en) * 2023-04-24 2024-10-31 Marengo Therapeutics, Inc. Multifunctional molecules binding to tcr and uses thereof
WO2025051339A1 (en) * 2023-09-05 2025-03-13 Tiber Biotech Srl SINGLE-CHAIN VARIABLE FRAGMENT AND MOLECULES DERIVING THEREFROM THAT BIND FRAGMENT TRVB5-1 OF THE β CHAIN OF HUMAN T-CELL RECEPTOR

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060115832A1 (en) * 2002-11-14 2006-06-01 Jon Wayne Cancer Institute Detection of cancer cells in body fluids
US20060275844A1 (en) * 2005-04-19 2006-12-07 Linke Steven P Diagnostic markers of breast cancer treatment and progression and methods of use thereof
WO2020142672A2 (en) * 2019-01-04 2020-07-09 Elstar Therapeutics, Inc. Anti-tcr antibody molecules and uses thereof
WO2021155112A1 (en) * 2020-01-29 2021-08-05 The Trustees Of The University Of Pennsylvania Compositions and methods of t cell receptor vb family member targeting for the treatment of t cell associated disease

Family Cites Families (663)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US861745A (en) 1906-11-21 1907-07-30 Jefferson D Maxwell Hydraulic dredging apparatus.
US4475196A (en) 1981-03-06 1984-10-02 Zor Clair G Instrument for locating faults in aircraft passenger reading light and attendant call control system
US4447233A (en) 1981-04-10 1984-05-08 Parker-Hannifin Corporation Medication infusion pump
US4433059A (en) 1981-09-08 1984-02-21 Ortho Diagnostic Systems Inc. Double antibody conjugate
US4444878A (en) 1981-12-21 1984-04-24 Boston Biomedical Research Institute, Inc. Bispecific antibody determinants
US4439196A (en) 1982-03-18 1984-03-27 Merck & Co., Inc. Osmotic drug delivery system
US4522811A (en) 1982-07-08 1985-06-11 Syntex (U.S.A.) Inc. Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides
US4447224A (en) 1982-09-20 1984-05-08 Infusaid Corporation Variable flow implantable infusion apparatus
US4487603A (en) 1982-11-26 1984-12-11 Cordis Corporation Implantable microinfusion pump system
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
US4486194A (en) 1983-06-08 1984-12-04 James Ferrara Therapeutic device for administering medicaments through the skin
WO1985000817A1 (en) 1983-08-10 1985-02-28 Amgen Microbial expression of interleukin ii
JPS6147500A (ja) 1984-08-15 1986-03-07 Res Dev Corp Of Japan キメラモノクロ−ナル抗体及びその製造法
EP0173494A3 (en) 1984-08-27 1987-11-25 The Board Of Trustees Of The Leland Stanford Junior University Chimeric receptors by dna splicing and expression
GB8422238D0 (en) 1984-09-03 1984-10-10 Neuberger M S Chimeric proteins
JPS61134325A (ja) 1984-12-04 1986-06-21 Teijin Ltd ハイブリツド抗体遺伝子の発現方法
US4596556A (en) 1985-03-25 1986-06-24 Bioject, Inc. Hypodermic injection apparatus
US4737456A (en) 1985-05-09 1988-04-12 Syntex (U.S.A.) Inc. Reducing interference in ligand-receptor binding assays
US5374548A (en) 1986-05-02 1994-12-20 Genentech, Inc. Methods and compositions for the attachment of proteins to liposomes using a glycophospholipid anchor
MX9203291A (es) 1985-06-26 1992-08-01 Liposome Co Inc Metodo para acoplamiento de liposomas.
US4676980A (en) 1985-09-23 1987-06-30 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Target specific cross-linked heteroantibodies
JPS63501765A (ja) 1985-11-01 1988-07-21 インタ−ナショナル、ジェネティック、エンジニアリング　インコ−ポレ−テッド 抗体遺伝子のモジュ−ル組立体、それにより産生された抗体及び用途
US5225539A (en) 1986-03-27 1993-07-06 Medical Research Council Recombinant altered antibodies and methods of making altered antibodies
US6548640B1 (en) 1986-03-27 2003-04-15 Btg International Limited Altered antibodies
GB8607679D0 (en) 1986-03-27 1986-04-30 Winter G P Recombinant dna product
US5869620A (en) 1986-09-02 1999-02-09 Enzon, Inc. Multivalent antigen-binding proteins
IL85035A0 (en) 1987-01-08 1988-06-30 Int Genetic Eng Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same
WO1988007089A1 (en) 1987-03-18 1988-09-22 Medical Research Council Altered antibodies
US4941880A (en) 1987-06-19 1990-07-17 Bioject, Inc. Pre-filled ampule and non-invasive hypodermic injection device assembly
US4790824A (en) 1987-06-19 1988-12-13 Bioject, Inc. Non-invasive hypodermic injection device
US5770701A (en) 1987-10-30 1998-06-23 American Cyanamid Company Process for preparing targeted forms of methyltrithio antitumor agents
US5606040A (en) 1987-10-30 1997-02-25 American Cyanamid Company Antitumor and antibacterial substituted disulfide derivatives prepared from compounds possessing a methyl-trithio group
US5057423A (en) 1987-12-18 1991-10-15 University Of Pittsburgh Method for the preparation of pure LAK-active lymphocytes
US5731116A (en) 1989-05-17 1998-03-24 Dai Nippon Printing Co., Ltd. Electrostatic information recording medium and electrostatic information recording and reproducing method
JPH021556A (ja) 1988-06-09 1990-01-05 Snow Brand Milk Prod Co Ltd ハイブリッド抗体及びその作製方法
EP0436597B1 (en) 1988-09-02 1997-04-02 Protein Engineering Corporation Generation and selection of recombinant varied binding proteins
US5223409A (en) 1988-09-02 1993-06-29 Protein Engineering Corp. Directed evolution of novel binding proteins
EP0368684B2 (en) 1988-11-11 2004-09-29 Medical Research Council Cloning immunoglobulin variable domain sequences.
US6905680B2 (en) 1988-11-23 2005-06-14 Genetics Institute, Inc. Methods of treating HIV infected subjects
US6352694B1 (en) 1994-06-03 2002-03-05 Genetics Institute, Inc. Methods for inducing a population of T cells to proliferate using agents which recognize TCR/CD3 and ligands which stimulate an accessory molecule on the surface of the T cells
US6534055B1 (en) 1988-11-23 2003-03-18 Genetics Institute, Inc. Methods for selectively stimulating proliferation of T cells
US5223426A (en) 1988-12-15 1993-06-29 T Cell Sciences, Inc. Monoclonal antibodies reactive with defined regions of the t-cell antigen receptor
US5766947A (en) 1988-12-14 1998-06-16 Astra Ab Monoclonal antibodies reactive with an epitope of a Vβ3.1 variable region of a T cell receptor
US5530101A (en) 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
US5116615A (en) 1989-01-27 1992-05-26 Immunolytics, Inc. Method for treating benign prostatic hypertrophy
GB8905669D0 (en) 1989-03-13 1989-04-26 Celltech Ltd Modified antibodies
US5108921A (en) 1989-04-03 1992-04-28 Purdue Research Foundation Method for enhanced transmembrane transport of exogenous molecules
US6291158B1 (en) 1989-05-16 2001-09-18 Scripps Research Institute Method for tapping the immunological repertoire
CA2018248A1 (en) 1989-06-07 1990-12-07 Clyde W. Shearman Monoclonal antibodies against the human alpha/beta t-cell receptor, their production and use
DE3920358A1 (de) 1989-06-22 1991-01-17 Behringwerke Ag Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung
WO1991000906A1 (en) 1989-07-12 1991-01-24 Genetics Institute, Inc. Chimeric and transgenic animals capable of producing human antibodies
US5776459A (en) 1989-07-19 1998-07-07 Connetics Corporation TCR V beta 5 peptides
AU6290090A (en) 1989-08-29 1991-04-08 University Of Southampton Bi-or trispecific (fab)3 or (fab)4 conjugates
CA2026147C (en) 1989-10-25 2006-02-07 Ravi J. Chari Cytotoxic agents comprising maytansinoids and their therapeutic use
US5208020A (en) 1989-10-25 1993-05-04 Immunogen Inc. Cytotoxic agents comprising maytansinoids and their therapeutic use
US5959177A (en) 1989-10-27 1999-09-28 The Scripps Research Institute Transgenic plants expressing assembled secretory antibodies
US5064413A (en) 1989-11-09 1991-11-12 Bioject, Inc. Needleless hypodermic injection device
US5312335A (en) 1989-11-09 1994-05-17 Bioject Inc. Needleless hypodermic injection device
US6075181A (en) 1990-01-12 2000-06-13 Abgenix, Inc. Human antibodies derived from immunized xenomice
EP1690934A3 (en) 1990-01-12 2008-07-30 Abgenix, Inc. Generation of xenogeneic antibodies
US6150584A (en) 1990-01-12 2000-11-21 Abgenix, Inc. Human antibodies derived from immunized xenomice
US5273743A (en) 1990-03-09 1993-12-28 Hybritech Incorporated Trifunctional antibody-like compounds as a combined diagnostic and therapeutic agent
US5427908A (en) 1990-05-01 1995-06-27 Affymax Technologies N.V. Recombinant library screening methods
GB9012995D0 (en) 1990-06-11 1990-08-01 Celltech Ltd Multivalent antigen-binding proteins
GB9015198D0 (en) 1990-07-10 1990-08-29 Brien Caroline J O Binding substance
EP0585287B1 (en) 1990-07-10 1999-10-13 Cambridge Antibody Technology Limited Methods for producing members of specific binding pairs
US6172197B1 (en) 1991-07-10 2001-01-09 Medical Research Council Methods for producing members of specific binding pairs
US5770429A (en) 1990-08-29 1998-06-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
ATE352612T1 (de) 1990-08-29 2007-02-15 Pharming Intellectual Pty Bv Homologe rekombination in säugetier-zellen
ATE300615T1 (de) 1990-08-29 2005-08-15 Genpharm Int Transgene mäuse fähig zur produktion heterologer antikörper
GB9022788D0 (en) 1990-10-19 1990-12-05 Cortecs Ltd Pharmaceutical formulations
CA2405246A1 (en) 1990-12-03 1992-06-11 Genentech, Inc. Enrichment method for variant proteins with alterred binding properties
US5582996A (en) 1990-12-04 1996-12-10 The Wistar Institute Of Anatomy & Biology Bifunctional antibodies and method of preparing same
US5571894A (en) 1991-02-05 1996-11-05 Ciba-Geigy Corporation Recombinant antibodies specific for a growth factor receptor
EP0575485A1 (en) 1991-03-01 1993-12-29 Dyax Corp. Process for the development of binding mini-proteins
DK0580737T3 (da) 1991-04-10 2004-11-01 Scripps Research Inst Heterodimere receptorbiblioteker ved anvendelse af phagemider
EP0519596B1 (en) 1991-05-17 2005-02-23 Merck & Co. Inc. A method for reducing the immunogenicity of antibody variable domains
DE4118120A1 (de) 1991-06-03 1992-12-10 Behringwerke Ag Tetravalente bispezifische rezeptoren, ihre herstellung und verwendung
US6511663B1 (en) 1991-06-11 2003-01-28 Celltech R&D Limited Tri- and tetra-valent monospecific antigen-binding proteins
EP1400536A1 (en) 1991-06-14 2004-03-24 Genentech Inc. Method for making humanized antibodies
US5637481A (en) 1993-02-01 1997-06-10 Bristol-Myers Squibb Company Expression vectors encoding bispecific fusion proteins and methods of producing biologically active bispecific fusion proteins in a mammalian cell
DE4122599C2 (de) 1991-07-08 1993-11-11 Deutsches Krebsforsch Phagemid zum Screenen von Antikörpern
GB9114948D0 (en) 1991-07-11 1991-08-28 Pfizer Ltd Process for preparing sertraline intermediates
US5747036A (en) 1991-08-28 1998-05-05 Brigham & Women's Hospital Methods and compositions for detecting and treating a subset of human patients having an autoimmune disease
WO1993006217A1 (en) 1991-09-19 1993-04-01 Genentech, Inc. EXPRESSION IN E. COLI OF ANTIBODY FRAGMENTS HAVING AT LEAST A CYSTEINE PRESENT AS A FREE THIOL, USE FOR THE PRODUCTION OF BIFUNCTIONAL F(ab')2 ANTIBODIES
FI941572L (fi) 1991-10-07 1994-05-27 Oncologix Inc Anti-erbB-2-monoklonaalisten vasta-aineiden yhdistelmä ja käyttömenetelmä
WO1993008829A1 (en) 1991-11-04 1993-05-13 The Regents Of The University Of California Compositions that mediate killing of hiv-infected cells
DE69232137T2 (de) 1991-11-25 2002-05-29 Enzon Inc Multivalente antigen-bindende proteine
US5932448A (en) 1991-11-29 1999-08-03 Protein Design Labs., Inc. Bispecific antibody heterodimers
DE69233408T2 (de) 1991-12-02 2005-09-22 Cambridge Antibody Technology Ltd., Melbourn Herstellung von Antikörpern auf Phagenoberflächen ausgehend von Antikörpersegmentbibliotheken.
ES2341666T3 (es) 1991-12-02 2010-06-24 Medimmune Limited Produccion de autoanticuerpos de repertorios de segmentos de anticue rpos expresados en la superficie de fagos.
GB9125768D0 (en) 1991-12-04 1992-02-05 Hale Geoffrey Therapeutic method
HU215180B (hu) 1992-01-23 1998-10-28 Merck Patent Gmbh. Eljárás monomer és dimer antitest-fragment fúziós fehérjék előállítására
AU675929B2 (en) 1992-02-06 1997-02-27 Curis, Inc. Biosynthetic binding protein for cancer marker
AU675223B2 (en) 1992-05-08 1997-01-30 Creative Biomolecules, Inc. Chimeric multivalent protein analogues and methods of use thereof
US5383851A (en) 1992-07-24 1995-01-24 Bioject Inc. Needleless hypodermic injection device
US6765087B1 (en) 1992-08-21 2004-07-20 Vrije Universiteit Brussel Immunoglobulins devoid of light chains
US6005079A (en) 1992-08-21 1999-12-21 Vrije Universiteit Brussels Immunoglobulins devoid of light chains
AU701578B2 (en) 1992-08-21 1999-02-04 Vrije Universiteit Brussel Immunoglobulins devoid of light chains
EP0669987B1 (en) 1992-09-25 2008-08-13 Aventis Pharma S.A. Adenovirus vectors for the transfer of foreign genes into cells of the central nervous system, particularly in brain
SG41929A1 (en) 1992-09-25 1997-08-15 Commw Scient Ind Res Org Target binding polypeptide
GB9221657D0 (en) 1992-10-15 1992-11-25 Scotgen Ltd Recombinant bispecific antibodies
US5837821A (en) 1992-11-04 1998-11-17 City Of Hope Antibody construct
MD1367C2 (ro) 1992-11-13 2000-11-30 Idec Pharmaceuticals Corporation Metode de tratament al limfomului celulelor B, anticorpi anti-CD20, hibridom.
GB9323648D0 (en) 1992-11-23 1994-01-05 Zeneca Ltd Proteins
US5635483A (en) 1992-12-03 1997-06-03 Arizona Board Of Regents Acting On Behalf Of Arizona State University Tumor inhibiting tetrapeptide bearing modified phenethyl amides
ATE199392T1 (de) 1992-12-04 2001-03-15 Medical Res Council Multivalente und multispezifische bindungsproteine, deren herstellung und verwendung
