Chimeric antigen receptor
The present invention relates to chimeric antigen receptor (CAR) which binds the cancer antigen disialoganglioside (GD2). T cells expressing such a CAR are useful in the treatment of cancerous diseases such as neuroblastoma.
1. A chimeric antigen receptor (CAR) comprising:
a) a disialoganglioside (GD2)-binding domain and spacer, shown as amino acids 21 to 311 of SEQ ID NO: 29;
b) a hydrophobic alpha helical transmembrane domain; and
c) a CD28-CD3Zeta endodomain shown as SEQ ID NO: 17.
2. A chimeric antigen receptor (CAR) which comprises the sequence shown as any of SEQ ID NO: 27 to 29 and 31 to 35.
3. A nucleic acid sequence which encodes a CAR according to claim 2 or 1 .
4. A nucleic acid according claim 3 which also encodes a suicide gene.
5. A nucleic acid sequence according to claim 3 which comprises the sequence shown as SEQ ID NO: 25 or a variant thereof having at least 90% sequence identity.
6. A vector which comprises a nucleic acid sequence according to claim 3 .
7. A T cell which expresses a CAR according to claim 2 or 1 .
8. A T cell which co-expresses a CAR according to claim 2 or 1 and a suicide gene.
9. A T cell according to claim 8 , wherein the suicide gene is inducible Caspase 9 (iCasp9) or RQR8.
10. A method for making a T cell which expresses a CAR, which comprises the step of introducing a nucleic acid according to claim 3 ex vivo into a T cell.
11. A pharmaceutical composition which comprises a T cell according to claim 7 , together with a pharmaceutically acceptable carrier, diluent or excipient.
12. A method for treating neuroblastoma which comprises the step of administering a T cell according to claim 7 to a subject.
13. A vector which comprises a nucleic acid sequence according to claim 4 .
14. A pharmaceutical composition which comprises a vector according to claim 6 , together with a pharmaceutically acceptable carrier, diluent or excipient.
15. A pharmaceutical composition which comprises a vector according to claim 13 , together with a pharmaceutically acceptable carrier, diluent or excipient.
16. The pharmaceutical composition according to claim 15 wherein the suicide gene is inducible Caspase 9 (iCasp9) or RQR8.
17. A T cell according to claim 8 comprising the sequence shown as SEQ ID NO: 34 or 35.