Abstract 4791: Inhibition of Tumor Formation in Mice following Vaccination with DNA Encoding a Novel Xenogeneic Tumor Associated Auto-Antigen

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Abstract Tumor protein D52 (TPD52) is a novel auto-antigen involved in cellular transformation, proliferation and metastasis. Its over-expression has been demonstrated in several human malignancies including prostate, breast, and ovarian carcinomas. Murine TPD52 (mD52) has been shown to induce anchorage independent growth in vitro and spontaneous metastasis in vivo. Importantly, mD52 mirrors the function and normal tissue expression patterns of the human orthologue of TPD52 (hD52) and shares 86% identity at the amino acid level. Thus, TPD52 represents a self, non-mutated tumor associated auto-antigen that is important for maintaining a tumorigenic phenotype. The Transgenic Adeno-carcinoma of the Mouse Prostate (TRAMP) model was employed to study TPD52 as a vaccine antigen. Naïve mice were immunized with either mD52 or hD52 DNA. Following immunization, mice were challenged with a subcutaneous, tumorigenic dose of mD52 positive, autochthonous TRAMP-C1 tumor cells. Greater than 70% of mice were tumor free more than 10 months post tumor challenge when immunized with hD52 as a xenogenic DNA vaccine. Survivors of the initial tumor challenge rejected a second tumor challenge with TRAMP-C2 tumor cells given in the opposite flank approximately 138 days after the first challenge with TRAMP-C1, and remained tumor free for more than 6 months. The T cell cytokine secretion patterns from tumor challenge survivors indicated that a cellular immune response was involved in tumor rejection. These data suggest that hD52 xenogeneic DNA vaccination induced a memory, cellular immune response that resulted in superior protection from challenge with murine prostate-derived tumors that naturally over-express mD52 protein. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4791.