We have evaluated the ability of bioballistic "gene gun" immunization of mice with plasmid DNA encoding clinically relevant tumor antigens to induce protective antitumor immunity. Mice immunized with plasmid cDNA encoding the cervical carcinoma-associated human papillomavirus 16-E7 gene product exhibited potent anti-E7-specific cytotoxic T lymphocytes and were protected completely against a subsequent challenge with the E7+ C3 sarcoma. Of perhaps greater clinical interest, genetic immunization using cDNA encoding the normal, germline-encoded murine melanosomal protein tyrosinase-related protein-2 (TRP-2) resulted in delayed outgrowth of TRP-2+ B16 melanoma in mice 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 antitumor efficacy of these gene-based melanoma vaccines.
Bibliographical noteFunding Information:
This work was supported in part by a fellowship from the Deutsche Forschungs Gemeinschaft (to T.T.), by National Institutes of Health Grants CA 57840 and CA 67407 (to W.J.S., who is also the recipient of a Clinical Investigator Award from the Cancer Research Institute), and by National Institutes of Health Grant CA 64623 to A.B.D.
- DNA immunization
- Tumor-associated antigens
- Tyrosinase-related protein-2