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-TRBC1 antigen-binding domain which comprises:
a) 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 and SEQ ID No. 18; and
b) 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, SEQ ID No. 34.
2 . A chimeric antigen receptor (CAR) which comprises an anti-TRBC1 antigen binding domain according to claim 1 .
3 . An antibody which comprises an anti-TRBC1 antigen binding domain according to claim 1 .
4 . A bispecific T-cell engager (BiTE) which comprises an anti-TRBC1 antigen binding domain according to claim 1 .
5 . An antibody-drug conjugate which comprises an anti-TRBC1 antigen binding domain according to claim 1 .
6 . A nucleic acid sequence which encodes a CAR according to claim 2 .
7 . A vector comprising a nucleic acid sequence according to claim 6 .
8 . A cell comprising a CAR according to claim 2 .
9 . A method for making a cell according to claim 8 , which comprises the step of introducing a nucleic acid according to claim 6 or a vector according to claim 7 into a cell.
10 . A pharmaceutical composition which comprises a plurality of cells according to claim 8 , an antibody according to claim 3 , a BiTE according to claim 4 or an antibody-drug conjugate according to claim 15 .
11 . A pharmaceutical composition according to claim 10 for use in treating a TRBC1-expressing T-cell lymphoma or leukaemia in a subject.
12 . 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 10 to a subject.
13 . The use of a pharmaceutical composition according to claim 10 in the manufacture of a medicament for treating a TRBC1-expressing T-cell lymphoma or leukaemia in a subject.
14 . A pharmaceutical composition for use according to claim 11 , a method according to claim 12 , or a use according to claim 13 , 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 and T-cell acute lymphoblastic leukaemia.