Abstract
Abstract Survivin is an attractive candidate for cancer immunotherapy since it is abundantly expressed in most human cancers and absent in normal adult tissues. Malignant mesothelioma (MM) is a deadly cancer associated with asbestos exposure with no successful therapies currently available. We evaluated a Survivin-based vaccine as therapeutic tool for malignant mesothelioma in different MM mouse models. BALB/c mice, injected subcutaneously or intraperitoneally with murine fiber-induced MM tumor cells, were vaccinated with recombinant Fowlpox virus replicons encoding Survivin. Vaccination generated immune responses in both models, which led to delayed tumor growth and improved survival. Flow cytometric and immunofluorescent analyses of tumors from vaccinated mice showed CD8+ T cells infiltration, and real-time PCR demonstrated increased mRNA and protein levels of immunostimulatory cytokines. ELISPOT and intracellular cytokine staining analyses of Survivin peptide pulsed spleen cells from vaccinated mice confirmed antigen-specific, interferon-γ-producing CD8+ T cell responses. In addition pentamer-based flow cytometry showed vaccination generated Survivin specific CD8+ T cells. Importantly, vaccination did not affect fertility or induce autoimmune abnormalities in mice. Our results demonstrate that vaccination with recombinant Fowlpox expressing Survivin improves targeting of aggressive MM cells by the immune system and may form the basis for promising clinical applications.
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