Chimeric infectious bursal disease virus-like particles as potent vaccines for eradication of established HPV-16 E7-dependent tumors

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 m...

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Authors: 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
Format: article
Status:Published version
Publication Date:2012
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/23562
Online Access:http://hdl.handle.net/10230/23562
http://dx.doi.org/10.1371/journal.pone.0052976
Access Level:Open access
Keyword:Papil·lomavirus -- Malalties
Úter -- Càncer
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spelling Chimeric infectious bursal disease virus-like particles as potent vaccines for eradication of established HPV-16 E7-dependent tumorsMartín Caballero, JuanGarzón, AnaGonzález-Cintado, LeticiaKowalczyk, WioletaJiménez Torres, IgnacioCalderita, GloriaRodríguez, MargaritaGondar, VirgíniaBernal, Juan JoseArdavín, CarlosAndreu Martínez, DavidZürcher, ThomasKobbe, Cayetano vonPapil·lomavirus -- MalaltiesÚter -- CàncerCervical 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.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.Public Library of Science (PLoS)201520152012info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/23562http://dx.doi.org/10.1371/journal.pone.0052976reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésPLoS ONE. 2012;7(12):e52976© 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 creditedinfo:eu-repo/semantics/openAccessoai:recercat.cat:10230/235622026-05-29T05:05:01Z
dc.title.none.fl_str_mv Chimeric infectious bursal disease virus-like particles as potent vaccines for eradication of established HPV-16 E7-dependent tumors
title Chimeric infectious bursal disease virus-like particles as potent vaccines for eradication of established HPV-16 E7-dependent tumors
spellingShingle Chimeric infectious bursal disease virus-like particles as potent vaccines for eradication of established HPV-16 E7-dependent tumors
Martín Caballero, Juan
Papil·lomavirus -- Malalties
Úter -- Càncer
title_short Chimeric infectious bursal disease virus-like particles as potent vaccines for eradication of established HPV-16 E7-dependent tumors
title_full Chimeric infectious bursal disease virus-like particles as potent vaccines for eradication of established HPV-16 E7-dependent tumors
title_fullStr Chimeric infectious bursal disease virus-like particles as potent vaccines for eradication of established HPV-16 E7-dependent tumors
title_full_unstemmed Chimeric infectious bursal disease virus-like particles as potent vaccines for eradication of established HPV-16 E7-dependent tumors
title_sort Chimeric infectious bursal disease virus-like particles as potent vaccines for eradication of established HPV-16 E7-dependent tumors
dc.creator.none.fl_str_mv 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
author Martín Caballero, Juan
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Papil·lomavirus -- Malalties
Úter -- Càncer
topic Papil·lomavirus -- Malalties
Úter -- Càncer
description 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.
publishDate 2012
dc.date.none.fl_str_mv 2012
2015
2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/23562
http://dx.doi.org/10.1371/journal.pone.0052976
url http://hdl.handle.net/10230/23562
http://dx.doi.org/10.1371/journal.pone.0052976
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv PLoS ONE. 2012;7(12):e52976
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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