Advances in Brief Genetic Vaccination against the Melanocyte Lineage-specific Antigen gplOO Induces Cytotoxic T Lymphocyte-mediated Tumor Protection 1

Melanocyte lineage-specific antigens, such as gplOO, have been shown to induce both cellular and humoral immune responses against melanoma. Therefore, these antigens are potential targets for specific antimelanoma immunotherapy. A novel approach to induce both cellular and humoral immunity is genetic vaccination, the injection of antigen-encoding naked plasmid DNA. In a mouse model, we investigated whether genetic vaccination against the human gplOO antigen results in specific antitumor immunity. The results demonstrate that vaccinated mice were protected against a lethal challenge with syngeneic B16 melanoma-expressing human gplOO, hut not control-transfected B16. Both cytotoxic T cells and IgG .specific for human gplOO could be detected in human gp 100-vaccinated mice. However, only adoptive transfer of spleen-derived lymphocytes, not of the serum. Isolated from protected mice was able to transfer antitumor immunity to nonvaccinated recipients, indicating that CTLs are the predominant effector cells. CTL lines generated from human gplOO-vaccinated mice specifically recog nized human gplOO. Interestingly, one of the CTL lines cross-reacted between human and mouse gplOO, indicating the recognition of a conserved epitope. However, these CTLs did not appear to be involved in the observed tumor protection. Collectively, our results indicate that genetic vaccination can result in a potent antitumor response in vivo and constitutes a potential immunotherapeutic strategy to fight cancer.