Prime/boost immunotherapy of HPV16-induced tumors with E7 protein delivered by Bordetella adenylate cyclase and modified vaccinia virus Ankara
| Autor: | L. Kutinová, Pavel Gabriel, Peter Sebo, Jana Stasikova, Petr Hainz, Sarka Nemeckova, Marcela Simsova, Jiri Masin, Jana Mackova |
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| Rok vydání: | 2005 |
| Předmět: |
Cancer Research
Papillomavirus E7 Proteins medicine.medical_treatment Immunology Immunization Secondary Vaccinia virus CD8-Positive T-Lymphocytes Cancer Vaccines Mice chemistry.chemical_compound Immune system Antigen Antigens Neoplasm MHC class I Tumor Cells Cultured medicine Animals Immunology and Allergy Cytotoxic T cell Orthopoxvirus Antigens Viral Human papillomavirus 16 Immunity Cellular biology Dendritic Cells Oncogene Proteins Viral Immunotherapy cyaA biology.organism_classification Virology Mice Inbred C57BL Oncology chemistry biology.protein Adenylate Cyclase Toxin Female Vaccinia |
| Zdroj: | Cancer Immunology, Immunotherapy. 55:39-46 |
| ISSN: | 1432-0851 0340-7004 |
| Popis: | The Bordetella adenylate cyclase toxoid (CyaA) targets cells expressing the alphaMbeta2 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. |
| Databáze: | OpenAIRE |
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