CELL EXPRESSING A CAR AND A TRANSCRIPTION FACTOR AND ITS USE
The present invention provides a cell which comprises a first exogenous nucleic acid molecule encoding a Chimeric Antigen Receptor (CAR) and a second exogenous nucleic acid molecule encoding a transcription factor.
1 . A cell which comprises a first exogenous nucleic acid molecule encoding a Chimeric Antigen Receptor (CAR) and a second exogenous nucleic acid molecule encoding a transcription factor.
2 . A cell according to claim 1 , wherein the transcription factor prevents or reduces differentiation and/or exhaustion of the cell.
3 . A cell according to claim 1 , wherein the transcription factor is an effector memory repressor.
4 . A cell according to claim 3 , wherein the transcription factor is BLIMP-1.
5 . A cell according to claim 1 , wherein the transcription factor is a central memory repressor.
6 . A cell according to claim 5 , wherein the transcription factor is BCL6 or Bach2.
7 . A cell according to claim 6 , wherein the transcription factor is or comprises Bach2.
8 . A cell according to claim 5 , wherein the transcription factor comprises a modified version of Bach2 which has reduced or removed capacity to be phosphorylated by ALK.
9 . A cell according to claim 8 , wherein the transcription factor comprises a modified version of Bach2 with a mutation at one or more of the following positions with reference to the amino acid sequence shown as SEQ ID No. 2: Ser-535, Ser-509, Ser-520.
10 . A nucleic acid construct which comprises a first nucleic acid sequence encoding a Chimeric Antigen Receptor (CAR) and a second nucleic acid sequence encoding a transcription factor.
11 . A nucleic acid construct according to claim 10 , which has the following structure:
CAR-coexpr-TF; or
TF-coexpr-CAR
in which:
CAR is a nucleic acid sequence encoding the CAR;
coexpr is a nucleic acid sequence enabling co-expression of the CAR and the transcription factor; and
TF is a nucleic acid sequence encoding the transcription factor.
12 . A nucleic acid construct according to claim 11 , wherein coexpr encodes a sequence comprising a self-cleaving peptide.
13 . A kit of nucleic acid sequences which comprises a first nucleic acid sequence encoding a Chimeric Antigen Receptor (CAR) and a second nucleic acid sequence encoding a transcription factor.
14 . A vector which comprises a nucleic acid construct according to claim 10 .
15 . A kit of vectors which comprises a first vector which comprises a first nucleic acid sequence encoding a Chimeric Antigen Receptor (CAR); and a second vector which comprises a second nucleic acid sequence encoding a transcription factor.
16 . A method for making a cell according to claim 1 , which comprises the step of introducing: a nucleic acid construct, a kit of nucleic acid sequences, a vector according to claim 14 , or a kit of vectors that comprise(s) a first nucleic acid sequence encoding a Chimeric Antigen Receptor (CAR) and a second nucleic acid sequence encoding a transcription factor, into a cell.
17 . (canceled)
18 . A pharmaceutical composition comprising a plurality of cells according to claim 1 .
19 . A method for treating and/or preventing a disease, which comprises the step of administering a pharmaceutical composition according to claim 18 to a subject.
20 . A method according to claim 19 , which comprises the following steps:
(i) isolation of a cell-containing sample from a subject;
(ii) transduction or transfection of the cells with: a nucleic acid construct, a kit of nucleic acid sequences, a vector, or a kit of vectors that comprise(s) a first nucleic acid sequence encoding a Chimeric Antigen Receptor (CAR) and a second nucleic acid sequence encoding a transcription factor; and
(iii) administering the cells from (ii) to the subject.
21 . A method according to claim 19 , wherein the disease is a cancer.
22 .- 23 . (canceled)