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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| Veröffentlicht in: | PloS one 2012-12, Vol.7 (12), p.e52976-e52976 |
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| creator | Martin Caballero, Juan Garzón, Ana González-Cintado, Leticia Kowalczyk, Wioleta Jimenez Torres, Ignacio Calderita, Gloria Rodriguez, Margarita Gondar, Virgínia Bernal, Juan Jose Ardavín, Carlos Andreu, David Zürcher, Thomas von Kobbe, Cayetano |
| 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. |
| doi_str_mv | 10.1371/journal.pone.0052976 |
| format | Article |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0052976</identifier><identifier>PMID: 23300838</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Antigen (tumor-associated) ; Antigens ; Biology ; Biomedical research ; Cancer ; Cancer immunotherapy ; Cancer treatment ; Cancer vaccines ; Cervical cancer ; Cervix ; Cytotoxicity ; Càncer ; Dendritic cells ; Deoxyribonucleic acid ; DNA ; E7 protein ; Female ; Genetic engineering ; Health risks ; Health sciences ; Histocompatibility antigen HLA ; HLA antigens ; Human papillomavirus ; Human papillomavirus 16 - immunology ; Immune response ; Immune system ; Immunology ; Immunotherapy ; Infectious bursal disease ; Infectious bursal disease virus - immunology ; Infectious diseases ; Laboratory animals ; Lymphocytes T ; Malalties ; Malignancy ; Medical research ; Medicine ; Mice ; Mice, Transgenic ; Oncology ; Papillomavirus E7 Proteins - immunology ; Papillomavirus infections ; Papillomavirus Infections - immunology ; Papillomavirus Infections - therapy ; Papillomavirus Vaccines - immunology ; Papillomavirus Vaccines - therapeutic use ; Papil·lomavirus ; Peptides ; Proteins ; T cells ; Transformation ; Transgenic mice ; Tumor cells ; Tumors ; Uterine Cervical Neoplasms - immunology ; Uterine Cervical Neoplasms - therapy ; Uterine Cervical Neoplasms - virology ; Vaccines ; Vaccines, Virus-Like Particle - immunology ; Vaccines, Virus-Like Particle - therapeutic use ; Virology ; Virus-like particles ; Viruses ; Úter</subject><ispartof>PloS one, 2012-12, Vol.7 (12), p.e52976-e52976</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Martin Caballero et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>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 info:eu-repo/semantics/openAccess</rights><rights>2012 Martin Caballero et al 2012 Martin Caballero et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c734t-dcc10871db3d12ae7e0f0ec68712b22d3c5bfa15bc87ef5fe9d9aeda856757033</citedby><cites>FETCH-LOGICAL-c734t-dcc10871db3d12ae7e0f0ec68712b22d3c5bfa15bc87ef5fe9d9aeda856757033</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3534127/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3534127/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2919,23857,26965,27915,27916,53782,53784,79361,79362</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23300838$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Rodrigues, Mauricio Martins</contributor><creatorcontrib>Martin Caballero, Juan</creatorcontrib><creatorcontrib>Garzón, Ana</creatorcontrib><creatorcontrib>González-Cintado, Leticia</creatorcontrib><creatorcontrib>Kowalczyk, Wioleta</creatorcontrib><creatorcontrib>Jimenez Torres, Ignacio</creatorcontrib><creatorcontrib>Calderita, Gloria</creatorcontrib><creatorcontrib>Rodriguez, Margarita</creatorcontrib><creatorcontrib>Gondar, Virgínia</creatorcontrib><creatorcontrib>Bernal, Juan Jose</creatorcontrib><creatorcontrib>Ardavín, Carlos</creatorcontrib><creatorcontrib>Andreu, David</creatorcontrib><creatorcontrib>Zürcher, Thomas</creatorcontrib><creatorcontrib>von Kobbe, Cayetano</creatorcontrib><title>Chimeric infectious bursal disease virus-like particles as potent vaccines for eradication of established HPV-16 E7-dependent tumors</title><title>PloS one</title><addtitle>PLoS One</addtitle><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.