CHIMERIC ANTIGEN RECEPTOR

1 . A chimeric antigen receptor (CAR) comprising a disialoganglioside (GD2)-binding domain which comprises

a) a heavy chain variable region (VH) having complementarity determining regions (CDRs) with the following sequences:

CDR1 

(SEQ ID No. 1)

SYNIH;

CDR2

(SEQ ID No. 2)

VIWAGGSTNYNSALMS

CDR3 

(SEQ ID No. 3)

RSDDYSWFAY;

and

b) a light chain variable region (VL) having CDRs with the following sequences:

CDR1 

(SEQ ID No. 4)

RASSSVSSSYLH;

CDR2 

(SEQ ID No. 5)

STSNLAS

CDR3

(SEQ ID No. 6)

QQYSGYPIT.

2 . A CAR according to claim 1 , wherein the GD2 binding domain comprises a VH domain having the sequence shown as SEQ ID No. 9, or SEQ ID NO 10; or a VL domain having the sequence shown as SEQ ID No 11, or SEQ ID No. 12 or a variant thereof having at least 90% sequence identity which retains the capacity to i) bind GD2 and ii) induce T cell signalling.

3 . A CAR according to claim 1 , wherein the GD2 binding domain comprises the sequence shown as SEQ ID No 7 or SEQ ID No. 8 or a variant thereof having at least 90% sequence identity which retains the capacity to i) bind GD2 and ii) induce T cell signalling.

4 . A CAR according to claim 1 , which comprises a transmembrane domain which comprises the sequence shown as SEQ ID No. 13 or a variant thereof having at least 80% sequence identity.

5 . A CAR according to claim 1 , wherein GD2-binding domain and the transmembrane domain are connected by a spacer.

6 . A CAR according to claim 4 , wherein the spacer comprises one of the following: a human an IgG1 Fc domain; an IgG1 hinge; an IgG1 hinge-CD8 stalk; or a CD8 stalk.

7 . A CAR according to claim 6 , wherein the spacer comprises an IgG1 hinge-CD8 stalk or a CD8 stalk.

8 . A CAR according to claim 6 , wherein the spacer comprises an IgG1 Fc domain or a variant thereof.

9 . A CAR according to claim 8 , wherein the spacer comprises an IgG1 Fc domain which comprises the sequence shown as SEQ ID No. 23 or SEQ ID No. 24 or a variant thereof having at least 80% sequence identity.

10 . A CAR according to claim 1 which also comprises an intracellular T cell signalling domain.

11 . A CAR according to claim 10 wherein the intracellular T cell signalling domain comprises one or more of the following endodomains: CD28 endodomain; OX40 and CD3-Zeta endodomain.

12 . A CAR according to claim 11 wherein the intracellular T cell signalling domain comprises all of the following endodomains: CD28 endodomain; OX40 and CD3-Zeta endodomain.

13 . A CAR according to claim 1 , which comprises the sequence shown as any of SEQ ID No. 26 to 35 or a variant thereof which has at least 80% sequence identity but retains the capacity to i) bind GD2 and ii) induce T cell signalling.

14 . A nucleic acid sequence which encodes a CAR according to claim 1 .

15 . A nucleic acid sequence according to claim 14 , which is codon-optimised.

16 . A nucleic acid sequence according to claim 14 which comprises the sequence shown as SEQ ID No 25 or a variant thereof having at least 90% sequence identity.

17 . A nucleic acid according to any of claim 14 which also encodes a suicide gene.

18 . A vector which comprises a nucleic acid sequence according to claim 14 .

19 . A T cell which expresses a CAR according to claim 1 .

20 . A T cell which co-expresses a CAR according to to claim 1 and a suicide gene.

21 . A T cell according to claim 20 , wherein the suicide gene is iCasp9 or RQR8.

22 . A method for making a T cell, which comprises the step of introducing a nucleic acid according to claim 14 into a T cell.

23 . A pharmaceutical composition which comprises a T cell according to claim 19 , together with a pharmaceutically acceptable carrier, diluent or excipient.

24 . A method for treating cancer which comprises the step of administering a T cell according to claim 19 to a subject.

25 . A method according to claim 24 , wherein the cancer is neuroblastoma.

26 - 27 . (canceled)