Mesothelin vaccines and model systems
Mesothelin can be used as an immunotherapeutic target. It induces a cytolytic T cell response. Portions of mesothelin which induce such responses are identified. Vaccines can be either polynucleotide- or polypeptide-based. Carriers for raising a cytolytic T cell response include bacteria and viruses. A mouse model for testing vaccines and other anti-tumor therapeutics and prophylactics comprises a strongly mesothelin-expressing, transformed peritoneal cell line.
1. A method of treating a patient with a cancer that overexpresses mesothelin relative to normal tissue from which the cancer is derived, said method comprising:
administering to the patient a composition comprising a polypeptide consisting of 9 to 25 contiguous amino acid residues of mesothelin, said polypeptide comprising VLPLTVAEV (SEQ ID NO: 2), under conditions in which a T-cell response to mesothelin is induced, wherein the composition does not comprise whole tumor cells.
2. The method of claim 1 wherein the patient has undergone surgery to remove the cancer.
3. The method of claim 1 wherein the cancer that overexpresses mesothelin is pancreatic cancer.
4. The method of claim 3 wherein the patient has undergone surgery to remove the pancreatic cancer.
5. The method of claim 1 wherein mesothelin-specific CD8 + T cells are induced in the patient.
6. The method of claim 1 wherein the composition is acellular.
7. The method of claim 1 wherein the composition comprises Listeria monocytogenes bacteria, and the bacteria express the polypeptide.
8. The method of claim 1 wherein the composition is administered in sufficient amount to keep the patient tumor-free after removal of the tumor.
9. The method of claim 1 wherein the composition comprises dendritic cells.
10. The method of claim 1 wherein the tumor is selected from the group consisting of: ovarian cancer, pancreatic cancer, mesothelioma, and squamous cell carcinomas of the esophagus, lung, and cervix.
11. The method of claim 1 wherein the polypeptide is fused to another polypeptide or a carrier protein.
12. The method of claim 11 wherein the polypeptide is fused to a carrier protein and the carrier protein is selected from the group consisting of CD40 ligand, OX-40 ligand, CTLA-4 antagonist, and GM-CSF.
13. The method of claim 1 wherein the polypeptide is less than 15 amino acid residues.
14. The method of claim 1 wherein the polypeptide is less than 14 amino acid residues.
15. The method of claim 1 wherein the polypeptide is less than 13 amino acid residues.
16. The method of claim 1 wherein the polypeptide is less than 12 amino acid residues.
17. The method of claim 1 wherein the polypeptide is less than 11 amino acid residues.
18. The method of claim 1 further comprising the step of measuring induction of a T cell response.
19. The method of claim 1 further comprising the step of measuring induction of mesothelin-specific CD8 + T cells.
20. The method of claim 1 further comprising the step of measuring induction of a DTH response.
21. The method of claim 1 further comprising the step of administering a carrier for stimulating a CD8+ T cell or CD4+ T cell immune response, wherein the carrier is selected from the group consisting of: (a) a bacterial cell that is transformed to express the polypeptide, (b) an antigen presenting cell on whose surface the polypeptide is bound, and (c) a protein selected from the group consisting of CD40, CD40 ligand, OX-40, OX-40 ligand, CTLA-4 antagonist, and GM-CSF.