Dna vaccine for use in pancreatic cancer patients

Abstract

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

1 . An attenuated mutant strain of  Salmonella typhi  comprising at least one copy of a recombinant DNA molecule comprising an expression cassette encoding a VEGF receptor protein, particularly a VEGF receptor protein selected from the group consisting of human VEGFR-2 and a homolog thereof that shares at least about 80% homology therewith, particularly wherein human VEGFR-2 has the amino acid sequence as found in SEQ ID NO 1, for use as a vaccine. 
     
     
         2 . A DNA vaccine comprising the attenuated mutant strain of  Salmonella typhi  of  claim 1 , wherein the attenuated mutant strain of  Salmonella typhi  is  Salmonella typhi  Ty21a, and wherein the expression cassette is a eukaryotic expression cassette, for use in cancer immunotherapy. 
     
     
         3 . The DNA vaccine of  claim 2 , wherein the DNA vaccine comprises the attenuated  Salmonella typhi  strain Ty21a transformed by a plasmid that contains a DNA encoding the VEGFR-2 protein of SEQ ID NO 1 for use in an anti-angiogenic cancer immunotherapy. 
     
     
         4 . The DNA vaccine of  claim 3 , wherein the plasmid is the 7580 bp pVAX10.VR2-1 as depicted in  FIG. 2  and has the sequence as found in SEQ ID NO 3 and the DNA vaccine is designated VXM01. 
     
     
         5 . The DNA vaccine of  claim 2 , wherein the cancer is pancreatic cancer. 
     
     
         6 . The DNA vaccine of  claim 5 , wherein said pancreatic cancer is stage IV or locally advanced pancreatic cancer. 
     
     
         7 . The DNA vaccine of  claim 2 , wherein the cancer includes metastases. 
     
     
         8 . The DNA vaccine of  claim 2 , wherein the treatment is accompanied by chemotherapy and/or radiotherapy. 
     
     
         9 . The DNA vaccine of  claim 8 , wherein the chemotherapeutic agent is gemcitabine. 
     
     
         10 . The DNA vaccine of  claim 8 , wherein the immunotherapeutic treatment with the vaccine is carried out during the chemotherapy treatment cycle. 
     
     
         11 . The DNA vaccine of  claim 2 , wherein the vaccine is administered orally. 
     
     
         12 . The DNA vaccine of  claim 2 , wherein the single dose of the vaccine is 1×10 5 , 1×10 6 , 1×10 7 , 1×10 8 , 1×10 9 , 1×10 10 , or 1×10 11  colony forming units (CFU). 
     
     
         13 . The DNA vaccine for use according to  claim 9 , wherein the single dose of the vaccine is less than 1×10 9  CFU, particularly wherein the single dose of the vaccine is from 1×10 8  to 1×10 9  CFU. 
     
     
         14 . The DNA vaccine for use according to  claim 9 , wherein the single dose of the vaccine is less than 1×10 8  CFU, particularly wherein the single dose of the vaccine is from 1×10 5  to 1×10 8  CFU, more particularly wherein the single dose of the vaccine is from 1×10 6  to 1×10 7  CFU. 
     
     
         15 . The DNA vaccine of  claim 2 , wherein the single dose comprises from about 10 5  to about 10 11 , particularly form 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). 
     
     
         16 . The DNA vaccine VXM01, comprising the attenuated  Salmonella typhi  strain Ty21a transformed by a plasmid that contains a DNA encoding the VEGFR-2 protein of SEQ ID NO 1, wherein the plasmid is a 7580 bp plasmid DNA and comprises the cDNA of VEGFR-2 that is under the control of the CMV promoter, the kanamycin resistance gene, and the pMB1 ori, and is designated as pVAX10.VR2-1.