Induction of tumor antigen-specific immunity using plasmid DNA immunization in mice

We have evaluated the ability of bioballistic "gene gun" immunization of mi ce with plasmid DNA encoding clinically relevant tumor antigens to induce p rotective antitumor immunity. Mice immunized with plasmid cDNA encoding the cervical carcinoma-associated human papillomavirus 16-E7 gene product exhi bited potent anti-E7-specific cytotoxic T lymphocytes and were protected co mpletely against a subsequent challenge with the E7(+) C3 sarcoma. Of perha ps greater clinical interest, genetic immunization using cDNA encoding the normal, germline-encoded murine melanosomal protein tyrosinase-related prot ein-2 (TRP-2) resulted in delayed outgrowth of TRP-2(+) B16 melanoma in mic e and was associated with an in vivo activation of TRP-2-specific cytotoxic T lymphocytes. Codelivery of plasmid cDNA encoding TRP-2 and the T helper 1-biasing cytokine murine interleukin-12 considerably enhanced the antitumo r efficacy of these gene-based melanoma vaccines.