METHODS
The present invention 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 . A method of determining whether the TCR beta constant region (TCRB) of a malignant T cell from a subject expresses TRBC1 or TRBC2 comprising determining by polymerase chain reaction (PCR), western blot, flow cytometry or fluorescent microscopy whether the TCRB expresses TRBC1 or TRBC2.
2 . A kit for carrying out the method of claim 3 .
3 . The method of claim 3 wherein the malignant T-cells in the subject are T-cell lymphoma or leukaemia cells.
4 . The method of claim 3 wherein 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.
5 . A method of diagnosing a T-cell lymphoma or leukaemia in a subject comprising the step of determining the proportion of total T-cells in a sample from the subject which is either TRBC1 or TRBC2 positive, wherein a proportion of TRBC1 or TRBC2 positive T-cells which is greater than about 80% indicates the presence of a T-cell lymphoma.
6 . The method of claim 5 wherein the sample is a peripheral blood sample or a biopsy.
7 . A method of selectively depleting malignant T-cells without depleting the entire T-cell compartment in a subject comprising:
determining whether the TCR beta constant region (TCRB) of a malignant T cell from a subject expresses T RBC1 or TRBC2, and
if the TCRB of the malignant cell expresses TRBC1, depleting the malignant and normal T-cells expressing TRBC1 in the subject, or if the TCRB of the malignant cells expresses TRBC2, depleting the malignant and normal T-cells expressing TRBC2 in the subject.
8 . The method of claim 7 wherein the malignant T-cells in the subject are T-cell lymphoma or leukaemia cells.
9 . The method of claim 8 wherein the malignant T-cells are from a 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.
10 . The method of claim 7 wherein the malignant T-cells are depleted by administration to the subject of an agent which binds to and depletes either the TRBC1-expressing or the TRBC2-expressing malignant T-cells.
11 . The method of claim 10 wherein the agent comprises a chemotherapeutic entity, a bispecific T-cell engager (BiTE) or a chimeric antigen receptor.
12 . A kit for carrying out the method of claim 7 .