Prime/boost immunotherapy of HPV16-induced tumors with E7 protein delivered by Bordetella adenylate cyclase and modified vaccinia virus Ankara |
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Authors: | Jana Mackova Jana Stasikova Luda Kutinova Jiri Masin Petr Hainz Marcela Simsova Pavel Gabriel Peter Sebo Sarka Nemeckova |
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Institution: | (1) Department of Experimental Virology, Institute of Hematology and Blood Transfusion, U Nemocnice 1, 128 20 Prague 2, Czech Republic;(2) Institute of Microbiology, Division of Cell and Molecular Microbiology, Laboratory of Molecular Biology of Bacterial Pathogens, Czech Academy of Sciences, Videnska 1083, 142 20 Prague 4, Czech Republic |
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Abstract: | The Bordetella adenylate cyclase toxoid (CyaA) targets cells expressing the αMβ2 integrin receptor CD11b/CD18 (CR3 or Mac-1) and can penetrate into cytosol of professional antigen-presenting cells, such
as dendritic cells. This allows us to use CyaA for delivery of passenger antigens into the cytosolic pathway of processing
and MHC class I-restricted presentation, which can promote induction of antigen-specific CD8+ cytotoxic T-lymphocyte immune responses. We show here that vaccination with a genetically detoxified CyaA336/E7 protein,
carrying the full-length oncoprotein E7 of the human papilloma virus 16 inserted at position 336 of the cell-invasive AC domain
of CyaA, induces an E7-specific CD8+ T-cell immune response and confers on mice protective, as well as therapeutic immunity against challenge with TC-1 tumor
cells expressing the E7 oncoprotein. The therapeutic efficacy of priming with the CyaA336/E7 vaccine could further be enhanced
by a heterologous booster immunization with a highly attenuated modified vaccinia virus Ankara (MVA) expressing the E7 protein
fused to the lysosome-associated membrane protein (LAMP1). These results establish the potential of CyaA as a new antigen
delivery tool for prime/boost immunotherapy of tumors.
This paper won the poster prize at the conference “Progress in Vaccination against Cancer 4”, PIVAC 4, held in Freudenstadt-Lauterbad,
Black Forest, Germany, from 22 to 25 September 2004. For further material on this conference, please see the series of Symposium
Papers, published |
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Keywords: | Vaccine HPV-E7 Vaccinia virus MVA Bordetella adenylate cyclase |
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