CAR T-cells comprising transcriptional circuits

1. A method for treating a disease by killing target cells in a subject, which comprises the following steps:

(a) isolation of a T cell-containing sample from a subject,

(b) transduction or transfection of T cells of the sample with a kit of vectors comprising:

(i) a first vector which comprises a first transgene which encodes a chimeric antigen receptor (CAR) which binds an antigen expressed on the target cells and a nucleotide sequence encoding a transcription factor, and

(ii) a second vector which comprises a second transgene which encodes an entity of interest (EOI) and a marker gene

wherein expression of the second transgene within the T cell is dependent upon expression of the transcription factor,

or

(i) a first vector which comprises a first transgene which encodes a chimeric antigen receptor (CAR) which binds an antigen expressed on the target cells and a nucleotide sequence encoding a first transcription factor,

(ii) a second vector which comprises a second transgene which encodes an entity of interest (EOI) and a nucleotide sequence encoding a second transcription factor, and

(iii) a third vector which comprises a third transgene which encodes an entity of interest (EOI) and a marker gene

wherein expression of the second transgene within the T cell is dependent upon expression of the first transcription factor, and expression of the third transgene within the T cell is dependent upon expression of the second transcription factor,

(c) selecting T cells which express the marker gene, and

(d) administering the T cells selected from step (c) to the subject to kill the target cells.

2. The method of claim 1 , wherein the disease is cancer.