Chimeric protein

1. A method for treating a cancer in a subject which comprises the step of administering a cell to the subject, which cell:

(i) expresses a T-cell receptor (TCR) or chimeric antigen receptor (CAR) and

(ii) comprises a chimeric protein having the formula:

Ht1-Ht2-Casp

wherein Casp is a caspase domain,

Ht1 is a first heterodimerization domain, and

Ht2 is a second heterodimerization domain;

wherein one heterodimerization domain comprises an FK506-binding protein (FKBP) and the other heterodimerization domain comprises an FRB domain of mTOR;

and wherein, in the presence of rapamycin or a rapamycin analog, an identical pair of the chimeric proteins interact such that Ht1 from one chimeric protein heterodimerizes with Ht2 from the other chimeric protein, causing homodimerization of the two caspase domains.

2. A method according to claim 1 , wherein the cancer is selected from the following: bladder cancer, breast cancer, colon cancer, endometrial cancer, kidney cancer (renal cell), leukemia, lung cancer, melanoma, non-Hodgkin lymphoma, pancreatic cancer, prostate cancer and thyroid cancer.

3. A method according to claim 1 which comprises the following steps:

(i) transducing or transfecting a sample of cells isolated from a subject with a vector which comprises a nucleic acid sequence encoding the chimeric protein, and

(ii) administering the transduced/transfected cells to a patient.

4. A method according to claim 3 , wherein in step (i) the sample of cells isolated from the subject is transduced or transfected with a vector which comprises a nucleic acid construct which comprises a nucleic acid sequence encoding the chimeric protein and a nucleic acid sequence encoding the TCR or CAR.

5. A method according to claim 3 , wherein in step (i) the sample of cells isolated from the subject is transduced or transfected with a vector which comprises a nucleic acid sequence encoding the chimeric protein and a nucleic acid sequence encoding the TCR or CAR.

6. A method according to claim 3 , wherein in step (i) the sample of cells isolated from the subject is transduced or transfected with a kit of vectors comprising a first vector which comprises a nucleic acid sequence encoding the chimeric protein and a second vector which comprises a nucleic acid sequence encoding the TCR or CAR.

7. A method according to claim 1 , which comprises the following steps:

(i) administering the cell to the subject;

(ii) monitoring the subject for the development of a pathological immune reaction; and

(iii) administering rapamycin or a rapamycin analog to the subject if the subject shows signs of developing or having developed a pathological immune reaction.

8. A method according to claim 7 , wherein the pathological immune reaction is selected from the following group: graft-versus-host disease; on-target, off-tumour toxicity; immune activation syndrome; and lymphoproliferative disorders.

9. A method according to claim 1 wherein Ht1 does not heterodimerize with Ht2 within the same chimeric protein.

10. A method according to claim 1 , wherein the caspase domain comprises an initiator caspase selected from the following group: caspase-8, caspase-9 and caspase-10.

11. A method according to claim 1 , wherein Ht1 comprises FRB and Ht2 comprises FKBP.

12. A method according to claim 1 , wherein the cell is a haematopoietic stem cell, a lymphocyte or a T cell.