US5780588A (en) 1993-01-26 1998-07-14 Arizona Board Of Regents Elucidation and synthesis of selected pentapeptides
WO1994025591A1 (en) 1993-04-29 1994-11-10 Unilever N.V. PRODUCTION OF ANTIBODIES OR (FUNCTIONALIZED) FRAGMENTS THEREOF DERIVED FROM HEAVY CHAIN IMMUNOGLOBULINS OF $i(CAMELIDAE)
JPH0787994A (ja) 1993-04-30 1995-04-04 Sumitomo Electric Ind Ltd Ｔ細胞抗原受容体Ｖβ２２に対するモノクローナル抗体及びその製造方法
AU691811B2 (en) 1993-06-16 1998-05-28 Celltech Therapeutics Limited Antibodies
US6476198B1 (en) 1993-07-13 2002-11-05 The Scripps Research Institute Multispecific and multivalent antigen-binding polypeptide molecules
DE69420024T2 (de) 1993-08-10 2000-02-24 W.L. Gore & Associates, Inc. Zelleinkapselungsvorrichtung
US5635602A (en) 1993-08-13 1997-06-03 The Regents Of The University Of California Design and synthesis of bispecific DNA-antibody conjugates
WO1995009917A1 (en) 1993-10-07 1995-04-13 The Regents Of The University Of California Genetically engineered bispecific tetravalent antibodies
GB9325182D0 (en) 1993-12-08 1994-02-09 T Cell Sciences Inc Humanized antibodies or binding proteins thereof specific for t cell subpopulations exhibiting select beta chain variable regions
SE9400088D0 (sv) 1994-01-14 1994-01-14 Kabi Pharmacia Ab Bacterial receptor structures
US5773001A (en) 1994-06-03 1998-06-30 American Cyanamid Company Conjugates of methyltrithio antitumor agents and intermediates for their synthesis
US5968753A (en) 1994-06-14 1999-10-19 Nexell Therapeutics, Inc. Positive and positive/negative cell selection mediated by peptide release
JP3659261B2 (ja) 1994-10-20 2005-06-15 モルフォシス・アクチェンゲゼルシャフト 組換体タンパク質の多機能性複合体への標的化ヘテロ結合
US5789199A (en) 1994-11-03 1998-08-04 Genentech, Inc. Process for bacterial production of polypeptides
FR2727867B1 (fr) 1994-12-13 1997-01-31 Rhone Poulenc Rorer Sa Transfert de genes dans les motoneurones medullaires au moyen de vecteurs adenoviraux
AU712441B2 (en) 1994-12-14 1999-11-04 Scripps Research Institute, The In vivo activation of tumor-specific cytotoxic T cells
US5840523A (en) 1995-03-01 1998-11-24 Genetech, Inc. Methods and compositions for secretion of heterologous polypeptides
US5731168A (en) 1995-03-01 1998-03-24 Genentech, Inc. Method for making heteromultimeric polypeptides
US5641870A (en) 1995-04-20 1997-06-24 Genentech, Inc. Low pH hydrophobic interaction chromatography for antibody purification
US5869046A (en) 1995-04-14 1999-02-09 Genentech, Inc. Altered polypeptides with increased half-life
CA2222055A1 (en) 1995-05-23 1996-11-28 Morphosys Gesellschaft Fur Proteinoptimierung Mbh Multimeric proteins
US5712374A (en) 1995-06-07 1998-01-27 American Cyanamid Company Method for the preparation of substantiallly monomeric calicheamicin derivative/carrier conjugates
US5626561A (en) 1995-06-07 1997-05-06 Gore Hybrid Technologies, Inc. Implantable containment apparatus for a therapeutical device and method for loading and reloading the device therein
WO1996039993A1 (en) 1995-06-07 1996-12-19 Gore Hybrid Technologies, Inc. An implantable containment apparatus for a therapeutical device and method for loading and reloading the device therein
US5714586A (en) 1995-06-07 1998-02-03 American Cyanamid Company Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates
US5811097A (en) 1995-07-25 1998-09-22 The Regents Of The University Of California Blockade of T lymphocyte down-regulation associated with CTLA-4 signaling
US6267958B1 (en) 1995-07-27 2001-07-31 Genentech, Inc. Protein formulation
AU6854696A (en) 1995-09-22 1997-04-09 Gore Hybrid Technologies, Inc. Improved cell encapsulation device
US5989830A (en) 1995-10-16 1999-11-23 Unilever Patent Holdings Bv Bifunctional or bivalent antibody fragment analogue
GB9603256D0 (en) 1996-02-16 1996-04-17 Wellcome Found Antibodies
US5849589A (en) 1996-03-11 1998-12-15 Duke University Culturing monocytes with IL-4, TNF-α and GM-CSF TO induce differentiation to dendric cells
ES2225961T3 (es) 1996-04-04 2005-03-16 Unilever N.V. Proteina de union a antigeno multivalente y multiespecifica.
WO1998014206A1 (en) 1996-10-04 1998-04-09 Thomas Jefferson University T cells mediating an immune response and methods of use
EP0981548A4 (en) 1997-04-30 2005-11-23 Enzon Inc GLYCOSYLATABLE SINGLE CHAIN ANTIGEN-BINDING PROTEINS, MANUFACTURE AND USE THEREOF
US20030207346A1 (en) 1997-05-02 2003-11-06 William R. Arathoon Method for making multispecific antibodies having heteromultimeric and common components
US20020062010A1 (en) 1997-05-02 2002-05-23 Genentech, Inc. Method for making multispecific antibodies having heteromultimeric and common components
AU736707B2 (en) 1997-06-11 2001-08-02 Anaphore, Inc. Trimerising module
EP1958962A3 (en) 1997-06-12 2013-05-01 Novartis International Pharmaceutical Ltd. Artificial antibody polypeptides
US6171586B1 (en) 1997-06-13 2001-01-09 Genentech, Inc. Antibody formulation
ATE296315T1 (de) 1997-06-24 2005-06-15 Genentech Inc Galactosylierte glykoproteine enthaltende zusammensetzungen und verfahren zur deren herstellung
DE69837706T2 (de) 1997-07-21 2008-01-10 Active Biotech Ab Zytolyse der geeigneten zielzellen mit superantigen konjugate mittels der induktion von t-zell aktivierung
US6040498A (en) 1998-08-11 2000-03-21 North Caroline State University Genetically engineered duckweed
DE19742706B4 (de) 1997-09-26 2013-07-25 Pieris Proteolab Ag Lipocalinmuteine
GB9722131D0 (en) 1997-10-20 1997-12-17 Medical Res Council Method
BR9813276A (pt) 1997-10-27 2000-08-22 Unilever Nv Proteìna multivalente de ligação de antìgeno, sequências de nucleotìdeos, vetor de expressão, célula hospedeira, processo para preparação de proteìna multivalente de ligação de antìgeno, e, uso da mesma
WO1999022764A1 (en) 1997-10-31 1999-05-14 Genentech, Inc. Methods and compositions comprising glycoprotein glycoforms
US6610833B1 (en) 1997-11-24 2003-08-26 The Institute For Human Genetics And Biochemistry Monoclonal human natural antibodies
ES2375931T3 (es) 1997-12-05 2012-03-07 The Scripps Research Institute Humanización de anticuerpo murino.
ES2234241T3 (es) 1998-01-23 2005-06-16 Vlaams Interuniversitair Instituut Voor Biotechnologie Derivados de anticuerpo de multiples fines.
AUPP221098A0 (en) 1998-03-06 1998-04-02 Diatech Pty Ltd V-like domain binding molecules
US6194551B1 (en) 1998-04-02 2001-02-27 Genentech, Inc. Polypeptide variants
ES2292236T3 (es) 1998-04-02 2008-03-01 Genentech, Inc. Variantes de anticuerpos y sus fragmentos.
HUP9900956A2 (hu) 1998-04-09 2002-04-29 Aventis Pharma Deutschland Gmbh. Egyláncú, több antigéntkötőhely kialakítására képes molekulák, előállításuk és alkalmazásuk
ES2434961T5 (es) 1998-04-20 2018-01-18 Roche Glycart Ag Ingeniería de glicosilación de anticuerpos para mejorar la citotoxicidad celular dependiente del anticuerpo
DE19819846B4 (de) 1998-05-05 2016-11-24 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Multivalente Antikörper-Konstrukte
GB9812545D0 (en) 1998-06-10 1998-08-05 Celltech Therapeutics Ltd Biological products
EP1100830B1 (en) 1998-07-28 2003-10-01 Micromet AG Heterominibodies
AU5245399A (en) 1998-07-29 2000-02-21 Heska Corporation T cell receptor proteins, nucleic acid molecules, and uses thereof
US6333396B1 (en) 1998-10-20 2001-12-25 Enzon, Inc. Method for targeted delivery of nucleic acids
US6818418B1 (en) 1998-12-10 2004-11-16 Compound Therapeutics, Inc. Protein scaffolds for antibody mimics and other binding proteins
DE69941267D1 (de) 1998-12-10 2009-09-24 Bristol Myers Squibb Co Proteingerüste für antikörper-nachahmer und andere bindende proteine
HU230769B1 (hu) 1999-01-15 2018-03-28 Genentech Inc. Módosított effektor-funkciójú polipeptid-változatok
US6737056B1 (en) 1999-01-15 2004-05-18 Genentech, Inc. Polypeptide variants with altered effector function
US20030095967A1 (en) 1999-01-25 2003-05-22 Mackay Fabienne BAFF, inhibitors thereof and their use in the modulation of B-cell response and treatment of autoimmune disorders
WO2000060070A1 (en) 1999-04-01 2000-10-12 Innogenetics N.V. A polypeptide structure for use as a scaffold
EP1176195B1 (en) 1999-04-09 2013-05-22 Kyowa Hakko Kirin Co., Ltd. Method for controlling the activity of immunologically functional molecule
US7527787B2 (en) 2005-10-19 2009-05-05 Ibc Pharmaceuticals, Inc. Multivalent immunoglobulin-based bioactive assemblies
US7534866B2 (en) 2005-10-19 2009-05-19 Ibc Pharmaceuticals, Inc. Methods and compositions for generating bioactive assemblies of increased complexity and uses
DE19932688B4 (de) 1999-07-13 2009-10-08 Scil Proteins Gmbh Design von Beta-Faltblatt-Proteinen des gamma-II-kristallins antikörperähnlichen
UA75049C2 (uk) 1999-08-17 2006-03-15 Байоджен Айдек Ма Інк. Фармацевтична композиція, що містить поліпептид, який являє собою білковий фактор дозрівання в-клітин (всма), що зв'язується з фактором активації в-клітин (baff), спосіб інгібування росту в-клітин, спосіб лікування аутоімунного захворювання, спосіб лікування гіпертонії, спосіб інгібування запалення та спосіб модулювання імунної відповіді у ссавця за допомогою всма
US7125978B1 (en) 1999-10-04 2006-10-24 Medicago Inc. Promoter for regulating expression of foreign genes
CN100427603C (zh) 1999-10-04 2008-10-22 麦迪卡格公司 调控外源基因转录的方法
UA74798C2 (uk) 1999-10-06 2006-02-15 Байоджен Айдек Ма Інк. Спосіб лікування раку у ссавця за допомогою поліпептиду, що протидіє взаємодії april з його рецепторами
CA2388245C (en) 1999-10-19 2012-01-10 Kyowa Kirin Co., Ltd. The use of serum-free adapted rat cells for producing heterologous polypeptides
US6979546B2 (en) 1999-11-15 2005-12-27 Universita Di Genova Triggering receptor involved in natural cytotoxicity mediated by human natural killer cells and antibodies that identify the same
ATE423848T1 (de) 1999-11-15 2009-03-15 Innate Pharma Auslösender rezeptor der an der natürlichen cytotoxizität der menschlichen natürlichen killerzellen (natural killer cells) beteiligt ist und antikörper die diesen rezeptor identifizieren
US7105149B1 (en) 1999-11-29 2006-09-12 The Trustees Of Columbia University In The City Of New York Isolation of five novel genes coding for new Fc receptors-type melanoma involved in the pathogenesis of lymphoma/myeloma
AU784983B2 (en) 1999-12-15 2006-08-17 Genentech Inc. Shotgun scanning, a combinatorial method for mapping functional protein epitopes
ATE344801T1 (de) 1999-12-29 2006-11-15 Immunogen Inc Doxorubicin- und daunorubicin-enthaltende, zytotoxische mittel und deren therapeutische anwendung
AU2001227966A1 (en) 2000-01-20 2001-07-31 Chiron Corporation Methods for treating tumors
US20040002068A1 (en) 2000-03-01 2004-01-01 Corixa Corporation Compositions and methods for the detection, diagnosis and therapy of hematological malignancies
CN101289511A (zh) 2000-04-11 2008-10-22 杰南技术公司 多价抗体及其应用
EP1299419A2 (en) 2000-05-24 2003-04-09 Imclone Systems, Inc. Bispecific immunoglobulin-like antigen binding proteins and method of production
DK2336187T3 (en) 2000-06-19 2016-08-22 Beth Israel Deaconess Medical Ct Inc Compositions and Methods of monoclonal and polyclonal antibodies which are specific for T-cell subpopulations
CA2410551A1 (en) 2000-06-30 2002-01-10 Vlaams Interuniversitair Instituut Voor Biotechnologie Vzw (Vib) Heterodimeric fusion proteins
IL137419A0 (en) 2000-07-20 2001-07-24 Yissum Res Dev Co Nk cells activating receptors and their therapeutic and diagnostic uses
JP2004523205A (ja) 2000-07-25 2004-08-05 イムノメディクス， インコーポレイテッド 多価標的結合タンパク質
US7064191B2 (en) 2000-10-06 2006-06-20 Kyowa Hakko Kogyo Co., Ltd. Process for purifying antibody
US6946292B2 (en) 2000-10-06 2005-09-20 Kyowa Hakko Kogyo Co., Ltd. Cells producing antibody compositions with increased antibody dependent cytotoxic activity
ES2639222T5 (es) 2000-10-06 2023-11-24 Kyowa Kirin Co Ltd Células que producen unas composiciones de anticuerpo
EP2351838A1 (en) 2000-10-20 2011-08-03 Chugai Seiyaku Kabushiki Kaisha Crosslinking agonistic antibodies
US6596541B2 (en) 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
CN1487996B (zh) 2000-11-30 2010-06-16 米德列斯公司 用于生产人类抗体的转基因转染色体啮齿动物
US7829084B2 (en) 2001-01-17 2010-11-09 Trubion Pharmaceuticals, Inc. Binding constructs and methods for use thereof
ES2365602T3 (es) 2001-03-05 2011-10-07 Yissum Research Development Company Of The Hebrew University Of Jerusalem Proteínas oligoméricas tipo chaperona, estables a desnaturalizantes y/o resistentes a proteasa, polinucleótidos que codifican las mismas y sus usos.
WO2002072635A2 (en) 2001-03-13 2002-09-19 University College London Specific binding members
US20050048512A1 (en) 2001-04-26 2005-03-03 Avidia Research Institute Combinatorial libraries of monomer domains
US20040175756A1 (en) 2001-04-26 2004-09-09 Avidia Research Institute Methods for using combinatorial libraries of monomer domains
US20050053973A1 (en) 2001-04-26 2005-03-10 Avidia Research Institute Novel proteins with targeted binding
ES2437875T3 (es) 2001-04-30 2014-01-14 Eli Lilly And Company Anticuerpos humanizados que reconocen el péptido beta-amiloide
DK1399484T3 (da) 2001-06-28 2010-11-08 Domantis Ltd Dobbelt-specifik ligand og anvendelse af denne
US6833441B2 (en) 2001-08-01 2004-12-21 Abmaxis, Inc. Compositions and methods for generating chimeric heteromultimers
