CHIMERIC CYTOKINE RECEPTOR

1 - 2 . (canceled)

3 . A chimeric cytokine receptor, which comprises two polypeptides:

(i) a first polypeptide which comprises:

(a) a first dimerisation domain; and

(b) a first chain of the cytokine receptor endodomain; and

(ii) a second polypeptide which comprises:

(a) a second dimerization domain, which dimerises with the first dimerization domain; and

(b) a second chain of the cytokine-receptor endodomain

wherein the first and/or second chain of the cytokine-receptor endodomain is/are truncated.

4 . A chimeric cytokine receptor according to claim 3 , wherein the first and second dimerization domains dimerise spontaneously.

5 . A chimeric cytokine receptor according to claim 3 , where the first and second dimerization domains dimerise in the presence of a chemical inducer of dimerization (CID) or the presence of a protein.

6 . A chimeric cytokine receptor according to claim 4 which comprises two polypeptides:

(i) a first polypeptide which comprises:

(a) a heavy chain constant domain (CH)

(b) a first chain of the cytokine receptor endodomain; and

(ii) a second polypeptide which comprises:

(a) a light chain constant domain (CL)

(b) a second chain of the cytokine-receptor endodomain.

7 . A chimeric cytokine receptor comprising:

an exodomain which binds to a ligand; and

a cytokine receptor endodomain comprising a first chain and a second chain

wherein the first and/or second chain of the cytokine-receptor endodomain is/are truncated.

8 . A chimeric cytokine receptor according to claim 7 , which comprises two polypeptides:

(i) a first polypeptide which comprises:

(a) a first antigen-binding domain which binds a first epitope of the ligand

(b) a first chain of the cytokine receptor endodomain; and

(ii) a second polypeptide which comprises:

(a) a second antigen-binding domain which binds a second epitope of the ligand

(b) a second chain of the cytokine-receptor endodomain.

9 - 13 . (canceled)

14 . A chimeric cytokine receptor according to claim 3 wherein the first and second chains of the cytokine receptor endodomain are selected from type I cytokine receptor endodomain α-, β-, and γ-chains.

15 . A chimeric cytokine receptor according to claim 14 , wherein the first and second chains of the cytokine receptor endodomain are selected from:

(i) IL-2 receptor β-chain endodomain

(ii) IL-7 receptor α-chain endodomain; or

(iii) IL-15 receptor α-chain endodomain; and/or

(iv) common γ-chain receptor endodomain.

16 . A chimeric cytokine receptor according to claim 3 , which comprises a truncated IL-2 receptor β-chain endodomain.

17 . A cell which comprises a chimeric cytokine receptor according to claim 3 .

18 . A cell according to claim 17 , which also comprises a chimeric antigen receptor.

19 . (canceled)

20 . A nucleic acid construct encoding a chimeric cytokine receptor according to claim 3 which comprises a first nucleic acid sequence encoding the first polypeptide; and a second nucleic acid sequence encoding the second polypeptide, the nucleic acid construct having the structure:

Dim1-TM1-endo1-coexpr-Dim2-TM2-endo2

in which

Dim1 is a nucleic acid sequence encoding the first dimerisation domain;

TM1 is a nucleic acid sequence encoding the transmembrane domain of the first polypeptide;

endo 1 is a nucleic acid sequence encoding the endodomain of the first polypeptide;

coexpr is a nucleic acid sequence enabling co-expression of both CCRs

Dim2 is a nucleic acid sequence encoding the second dimerization domain;

TM2 is a nucleic acid sequence encoding the transmembrane domain of the second polypeptide;

endo 2 is a nucleic acid sequence encoding the endodomain of the second polypeptide.

21 . A nucleic acid construct encoding a chimeric cytokine receptor according to claim 7 , which comprises a first nucleic acid sequence encoding the first polypeptide and a second nucleic acid sequence encoding the second polypeptide, the nucleic acid construct having the structure:

AgB1-spacer1-TM1-endo1-coexpr-AbB2-spacer2-TM2-endo2

in which

AgB1 is a nucleic acid sequence encoding the antigen-binding domain of the first polypeptide;

spacer 1 is a nucleic acid sequence encoding the spacer of the first polypeptide;

TM1 is a nucleic acid sequence encoding the transmembrane domain of the first polypeptide;

endo 1 is a nucleic acid sequence encoding the endodomain of the first polypeptide;

coexpr is a nucleic acid sequence enabling co-expression of both polypeptides

AgB2 is a nucleic acid sequence encoding the antigen-binding domain of the second polypeptide;

spacer 2 is a nucleic acid sequence encoding the spacer of the second polypeptide;

TM2 is a nucleic acid sequence encoding the transmembrane domain of the second polypeptide;

endo 2 is a nucleic acid sequence encoding the endodomain of the second polypeptide.

22 - 25 . (canceled)

26 . A vector comprising a nucleic acid construct according to claim 20 .

27 - 28 . (canceled)

29 . A method for making a cell according to claim 17 , which comprises the step of introducing into a cell:

(i) a first nucleic acid sequence encoding a first polypeptide which comprises:

(a) a first dimerisation domain; and

(b) a first chain of the cytokine receptor endodomain; and

(ii) a second nucleic acid sequence encoding a second polypeptide which comprises:

(a) a second dimerization domain, which dimerises with the first dimerization domain; and

(b) a second chain of the cytokine-receptor endodomain

wherein the first and/or second chain of the cytokine-receptor endodomain is/are truncated.

30 . (canceled)

31 . A pharmaceutical composition comprising a plurality of cells according to claim 17 .

32 . A method for treating and/or preventing a disease, which comprises the step of administering a pharmaceutical composition according to claim 31 to a subject.

33 - 37 . (canceled)

38 . A cell which comprises a chimeric cytokine receptor according to claim 7 .

39 . A vector comprising a nucleic acid construct according to claim 21 .