Memory and protective cellular immunity induced by the murine orthologue of metastasis associated protein TPD52 (B155)

Abstract

Abstract Tumor protein D52 (TPD52) is involved in tumor cell proliferation, trafficking and metastasis. TPD52 over expression has been demonstrated in prostate, breast, lung and colon carcinomas. Murine TPD52 (mD52) has been shown to induce transformation and metastasis, and mirrors the known function and expression patterns of the human orthologue. We believe TPD52 represents a self, non-mutated tumor associated antigen (TAA) with direct relevance to human cancers. The Transgenic Adeno-carcinoma of the Mouse Prostate (TRAMP) model was employed to study mD52 as a vaccine antigen. Naïve mice were immunized with plasmid DNA encoding the full length cDNA of mD52. Following the final immunization, mice were challenged s.c. with a tumorigenic dose of mD52 positive, autochthonous TRAMP-C tumor cells. Greater than 60% of mice were tumor free 85 days post challenge with TRAMP-C1 and 40% were tumor free post challenge with TRAMP-C2 tumor cells, without induction of observable autoimmunity. Survivors of TRAMP-C2 initial tumor challenge rejected a second TRAMP-C2 tumor challenge 73 days later and remained tumor free greater than 90 days. The T cell cytokine secretion patterns from tumor challenge survivors indicated that a TH1 cellular immune response was involved in tumor rejection. These data suggest that mD52 vaccination induced a memory immune response that resulted in rejection of mD52+ tumors without inducing autoimmunity.