Anti TRBC1 antigen binding domains
The present disclosure relates to anti-TRBC1 antigen binding domains characterized by the sequences of the variable chains. The CDRs sequences of the variable chains are: (VH CDR1) GYTFT, (VH CDR2) NPYNDDIQS, (VH CDR3) GAGY-NFDGAYRFFDF; and (VL CDR1) RSSQRLVHSNGNTYL, (VL CDR2) RVSNRFP, (VL CDR3) SQSTHVPYT. The claimed humanized antibodies derive from the murine JOVI antibody. Uses in cancer therapy.
1. An anti-T-cell Receptor β-constant region (TRBC) 1 antigen-binding domain which comprises:
a) a heavy chain variable region domain having an amino acid sequence selected from SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17 or SEQ ID NO: 18; and
b) a light chain variable region domain having an amino acid sequence selected from SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, or SEQ ID NO: 34.
2. A chimeric antigen receptor (CAR) which comprises an anti-TRBC1 antigen binding domain according to claim 1 .
3. A nucleic acid which encodes a CAR according to claim 2 .
4. A vector comprising a nucleic acid according to claim 3 .
5. A nucleic acid construct which comprises a first nucleic acid encoding a CAR according to claim 2 ; and a second nucleic acid encoding a suicide gene.
6. A vector comprising a nucleic acid construct according to claim 5 .
7. A cell comprising a CAR according to claim 2 .
8. A method for making a cell according to claim 7 , which comprises the step of introducing in the cell:
(a) a nucleic acid which encodes a CAR which comprises anti-TRBC1 antigen-binding domain which comprises:
i) a VH domain having an amino acid sequence selected from SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17 or SEQ ID NO: 18; and
ii) a VL domain having an amino acid sequence selected from SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, or SEQ ID NO: 34;
(b) a vector comprising the nucleic acid of (a); or
(c) a vector comprising the nucleic acid of (a) and a nucleic acid encoding a suicide gene.
9. A pharmaceutical composition which comprises:
(a) a plurality of cells comprising a CAR, and
(b) a carrier, diluent or excipient,
wherein the CAR comprises an anti-TRBC1 antigen binding domain according to claim 1 , a spacer, a transmembrane domain and a 41BB-CD3zeta endodomain.
10. A method for treating a TRBC1-expressing T-cell lymphoma or leukaemia in a subject, which comprises the step of administering a pharmaceutical composition according to claim 9 to a subject.
11. The method according to claim 10 , wherein the TRBC1-expressing T-cell lymphoma or leukaemia is selected from: peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS); angio-immunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL), enteropathy-associated T-cell lymphoma (EATL), hepatosplenic T-cell lymphoma (HSTL), extranodal NK/T-cell lymphoma nasal type, cutaneous T-cell lymphoma, primary cutaneous ALCL, T cell prolymphocytic leukaemia or T-cell acute lymphoblastic leukaemia.