EP2180044A1 (en) 2001-08-03 2010-04-28 GlycArt Biotechnology AG Antibody glycosylation variants having increased anti-body-dependent cellular cytotoxicity
CA2763913C (en) 2001-08-10 2014-10-28 Aberdeen University Antigen binding domains
DE60124912T2 (de) 2001-09-14 2007-06-14 Affimed Therapeutics Ag Multimerische, einzelkettige, Tandem-Fv-Antikörper
US7084257B2 (en) 2001-10-05 2006-08-01 Amgen Inc. Fully human antibody Fab fragments with human interferon-gamma neutralizing activity
HUP0600342A3 (en) 2001-10-25 2011-03-28 Genentech Inc Glycoprotein compositions
PT1454138E (pt) 2001-12-04 2012-03-28 Merck Patent Gmbh Imunocitoquinas com seletividade modulada
US20030211078A1 (en) 2001-12-07 2003-11-13 Heavner George A. Pseudo-antibody constructs
US20040093621A1 (en) 2001-12-25 2004-05-13 Kyowa Hakko Kogyo Co., Ltd Antibody composition which specifically binds to CD20
JP4820055B2 (ja) 2001-12-27 2011-11-24 グライコフィ， インコーポレイテッド 哺乳動物型糖質構造を操作するための方法
AU2003209272A1 (en) 2002-01-16 2003-09-02 Zyomyx, Inc. Engineered binding proteins
AU2003221256A1 (en) 2002-02-21 2003-09-09 Biogen Idec Ma Inc. Use of bcma as an immunoregulatory agent
CA2478011C (en) 2002-03-01 2013-05-21 Immunomedics, Inc. Bispecific antibody point mutations for enhancing rate of clearance
JP4832719B2 (ja) 2002-04-09 2011-12-07 協和発酵キリン株式会社 ＦｃγＲＩＩＩａ多型患者に適応する抗体組成物含有医薬
US20040259150A1 (en) 2002-04-09 2004-12-23 Kyowa Hakko Kogyo Co., Ltd. Method of enhancing of binding activity of antibody composition to Fcgamma receptor IIIa
ATE503829T1 (de) 2002-04-09 2011-04-15 Kyowa Hakko Kirin Co Ltd Zelle mit erniedrigter oder deletierter aktivität eines am gdp-fucosetransport beteiligten proteins
CA2481920A1 (en) 2002-04-09 2003-10-16 Kyowa Hakko Kogyo Co., Ltd. Antibody composition-containing medicament
EA200401325A1 (ru) 2002-04-09 2005-04-28 Киова Хакко Когио Ко., Лтд. Клетки с модифицированным геномом
US20040132140A1 (en) 2002-04-09 2004-07-08 Kyowa Hakko Kogyo Co., Ltd. Production process for antibody composition
EP1500665B1 (en) 2002-04-15 2011-06-15 Chugai Seiyaku Kabushiki Kaisha METHODS FOR CONSTRUCTING scDb LIBRARIES
JP2006506954A (ja) 2002-04-29 2006-03-02 ゲンパト７７ ファーマコジェネティクス エージー Ｔｃｒ及びｔｉｒｃ７に結合する新規な抗体、並びに治療及び診断におけるその使用
US7829289B2 (en) 2002-05-14 2010-11-09 Institut National De La Sante Et De Recherche Medicale T cell subpopulation regulating gut immunity
EP1513879B1 (en) 2002-06-03 2018-08-22 Genentech, Inc. Synthetic antibody phage libraries
US7906118B2 (en) 2005-04-06 2011-03-15 Ibc Pharmaceuticals, Inc. Modular method to prepare tetrameric cytokines with improved pharmacokinetics by the dock-and-lock (DNL) technology
ES2263984T3 (es) 2002-06-28 2006-12-16 Domantis Limited Ligandos doble-especificos con una vida media serica aumentada.
NZ537277A (en) 2002-07-18 2008-04-30 Crucell Holland Bv Recombinant production of mixtures of antibodies
DE60333201D1 (de) 2002-09-12 2010-08-12 Greenovation Biotech Gmbh Verfahren zur herstellung von proteinen
AU2003271904B2 (en) 2002-10-09 2009-03-05 Adaptimmune Limited Single chain recombinant T cell receptors
US7361740B2 (en) 2002-10-15 2008-04-22 Pdl Biopharma, Inc. Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis
WO2004053054A2 (en) 2002-12-09 2004-06-24 Natspears Ltd. Nk cell receptor conjugates for treating malignancies
EP3263596A1 (en) 2002-12-16 2018-01-03 Genentech, Inc. Immunoglobulin variants and uses thereof
US7781197B2 (en) 2002-12-20 2010-08-24 Greenovation Biotech Gmbh Transformed bryophyte cell having disrupted endogenous alpha 1,3-fucosyl and beta 1,2-xylosyl transferase encoding nucleotide sequences for the production of heterologous glycosylated proteins
DE10261223A1 (de) 2002-12-20 2004-07-08 MedInnova Gesellschaft für medizinische Innovationen aus akademischer Forschung mbH Steigerung der Immunantwort durch Substanzen, welche die Funktion von Natürlichen Killerzellen beeinflussen
CN1753912B (zh) 2002-12-23 2011-11-02 惠氏公司 抗pd-1抗体及其用途
WO2004056392A1 (en) 2002-12-23 2004-07-08 Innate Pharma Pharmaceutical compositions having an effect on the proliferation of nk cells and a method using the same
AU2003290330A1 (en) 2002-12-27 2004-07-22 Domantis Limited Dual specific single domain antibodies specific for a ligand and for the receptor of the ligand
GB0230203D0 (en) 2002-12-27 2003-02-05 Domantis Ltd Fc fusion
JP2006524039A (ja) 2003-01-09 2006-10-26 マクロジェニクス，インコーポレーテッド 変異型Ｆｃ領域を含む抗体の同定および作製ならびにその利用法
CA2510003A1 (en) 2003-01-16 2004-08-05 Genentech, Inc. Synthetic antibody phage libraries
CN103540600B (zh) 2003-01-22 2017-12-01 罗氏格黎卡特股份公司 融合构建体及其用来生产Fc受体结合亲和性和效应子功能提高的抗体的用途
US7871607B2 (en) 2003-03-05 2011-01-18 Halozyme, Inc. Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminoglycanases
ES2532399T3 (es) 2003-03-05 2015-03-26 Halozyme, Inc. Glicoproteína hialuronidasa soluble (sHASEGP), proceso para prepararla, usos y composiciones farmacéuticas que la comprenden
US20060104968A1 (en) 2003-03-05 2006-05-18 Halozyme, Inc. Soluble glycosaminoglycanases and methods of preparing and using soluble glycosaminogly ycanases
GB0305702D0 (en) 2003-03-12 2003-04-16 Univ Birmingham Bispecific antibodies
WO2004094620A2 (en) 2003-03-28 2004-11-04 Biogen Idec Ma Inc. Truncated baff receptors
US20050003403A1 (en) 2003-04-22 2005-01-06 Rossi Edmund A. Polyvalent protein complex
WO2005028517A2 (en) 2003-05-09 2005-03-31 The General Hospital Corporation SOLUBLE TGF-β TYPE III RECEPTOR FUSION PROTEINS
CA2525251C (en) 2003-05-09 2015-10-27 Duke University Cd20-specific antibodies and methods employing same
US20090005257A1 (en) 2003-05-14 2009-01-01 Jespers Laurent S Process for Recovering Polypeptides that Unfold Reversibly from a Polypeptide Repertoire
US20070105105A1 (en) 2003-05-23 2007-05-10 Mount Sinai School Of Medicine Of New York University Surrogate cell gene expression signatures for evaluating the physical state of a subject
DE10324447A1 (de) 2003-05-28 2004-12-30 Scil Proteins Gmbh Generierung künstlicher Bindungsproteine auf der Grundlage von Ubiquitin
ES2408582T3 (es) 2003-05-30 2013-06-21 Merus B.V. Biblioteca de Fab para la preparación de una mezcla de anticuerpos
CA2529945A1 (en) 2003-06-27 2005-01-06 Biogen Idec Ma Inc. Use of hydrophobic-interaction-chromatography or hinge-region modifications for the production of homogeneous antibody-solutions
CN1845938B (zh) 2003-06-30 2010-05-26 杜门蒂斯有限公司 多肽
KR20060041205A (ko) 2003-07-01 2006-05-11 이뮤노메딕스, 인코오포레이티드 양특이성 항체들의 다가 담체들
US7803376B2 (en) 2003-07-24 2010-09-28 Innate Pharma S.A. Methods and compositions for increasing the efficiency of therapeutic antibodies using NK cell potentiating compounds
US7696322B2 (en) 2003-07-28 2010-04-13 Catalent Pharma Solutions, Inc. Fusion antibodies
US20080241884A1 (en) 2003-10-08 2008-10-02 Kenya Shitara Fused Protein Composition
JPWO2005035778A1 (ja) 2003-10-09 2006-12-21 協和醗酵工業株式会社 α１，６−フコシルトランスフェラーゼの機能を抑制するＲＮＡを用いた抗体組成物の製造法
AU2004285455A1 (en) 2003-10-20 2005-05-12 Biogen Idec Ma Inc. Therapeutic regimens for BAFF antagonists
ES2672640T3 (es) 2003-11-05 2018-06-15 Roche Glycart Ag Moléculas de unión a antígeno con afinidad de unión a receptores Fc y función efectora incrementadas
US7498298B2 (en) 2003-11-06 2009-03-03 Seattle Genetics, Inc. Monomethylvaline compounds capable of conjugation to ligands
WO2005053742A1 (ja) 2003-12-04 2005-06-16 Kyowa Hakko Kogyo Co., Ltd. 抗体組成物を含有する医薬
GB0328363D0 (en) 2003-12-06 2004-01-14 Imp College Innovations Ltd Therapeutically useful molecules
US20050136051A1 (en) 2003-12-22 2005-06-23 Bernard Scallon Methods for generating multimeric molecules
GB0329825D0 (en) 2003-12-23 2004-01-28 Celltech R&D Ltd Biological products
US20050266425A1 (en) 2003-12-31 2005-12-01 Vaccinex, Inc. Methods for producing and identifying multispecific antibodies
US8383575B2 (en) 2004-01-30 2013-02-26 Paul Scherrer Institut (DI)barnase-barstar complexes
AU2005227322A1 (en) 2004-03-23 2005-10-06 Biogen Idec Ma Inc. Receptor coupling agents and therapeutic uses thereof
CN1961003B (zh) 2004-03-31 2013-03-27 健泰科生物技术公司 人源化抗TGF-β抗体
US7785903B2 (en) 2004-04-09 2010-08-31 Genentech, Inc. Variable domain library and uses
KR100891620B1 (ko) 2004-04-13 2009-04-02 에프. 호프만-라 로슈 아게 항-ｐ-셀렉틴 항체
WO2005105848A1 (en) 2004-04-30 2005-11-10 Innate Pharma Compositions and methods for enhancing nk cell activity
WO2005105849A1 (en) 2004-04-30 2005-11-10 Innate Pharma Compositions and methods for treating proliferative disorders such as nk-type ldgl
US7501121B2 (en) 2004-06-17 2009-03-10 Wyeth IL-13 binding agents
US20060008844A1 (en) 2004-06-17 2006-01-12 Avidia Research Institute c-Met kinase binding proteins
US8361794B2 (en) 2004-06-29 2013-01-29 Immunocore Limited Cells expressing a modified T cell receptor
JP2008512352A (ja) 2004-07-17 2008-04-24 イムクローン システムズ インコーポレイティド 新規な四価の二重特異性抗体
EP1773885B1 (en) 2004-08-05 2010-04-21 Genentech, Inc. Humanized anti-cmet antagonists
EP1789446A2 (en) 2004-09-02 2007-05-30 Genentech, Inc. Heteromultimeric molecules
TWI309240B (en) 2004-09-17 2009-05-01 Hoffmann La Roche Anti-ox40l antibodies
KR101270829B1 (ko) 2004-09-23 2013-06-07 제넨테크, 인크. 시스테인 유전자조작 항체 및 접합체
EA011879B1 (ru) 2004-09-24 2009-06-30 Эмджин Инк. МОЛЕКУЛЫ С МОДИФИЦИРОВАННЫМ Fc ФРАГМЕНТОМ
WO2006039238A2 (en) 2004-09-30 2006-04-13 The Goverment Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Irta2 antibodies and methods of use
JO3000B1 (ar) 2004-10-20 2016-09-05 Genentech Inc مركبات أجسام مضادة .
CN101072793B (zh) 2004-12-09 2012-06-20 默克专利有限公司 具有降低的免疫原性的il-7变体
US20080247944A1 (en) 2005-01-12 2008-10-09 Robert Graziano Irta-2 Antibodies and Their Uses
AU2006207987B2 (en) 2005-01-27 2011-09-15 Novartis Vaccines And Diagnostics Inc. Methods for treating renal cell carcinoma
AU2005325801A1 (en) 2005-01-31 2006-08-03 Ablynx N.V. Method for generating variable domain sequences of heavy chain antibodies
US7431380B1 (en) 2005-02-24 2008-10-07 Theodore Allen Buresh Louver kit
EP3050963B1 (en) 2005-03-31 2019-09-18 Chugai Seiyaku Kabushiki Kaisha Process for production of polypeptide by regulation of assembly
EP1874824A4 (en) 2005-04-06 2009-12-30 Ibc Pharmaceuticals Inc METHODS OF GENERATING STABLE COMPOUND RELATED COMPLEXES OF HOMODIMERS, HOMOTRATEERS OR DIMER SIZES AND USES THEREOF
EP3479844B1 (en) 2005-04-15 2023-11-22 MacroGenics, Inc. Covalent diabodies and uses thereof
AU2006237329B2 (en) 2005-04-18 2012-04-12 Novo Nordisk A/S IL-21 variants
RU2494107C2 (ru) 2005-05-09 2013-09-27 Оно Фармасьютикал Ко., Лтд. Моноклональные антитела человека к белку программируемой смерти 1 (pd-1) и способы лечения рака с использованием анти-pd-1-антител самостоятельно или в комбинации с другими иммунотерапевтическими средствами
US20060263367A1 (en) 2005-05-23 2006-11-23 Fey Georg H Bispecific antibody devoid of Fc region and method of treatment using same
WO2006135886A2 (en) 2005-06-13 2006-12-21 The Regents Of The University Of Michigan Compositions and methods for treating and diagnosing cancer
JP2006345852A (ja) 2005-06-16 2006-12-28 Virxsys Corp 抗体複合体
CN103145839A (zh) 2005-06-30 2013-06-12 Abbvie公司 Il-12/p40结合蛋白
CN104356236B (zh) 2005-07-01 2020-07-03 E.R.施贵宝&圣斯有限责任公司 抗程序性死亡配体1(pd-l1)的人单克隆抗体
ES2401706T3 (es) 2005-07-27 2013-04-23 Eli Lilly And Company Un método de tratar células cancerosas para crear una célula cancerosa modificada que provoca una respuesta inmunogénica
US7612181B2 (en) 2005-08-19 2009-11-03 Abbott Laboratories Dual variable domain immunoglobulin and uses thereof
ATE452913T1 (de) 2005-08-26 2010-01-15 Pls Design Gmbh Bivalente igy antikörperkonstrukte für diagnostische und therapeutische anwendungen
EP3190125A1 (en) 2005-08-31 2017-07-12 Merck Sharp & Dohme Corp. Engineered anti-il-23 antibodies
EP1929302A2 (en) 2005-09-23 2008-06-11 Novo Nordisk A/S Methods of identifying antibodies to ligands of orphan receptors
WO2007042809A2 (en) 2005-10-11 2007-04-19 Domantis Limited Antibody polypeptide library screening and selected antibody polypeptides
WO2007044887A2 (en) 2005-10-11 2007-04-19 Transtarget, Inc. Method for producing a population of homogenous tetravalent bispecific antibodies
WO2007047335A2 (en) 2005-10-13 2007-04-26 Biogen Idec Ma Inc. Methods for use with baff antagonists
AU2006301163B2 (en) 2005-10-14 2012-02-23 Innate Pharma Compositions and methods for treating proliferative disorders
WO2007048849A1 (en) 2005-10-28 2007-05-03 Novo Nordisk A/S Fusion proteins that bind effector lymphocytes and target cells
EP1957531B1 (en) 2005-11-07 2016-04-13 Genentech, Inc. Binding polypeptides with diversified and consensus vh/vl hypervariable sequences
US10155816B2 (en) 2005-11-28 2018-12-18 Genmab A/S Recombinant monovalent antibodies and methods for production thereof
WO2007062466A1 (en) 2005-11-29 2007-06-07 The University Of Sydney Demibodies: dimerisation-activated therapeutic agents
WO2007064919A2 (en) 2005-12-02 2007-06-07 Genentech, Inc. Binding polypeptides with restricted diversity sequences
WO2007095338A2 (en) 2006-02-15 2007-08-23 Imclone Systems Incorporated Functional antibodies
EP1991679A2 (fr) 2006-03-08 2008-11-19 Biomethodes Variants de l'interferon- gamma humain (ifngamma)
KR101516823B1 (ko) 2006-03-17 2015-05-07 바이오겐 아이덱 엠에이 인코포레이티드 안정화된 폴리펩티드 조성물
US8946391B2 (en) 2006-03-24 2015-02-03 The Regents Of The University Of California Construction of a multivalent scFv through alkyne-azide 1,3-dipolar cycloaddition
US8871912B2 (en) 2006-03-24 2014-10-28 Merck Patent Gmbh Engineered heterodimeric protein domains
