CHIMERIC ANTIGEN RECEPTOR (CAR) WITH ANTIGEN BINDING DOMAINS TO THE T CELL RECEPTOR BETA CONSTANT REGION
The present disclosure relates to a chimeric antigen receptor (CAR) which comprises an antigen-binding domain which selectively binds TCR beta constant region 1 (TRBC1) or TRBC2; cells; such a T cells comprising such a CAR; and the use of such cells for the treatment of a T-cell lymphoma or leukaemia in a subject.
1 - 19 . (canceled)
20 . An agent which selectively binds TCR beta constant region 1 (TRBC1) or TRBC2.
21 . The agent according to claim 20 , which selectively binds TRBC1.
22 . The agent according to claim 20 , which selectively binds TRBC2.
23 . The agent according to claim 20 which is a depleting monoclonal antibody
24 . The agent according to claim 20 which is a conjugated antibody
25 . The agent according to claim 24 , which comprises a chemotherapeutic entity
26 . The agent according to claim 25 , wherein the chemotherapeutic entity is a cytotoxic drug.
27 . The agent according to claim 20 , which is a bispecific T-cell engager (BiTE)
28 . A method for treating a T-cell lymphoma or leukaemia in a subject which comprises the step of administering the agent according to claim 20 to the subject.
29 . The method according to claim 28 , wherein the agent causes selective depletion of the malignant T-cells, together with normal T-cells expressing the same TRBC as the malignant T-cells, but does not cause depletion of normal T-cells expressing the TRBC not expressed by the malignant T-cells.
30 . The method according to claim 28 which also comprises the step of investigating the TCR beta constant region (TCRB) of a malignant T cell from the subject to determine whether it expresses TRBC1 or TRBC2.
31 . The method according to claim 28 , wherein the 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.
32 . A method for targeting the delivery of a chemotherapeutic entity to a cell which expresses either TRBC1 or TRBC2 in a subject, which comprises the step of administering an agent according to claim 25 to the subject.
33 . A nucleic acid which encodes a BiTE according to claim 27 .
34 . A vector which comprises a nucleic acid according to claim 33 .
35 . A pharmaceutical composition which comprises an agent according to claim 20 and a pharmaceutically acceptable carrier, diluent, excipient or adjuvant.