Chimeric antigen receptor comprising a cartilage-oligomeric matrix protein (comp) coiled-coil spacer domain
The present invention provides a chimeric antigen-receptor (CAR)-forming polypeptide comprising: (i) an antigen-binding domain; (ii) a coiled-coil spacer domain; (iii) a transmembrane domain; and (iv) an endodomain. The invention also provides a multimeric CAR formed by association of a plurality of CAR-forming polypeptides by virtue of association of their coiled-coil spacer domains.
1. A pentameric chimeric antigen receptor (CAR) comprising five CAR-forming polypeptides, wherein the CAR-forming polypeptides comprise in order from the amino terminus:
(i) an antigen-binding domain,
(ii) a cartilage-oligomeric matrix protein (COMP) coiled-coil spacer domain,
(iii) a transmembrane domain and
(iv) an endodomain comprising an intracellular signalling domain or an endodomain that interacts with an intracellular signaling molecule.
2. The pentameric CAR according claim 1 wherein the CAR-forming polypeptides comprise different intracellular signalling domains.
3. The pentameric CAR according to claim 1 wherein at least two of the CAR-forming polypeptides comprise different antigen-binding domains.
4. A nucleic acid construct which encodes a CAR-forming polypeptide, wherein the CAR-forming polypeptide comprises in order from the amino terminus:
(i) an antigen-binding domain,
(ii) a cartilage-oligomeric matrix protein (COMP) coiled-coil spacer domain,
(iii) a transmembrane domain and
(iv) an endodomain comprising an intracellular signalling domain or an endodomain that interacts with an intracellular signaling molecule.
5. A vector which comprises a nucleic acid construct according to claim 4 .
6. A cell which expresses a pentameric CAR according claim 1 .
7. The cell according to claim 6 which is a T cell or NK cell.
8. A pharmaceutical composition comprising the cell according to claim 6 .
9. A method for treating a disease comprising the step of administering the cell according to claim 7 to a subject in need thereof.
10. The method according to claim 9 wherein the disease is cancer.
11. A method for making a cell that expresses a pentameric CAR, which comprises the step of introducing a nucleic acid construct according to 4 into the cell.
12. The pentameric CAR according to claim 1 , wherein the COMP coiled-coil spacer domain is the COMP coiled- coli spacer domain shown as SEQ ID No. 1.
13. The nucleic acid construct according to claim 4 , wherein the COMP coiled-coil spacer domain is the COMP coiled- coli spacer domain shown as SEQ ID No. 1.