US9670269B2 (en) 2006-03-31 2017-06-06 Chugai Seiyaku Kabushiki Kaisha Methods of modifying antibodies for purification of bispecific antibodies
JP2009536527A (ja) 2006-05-09 2009-10-15 ジェネンテック・インコーポレーテッド 最適化されたスキャフォールドを備えた結合ポリペプチド
JP5189082B2 (ja) 2006-05-25 2013-04-24 バイエル・ファルマ・アクチェンゲゼルシャフト 二量体分子複合体
US20070274985A1 (en) 2006-05-26 2007-11-29 Stefan Dubel Antibody
WO2007146968A2 (en) 2006-06-12 2007-12-21 Trubion Pharmaceuticals, Inc. Single-chain multivalent binding proteins with effector function
WO2008017859A2 (en) 2006-08-10 2008-02-14 Isis Innovation Limited Ligand for the g6b receptor on blood platelets
WO2008073160A2 (en) 2006-08-17 2008-06-19 The Trustees Of Columbia University In The City Of New York Methods for converting or inducing protective immunity
WO2008022349A2 (en) 2006-08-18 2008-02-21 Armagen Technologies, Inc. Agents for blood-brain barrier delivery
WO2008027236A2 (en) 2006-08-30 2008-03-06 Genentech, Inc. Multispecific antibodies
ES2566502T3 (es) 2006-09-13 2016-04-13 The Trustees Of Columbia University In The City Of New York Agentes y métodos para provocar una respuesta inmune antitumoral
CA2668208C (en) 2006-11-02 2017-09-12 Daniel J. Capon Hybrid immunoglobulins with moving parts
US20080226635A1 (en) 2006-12-22 2008-09-18 Hans Koll Antibodies against insulin-like growth factor I receptor and uses thereof
WO2008087219A1 (en) 2007-01-19 2008-07-24 INSERM (Institut National de la Santé et de la Recherche Médicale) Compositions and methods for regulating t cell activity
WO2008119353A1 (en) 2007-03-29 2008-10-09 Genmab A/S Bispecific antibodies and methods for production thereof
EP2144930A1 (en) 2007-04-18 2010-01-20 ZymoGenetics, Inc. Single chain fc, methods of making and methods of treatment
DK2160401T3 (da) 2007-05-11 2014-10-20 Altor Bioscience Corp Fusionsmolekyler og il-15-varianter
TW201531484A (zh) 2007-05-21 2015-08-16 Alder Biopharmaceuticals Inc 抗ＴＮＦ-α之抗體及其用途
CN100592373C (zh) 2007-05-25 2010-02-24 群康科技(深圳)有限公司 液晶显示面板驱动装置及其驱动方法
HRP20131167T1 (hr) 2007-06-18 2014-01-03 Merck Sharp & Dohme B.V. Antitijela za humani receptor programirane smrti pd-1
EP2014680A1 (en) 2007-07-10 2009-01-14 Friedrich-Alexander-Universität Erlangen-Nürnberg Recombinant, single-chain, trivalent tri-specific or bi-specific antibody derivatives
KR20100058509A (ko) 2007-07-31 2010-06-03 메디뮨 엘엘씨 다중특이적 에피토프 결합 단백질 및 이의 용도
WO2009021754A2 (en) 2007-08-15 2009-02-19 Bayer Schering Pharma Aktiengesellschaft Monospecific and multispecific antibodies and method of use
AU2008304748C1 (en) 2007-09-26 2014-06-12 Chugai Seiyaku Kabushiki Kaisha Modified antibody constant region
KR101662622B1 (ko) 2007-10-04 2016-10-05 지모제넥틱스, 인코포레이티드 Ｂ7 패밀리 구성원 ｚＢ7Ｈ6 및 관련된 조성물 및 방법
UA104132C2 (en) 2007-11-13 2014-01-10 Тева Биофармасьютикалз Юесей, Инк. Humanized antibodies against tl1a
EP2220120A2 (en) 2007-11-27 2010-08-25 Ablynx N.V. Amino acid sequences directed against heterodimeric cytokines and/or their receptors and polypeptides comprising the same
AU2008328726B2 (en) 2007-11-30 2014-06-12 Glaxo Group Limited Antigen-binding constructs
RU2570559C2 (ru) 2007-12-17 2015-12-10 Пфайзер Лимитед Лечение интерстициального цистита
US8242247B2 (en) 2007-12-21 2012-08-14 Hoffmann-La Roche Inc. Bivalent, bispecific antibodies
US8227577B2 (en) 2007-12-21 2012-07-24 Hoffman-La Roche Inc. Bivalent, bispecific antibodies
US9266967B2 (en) 2007-12-21 2016-02-23 Hoffmann-La Roche, Inc. Bivalent, bispecific antibodies
US20090162359A1 (en) 2007-12-21 2009-06-25 Christian Klein Bivalent, bispecific antibodies
ES2563027T3 (es) 2008-01-07 2016-03-10 Amgen Inc. Método para fabricación de moléculas heterodímeras Fc de anticuerpos utilizando efectos de conducción electrostática
PT2242773T (pt) 2008-02-11 2017-09-15 Cure Tech Ltd Anticorpos monoclonais para o tratamento de tumores
CA2712474A1 (en) 2008-02-21 2009-08-27 Baxter Healthcare S.A. Procedure for the generation of a high producer cell line for the expression of a recombinant anti-cd34 antibody
WO2009114335A2 (en) 2008-03-12 2009-09-17 Merck & Co., Inc. Pd-1 binding proteins
KR102057826B1 (ko) 2008-04-11 2019-12-20 추가이 세이야쿠 가부시키가이샤 복수 분자의 항원에 반복 결합하는 항원 결합 분자
US9593376B2 (en) 2008-06-02 2017-03-14 Institut Gustave Roussy Natural killer p30 (NKp30) dysfunction and the biological applications thereof
AR072999A1 (es) 2008-08-11 2010-10-06 Medarex Inc Anticuerpos humanos que se unen al gen 3 de activacion linfocitaria (lag-3) y los usos de estos
CN102203132A (zh) 2008-08-25 2011-09-28 安普利穆尼股份有限公司 Pd-1拮抗剂的组合物和使用方法
WO2010098788A2 (en) 2008-08-25 2010-09-02 Amplimmune, Inc. Pd-i antagonists and methods for treating infectious disease
AU2009288354A1 (en) 2008-08-26 2010-03-11 Macrogenics Inc. T-cell receptor antibodies and methods of use thereof
TWI516501B (zh) 2008-09-12 2016-01-11 禮納特神經系統科學公司 Ｐｃｓｋ９拮抗劑類
EP2326670A4 (en) 2008-09-17 2014-04-16 Nat Res Council Canada HETERO MULTIVALENT BINDING AGENT FOR ELEMENTS OF THE TGF-BETA SUPERFAMILY
AU2009333580B2 (en) 2008-12-09 2016-07-07 Genentech, Inc. Anti-PD-L1 antibodies and their use to enhance T-cell function
US8580267B2 (en) 2008-12-19 2013-11-12 Philogen S.P.A. Immunocytokines for tumour therapy with chemotherapeutic agents
WO2010089411A2 (en) 2009-02-09 2010-08-12 Universite De La Mediterranee Pd-1 antibodies and pd-l1 antibodies and uses thereof
EP2406284B9 (en) 2009-03-10 2017-03-01 Biogen MA Inc. Anti-bcma antibodies
WO2010120561A1 (en) 2009-04-01 2010-10-21 Genentech, Inc. Anti-fcrh5 antibodies and immunoconjugates and methods of use
MX2011010265A (es) 2009-04-01 2011-10-11 Genentech Inc Anticuerpos anti-fcrh5 e inmunoconjugados y metodos de uso.
PE20120591A1 (es) 2009-04-02 2012-05-23 Roche Glycart Ag Anticuerpos multiespecificos que comprenden anticuerpos de longitud completa y fragmentos fab de cadena sencilla
JP5616428B2 (ja) 2009-04-07 2014-10-29 ロシュ グリクアート アクチェンゲゼルシャフト 三価の二重特異性抗体
JP2012525149A (ja) 2009-04-27 2012-10-22 オンコメッド ファーマシューティカルズ インコーポレイテッド ヘテロ多量体分子を作製するための方法
US9676845B2 (en) 2009-06-16 2017-06-13 Hoffmann-La Roche, Inc. Bispecific antigen binding proteins
US8703132B2 (en) 2009-06-18 2014-04-22 Hoffmann-La Roche, Inc. Bispecific, tetravalent antigen binding proteins
JP5816170B2 (ja) 2009-06-26 2015-11-18 リジェネロン・ファーマシューティカルズ・インコーポレイテッドＲｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． 天然の免疫グロブリン形式を有する容易に単離される二重特異性抗体
US8497071B2 (en) 2009-06-29 2013-07-30 California Institute Of Technology Isolation of unknown rearranged T-cell receptors from single cells
ES2534085T3 (es) 2009-08-17 2015-04-17 Roche Glycart Ag Inmunoconjugados dirigidos
KR20120060877A (ko) 2009-09-01 2012-06-12 아보트 러보러터리즈 이원 가변 도메인 면역글로불린 및 이의 용도
US9493578B2 (en) 2009-09-02 2016-11-15 Xencor, Inc. Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens
ES2688978T3 (es) 2009-11-23 2018-11-07 Amgen Inc. Anticuerpo monomérico Fc
WO2011066342A2 (en) 2009-11-24 2011-06-03 Amplimmune, Inc. Simultaneous inhibition of pd-l1/pd-l2
EP2507381A4 (en) 2009-12-04 2016-07-20 Hoffmann La Roche MULTISPECIFIC ANTIBODIES, ANTIBODY ANALOGS, COMPOSITIONS AND METHODS
EP2510011B2 (en) 2009-12-09 2021-03-31 Institut National de la Santé et de la Recherche Médicale Monoclonal antibodies that bind b7h6 and uses thereof
US20130129723A1 (en) 2009-12-29 2013-05-23 Emergent Product Development Seattle, Llc Heterodimer Binding Proteins and Uses Thereof
CN102958942A (zh) 2009-12-29 2013-03-06 新兴产品开发西雅图有限公司 异二聚体结合蛋白及其应用
WO2011085178A1 (en) 2010-01-11 2011-07-14 Trustees Of Dartmouth College Monomeric bi-specific fusion protein
EP3907242A1 (en) 2010-01-29 2021-11-10 Chugai Seiyaku Kabushiki Kaisha Anti-dll3 antibody
CA3083324A1 (en) 2010-03-05 2011-09-09 The Johns Hopkins University Compositions and methods for targeted immunomodulatory antibodies and fusion proteins
TW201138821A (en) 2010-03-26 2011-11-16 Roche Glycart Ag Bispecific antibodies
DK2560993T3 (da) 2010-04-20 2024-10-14 Genmab As Heterodimeric antibody fc-containing proteins and methods for production thereof
BR112012030311A2 (pt) 2010-06-08 2017-01-24 Genentech Inc anticorpo
WO2011155607A1 (ja) 2010-06-11 2011-12-15 協和発酵キリン株式会社 抗ｔｉｍ－３抗体
US9018006B2 (en) 2010-07-23 2015-04-28 The University Of Toledo Stable Tregs and related materials and methods
PL2606064T3 (pl) 2010-08-16 2015-07-31 Novimmune Sa Sposoby wytwarzania wieloswoistych i wielowartościowych przeciwciał
WO2012025530A1 (en) 2010-08-24 2012-03-01 F. Hoffmann-La Roche Ag Bispecific antibodies comprising a disulfide stabilized - fv fragment
MX340556B (es) 2010-08-24 2016-07-14 Roche Glycart Ag Anticuerpos biespecificos activables.
CN101985476B (zh) 2010-10-29 2012-11-21 中国科学技术大学 抗人NKp30单克隆抗体的制备、鉴定及应用
PL2635607T3 (pl) 2010-11-05 2020-05-18 Zymeworks Inc. Projekt stabilnego przeciwciała heterodimerowego z mutacjami w domenie FC
EP3974453A3 (en) 2010-11-16 2022-08-03 Amgen Inc. Agents and methods for treating diseases that correlate with bcma expression
PH12013501201A1 (en) 2010-12-09 2013-07-29 Univ Pennsylvania Use of chimeric antigen receptor-modified t cells to treat cancer
WO2012088309A1 (en) 2010-12-21 2012-06-28 The Board Of Trustees Of The Leland Stanford Junior University Therapeutic and diagnostic methods for manipulating phagocytosis through calreticulin and low density lipoprotein-related receptor
WO2012088302A2 (en) 2010-12-22 2012-06-28 Abbott Laboratories Half immunoglobulin binding proteins and uses thereof
US10689447B2 (en) 2011-02-04 2020-06-23 Genentech, Inc. Fc variants and methods for their production
HUE029139T2 (hu) 2011-02-10 2017-02-28 Roche Glycart Ag Mutáns interleukin-2 polipeptidek
WO2012118622A1 (en) 2011-02-19 2012-09-07 Baylor Research Institute Diagnostic and therapeutic uses for b cell maturation antigen
EP2681242B1 (en) 2011-03-01 2018-01-24 Amgen Inc. Sclerostin and dkk-1 bispecific binding agents
US9683052B2 (en) 2011-03-25 2017-06-20 Glenmark Pharmaceuticals S.A. Hetero-dimeric immunoglobulins
EP2694549B1 (en) 2011-04-08 2018-08-15 The United States of America, as represented by The Secretary, Department of Health and Human Services Anti-epidermal growth factor receptor variant iii chimeric antigen receptors and use of same for the treatment of cancer
US20130101599A1 (en) 2011-04-21 2013-04-25 Boehringer Ingelheim International Gmbh Bcma-based stratification and therapy for multiple myeloma patients
EA201892619A1 (ru) 2011-04-29 2019-04-30 Роше Гликарт Аг Иммуноконъюгаты, содержащие мутантные полипептиды интерлейкина-2
WO2012158818A2 (en) 2011-05-16 2012-11-22 Fabion Pharmaceuticals, Inc. Multi-specific fab fusion proteins and methods of use
US9574002B2 (en) 2011-06-06 2017-02-21 Amgen Inc. Human antigen binding proteins that bind to a complex comprising β-Klotho and an FGF receptor
JP2014520123A (ja) 2011-06-17 2014-08-21 アムジエン・インコーポレーテツド Ｃｌｅｃ−２を使用して代謝性障害を治療または改善させる方法
EP2723380B1 (en) 2011-06-24 2019-08-21 Stephen D. Gillies Light chain immunoglobulin fusion proteins and methods of use thereof
CN109517059B (zh) 2011-06-30 2023-03-28 中外制药株式会社 异源二聚化多肽
UA117901C2 (uk) 2011-07-06 2018-10-25 Ґенмаб Б.В. Спосіб посилення ефекторної функції вихідного поліпептиду, його варіанти та їх застосування
EP3549611B1 (en) 2011-07-29 2021-06-30 The Trustees of the University of Pennsylvania Switch costimulatory receptors
MY169358A (en) 2011-08-23 2019-03-26 Roche Glycart Ag Bispecific t cell activating antigen binding molecules
US9833476B2 (en) 2011-08-31 2017-12-05 The Trustees Of Dartmouth College NKP30 receptor targeted therapeutics
UY34317A (es) * 2011-09-12 2013-02-28 Genzyme Corp Anticuerpo antireceptor de célula T (alfa)/ß
CA2791109C (en) 2011-09-26 2021-02-16 Merus B.V. Generation of binding molecules
EP2768857B1 (en) 2011-10-19 2020-01-01 NovImmune SA Methods of purifying antibodies
SG10201604104PA (en) 2011-10-25 2016-07-28 Prothena Therapeutics Ltd Antibody formulations and methods
US10344050B2 (en) 2011-10-27 2019-07-09 Genmab A/S Production of heterodimeric proteins
US20130273089A1 (en) 2011-11-03 2013-10-17 Tolera Therapeutics, Inc. Antibody and methods for selective inhibition of t-cell responses
CA2854233C (en) 2011-11-04 2020-05-12 Zymeworks Inc. Stable heterodimeric antibody design with mutations in the fc domain
TWI679212B (zh) 2011-11-15 2019-12-11 美商安進股份有限公司 針對ｂｃｍａ之e3以及ｃｄ３的結合分子
HRP20201595T1 (hr) 2011-11-28 2020-12-11 Merck Patent Gmbh Anti-pd-l1 protutijela i njihova uporaba
LT2794658T (lt) 2011-12-19 2017-05-10 Synimmune Gmbh Bispecifinė antikūno molekulė
LT2794905T (lt) 2011-12-20 2020-07-10 Medimmune, Llc Modifikuoti polipeptidai, skirti bispecifinių antikūnų karkasams
US20130165638A1 (en) 2011-12-27 2013-06-27 Development Center For Biotechnology Light chain-bridged bispecific antibody
JP6153947B2 (ja) 2012-01-05 2017-06-28 ヴィザ インターナショナル サーヴィス アソシエイション 取引映像キャプチャ装置、方法およびシステム
WO2013119966A2 (en) 2012-02-10 2013-08-15 Genentech, Inc. Single-chain antibodies and other heteromultimers
GB201203051D0 (en) 2012-02-22 2012-04-04 Ucb Pharma Sa Biological products
PE20190658A1 (es) 2012-02-24 2019-05-08 Abbvie Stemcentrx Llc Moduladores y metodos de empleo novedosos
PT2825559T (pt) 2012-03-13 2019-06-07 Novimmune Sa Anticorpos biespecíficos prontamente isolados com formato de imunoglobulina nativo
MX361875B (es) 2012-03-14 2018-12-18 Regeneron Pharma Moléculas de unión de antígeno multiespecifícas y usos de las mismas.
