Induction of a systemic immune response by a polyvalent melanoma-associated antigen DNA vaccine for prevention and treatment of malignant melanoma.

Studies have demonstrated that active-specific immunotherapy has potential for controlling melanoma progression. We developed a polyvalent melanoma gene vaccine using a plasmid vector to deliver the immunogenic human melanoma-associated antigens (MAAs) gp100 and TRP-2. The MAA-containing plasmids were delivered individually in vivo using the hemagglutinating virus Japan (HVJ)-anionic liposome delivery system. C57BL/6 mice were immunized weekly by intramuscular (i.m.) injection or intranasal (i.n.) inoculation for 3 weeks. Although both i.m. and i.n. immunization induced Th1 (T helper) and Th2 cell responses to gp100 and TRP2, the i.m. route induced a better Th1 response. MAA-specific IgG2a, IgG1, and delayed-type hypersensitivity (DTH) responses were induced against both MAAs by i.m. immunization. We assessed the vaccine for its prophylactic and therapeutic effect against the murine B16 F10 melanoma. Animals vaccinated and subsequently challenged with a lethal dose of B16 cells were significantly (P<0.01) protected against tumor progression and had significantly (P<0.01) enhanced survival compared with treatment using control plasmid. We also developed a therapeutic model in which mice were given B16 cells and subsequently immunized with the vaccine or treated with control plasmid. In animals treated with the vaccine, tumor growth was significantly (P<0.01) controlled, and survival was prolonged compared with controls. These studies demonstrate that the polyvalent DNA vaccine induces an effective systemic Th response.