PD1-specific chimeric antigen receptor as an immunotherapy
Provided herein are methods and compositions useful for treating PDL1 and/or PDL2 positive cancers through adoptive cell transfer of T cells genetically engineered to express a PD1-specific chimeric antigen receptor. Co-stimulatory domains such as Dap 10 may be included to enhance efficacy.
1. A chimeric antigen receptor (CAR) polypeptide comprising the CAR polypeptide sequence of SEQ ID NO: 3.
2. A vector comprising a nucleic acid encoding the CAR polypeptide according to claim 1 .
3. A T lymphocyte genetically modified to express a CAR according to claim 1 .
4. A composition for adoptive cell transfer comprising T lymphocytes according to claim 3 and a pharmaceutically acceptable carrier.
5. The composition of claim 4 , further comprising one or more chemotherapeutic or radiotherapeutic agents.
6. A method of treating cancer in a subject in need thereof, wherein cells of said cancer express at least one of PDL1 and PDL2, comprising: administering to the subject a therapeutically effective amount of a composition for adoptive cell transfer comprising T lymphocytes comprising a polynucleotide encoding the CAR polypeptide of claim 1 .
7. The method of claim 6 , wherein the polynucleotide encoding the CAR polypeptide comprises a sequence at least 90% identical to SEQ ID NO: 2.
8. The method of claim 6 , wherein said cancer is selected from the group consisting of lymphoma, melanoma, myeloma, pancreatic cancer, breast cancer, and ovarian cancer.
9. The method of claim 6 , further comprising a step of administering one or more of a chemotherapeutic or radiotherapeutic agent.