SI2838917T1 (sl) 2012-04-20 2019-11-29 Merus Nv Postopki in sredstva za produkcijo heterodimernih IG-podobnih molekul
DK2847231T3 (da) 2012-05-10 2019-10-14 Bioatla Llc Multispecifikke monoklonale antistoffer
WO2013166594A1 (en) 2012-05-10 2013-11-14 Zymeworks Inc. Heteromultimer constructs of immunoglobulin heavy chains with mutations in the fc domain
EP2855531A1 (en) 2012-05-24 2015-04-08 F. Hoffmann-La Roche AG Multispecific antibodies
WO2014004586A1 (en) 2012-06-25 2014-01-03 Zymeworks Inc. Process and methods for efficient manufacturing of highly pure asymmetric antibodies in mammalian cells
CA2871386A1 (en) 2012-06-27 2014-01-03 F. Hoffmann-La Roche Ag Method for the selection and production of tailor-made, selective and multi-specific therapeutic molecules comprising at least two different targeting entities and uses thereof
AR091649A1 (es) 2012-07-02 2015-02-18 Bristol Myers Squibb Co Optimizacion de anticuerpos que se fijan al gen de activacion de linfocitos 3 (lag-3) y sus usos
BR112015000167B1 (pt) 2012-07-06 2021-11-23 Genmab B.V. Proteína dimérica, proteína, composição, kit de partes e seus usos, bem como método para aumentar a oligomerização em solução de uma proteína dimérica compreendendo um primeiro e segundo polipeptídeo, cada um compreendendo pelo menos as regiões ch2 e ch3 de uma cadeia pesada de igg1 humana e proteína dimérica variante
US20140072581A1 (en) 2012-07-23 2014-03-13 Zymeworks Inc. Immunoglobulin Constructs Comprising Selective Pairing of the Light and Heavy Chains
CN104684928A (zh) 2012-08-02 2015-06-03 Jn生物科学有限责任公司 通过半胱氨酸突变和μ尾端多聚化的抗体或融合蛋白
US20150203591A1 (en) 2012-08-02 2015-07-23 Regeneron Pharmaceuticals, Inc. Mutivalent antigen-binding proteins
AR092044A1 (es) 2012-08-07 2015-03-18 Roche Glycart Ag Inmunoterapia mejorada
US20140044675A1 (en) 2012-08-10 2014-02-13 Roche Glycart Ag Interleukin-2 fusion proteins and uses thereof
US9682143B2 (en) 2012-08-14 2017-06-20 Ibc Pharmaceuticals, Inc. Combination therapy for inducing immune response to disease
CN104769103B (zh) 2012-09-04 2018-06-08 塞勒克提斯公司 多链嵌合抗原受体和其用途
US20140079691A1 (en) 2012-09-20 2014-03-20 Anaptysbio, Inc. Thermostable antibody framework regions
CN105121630B (zh) 2012-10-03 2018-09-25 酵活有限公司 定量重链和轻链多肽对的方法
EP2904016B1 (en) 2012-10-08 2018-11-14 Roche Glycart AG Fc-free antibodies comprising two fab-fragments and methods of use
UY35148A (es) 2012-11-21 2014-05-30 Amgen Inc Immunoglobulinas heterodiméricas
US9914785B2 (en) 2012-11-28 2018-03-13 Zymeworks Inc. Engineered immunoglobulin heavy chain-light chain pairs and uses thereof
US9243058B2 (en) 2012-12-07 2016-01-26 Amgen, Inc. BCMA antigen binding proteins
WO2014100490A1 (en) 2012-12-19 2014-06-26 Adimab, Llc Multivalent antibody analogs, and methods of their preparation and use
AU2013204922B2 (en) 2012-12-20 2015-05-14 Celgene Corporation Chimeric antigen receptors
MX2015008117A (es) 2012-12-21 2016-03-31 Amplimmune Inc Anticuerpos anti-h7cr.
US10766960B2 (en) 2012-12-27 2020-09-08 Chugai Seiyaku Kabushiki Kaisha Heterodimerized polypeptide
KR20200024345A (ko) 2013-01-10 2020-03-06 젠맵 비. 브이 인간 IgG1 Fc 영역 변이체 및 그의 용도
EP2948475A2 (en) 2013-01-23 2015-12-02 AbbVie Inc. Methods and compositions for modulating an immune response
TWI682941B (zh) 2013-02-01 2020-01-21 美商再生元醫藥公司 含嵌合恆定區之抗體
US9989524B2 (en) 2013-02-05 2018-06-05 Sanofi Immuno imaging agent for use with antibody-drug conjugate therapy
JP6636803B2 (ja) 2013-02-05 2020-01-29 エンクマフ エスアーエールエル Ｂｃｍａに対する抗体の選択のための方法
US10047163B2 (en) 2013-02-08 2018-08-14 Abbvie Stemcentrx Llc Multispecific constructs
CA2900529A1 (en) 2013-02-08 2014-08-14 Institute For Myeloma & Bone Cancer Research Improved diagnostic, prognostic, and monitoring methods for multiple myeloma, chronic lymphocytic leukemia, and b-cell non-hodgkin lymphoma
GB201302447D0 (en) 2013-02-12 2013-03-27 Oxford Biotherapeutics Ltd Therapeutic and diagnostic target
TW201446794A (zh) 2013-02-20 2014-12-16 Novartis Ag 利用抗－ｃｄ１２３嵌合抗原受體工程化ｔ細胞之初級人類白血病有效靶向
BR112015019909A2 (pt) 2013-02-22 2017-08-29 Abbvie Stemcentrx Llc Conjugados anticorpo-fármaco, composição farmacêutica, usos dos mesmos, e kit
CN105143270B (zh) 2013-02-26 2019-11-12 罗切格利卡特公司 双特异性t细胞活化抗原结合分子
EP3447072A3 (en) 2013-03-05 2019-05-22 Baylor College of Medicine Engager cells comprising cd3 scfv and an antigen recognition domain that binds a tumor antigen for immunotherapy
JP6676521B2 (ja) 2013-03-14 2020-04-08 マクロジェニクス，インコーポレーテッド 二重特異性分子、薬学的組成物及びそれらの使用
US20140302037A1 (en) 2013-03-15 2014-10-09 Amgen Inc. BISPECIFIC-Fc MOLECULES
US20140308285A1 (en) 2013-03-15 2014-10-16 Amgen Inc. Heterodimeric bispecific antibodies
NZ710929A (en) 2013-03-15 2018-02-23 Novartis Ag Antibody drug conjugates
US10858417B2 (en) 2013-03-15 2020-12-08 Xencor, Inc. Heterodimeric proteins
AR095374A1 (es) 2013-03-15 2015-10-14 Amgen Res Munich Gmbh Moléculas de unión para bcma y cd3
US10047167B2 (en) 2013-03-15 2018-08-14 Eli Lilly And Company Methods for producing fabs and bi-specific antibodies
RU2687043C2 (ru) 2013-04-29 2019-05-06 Ф. Хоффманн-Ля Рош Аг МОДИФИЦИРОВАННЫЕ АСИММЕТРИЧНЫЕ АНТИТЕЛА, СВЯЗЫВАЮЩИЕ Fc-РЕЦЕПТОР, И СПОСОБЫ ИХ ПРИМЕНЕНИЯ
WO2014186905A1 (en) 2013-05-24 2014-11-27 Zymeworks Inc. Modular protein drug conjugate therapeutic
WO2014190441A1 (en) 2013-05-31 2014-12-04 Zymeworks Inc. Heteromultimers with reduced or silenced effector function
TWI725931B (zh) 2013-06-24 2021-05-01 美商建南德克公司 抗ｆｃｒｈ５抗體
ES2865473T3 (es) 2013-07-10 2021-10-15 Sutro Biopharma Inc Anticuerpos que comprenden múltiples residuos de aminoácidos no naturales sitio-específicos, métodos para su preparación y métodos de uso
CA2921805C (en) 2013-08-22 2023-03-07 Acceleron Pharma, Inc. Tgf-beta receptor type ii variants and uses thereof
PT2808338E (pt) 2013-09-16 2016-06-15 Cemm - Forschungszentrum Für Molekulare Medizin Gmbh Calreticulina mutante para o diagnóstico de malignidades mieloides
JP6534615B2 (ja) 2013-09-27 2019-06-26 中外製薬株式会社 ポリペプチド異種多量体の製造方法
GB201317928D0 (en) 2013-10-10 2013-11-27 Ucl Business Plc Molecule
KR20160044060A (ko) 2013-10-11 2016-04-22 에프. 호프만-라 로슈 아게 다중특이적 도메인 교환된 통상의 가변 경쇄 항체
SG11201603193PA (en) 2013-10-30 2016-05-30 Genzyme Corp Methods for enhancing immunosuppressive therapy by multiple administration of alpha beta tcr-binding polypeptide
UA129760C2 (uk) 2013-12-17 2025-07-30 Дженентек, Інк. Анти-cd3 антитіло та спосіб його застосування
EP3082853A2 (en) 2013-12-20 2016-10-26 The Broad Institute, Inc. Combination therapy with neoantigen vaccine
EP3094649A1 (en) 2014-01-15 2016-11-23 F. Hoffmann-La Roche AG Fc-region variants with modified fcrn-binding properties
RU2727639C2 (ru) 2014-01-15 2020-07-22 Ф.Хоффманн-Ля Рош Аг Варианты fc-области с модифицированной способностью связываться с fcrn и с сохраненной способностью связываться с белком а
RU2698969C2 (ru) 2014-01-15 2019-09-02 Ф.Хоффманн-Ля Рош Аг Варианты fc-области с улучшенной способностью связываться с белком а
KR102042246B1 (ko) 2014-02-06 2019-11-28 에프. 호프만-라 로슈 아게 인터류킨-2 융합 단백질 및 이의 용도
US9676863B2 (en) 2014-02-10 2017-06-13 Merck Patent Gmbh Targeted TGFβ inhibitors
DK3105252T3 (da) 2014-02-12 2019-10-14 Michael Uhlin Bispecifikke antistoffer til anvendelse ved stamcelletransplantation
PE20161209A1 (es) 2014-02-21 2016-11-10 Abbvie Stemcentrx Llc Conjugados de anticuerpos anti-drosophila similar a delta 3 (anti-dll3) y medicamentos para usarse en el tratamiento contra melanoma
EP3107565A4 (en) 2014-02-21 2017-08-23 Regeneron Pharmaceuticals, Inc. Methods, compositions and kits for cell specific modulation of target antigens
CN112094347A (zh) 2014-03-05 2020-12-18 奥托路斯有限公司 具有针对T细胞受体beta恒定区的抗原结合域的嵌合抗原受体(CAR)
US11385233B2 (en) 2015-03-05 2022-07-12 Autolus Limited Methods of depleting malignant T-cells
MX373460B (es) 2014-03-11 2020-04-07 Cellectis Metodo para generar celulas t compatibles para el trasplante alogenico.
EP3593812A3 (en) 2014-03-15 2020-05-27 Novartis AG Treatment of cancer using chimeric antigen receptor
EP3122779B1 (en) 2014-03-24 2019-05-22 Cancer Research Technology Limited Modified antibodies containing modified igg2 domains which elicit agonist or antagonistic properties and use thereof
UA117289C2 (uk) 2014-04-02 2018-07-10 Ф. Хоффманн-Ля Рош Аг Мультиспецифічне антитіло
EP2930188A1 (en) 2014-04-13 2015-10-14 Affimed Therapeutics AG Trifunctional antigen-binding molecule
WO2015164815A1 (en) 2014-04-24 2015-10-29 The Board Of Trustees Of The Leland Stanford Junior University Superagonists, partial agonists and antagonists of interleukin-2
KR102632731B1 (ko) 2014-04-30 2024-02-01 막스-델부뤽-센트럼 퓌어 몰레쿨라레 메디친 인 데어 헬름홀츠-게마인샤프트 Ｃｄ269에 대한 인간화 항체
RU2729467C2 (ru) 2014-05-28 2020-08-06 Займворкс Инк. Модифицированные антигенсвязывающие полипептидные конструкции и их применение
IL290655B2 (en) 2014-05-29 2024-05-01 Us Health Anti-human papillomavirus 16 E7 T-cell chelates
EP3152235B1 (en) 2014-05-29 2021-08-25 MacroGenics, Inc. Tri-specific binding molecules and methods of use thereof
CA2952532A1 (en) 2014-06-27 2015-12-30 Innate Pharma Multispecific antigen binding proteins
WO2015197582A1 (en) 2014-06-27 2015-12-30 Innate Pharma Monomeric multispecific antigen binding proteins
JP6822849B2 (ja) 2014-06-27 2021-01-27 イナート・ファルマ・ソシエテ・アノニムＩｎｎａｔｅ Ｐｈａｒｍａ Ｐｈａｒｍａ Ｓ．Ａ． 多重特異的ＮＫｐ４６結合タンパク質
WO2016016299A1 (en) 2014-07-29 2016-02-04 F. Hoffmann-La Roche Ag Multispecific antibodies
EP2982692A1 (en) 2014-08-04 2016-02-10 EngMab AG Bispecific antibodies against CD3epsilon and BCMA
JP6464255B2 (ja) 2014-08-04 2019-02-06 エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト 二重特異性ｔ細胞活性化抗原結合分子
WO2016019969A1 (en) 2014-08-08 2016-02-11 Ludwig-Maximilians-Universität München Subcutaneously administered bispecific antibodies for use in the treatment of cancer
GB201414823D0 (en) 2014-08-20 2014-10-01 Argen X Bv Multispecific antibodies
HRP20190881T1 (hr) 2014-08-28 2019-07-12 Halozyme, Inc. Kombinacijska terapija s hijaluronan-razgrađujućim enzimom i inhibitorom imunološke kontrolne točke
BR112017004270B1 (pt) 2014-09-04 2023-03-07 Stemcell Technologies Inc Método de ativação de células t ou células nk
MA40764A (fr) 2014-09-26 2017-08-01 Chugai Pharmaceutical Co Ltd Agent thérapeutique induisant une cytotoxicité
WO2016051205A1 (en) 2014-10-03 2016-04-07 Isis Innovation Limited Analysis of t-cell monotypia
WO2016069282A1 (en) 2014-10-31 2016-05-06 The Trustees Of The University Of Pennsylvania Altering gene expression in modified t cells and uses thereof
BR112017006591A2 (pt) 2014-11-06 2018-01-16 Hoffmann La Roche polipeptídeo heterodimérico, formulação farmacêutica e uso de um polipeptídeo heterodimérico
RS59340B1 (sr) 2014-11-06 2019-10-31 Hoffmann La Roche Varijante fc regiona sa modifikovanim vezivanjem za fcrn i metode upotrebe
EP3023437A1 (en) 2014-11-20 2016-05-25 EngMab AG Bispecific antibodies against CD3epsilon and BCMA
SI3221357T1 (sl) 2014-11-20 2020-09-30 F. Hoffmann-La Roche Ag Pogoste lahke verige in načini uporabe
US20170269092A1 (en) 2014-12-02 2017-09-21 Cemm - Forschungszentrum Fuer Molekulare Medizin Gmbh Anti-mutant calreticulin antibodies and their use in the diagnosis and therapy of myeloid malignancies
EP3029068A1 (en) 2014-12-03 2016-06-08 EngMab AG Bispecific antibodies against CD3epsilon and BCMA for use in the treatment of diseases
CN107001482B (zh) 2014-12-03 2021-06-15 豪夫迈·罗氏有限公司 多特异性抗体
KR20240135036A (ko) 2014-12-05 2024-09-10 메모리얼 슬로안 케터링 캔서 센터 B-세포 성숙화 항원을 표적화하는 항체 및 사용 방법
ES2935274T3 (es) 2014-12-05 2023-03-03 Merck Patent Gmbh Anticuerpo con intercambio de dominios
WO2016090337A1 (en) 2014-12-05 2016-06-09 Memorial Sloan-Kettering Cancer Center Chimeric antigen receptors targeting fc receptor-like 5 and uses thereof
US9767555B2 (en) 2015-01-05 2017-09-19 Case Western Reserve University Disease characterization from fused pathology and radiology data
EP3623386B1 (en) 2015-01-08 2022-04-13 BioNTech SE Agonistic tnf receptor binding agents
WO2016115274A1 (en) 2015-01-14 2016-07-21 Compass Therapeutics Llc Multispecific immunomodulatory antigen-binding constructs
PT3247728T (pt) 2015-01-20 2020-07-16 Igm Biosciences Inc Moléculas de ligação do recetor da superfamília do fator de necrose tumoral (fnt) e utilização das mesmas
US20170151281A1 (en) 2015-02-19 2017-06-01 Batu Biologics, Inc. Chimeric antigen receptor dendritic cell (car-dc) for treatment of cancer
WO2016146594A1 (en) 2015-03-13 2016-09-22 Novimmune Sa Methods of purifying bispecific antibodies
PL3988117T3 (pl) 2015-04-13 2025-03-10 Pfizer Inc. Przeciwciała terapeutyczne i ich zastosowania
BR112017020952A2 (pt) 2015-04-13 2018-07-10 Five Prime Therapeutics Inc método de tratamento de câncer, composição e uso da composição
WO2016176756A1 (en) 2015-05-05 2016-11-10 University Health Network Nk cells and antibodies for cancer treatment
PT3294768T (pt) 2015-05-13 2019-11-05 Ablynx Nv Polipétidos de recrutamento de células t com base na reatividade do tcr alfa/beta
WO2016193300A1 (en) 2015-06-01 2016-12-08 Medigene Immunotherapies Gmbh Method for generating antibodies against t cell receptor
WO2016193301A1 (en) * 2015-06-01 2016-12-08 Medigene Immunotherapies Gmbh T-cell receptor specific antibodies
TWI731861B (zh) 2015-06-16 2021-07-01 美商建南德克公司 FcRH5之人源化及親和力成熟抗體及使用方法
SI3115376T1 (sl) 2015-07-10 2018-12-31 Merus N.V. Humana protitelesa, ki vežejo CD3
