Vaccination with the Prostate Cancer Over-Expressed Tumor Self-Protein TPD52 Elicits Protective Tumor Immunity and a Potentially Unique Subset of CD8+ T Cells

Tumor protein D52 (D52) is expressed at low levels in normal cells, but over-expressed in prostate carcinomas and numerous other malignancies. Murine D52 (mD52) parallels the expression pattern of the human orthologue (hD52) and shares ~ 86% amino acid identity. Over-expression of mD52 in nontransformed murine fibroblasts induces anchorage independent growth and spontaneous metastasis. The TRAMP model was employed to study DNA-based D52 vaccines against prostate cancer. Immunizations consisted of mD52-DNA, hD52-DNA or a combination of both, followed by challenge with mD52 positive, TRAMP-C1 tumor cells. Greater protection (70%) was observed 10 months post challenge in mice immunized with hD52 DNA. Survivors of the initial tumor challenge rejected a second tumor challenge with mD52 positive, autochthonous TRAMP-C2 tumor cells given in the opposite flank more than four months after the first challenge. Analysis of the T cell function from survivors indicated that a Th1-type cellular immune response was involved in tumor rejection. A potentially unique subset of CD8+ IL-10+ T cells was also elicited and may play a role in inhibiting vaccine induced tumor immunity, suggesting that a deeper mechanistic understanding of these T cells in D52 vaccine-induced immunity may be important for developing a more potent cancer vaccine.