Title:
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Chimeric infectious bursal disease virus-like particles as potent vaccines for eradication of established HPV-16 E7-dependent tumors
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Author:
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Martín Caballero, Juan; Garzón, Ana; González-Cintado, Leticia; Kowalczyk, Wioleta; Jiménez Torres, Ignacio; Calderita, Gloria; Rodríguez, Margarita; Gondar, Virgínia; Bernal, Juan Jose; Ardavín, Carlos; Andreu Martínez, David; Zürcher, Thomas; Kobbe, Cayetano von
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Abstract:
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Cervical cancer is caused by persistent high-risk human papillomavirus (HR-HPV) infection and represents the second most frequent gynecological malignancy in the world. The HPV-16 type accounts for up to 55% of all cervical cancers. The HPV-16 oncoproteins E6 and E7 are necessary for induction and maintenance of malignant transformation and represent tumor-specific antigens for targeted cytotoxic T lymphocyte–mediated immunotherapy. Therapeutic cancer vaccines have become a challenging area of oncology research in recent decades. Among current cancer immunotherapy strategies, virus-like particle (VLP)–based vaccines have emerged as a potent and safe approach. We generated a vaccine (VLP-E7) incorporating a long C-terminal fragment of HPV-16 E7 protein into the infectious bursal disease virus VLP and tested its therapeutic potential in HLA-A2 humanized transgenic mice grafted with TC1/A2 tumor cells. We performed a series of tumor challenge experiments demonstrating a strong immune response against already-formed tumors (complete eradication). Remarkably, therapeutic efficacy was obtained with a single dose without adjuvant and against two injections of tumor cells, indicating a potent and long-lasting immune response. |
Abstract:
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This work was supported in part by grants PIE/473/2009 and PIE/506/2008 from Instituto Madrileño de Desarrollo, 25/2008 from Comunidad Autónoma de Madrid, CIT-010000-2008-18 from Ministerio de Educación, FIT-010000-2007-68 from Ministerio de Industria, Turismo y Comercio, and CIT-010000-2007-34 from Ministerio de Ciencia e Innovación (PROFIT). Additional support was provided by Consorci Parc de Recerca Biomédica de Barcelona. |
Subject(s):
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-Papil·lomavirus -- Malalties -Úter -- Càncer |
Rights:
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© 2012 Martin Caballero et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
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Document type:
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Article Article - Published version |
Published by:
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Public Library of Science (PLoS)
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