AU2016297249B2 (en) 2015-07-23 2020-11-12 Inhibrx Biosciences, Inc. Multivalent and multispecific GITR-binding fusion proteins
TWI793062B (zh) 2015-07-31 2023-02-21 德商安美基研究（慕尼黑）公司 Ｄｌｌ３及ｃｄ３抗體構築體
EA039859B1 (ru) 2015-07-31 2022-03-21 Эмджен Рисерч (Мюник) Гмбх Биспецифические конструкты антител, связывающие egfrviii и cd3
US10683369B2 (en) 2015-08-03 2020-06-16 Engmab Sàrl Monoclonal antibodies against BCMA
US10072088B2 (en) 2015-08-17 2018-09-11 Janssen Pharmaceutica, Nv Anti-BCMA antibodies and uses thereof
US20200231652A1 (en) 2015-08-31 2020-07-23 National Research Council Of Canada Tgf-b-receptor ectodomain fusion molecules and uses thereof
JP6905163B2 (ja) 2015-09-03 2021-07-21 ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルバニア サイトカイン放出症候群を予測するバイオマーカー
US20170096485A1 (en) 2015-10-02 2017-04-06 Hoffmann-La Roche Inc. Bispecific t cell activating antigen binding molecules
MX389194B (es) 2015-10-06 2025-03-20 Univ Minnesota Compuestos terapéuticos y métodos.
AU2016334063B2 (en) 2015-10-08 2023-05-25 Zymeworks Bc Inc. Antigen-binding polypeptide constructs comprising kappa and lambda light chains and uses thereof
US11702477B2 (en) 2015-11-06 2023-07-18 Orionis Biosciences BV Bi-functional chimeric proteins and uses thereof
WO2017165464A1 (en) 2016-03-21 2017-09-28 Elstar Therapeutics, Inc. Multispecific and multifunctional molecules and uses thereof
WO2017167350A1 (en) 2016-03-30 2017-10-05 Horst Lindhofer Multispecific antibodies for use in the treatment of a neoplasm of the urinary tract
IL262241B2 (en) 2016-04-13 2024-05-01 Sanofi Sa Trispecific and/or trivalent binding proteins with a crossover dual variable domain arm and a traditional antibody fab arm, pharmaceutical composition comprising said binding proteins and their uses in preventing and/or treating cancer or inflammatory diseases
CA2937157A1 (en) 2016-07-25 2018-01-25 Ucl Business Ltd Protein-based t-cell receptor knockdown
CN109906232B (zh) 2016-09-23 2023-11-07 马伦戈治疗公司 包含λ轻链和κ轻链的多特异性抗体分子
EP3523331A1 (en) 2016-10-07 2019-08-14 Novartis AG Chimeric antigen receptors for the treatment of cancer
US11851491B2 (en) 2016-11-22 2023-12-26 TCR2 Therapeutics Inc. Compositions and methods for TCR reprogramming using fusion proteins
CA3051866A1 (en) 2017-02-01 2018-08-09 Nant Holdings Ip, Llc Calreticulin-mediated cancer treatment
WO2018151820A1 (en) 2017-02-16 2018-08-23 Elstar Therapeutics, Inc. Multifunctional molecules comprising a trimeric ligand and uses thereof
US12134654B2 (en) 2017-04-19 2024-11-05 Marengo Therapeutics, Inc. Multispecific molecules and uses thereof
WO2018193103A1 (en) 2017-04-20 2018-10-25 Adc Therapeutics Sa Combination therapy with an anti-psma antibody-drug conjugate
CA3059769A1 (en) 2017-04-28 2018-11-01 Elstar Therapeutics, Inc. Multispecific molecules comprising a non-immunoglobulin heterodimerization domain and uses thereof
JP2020521452A (ja) 2017-05-24 2020-07-27 パンディオン・セラピューティクス・インコーポレイテッド 標的化免疫寛容
JP2020522254A (ja) 2017-05-31 2020-07-30 エルスター セラピューティクス， インコーポレイテッド 骨髄増殖性白血病（ｍｐｌ）タンパク質に結合する多特異性分子およびその使用
GB201709203D0 (en) 2017-06-09 2017-07-26 Autolus Ltd Antigen-binding domain
US12195529B2 (en) 2017-06-21 2025-01-14 Gsbio, Llc Heterodimeric bispecific antibodies
TWI828625B (zh) 2017-06-25 2024-01-11 美商西雅圖免疫公司 引導及導航控制蛋白質以及彼之製造及使用方法
US20210017247A1 (en) 2017-07-03 2021-01-21 Torque Therapeutics, Inc. Fusion Molecules Targeting Immune Regulatory Cells and Uses Thereof
EP3654991A1 (en) 2017-07-19 2020-05-27 Rubius Therapeutics, Inc. Compositions and methods related to multimodal therapeutic cell systems for infectious disease
IL316357A (en) 2017-07-31 2024-12-01 Trishula Therapeutics Inc Anti-cd39 antibodies, compositions comprising anti-cd39 antibodies and methods of using anti-cd39 antibodies
WO2019028419A1 (en) 2017-08-03 2019-02-07 Synthorx, Inc. CYTOKINE CONJUGATES FOR THE TREATMENT OF PROLIFERATIVE AND INFECTIOUS DISEASES
WO2019035938A1 (en) 2017-08-16 2019-02-21 Elstar Therapeutics, Inc. MULTISPECIFIC MOLECULES BINDING TO BCMA AND USES THEREOF
US10578740B2 (en) 2017-08-23 2020-03-03 Mezmeriz Inc. Coherent optical distance measurement apparatus and method
EP3672990A1 (en) 2017-08-25 2020-07-01 Five Prime Therapeutics, Inc. B7-h4 antibodies and methods of use thereof
SG11202002298PA (en) 2017-09-14 2020-04-29 Dragonfly Therapeutics Inc Proteins binding nkg2d, cd16, and c-type lectin-like molecule-1 (cll-1)
MX2020004185A (es) 2017-09-27 2021-01-08 Univ Southern California Nuevas plataformas para coestimulacion, nuevos diseños car y otras mejoras para terapia celular adoptiva.
GB201718088D0 (en) 2017-11-01 2017-12-13 Autolus Ltd Vectors
US20200299349A1 (en) 2017-11-21 2020-09-24 The Board Of Trustees Of The Leland Stanford Junior University Partial agonists of interleukin-2
AU2018371114A1 (en) 2017-11-21 2020-05-07 Innate Pharma Multispecific antigen binding proteins
JP7348899B2 (ja) 2017-12-08 2023-09-21 マレンゴ・セラピューティクス，インコーポレーテッド 多重特異性分子及びその使用
RU2694412C9 (ru) 2017-12-25 2019-09-18 Федеральное государственное бюджетное образовательное учреждение высшего образования "Российский национальный исследовательский медицинский университет им. Н.И. Пирогова" Министерства здравоохранения Российской Федерации (ФГБОУ ВО РНИМУ им. Н.И. Пирогова Минздрава России) Моноклональные антитела и способы их применения
CN111527109B (zh) 2017-12-26 2024-11-01 南京金斯瑞生物科技有限公司 以抗体Fc区为骨架的融合蛋白二聚体及其应用
US11667713B2 (en) 2017-12-28 2023-06-06 Chugai Seiyaku Kabushiki Kaisha Cytotoxicity-inducing therapeutic agent
EP3737692A4 (en) 2018-01-09 2021-09-29 Elstar Therapeutics, Inc. CALRETICULIN AND MODIFIED T-LYMPHOCYTES BINDING CONSTRUCTIONS FOR THE TREATMENT OF DISEASES
GB201800298D0 (en) 2018-01-09 2018-02-21 Autolus Ltd Method
WO2019158764A1 (en) 2018-02-16 2019-08-22 Iltoo Pharma Use of interleukin 2 for treating sjögren's syndrome
US12152073B2 (en) 2018-03-14 2024-11-26 Marengo Therapeutics, Inc. Multifunctional molecules that bind to calreticulin and uses thereof
WO2019178364A2 (en) 2018-03-14 2019-09-19 Elstar Therapeutics, Inc. Multifunctional molecules and uses thereof
US20210024631A1 (en) 2018-03-28 2021-01-28 Orionis Biosciences, Inc. Bi-functional proteins and construction thereof
CA3099308A1 (en) 2018-05-21 2019-11-28 Compass Therapeutics Llc Compositions and methods for enhancing the killing of target cells by nk cells
EA202091977A1 (ru) 2018-05-28 2021-02-09 Драгонфлай Терапьютикс, Инк. Мультиспецифические связывающие белки, которые связывают cd33, nkg2d и cd16, и способы применения
EP3810640A1 (en) 2018-06-25 2021-04-28 University of Washington De novo design of potent and selective interleukin mimetics
EP3818083A2 (en) 2018-07-03 2021-05-12 Elstar Therapeutics, Inc. Anti-tcr antibody molecules and uses thereof
US20210277120A1 (en) 2018-07-18 2021-09-09 The General Hospital Corporation Compositions and methods for treatment of t cell malignancies
CN108949698B (zh) 2018-07-31 2019-05-31 广东和信健康科技有限公司 杂交瘤细胞株c11-6f7及其产生的hcmv单克隆抗体和应用
JOP20210022A1 (ar) 2018-08-03 2021-01-28 Amgen Inc بنيات جسم مضاد لـ cldn18.2وcd3
GB201812650D0 (en) 2018-08-03 2018-09-19 Autolus Ltd Molecular assessment of TRBC usage
EA202091888A1 (ru) 2018-08-08 2020-10-23 Драгонфлай Терапьютикс, Инк. Вариабельные домены антител, нацеленные на рецептор nkg2d
WO2020057646A1 (zh) 2018-09-21 2020-03-26 信达生物制药(苏州)有限公司 新型白介素2及其用途
SG11202103022WA (en) 2018-09-25 2021-04-29 Harpoon Therapeutics Inc Dll3 binding proteins and methods of use
JP2022502443A (ja) 2018-09-28 2022-01-11 ピエール、ファーブル、メディカマン 癌の処置のための新規な免疫サイトカイン
CN113194984A (zh) 2018-10-18 2021-07-30 金德雷德生物科学股份有限公司 兽用的与新生儿Fc受体(FcRn)结合改变的Fc变体
GB201817172D0 (en) 2018-10-22 2018-12-05 Autolus Ltd Antibody
AU2019366956B2 (en) 2018-10-23 2025-10-30 Dragonfly Therapeutics, Inc. Heterodimeric Fc-fused proteins
US12378295B2 (en) 2018-10-29 2025-08-05 1Globe Biomedical Co., Ltd. Rationally designed protein compositions
GB201817822D0 (en) 2018-10-31 2018-12-19 Autolus Ltd Binding domain
EP3883956A1 (en) 2018-11-20 2021-09-29 University of Washington Split interleukin mimetics and their use
AR117735A1 (es) 2018-12-25 2021-08-25 Joint Stock Company “Biocad” ANTICUERPOS MONOCLONALES QUE SE UNEN ESPECÍFICAMENTE A LA REGIÓN b DE LA FAMILIA TRBV-9 DEL RECEPTOR DE CÉLULAS T HUMANO, Y LOS MÉTODOS PARA SU USO
RU2712251C1 (ru) 2018-12-25 2020-01-27 Федеральное государственное автономное образовательное учреждение высшего образования "Российский национальный исследовательский медицинский университет имени Н.И. Пирогова" Министерства здравоохранения Российской Федерации (ФГАОУ ВО РНИМУ им. Н.И. Пирогова Минздрава России) Гуманизированные антитела против участка бета цепи 9-го семейства TRBV9 TKP человека, и способы их применения
WO2020154032A1 (en) 2019-01-23 2020-07-30 Massachusetts Institute Of Technology Combination immunotherapy dosing regimen for immune checkpoint blockade
WO2020172601A1 (en) 2019-02-21 2020-08-27 Elstar Therapeutics, Inc. Multifunctional molecules that bind to calreticulin and uses thereof
JP7710373B2 (ja) 2019-02-21 2025-07-18 マレンゴ・セラピューティクス，インコーポレーテッド Ｔ細胞関連のがん細胞に結合する多機能性分子およびその使用
AU2020226904B2 (en) 2019-02-21 2025-05-01 Marengo Therapeutics, Inc. Anti-TCR antibody molecules and uses thereof
AU2020224681A1 (en) 2019-02-21 2021-09-16 Marengo Therapeutics, Inc. Antibody molecules that bind to NKp30 and uses thereof
EP3927745A1 (en) 2019-02-21 2021-12-29 Marengo Therapeutics, Inc. Multifunctional molecules that bind to t cells and uses thereof to treat autoimmune disorders
WO2020180591A1 (en) 2019-03-01 2020-09-10 Allogene Therapeutics, Inc. Dll3 targeting chimeric antigen receptors and binding agents
JP7566766B2 (ja) 2019-03-11 2024-10-15 ヤンセン バイオテツク，インコーポレーテツド 抗Ｖβ１７／抗ＣＤ１２３二重特異性抗体
WO2020249757A1 (en) 2019-06-14 2020-12-17 Philogen S.P.A Immunoconjugates comprising a single chain diabody and interleukin-15 or interleukin-15 and a sushi domain of interleukin-15 receptor alpha
EP4054633A1 (en) 2019-11-05 2022-09-14 Merck Patent GmbH Combined inhibition of pd-1, tgfb and tigit for the treatment of cancer
JP7590430B2 (ja) 2019-11-14 2024-11-26 マレンゴ・セラピューティクス，インコーポレーテッド 抗ｔｃｒ抗体分子およびその使用
CN116234829A (zh) 2020-01-03 2023-06-06 马伦戈治疗公司 抗tcr抗体分子及其用途
WO2021138407A2 (en) 2020-01-03 2021-07-08 Marengo Therapeutics, Inc. Multifunctional molecules that bind to cd33 and uses thereof
KR20220147583A (ko) 2020-01-09 2022-11-03 바이오뮤넥스 파마슈티컬스 Mait 및 종양 세포 둘 모두에 결합하는 다중특이적 항체
WO2021188454A1 (en) 2020-03-16 2021-09-23 Marengo Therapeutics, Inc. Engineered cell compositions and methods of use thereof
GB2612450A (en) 2020-04-24 2023-05-03 Marengo Therapeutics Inc Multifunctional molecules that bind to T cell related cancer cells and uses thereof
CA3190755A1 (en) 2020-08-26 2022-03-03 Andreas Loew Multifunctional molecules that bind to calreticulin and uses thereof
AU2021331076A1 (en) 2020-08-26 2023-04-06 Marengo Therapeutics, Inc. Antibody molecules that bind to NKp30 and uses thereof
KR20230074487A (ko) 2020-08-26 2023-05-30 마렝고 테라퓨틱스, 인크. Trbc1 또는 trbc2를 검출하는 방법
TW202246338A (zh) 2021-02-17 2022-12-01 英商適應生物治療有限公司 抗ＴＣＲδ可變1抗體
WO2022179580A1 (zh) 2021-02-26 2022-09-01 盛禾(中国)生物制药有限公司 一种抗NKp30抗体及其应用
CA3214757A1 (en) 2021-04-08 2022-10-13 Andreas Loew Multifuntional molecules binding to tcr and uses thereof
US20240317856A1 (en) 2021-05-10 2024-09-26 Amgen Inc. Dosing regimen for combination therapy targeting dll3 and pd-1
WO2023081412A2 (en) 2021-11-05 2023-05-11 Marengo Therapeutics, Inc. Immune cell populations and uses thereof
CN118786150A (zh) 2021-12-22 2024-10-15 马伦戈治疗公司 与tcr结合的多功能分子及其用途
EP4466019A4 (en) 2022-01-21 2026-01-07 Marengo Therapeutics Inc MULTIFUNCTIONAL MOLECULES COMPRISING A G6B BINDER AND/OR A CD34 BINDER AND THEIR USES
AU2023361491A1 (en) 2022-10-12 2025-05-08 Marengo Therapeutics, Inc. Multifunctional molecules binding to tcr and uses thereof
EP4601747A1 (en) 2022-10-12 2025-08-20 Marengo Therapeutics, Inc. Multifunctional molecules binding to tcr and uses thereof
WO2024197082A2 (en) 2023-03-21 2024-09-26 Marengo Therapeutics, Inc. Tcr targeting molecules and uses thereof
WO2024226532A2 (en) 2023-04-24 2024-10-31 Marengo Therapeutics, Inc. Multifunctional molecules binding to tcr and uses thereof
AU2024264260A1 (en) 2023-04-27 2025-11-13 Marengo Therapeutics, Inc. Combination therapies using molecules binding to tcr
EP4724500A2 (en) 2023-06-09 2026-04-15 Marengo Therapeutics, Inc. Multispecific molecules binding to tcr and uses thereof
WO2025049771A1 (en) 2023-08-30 2025-03-06 Marengo Therapeutics, Inc. Multifunctional molecules binding to tcr and uses thereof
WO2025080685A2 (en) 2023-10-10 2025-04-17 Marengo Therapeutics, Inc. Antibody molecules that bind to nkp30 and uses thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060115832A1 (en) * 2002-11-14 2006-06-01 Jon Wayne Cancer Institute Detection of cancer cells in body fluids
US20060275844A1 (en) * 2005-04-19 2006-12-07 Linke Steven P Diagnostic markers of breast cancer treatment and progression and methods of use thereof
WO2020142672A2 (en) * 2019-01-04 2020-07-09 Elstar Therapeutics, Inc. Anti-tcr antibody molecules and uses thereof
WO2021155112A1 (en) * 2020-01-29 2021-08-05 The Trustees Of The University Of Pennsylvania Compositions and methods of t cell receptor vb family member targeting for the treatment of t cell associated disease

