DNA vaccine for use in pancreatic cancer patients
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. A method of treating pancreatic cancer comprising administering to a patient in need thereof a vaccine comprising an attenuated mutant strain of Salmonella typhi Ty21a comprising at least one copy of a recombinant DNA molecule comprising an expression cassette encoding a VEGF receptor protein having the amino acid sequence as found in SEQ ID NO 1, wherein the vaccine is administered in a single dose of 1×10 9 CFU or less than 1×10 9 CFU.
2. The method of claim 1 , wherein the expression cassette is a eukaryotic expression cassette.
3. The method of claim 1 , wherein the vaccine comprises the attenuated Salmonella typhi strain Tya21 a transformed by a plasmid that contains a DNA encoding the VEGFR-2 protein of SEQ ID NO 1.
4. The method 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 method of claim 1 , wherein said pancreatic cancer is stage IV or locally advanced pancreatic cancer.
6. The method of claim 1 , wherein the cancer includes metastases.
7. The method of claim 3 , further comprising administering chemotherapy and/or radiotherapy to the patient.
8. The method of claim 7 , wherein the chemotherapeutic agent is gemcitabine.
9. The method of claim 7 , wherein the immunotherapeutic treatment with the vaccine is carried out during the chemotherapy treatment cycle.
10. The method of claim 1 , wherein the vaccine is administered orally.
11. The method of claim 1 , wherein the single dose of the vaccine is administered in dose selected from the group of 1×10 5 , 1×10 6 , 1×10 7 , 1×10 8 , and 1×10 9 colony forming units (CFU).
12. The method of claim 1 , wherein the single dose of the vaccine is administered in a dose from 1×10 8 to 1×10 9 CFU.
13. The method of claim 1 , wherein the single dose of the vaccine is administered in a dose selected from the group of less than 1×10 8 CFU, from 1×10 5 to 1×10 8 CFU, and from 1×10 6 to 1×10 7 CFU.
14. The method of claim 1 , wherein the single dose comprises a dose selected from the group of from about 10 5 to about 10 9 , from about 10 6 to about 10 9 , from about 10 6 to about 10 8 , and from about 10 6 to about 10 7 colony forming units (CFU).