Fowlpox-based survivin vaccination for malignant mesothelioma therapy

Survivin protein is an attractive candidate for cancer immunotherapy since it is abundantly expressed in most common human cancers and mostly absent in normal adult tissues. Malignant mesothelioma (MM) is a deadly cancer associated with asbestos or erionite exposure for which no successful therapies are currently available. In this study, we evaluated the therapeutic efficacy of a novel survivin-based vaccine by subcutaneous or intraperitoneum injection of BALB/c mice with murine fiber-induced MM tumor cells followed by vaccination with recombinant Fowlpox virus replicons encoding survivin. Vaccination generated significant immune responses in both models, leading to delayed tumor growth and improved animal survival. Flow cytometry and immunofluorescence analyses of tumors from vaccinated mice showed CD8⁺ T-cell infiltration, and real-time PCR demonstrated increased mRNA and protein levels of immunostimulatory cytokines. Analyses of survivin peptide-pulsed spleen and lymph node cells from vaccinated mice using ELISPOT and intracellular cytokine staining confirmed antigen-specific, interferon-γ-producing CD8 ⁺ T-cell responses. In addition pentamer-based flow cytometry showed that 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 T-cell responses against aggressive MM tumors and may form the basis for promising clinical applications. What's new? Malignant mesothelioma (MM) is an aggressive cancer with poor prognosis. However, some patients demonstrate improved survival in association with an anti-tumor immune response, suggesting that immunotherapy may be a useful treatment strategy for the disease. In this study, a novel vaccine based on Fowlpox vector expression of the inhibitory apoptotic protein survivin was found to successfully trigger an immune response in an MM mouse model. The response resulted in delayed tumor growth and improved survival, indicating that the vaccine could serve as the basis for the development of clinically relevant MM immune-based treatments.