Non-Patent Citations (12)

* Cited by examiner, † Cited by third party
Title
Baker (Immunity, Vol. 13, Pg. 475-484, 2000) (Year: 2000) *
Baxevanis (Expert Opinion: Drug Discovery, Vol. 3, No. 4, Pg. 441-452, 2008) (Year: 2008) *
Bendig M. M. (Methods: A Companion to Methods in Enzymology, 1995; 8:83-93) (Year: 1995) *
Burgess et al., J of Cell Bio. 111:2129-2138, 1990 (Year: 1990) *
Huang (The Journal of Biological Chemistry, Vol. 272, No. 43, Pg. 27155-27159, 1997) (Year: 1997) *
Ju (Proceedings of the National Academy of Sciences, U.S.A., Vol. 88, Pg. 2658-2662, 1991) (Year: 1991) *
Lazar et al. Molecular and Cellular Biology 8:1247-1252, 1988 (Year: 1988) *
Martindale (Nature Genetics, Vol. 18, Pg. 150-154, 1998) (Year: 1998) *
Montrose-Rafizadeh (The Journal of Biological Chemistry, Vol. 272, Pg. 21201-21206, 1997) (Year: 1997) *
Nonaka (Human Molecular Genetics, Vol. 18, No. 18, Pg. 3353-3364, 2009) (Year: 2009) *
Paul, Fundamental Immunology, 3rd Edition, 1993, pp. 292-295 (Year: 1993) *
Rudikoff et al. (Proceedings of the National Academy of Sciences USA, Vol., 79, Pg. 1979-1983, 1982) (Year: 1982) *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12247060B2 (en) 2018-01-09 2025-03-11 Marengo Therapeutics, Inc. Calreticulin binding constructs and engineered T cells for the treatment of diseases
US12286477B2 (en) 2018-07-03 2025-04-29 Marengo Therapeutics, Inc. Anti-TCR antibody molecules and uses thereof
US12351632B2 (en) 2018-07-03 2025-07-08 Marengo Therapeutics, Inc. Anti-TCR antibody molecules and uses thereof
US12358982B2 (en) 2019-02-21 2025-07-15 Marengo Therapeutics, Inc. Multifunctional molecules that bind to T cell related cancer cells and uses thereof
US12384842B2 (en) 2019-02-21 2025-08-12 Marengo Therapeutics, Inc. Antibody molecules that bind to NKP30 and uses thereof
US12486326B2 (en) 2020-01-03 2025-12-02 Marengo Therapeutics, Inc. Anti-TCR antibody molecules and uses thereof
WO2024197296A1 (en) 2023-03-23 2024-09-26 Bodhi Bio Llc Compositions and methods for antigen-specific therapy