</description><subject>Animals</subject><subject>Antigen (tumor-associated)</subject><subject>Antigens</subject><subject>Biology</subject><subject>Biomedical research</subject><subject>Cancer</subject><subject>Cancer immunotherapy</subject><subject>Cancer treatment</subject><subject>Cancer vaccines</subject><subject>Cervical cancer</subject><subject>Cervix</subject><subject>Cytotoxicity</subject><subject>Càncer</subject><subject>Dendritic cells</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>E7 protein</subject><subject>Female</subject><subject>Genetic engineering</subject><subject>Health risks</subject><subject>Health sciences</subject><subject>Histocompatibility antigen HLA</subject><subject>HLA antigens</subject><subject>Human papillomavirus</subject><subject>Human papillomavirus 16 - immunology</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunology</subject><subject>Immunotherapy</subject><subject>Infectious bursal disease</subject><subject>Infectious bursal disease virus - immunology</subject><subject>Infectious diseases</subject><subject>Laboratory animals</subject><subject>Lymphocytes T</subject><subject>Malalties</subject><subject>Malignancy</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>Oncology</subject><subject>Papillomavirus E7 Proteins - immunology</subject><subject>Papillomavirus infections</subject><subject>Papillomavirus Infections - immunology</subject><subject>Papillomavirus Infections - therapy</subject><subject>Papillomavirus Vaccines - immunology</subject><subject>Papillomavirus Vaccines - therapeutic 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Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Recercat</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Martin Caballero, Juan</au><au>Garzón, Ana</au><au>González-Cintado, Leticia</au><au>Kowalczyk, Wioleta</au><au>Jimenez Torres, Ignacio</au><au>Calderita, Gloria</au><au>Rodriguez, Margarita</au><au>Gondar, Virgínia</au><au>Bernal, Juan Jose</au><au>Ardavín, Carlos</au><au>Andreu, David</au><au>Zürcher, Thomas</au><au>von Kobbe, Cayetano</au><au>Rodrigues, Mauricio Martins</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chimeric infectious bursal disease virus-like particles as potent vaccines for eradication of established HPV-16 E7-dependent tumors</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-12-31</date><risdate>2012</risdate><volume>7</volume><issue>12</issue><spage>e52976</spage><epage>e52976</epage><pages>e52976-e52976</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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><cop>United States</cop><pub>Public Library of Science</pub><pmid>23300838</pmid><doi>10.1371/journal.pone.0052976</doi><tpages>e52976</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-12, Vol.7 (12), p.e52976-e52976 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1327231406 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); Recercat; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Animals Antigen (tumor-associated) Antigens Biology Biomedical research Cancer Cancer immunotherapy Cancer treatment Cancer vaccines Cervical cancer Cervix Cytotoxicity Càncer Dendritic cells Deoxyribonucleic acid DNA E7 protein Female Genetic engineering Health risks Health sciences Histocompatibility antigen HLA HLA antigens Human papillomavirus Human papillomavirus 16 - immunology Immune response Immune system Immunology Immunotherapy Infectious bursal disease Infectious bursal disease virus - immunology Infectious diseases Laboratory animals Lymphocytes T Malalties Malignancy Medical research Medicine Mice Mice, Transgenic Oncology Papillomavirus E7 Proteins - immunology Papillomavirus infections Papillomavirus Infections - immunology Papillomavirus Infections - therapy Papillomavirus Vaccines - immunology Papillomavirus Vaccines - therapeutic use Papil·lomavirus Peptides Proteins T cells Transformation Transgenic mice Tumor cells Tumors Uterine Cervical Neoplasms - immunology Uterine Cervical Neoplasms - therapy Uterine Cervical Neoplasms - virology Vaccines Vaccines, Virus-Like Particle - immunology Vaccines, Virus-Like Particle - therapeutic use Virology Virus-like particles Viruses Úter |
| title | Chimeric infectious bursal disease virus-like particles as potent vaccines for eradication of established HPV-16 E7-dependent tumors |
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