CELL
The present invention relates to a cell which comprises; (a) a chimeric antigen receptor (CAR) or a transgenic T-cell receptor (TCR); and (b) a FasL-binding receptor (FLBR) comprising; (i) a Fas ectodomain and a TNFR endodomain, wherein the TNFR endodomain comprises the signalling portion of the decoy receptor 2 (DcR2), GITR, CD30, XEDAR, CD40, CD27, BCMA or Fn14 endodomain, or (ii) a membrane-bound decoy receptor 3 (DcR3).
1 . A cell which comprises;
(a) a chimeric antigen receptor (CAR) or a transgenic T-cell receptor (TCR); and
(b) a FasL-binding receptor (FLBR) comprising;
a Fas ectodomain and an endodomain from CD40 or CD27.
2 . (canceled)
3 . A cell according to claim 1 , wherein the FLBR comprises a Fas ectodomain and a CD40 endodomain.
4 . A cell according to claim 3 , wherein the CD40 endodomain comprises the sequence shown as SEQ ID No. 4.
5 - 9 . (canceled)
10 . A cell according to claim 1 wherein the FLBR is selected from Fas-CD27 (SEQ ID NO: 39) and Fas-CD40 (SEQ ID NO: 41).
11 . A FasL-binding receptor (FLBR) comprising a Fas ectodomain and an endodomain from CD40 or CD27.
12 . A FasL-binding receptor (FLBR) according to claim 11 , comprising a Fas ectodomain and a CD40 endodomain.
13 . A nucleic acid sequence encoding an FLBR according to claim 11 .
14 . A nucleic acid construct which comprises:
(a) a first nucleic acid sequence which encodes a chimeric antigen receptor (CAR) or a transgenic T-cell receptor (TCR); and
(b) a second nucleic acid sequence which encodes a FasL-binding receptor (FLBR) according to claim 11 .
15 . A nucleic acid construct according to claim 14 wherein the first and second nucleic acid sequences are separated by a co-expression site.
16 . (canceled)
17 . A vector which comprises a nucleic acid sequence according to claim 13 .
18 . A kit of vectors which comprises:
(a) a first vector which comprises a nucleic acid sequence which encodes a chimeric antigen receptor (CAR) or a transgenic T-cell receptor (TCR); and
(b) a second vector which comprises a nucleic acid sequence which encodes a FasL-binding receptor (FLBR) according to claim 11 .
19 . A pharmaceutical composition which comprises a plurality of cells according to claim 1 .
20 . (canceled)
21 . A method for treating and/or preventing a disease, which comprises the step of administering a pharmaceutical composition according to claim 19 to a subject in need thereof.
22 . A method according to claim 21 , which comprises the following steps:
(i) isolation of a cell containing sample;
(ii) transduction or transfection of the cell with a nucleic acid sequence encoding a FasL-binding receptor (FLBR) comprising a Fas ectodomain and an endodomain from CD40 or CD27; and
(iii) administering the cells from (ii) to a subject.
23 . The method according to claim 22 wherein the cell is autologous.
24 . The method according to claim 21 wherein the cell is allogenic.
25 . (canceled)
26 . A method according to claim 22 , wherein the disease is cancer.
27 . A method for making a cell according to claim 1 , which comprises the step of introducing: a nucleic acid sequence encoding a FasL-binding receptor (FLBR) comprising a Fas ectodomain and an endodomain from CD40 or CD27 into the cell ex vivo.
28 . A method according to claim 27 , wherein the cell is from a sample isolated from a subject.