METHODS

1 - 12 . (canceled)

13 . A method of depleting malignant T-cells in a human subject with a TRBC1 positive T-cell lymphoma or leukaemia, the method comprising:

determining the percentage of total T-cells in a sample from the subject which is TRBC1 positive and determining the percentage of total T-cells in the sample which is TRBC2 positive,

detecting a percentage of TRBC1 positive T-cells that is greater than 80% or detecting a percentage of TRBC2 positive T-cells that is greater than 80%,

diagnosing the subject as having a TRBC1 positive T-cell lymphoma or leukaemia when the percentage of TRBC1 positive cells is greater than 80%, and

selectively depleting T-cells in the subject determined to have the TRBC1 positive T cell lymphoma or leukaemia by administering an agent that selectively binds to and depletes malignant and normal T cells that are TRBC1-positive,

wherein the agent is an engineered T-cell expressing a CAR which selectively binds TRBC1 and which comprises: (i) a spacer comprising an IgG1 hinge or a CD8 stalk, and (ii) an antigen-binding domain comprising a variable heavy chain (VH) comprising: a VH CDR1 of SEQ ID NO: 7, a VH CDR2 of SEQ ID NO: 8, and a VH CDR3 of SEQ ID NO: 9, and a variable light chain (VL) comprising a VL CDR1 of SEQ ID NO: 10, a VL CDR2 of SEQ ID NO: 11, and a VL CDR3 of SEQ ID NO: 12, and (iii) an endodomain comprising a CD28 co-stimulatory component and a CD3-Zeta component.

14 . The method of claim 13 wherein the sample is a peripheral blood sample or a biopsy.

15 . A method of selectively depleting TRBC1 positive malignant T-cells without depleting the entire T-cell compartment in a human subject, the method comprising:

determining whether a malignant T cell in a sample containing T cells from the subject expresses TRBC1 or TRBC2, and

when the malignant T cell expresses TRBC1, selectively depleting malignant and normal T-cells in the subject that express TRBC1 by administering to the subject an agent that selectively binds to TRBC1 and that depletes said malignant and normal T-cells, wherein the agent is an engineered T-cell expressing a CAR that selectively binds to TRBC1 and that comprises: (i) a spacer comprising an IgG1 hinge or a CD8 stalk, and (ii) an antigen-binding domain comprising a variable heavy chain (VH) comprising: a VH CDR1 of SEQ ID NO: 7, a VH CDR2 of SEQ ID NO: 8, and a VH CDR3 of SEQ ID NO: 9, and a variable light chain (VL) comprising a VL CDR1 of SEQ ID NO: 10, a VL CDR2 of SEQ ID NO: 11, and a VL CDR3 of SEQ ID NO: 12, and (iii) an endodomain comprising a CD28 co-stimulatory component and a CD3-Zeta component.

16 . The method of claim 15 wherein the malignant T-cells in the subject are T-cell lymphoma or leukaemia cells.

17 . The method of claim 16 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.

18 . The method of claim 13 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.

19 . The method of claim 13 wherein the IgG1 hinge is an IgG1 hinge altered to remove Fc binding motifs.

20 . The method of claim 15 wherein the IgG1 hinge is an IgG1 hinge altered to remove Fc binding motifs.