Vaccination against
tumors relies on
tumor-associated
antigens, and has been quite successful with synthetic
peptides used as immunogens. Gp100 is a human
melanoma-associated
antigen (hgp100) with a highly homologous mouse counterpart, pmel17/gp100 (mgp100), that is expressed in melanocytes and highly tumorigenic
B16 melanoma cells. Since mgp100 is poorly immunogenic in mice, we used a xenoimmunization approach and vaccinated with the hgp100 immunogene. To that end, plasmid
DNA encoding hgp100 was applied as a
vaccine in combination with three synthetic
peptides corresponding to putative cytotoxic T cell
epitopes of hgp100. Immunization with
DNA and
peptide-pulsed spleen cells had a synergistic effect and provided significant protection against 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 growth 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 vaccination with
DNA encoding hgp100 in combination with
peptides appears to depend on CD4+ T cells only. Furthermore, we could also demonstrate a
therapeutic effect of the combined
DNA/
peptide regime. A single treatment cycle consisting of
injections of plasmid
DNA and
peptide-pulsed spleen cells led to a fourfold reduction in the growth rate of preexisting
tumors. The data presented demonstrate that immunization with
xenoantigens induces cross-species priming leading to an immunological response against the
tumor-specific
antigens.