Synergistic effect of a combined DNA and peptide vaccine against gp100 in a malignant melanoma mouse model

Vaccination against tumors relies on tumor-associated antigens, and has bee n quite successful with synthetic peptides used as immunogens. Gp100 is a h uman melanoma-associated antigen (hgp100) with a highly homologous mouse co unterpart, pme117/gp100 (mgp100), that is expressed in melanocytes and high ly tumorigenic B16 melanoma cells. Since mgp100 is poorly immunogenic in mi ce, we used a xenoimmunization approach and vaccinated with the hgp100 immu nogene. To that end, plasmid DNA encoding hgp100 was applied as a vaccine i n combination with three synthetic peptides corresponding to putative cytot oxic T cell epitopes of hgp100. Immunization with DNA and peptide-pulsed sp leen cells had a synergistic effect and provided significant protection aga inst a challenge with poorly immunogenic B16-F0 malignant melanoma cells in the syngeneic C57BL/6 mouse model. Vaccination with either plasmid DNA or peptides alone delayed the onset of tumor formation, and reduced tumor grow th 2-fold and 30-fold, respectively. However, while all animals vaccinated with DNA encoding hgp100 or with peptides eventually developed tumors, 30% of the animals treated with both vaccines remained tumor free and survived for the entire observation period of 150 days. Depletion of T cell subsets revealed that the protective effect observed after vaccination with plasmid DNA was mediated by CD4+ and CD8+ T cells, while protection following Vacc ination with DNA encoding hgp100 in combination with peptides appears to de pend on CD4+ T cells only. Furthermore, we could also demonstrate a therape utic effect of the combined DNA/peptide regime. A single treatment cycle co nsisting of injections of plasmid DNA and peptide-pulsed spleen cells led t o a fourfold reduction in the growth rate of preexisting tumors. The data p resented demonstrate that immunization with xenoantigens induces cross-spec ies priming leading to an immunological response against the tumor-specific antigens.