Novel msln targeting dna vaccine for cancer immunotherapy

Abstract

The present invention relates to an attenuated mutant strain of Salmonella comprising a recombinant DNA molecule encoding Mesothelin. In particular, the present invention relates to the use of said attenuated mutant strain of Salmonella in cancer immunotherapy.

1 . An attenuated mutant strain of  Salmonella  comprising at least one copy of a recombinant DNA molecule comprising an expression cassette encoding Mesothelin (MSLN). 
     
     
         2 . The attenuated mutant strain of  Salmonella  of  claim 1 , wherein the attenuated mutant strain of  Salmonella  is of the species  Salmonella enterica , particularly wherein the attenuated mutant strain of  Salmonella  is  Salmonella typhi  Ty21a. 
     
     
         3 . The attenuated mutant strain of  Salmonella  of  claim 1 , wherein the expression cassette is a eukaryotic expression cassette. 
     
     
         4 . The attenuated mutant strain of  Salmonella  of  claim 1 , wherein MSLN is selected from the group consisting of human MSLN and a protein that shares at least 80% sequence identity therewith, particularly wherein MSLN has the amino acid sequence as found in SEQ ID NO 1. 
     
     
         5 . The attenuated mutant strain of  Salmonella  of  claim 3 , wherein the recombinant DNA molecule comprises the kanamycin antibiotic resistance gene, the pMB1 ori, and a eukaryotic expression cassette encoding human MSLN or a protein that shares at least 80% sequence identity therewith under the control of a CMV promoter, particularly wherein human MSLN has the nucleic acid sequence as found in SEQ ID NO 2. 
     
     
         6 . The attenuated mutant strain of  Salmonella  of  claim 1  for use as a medicament. 
     
     
         7 . The attenuated mutant strain of  Salmonella  of  claim 6  for use as a vaccine. 
     
     
         8 . The attenuated mutant strain of  Salmonella  of  claim 7  for use in cancer immunotherapy. 
     
     
         9 . The attenuated mutant strain of  Salmonella  of  claim 8 , wherein cancer immunotherapy further comprises administration of one or more further attenuated mutant strain(s) of  Salmonella  comprising at least one copy of a recombinant DNA molecule comprising an expression cassette encoding a tumor antigen and/or a tumor stroma antigen, particularly wherein said one or more further attenuated mutant strain(s) of  Salmonella  is/are  Salmonella typhi  Ty21a comprising a eukaryotic expression cassette, more particularly wherein said one or more further attenuated mutant strain(s) of  Salmonella  comprise(s) an attenuated mutant strain of  Salmonella  encoding human VEGFR-2 and/or human Wilms' Tumor Protein (WT1). 
     
     
         10 . The attenuated mutant strain of  Salmonella  of  claim 9 , wherein the attenuated mutant strain of  Salmonella  is co-administered with said one or more further attenuated mutant strain(s) of  Salmonella.    
     
     
         11 . The attenuated mutant strain of  Salmonella  of  claim 8 , wherein cancer immunotherapy is accompanied by chemotherapy, radiotherapy or biological cancer therapy, particularly wherein the attenuated mutant strain of  Salmonella  is administered before or during the chemotherapy or the radiotherapy treatment cycle or before or during biological cancer therapy, or before and during the chemotherapy or the radiotherapy treatment cycle or the biological cancer therapy. 
     
     
         12 . The attenuated mutant strain of  Salmonella  of  claim 6 , wherein the attenuated mutant strain of  Salmonella  is administered orally. 
     
     
         13 . The attenuated mutant strain of  Salmonella  of  claim 8 , wherein the cancer is selected from mesotheliomas, ovarian and pancreatic cancers, squamous cell carcinomas of the cervix, head and neck, vulva, lung and esophagus, lung adenocarcinomas, endometrial carcinomas, biphasic synovial sarcomas, desmoplastic small round cell tumors and gastric adenocarcinomas. 
     
     
         14 . The attenuated mutant strain of  Salmonella  of  claim 6 , wherein the single dose comprises from about 10 5  to about 10 11 , particularly from about 10 6  to about 10 10 , more particularly from about 10 6  to about 10 9 , more particularly from about 10 6  to about 10 8 , most particularly from about 10 6  to about 10 7  colony forming units (CFU). 
     
     
         15 . The attenuated mutant strain of  Salmonella  of  claim 8  for use in individualized cancer immunotherapy comprising the step of assessing the MSLN expression pattern and/or the pre-immune response against MSLN of a patient.