Immunization with DNA coding for gp100 results in CD4(+) T-cell independent antitumor immunity

Background. Xenogeneic DNA immunization can exploit small differences in ex pressed protein sequence resulting in immune recognition of self-molecules. We hypothesized that immunizing mice with xenogeneic DNA coding for the hu man melanosomal membrane glycoprotein gp100 would overcome immune ignorance or tolerance and result in tumor immunity. We also investigated the immuno logic mechanisms of the antitumor immunity. Methods. C57BL/6 mice were immunized with DNA coding for human gp100, mouse gp100, or control vector by gene gun. After immunization, mice were challe nged with a syngeneic melanoma expressing gp100, and tumor growth was analy zed. Mice deficient in major histocompatibility complex class I or class II molecules were similarly studied to assess the immunologic mechanism of th e tumor protection. Results. There was significant tumor protection after vaccination with xeno geneic human gp100 DNA. Class I, but not class II, major histocompatibility complex molecules were required for tumor immunity. In addition, mice immu nized with human gp100 demonstrated autoimmunity manifested as coat color d epigmentation. Conclusions. Immunization with xenogeneic DNA coding for the melanosomal gl ycoprotein gp100 results in tumor protection and autoimmune depigmentation. These results show that xenogeneic DNA vaccines can lead to cancer immunit y without CD4(+) T-cell help with potential implications for rational vacci ne design.