title: Fowlpox-based survivin vaccination for malignant mesothelioma therapy.
abstract: 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.
authors: Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawai'i, Honolulu, HI 96813, USA. pbertino@hawaii.edu
authors: Pietro
authors: P
authors: Bertino
authors: Maddalena
authors: M
authors: Panigada
authors: Elisa
authors: E
authors: Soprana
authors: Valentina
authors: V
authors: Bianchi
authors: Sabrina
authors: S
authors: Bertilaccio
authors: Francesca
authors: F
authors: Sanvito
authors: Aaron H
authors: AH
authors: Rose
authors: Haining
authors: H
authors: Yang
authors: Giovanni
authors: G
authors: Gaudino
authors: Peter R
authors: PR
authors: Hoffmann
authors: Antonio
authors: A
authors: Siccardi
authors: Michele
authors: M
authors: Carbone
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D005587:Fowlpox virus / Q000235:genetics / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D008198:Lymph Nodes / Q000276:immunology; D008654:Mesothelioma / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D000086002:Mesothelioma, Malignant; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012097:Repressor Proteins / Q000235:genetics* / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D000077022:Survivin; D014611:Vaccination
chemical_list: C117749:Birc5 protein, mouse; D019496:Cancer Vaccines; D051034:Inhibitor of Apoptosis Proteins; D012097:Repressor Proteins; D000077022:Survivin; D007371:Interferon-gamma