Constitutive expression of costimulatory ligands on adoptively transferred T lymphocytes
The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing at least one of an antigen-recognizing receptor and a co-stimulatory ligand and methods of use therefore for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.
1. A method of treating leukemia or ovarian cancer in a subject, comprising administering an effective amount of immunoresponsive cells to the subject, wherein the immunoresponsive cell comprises:
a) a chimeric antigen receptor (CAR) that binds to a tumor antigen expressed by leukemia or ovarian cancer, and b) a nucleic acid molecule encoding a recombinant IL-12.
2. The method of claim 1 , wherein the cell is a T cell.
3. The method of claim 1 , wherein the cell comprises a cytotoxic T lymphocyte.
4. The method of claim 1 , wherein the nucleic acid molecule is comprised on a vector.
5. The method of claim 4 , wherein the vector is a viral vector.
6. The method of claim 5 , wherein the vector is a retroviral vector.
7. The method of claim 6 , wherein the retroviral vector is a gamma-retroviral vector or a lentiviral vector.
8. The method of claim 1 , wherein the tumor antigen is CD 19 .
9. The method of claim 1 , wherein the tumor antigen is expressed by a tumor expressing CD 19 .
10. The method of claim 1 , wherein the CAR comprises a ζ chain signaling domain.
11. The method of claim 1 , wherein the CAR further comprises a domain that provides a costimulatory signal.
12. The method of claim 1 , wherein the CAR comprises a CD28 signaling element.
13. The method of claim 1 , wherein the immunoresponsive cell is a T cell, and the tumor antigen is expressed by ovarian cancer.
14. The method of claim 1 , wherein the immunoresponsive cell is a T cell, and the tumor antigen is expressed by leukemia.
15. The method of claim 1 , wherein the leukemia is acute lymphocytic leukemia.