DNA vector and transformed tumor cell vaccines
Customized whole cell cancer vaccines can be produced from autologous (ex vivo or in situ) or allogeneic human or veterinary patient cell lines. Cells are transformed with S. pyogenes DNA that expresses an Emm protein on the cell surface and cytosol. Treatment of cancer patients with an Emm vector vaccine induces an immunologic response to the cancer by enhancing immunogenicity of a tumor. Emm vaccines can be used in patients where the cancer is not identified due to lower tumor burden or used to treat a specific cancer and subsequently treat for a second type that may have arisen through metastasis.
1. A plasmid DNA vaccine comprising a plasmid DNA vector comprising a nucleic acid sequence set forth as SEQ ID NO: 1 operatively linked to a promoter expressing an immunogenic polypeptide on the cell surface.
2. The plasmid DNA vaccine of claim 1 wherein an immunogenic polypeptide is expressed on the surface of tumor cells when administered in vivo to a cancer patient.
3. The plasmid DNA vaccine of claim 2 wherein the expressed immunogenic polypeptide has the amino acid sequence of SEQ ID NO:2.
4. The plasmid DNA vaccine of claim 1 further comprising a nucleic acid that expresses an immunologic molecule selected from IL-2, IL-12, IL-18, MHC and checkpoint inhibitor.
5. The plasmid DNA vaccine of claim 2 wherein administration in vivo is directly into a tumor or tumor draining lymph node.
6. The plasmid DNA vaccine of claim 2 in a pharmaceutically acceptable excipient, wherein the polypeptide expressed on the tumor cell surface of a cancer patient induces an immunogenic effect upon in vivo administration.
7. The plasmid DNA vaccine of claim 2 wherein administration in vivo is directly into a tumor wherein the tumor is a carcinoma, sarcoma, myeloma, lymphoma, leukemia or mixed.
8. The plasmid DNA vaccine of claim 2 wherein administration in vivo is by needleless injection.
9. The plasmid DNA vaccine of claim 2 wherein the cancer patient is treated by radiation, chemotherapy or checkpoint inhibitor prior to or concurrently with administration of the vaccine.
10. A vaccine comprising tumor cells transformed in vitro with a plasmid DNA vector comprising a nucleic acid sequence set forth as SEQ ID NO: 1 operatively linked to a promoter, said transformed cells expressing an immunogenic polypeptide on the cell surface.
11. The vaccine of claim 10 wherein the transformed tumor cells express an immunogenic polypeptide having the amino acid sequence of SEQ ID NO:2.
12. The vaccine of claim 10 wherein the transformed tumor cells express an immunologic molecule selected from IL-2, IL-12, IL-18, MHC and checkpoint inhibitor.
13. The vaccine of claim 10 wherein the tumor cells are from two or more different cancers.
14. The vaccine of claim 10 wherein the tumor cells are from the same or different cancers selected from carcinoma, sarcoma, myeloma, lymphoma, leukemia or mixed.
15. The vaccine of claim 10 in a pharmaceutically acceptable excipient, wherein the polypeptide expressed on the tumor cell surface of a cancer patient induces an immunogenic effect upon in vivo administration.
16. The vaccine of claim 15 wherein the vaccine administered to the cancer patient has transformed tumor cells from at least one cancer comprised by the vaccine.
17. The vaccine of claim 15 wherein administration to the cancer patient is intradermal, subcutaneous, intravenous or intranodal.
18. The vaccine of claim 15 wherein the cancer patient is treated by radiation, chemotherapy or checkpoint inhibitor prior to or concurrently with administration of the vaccine.