Immunologic mechanisms against an SV40 viral oncoprotein require humoral and cell-mediated pathways to achieve tumor immunity (40.25)

Abstract

Abstract Malignant pleural mesothelioma (MPM) is an aggressive disease with survival prognosis less than one year. Interestingly, MPM samples have been reported to express the viral oncoprotein, Simian virus 40 (SV40) large tumor antigen (Tag). To this end, our laboratory has characterized protective SV40 Tag-specific immunologic mechanisms following prophylactic immunization in a murine experimental pulmonary metastasis model. Recent results indicate that ADCC functions as a primary in vivo anti-tumor mechanism since SV40 Tag antibody and Fcγ receptors are required immunologic-components in the observed protection from lung metastasis. We also find that with an antibody response due to vaccination, CD8+ T lymphocytes are required T cell subsets in the effector phase response of tumor challenge in vivo. The nature of the CD8+ T cell response appears to be CTL-driven based upon a systemic increase in Th1 cytokines by flow cytometry and tumor antigen-specific splenocyte production of IFN-γ when assessed by ELISpot and ELISA assays. In all, our results support the hypothesis that an SV40 Tag antibody-based ADCC pathway drives the activation of a cell-mediated response leading to protection from tumorigenic growth. These data also have implications for the construction of an effective MPM-specific vaccine that elicits broad-based immunity in individuals at high-risk for developing SV40 Tag-expressing tumor cells.