Furin-knockdown and GM-CSF-augmented (FANG) cancer vaccine
Compositions and methods for cancer treatment are disclosed herein. More specifically, the present invention describes an autologous cancer vaccine genetically modified for Furin knockdown and GM-CSF expression. The vaccine described herein attenuates the immunosuppressive activity of TGF-β through the use of bi-functional shRNAs to knock down the expression of furin in cancer cells, and to segment tumor antigen expression, presentation, and processing through expression of the GM-CSF transgene.
1. A method of treating a cancer in an individual in need thereof comprising:
a. transfecting an autologous tumor cell from the individual with an expression vector comprising:
i. a first insert comprising a nucleic acid sequence encoding a Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) sequence; and
ii. a second insert comprising a sequence according to SEQ ID NO: 2; and
b. administering the transfected tumor cell to the individual.
2. The method of claim 1 , wherein the GM-CSF is a human GM-CSF sequence.
3. The method of claim 1 , wherein the expression vector further comprises a promoter.
4. The method of claim 3 , wherein the promoter is a cytomegalovirus (CMV) mammalian promoter.
5. The method of claim 4 , wherein the expression vector further comprises a CMV enhancer sequence and a CMV intron sequence.
6. The method of claim 3 , wherein the first insert and the second insert are operably linked to the promoter.
7. The method of claim 1 , wherein the expression vector further comprises a nucleic acid sequence encoding a picornaviral 2A ribosomal skip peptide between the first and the second nucleic acid inserts.
8. The method of claim 1 , wherein the cancer is a melanoma, non-small cell lung cancer (NSCLC), gall bladder cancer, colorectal cancer, breast cancer, ovarian cancer, liver cancer, liver cancer metastases, or Ewing's sarcoma.
9. The method of claim 1 , wherein the transfected tumor cell is administered to the individual as a dose of about 1×10 7 cells to about 5×10 7 cells.
10. The method of claim 9 , wherein the transfected tumor cells are administered to the individual once a month.
11. The method of claim 1 , wherein the transfected tumor cell is administered to the individual by intradermal injection.