Methods

Abstract

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 .