Mesothelin Vaccines and Model Systems and Control of Tumors

Abstract

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 - 39 . (canceled) 
     
     
         40 . A method of inducing a T-cell response to tumor cells that overexpress mesothelin relative to normal cells from which the tumor cells are derived, said method comprising:
 administering to a patient who is at risk of developing a tumor that overexpresses mesothelin a vaccine comprising a polynucleotide encoding a polypeptide comprising an MHC class I-binding epitope of mesothelin or an MHC class II-binding epitope of mesothelin, wherein the epitope binds to an allelic form of MHC class I or class II which is expressed by the patient, whereby a T-cell response to mesothelin is induced, wherein the vaccine does not comprise whole tumor cells.   
     
     
         41 . The method of  claim 40  wherein the patient has been exposed to a carcinogen which is known to induce tumors which overexpress mesothelin relative to normal tissue from which the tumor is derived. 
     
     
         42 . The method of  claim 41  wherein the carcinogen is asbestos. 
     
     
         43 - 95 . (canceled) 
     
     
         96 . A method of predicting future response to a tumor vaccine in a patient who has received the vaccine, comprising:
 testing the patient to determine if the patient has a delayed type hypersensitivity (DTH) response to mesothelin, wherein the presence of said response predicts a longer survival time than the absence of said response.   
     
     
         97 . The method of  claim 96  wherein the vaccine comprises whole tumor cells. 
     
     
         98 . The method of  claim 96  wherein the vaccine comprises pancreatic tumor cells. 
     
     
         99 . The method of  claim 96  wherein the vaccine comprises ovarian tumor cells. 
     
     
         100 . The method of  claim 96  wherein the vaccine comprises mesothelioma cells. 
     
     
         101 - 112 . (canceled) 
     
     
         113 . A method of treating mammal having a tumor which overexpresses mesothelin relative to normal tissue from which it is derived, said method comprising:
 administering to a mammal who has said tumor or who has had said tumor removed, a composition comprising a polynucleotide encoding mesothelin, wherein the composition does not comprise whole tumor cells; and   administering to the mammal antibodies which specifically bind to mesothelin.   
     
     
         114 . The method of  claim 113  wherein the tumor is selected from the group consisting of ovarian cancer, pancreatic cancer, mesothelioma, and squamous cell carcinoma. 
     
     
         115 . The method of  claim 113  wherein the tumor is a pancreatic cancer. 
     
     
         116 . The method of  claim 113  wherein the tumor is an ovarian cancer.