Also Published As

Publication number Publication date
GB2609554A (en) 2023-02-08
JP2026027226A (ja) 2026-02-18
CA3166629A1 (en) 2021-07-08
WO2021138474A3 (en) 2021-09-02
AU2020416273A1 (en) 2022-07-28
WO2021138474A2 (en) 2021-07-08
US20260022173A1 (en) 2026-01-22
GB202210131D0 (en) 2022-08-24
US12486326B2 (en) 2025-12-02
EP4084823A2 (en) 2022-11-09
EP4084823A4 (en) 2024-05-15
US20230374133A1 (en) 2023-11-23
CN116234829A (zh) 2023-06-06
GB2609554B (en) 2025-08-20
JP2023509708A (ja) 2023-03-09

Similar Documents

Publication Publication Date Title
US12351632B2 (en) Anti-TCR antibody molecules and uses thereof
US12486326B2 (en) Anti-TCR antibody molecules and uses thereof
US20250099579A1 (en) Multispecific molecules binding to tcr and uses thereof
US20250297007A1 (en) Multifunctional molecules binding to tcr and uses thereof
US20240409636A1 (en) Multifunctional molecules binding to tcr and uses thereof
AU2021331075A1 (en) Multifunctional molecules that bind to calreticulin and uses thereof
US20240400990A1 (en) Immune cell populations and uses thereof
WO2024226532A2 (en) Multifunctional molecules binding to tcr and uses thereof
WO2025049771A1 (en) Multifunctional molecules binding to tcr and uses thereof
WO2025222063A2 (en) Multifunctional molecules binding to tcr and uses thereof

Legal Events

Date Code Title Description
AS Assignment

Owner name: ELSTAR THERAPEUTICS, INC., MASSACHUSETTS

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:TAN, SENG-LAI;VASH, BRIAN EDWARD;HSU, JONATHAN;AND OTHERS;SIGNING DATES FROM 20210216 TO 20210303;REEL/FRAME:063254/0168

Owner name: MARENGO THERAPEUTICS, INC., MASSACHUSETTS

Free format text: CHANGE OF NAME;ASSIGNOR:ELSTAR THERAPEUTICS, INC.;REEL/FRAME:063269/0692

Effective date: 20210129

STPP Information on status: patent application and granting procedure in general

Free format text: DOCKETED NEW CASE - READY FOR EXAMINATION

STPP Information on status: patent application and granting procedure in general

Free format text: NON FINAL ACTION MAILED

STPP Information on status: patent application and granting procedure in general

Free format text: RESPONSE TO NON-FINAL OFFICE ACTION ENTERED AND FORWARDED TO EXAMINER

STPP Information on status: patent application and granting procedure in general

Free format text: RESPONSE TO NON-FINAL OFFICE ACTION ENTERED AND FORWARDED TO EXAMINER