Chimeric antigen receptors, and T cells in which chimeric antigen receptor is expressed
Disclosed is a chimeric antigen receptor comprising an antigen binding domain; a hinge region; a transmembrane domain; a costimulatory domain; and a cytoplasmic signaling domain.
1. A chimeric antigen receptor (CAR) comprising an antigen binding domain that binds to IL13Rα2; a hinge region; a transmembrane domain; a costimulatory domain; and a cytoplasmic signaling domain, wherein the antigen binding domain that binds to IL13Rα2 comprises the amino acid sequence set forth in SEQ ID NO: 1 but in which the amino acids at the 11 th and 107 th positions of SEQ ID NO: 1 are each replaced with lysine and the amino acids at the 64 th and 67 th positions of SEQ ID NO: 1 are each replaced with aspartic acid.
2. The CAR according to claim 1 , wherein the CAR further comprises three glycines between the antigen binding domain and the hinge region.
3. The CAR according to claim 1 , wherein the hinge region is a CD8 hinge region comprising the amino acid sequence set forth in SEQ ID NO: 9 or 10.
4. The CAR according to claim 1 , wherein the transmembrane domain comprises SEQ ID NO: 11 or SEQ ID NO: 12.
5. The CAR according to claim 1 , wherein the costimulatory domain comprises a CD28 costimulatory domain as set forth in SEQ ID NO: 27 and/or a TNFRSF9 costimulatory domain as set forth in SEQ ID NO: 8.
6. The CAR according to claim 1 , wherein the cytoplasmic signaling domain is a CD3ζ signaling domain.
7. The CAR according to claim 6 , wherein the CD3ζ signaling domain comprises the amino acid sequence set forth in SEQ ID NO: 13.
8. The CAR according to claim 1 , wherein the CAR comprises the amino acid sequence set forth in SEQ ID NO: 14.
9. The CAR according to claim 1 , wherein the CAR comprises the amino acid sequence set forth in SEQ ID NO: 15.
10. An expression vector encoding the CAR according to claim 1 .
11. An expression vector encoding the CAR according to claim 8 .
12. An expression vector encoding the CAR according to claim 9 .
13. A T cell expressing the CAR according to claim 1 .
14. A T cell expressing the CAR according to claim 8 .
15. A T cell expressing the CAR according to claim 9 .
16. A T cell expressing a chimeric antigen receptor (CAR) comprising the amino acid sequence set forth in SEQ ID NO: 14.
17. A T cell expressing a chimeric antigen receptor (CAR) comprising the amino acid sequence set forth in SEQ ID NO: 15.
18. A method of treating glioblastoma, the method comprising administering to a patient with glioblastoma a therapeutically effective amount of T cells that expresses the CAR according to claim 1 .
19. A method of treating glioblastoma, the method comprising administering to a patient with glioblastoma a therapeutically effective amount of T cells that expresses the CAR according to claim 8 .
20. A method of treating glioblastoma, the method comprising administering to a patient with glioblastoma a therapeutically effective amount of T cells that expresses the CAR according to claim 9 .