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. An immunogenic composition which induces a CD8™ T cell or CD4″ T cell response, comprising: a polypeptide comprising a human leukocyte antigen (HLA) Class I- or Class II restricted mesothelin; and
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 protein that is fused to the polypeptide, said protein selected from the group consisting of CD40, CD40 ligand, OX-40, OX-40 ligand, CTLA-4 antagonist, and GM-CSF; and
(b) a bacterial cell that is transformed to express the polypeptide; and
(c) an antigen presenting cell on whose surface the polypeptide is bound.
2. The immunogenic composition of claim 1 wherein the carrier is CD40 or CD40 ligand.
3. The immunogenic composition of claim 1 wherein the carrier is OX-40 or OX-40 ligand.
4. The immunogenic composition of claim 1 wherein the carrier is a CTLA-4 antagonist.
5. The immunogenic composition of claim 1 wherein the carrier is GM-CSF.
6. The immunogenic composition of claim 1 , which comprises a bacterial cell.
7. The immunogenic composition of claim 1 wherein the carrier is an antigen-presenting cell.
8. The immunogenic composition of claim 6 wherein the bacterium is selected from the group consisting of: Listeria monocytogenes, Shigella flexneri, E. coli, Yersinia enterocolitica, Salmonella typhimurium, Salmonella typhi , and mycobacterium.
9. The immunogenic composition of claim 8 wherein the bacterium is Listeria monocytogenes.