Document Detail


Fowlpox-based survivin vaccination for malignant mesothelioma therapy.
MedLine Citation:
PMID:  23335100     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Pietro Bertino; Maddalena Panigada; Elisa Soprana; Valentina Bianchi; Sabrina Bertilaccio; Francesca Sanvito; Aaron H Rose; Haining Yang; Giovanni Gaudino; Peter R Hoffmann; Antonio Siccardi; Michele Carbone
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-02-25
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  133     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2013 Aug 
Date Detail:
Created Date:  2013-05-22     Completed Date:  2013-07-25     Revised Date:  2014-08-05    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  612-23     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 UICC.
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MeSH Terms
Descriptor/Qualifier:
Animals
CD8-Positive T-Lymphocytes / immunology
Cancer Vaccines / immunology*
Cell Line, Tumor
Female
Fowlpox virus / genetics,  immunology
Humans
Immunotherapy
Inhibitor of Apoptosis Proteins / genetics*,  immunology*
Interferon-gamma / immunology
Lung Neoplasms* / immunology,  prevention & control,  therapy
Lymph Nodes / immunology
Mesothelioma* / immunology,  prevention & control,  therapy
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Repressor Proteins / genetics*,  immunology*
Spleen / immunology
Vaccination
Grant Support
ID/Acronym/Agency:
G12MD007601/MD/NIMHD NIH HHS; G12RR003061/RR/NCRR NIH HHS; P01CA114047/CA/NCI NIH HHS; P20 GM103516/GM/NIGMS NIH HHS; P20GM103516/GM/NIGMS NIH HHS; P30 CA071789/CA/NCI NIH HHS; R01 AI089999/AI/NIAID NIH HHS; R01AI089999/AI/NIAID NIH HHS; R01CA160715/CA/NCI NIH HHS; R21 AT004844/AT/NCCAM NIH HHS
Chemical
Reg. No./Substance:
0/Birc5 protein, mouse; 0/Cancer Vaccines; 0/Inhibitor of Apoptosis Proteins; 0/Repressor Proteins; 82115-62-6/Interferon-gamma
Comments/Corrections

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