Enhancement of DNA cancer vaccine efficacy by combination with anti-angiogenesis in regression of established subcutaneous B16 melanoma.
Immunotherapy of cancer offers great promise, however translation into human studies has yielded relatively poor results to date. The concept of combining cancer vaccination with angiogenesis inhibition is appealing, due to favorable safety profile of both approaches, as well as possible biological synergies. Here we studied the anti-tumor effects of combining plasmid DNA (pDNA) vaccination and anti-angiogenesis in B16F10 murine model. By using electroporation-mediated gene/pDNA delivery, the anti-tumor efficacy of vaccination with pDNAs encoding gp100, TRP2 and Ii-PADRE was facilitated by administration of soluble form of EphB4 fused with human serum albumin (sEphB4-HSA), or by co-delivery of pDNAs encoding Angiostatin and/or Endostatin. In an optimized administration protocol, melanoma vaccination together with intratumoral delivery of pDNAs encoding Angiostatin and Endostatin resulted in 57% tumor-free survival over 90 days after challenge. These data support the general concept that suppression of angiogenesis may allow for enhanced efficacy of anti-tumor immunity, suggesting the synergetic effects of therapeutic pDNA vaccination and angiogenesis inhibition in cancer therapy.
Department of Research and Development, Inovio Biomedical Corporation, San Diego, CA 92121-1318, USA.
Ray Chun-Fai
RC
Chan
Benjamin
B
Gutierrez
Thomas E
TE
Ichim
Feng
F
Lin
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D043168:Angiostatins / Q000494:pharmacology*; D000818:Animals; D019496:Cancer Vaccines / Q000276:immunology / Q000494:pharmacology*; D003131:Combined Modality Therapy; D018274:Electroporation; D043169:Endostatins / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007167:Immunotherapy; D019746:Intramolecular Oxidoreductases / Q000235:genetics; D008546:Melanoma, Experimental / Q000098:blood supply / Q000276:immunology / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000517:prevention & control* / Q000628:therapy; D010957:Plasmids / Q000008:administration & dosage; D036224:Receptor, EphB4 / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology / Q000494:pharmacology*; D058951:gp100 Melanoma Antigen
D020533:Angiogenesis Inhibitors; D019496:Cancer Vaccines; D043169:Endostatins; D008562:Membrane Glycoproteins; C548637:PMEL protein, human; C548642:Pmel protein, mouse; D019444:Vaccines, DNA; D058951:gp100 Melanoma Antigen; D043168:Angiostatins; D036224:Receptor, EphB4; D019746:Intramolecular Oxidoreductases; C042501:dopachrome isomerase