Therapeutic tumor immunity induced by polyimmunization with melanoma antigens gp100 and TRP-2

To improve the immunogenicity of melanoma self-antigens, we used a novel st rategy of nonviral genetic vaccination coupled with muscle electroporation. Electroporation-enhanced immunization with plasmids encoding either human gp100 or mouse TRP-2 antigens induced only partial rejection of B16 melanom a challenge. However, immunization with a combination of these two antigens caused tumor rejection in 100% of the immunized mice. Splenocytes from com bination-immunized animals killed syngeneic targets loaded with peptides de rived from both gp100 and TRP-2. Immune fell depletion experiments identifi ed CD8(+) T lymphocytes as the primary effecters of antitumor immunity. Mos t importantly, polyimmunization led to the generation of a therapeutic immu ne response that significantly improved the mean survival time of mice bear ing established lung metastases. These results validated the usefulness of electroporation-enhanced, nonviral genetic immunization for the active immu notherapy of cancer and indicated that using a combination of different tum or antigens may be a decisive strategy for a successful therapeutic vaccina tion.