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Vaccinia Virus Shuffling: deVV5, a Novel Chimeric Poxvirus with Improved Oncolytic Potency
Oncolytic virus (OV) therapy has emerged as a promising approach for cancer treatment with the potential to be less toxic and more efficient than classic cancer therapies. Various types of OVs in clinical development, including Vaccinia virus (VACV)-derived OVs, have shown good safety profiles, but...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070928/ https://www.ncbi.nlm.nih.gov/pubmed/29996551 http://dx.doi.org/10.3390/cancers10070231 |
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author | Ricordel, Marine Foloppe, Johann Antoine, Delphine Findeli, Annie Kempf, Juliette Cordier, Pascale Gerbaud, Aude Grellier, Benoit Lusky, Monika Quemeneur, Eric Erbs, Philippe |
author_facet | Ricordel, Marine Foloppe, Johann Antoine, Delphine Findeli, Annie Kempf, Juliette Cordier, Pascale Gerbaud, Aude Grellier, Benoit Lusky, Monika Quemeneur, Eric Erbs, Philippe |
author_sort | Ricordel, Marine |
collection | PubMed |
description | Oncolytic virus (OV) therapy has emerged as a promising approach for cancer treatment with the potential to be less toxic and more efficient than classic cancer therapies. Various types of OVs in clinical development, including Vaccinia virus (VACV)-derived OVs, have shown good safety profiles, but limited therapeutic efficacy as monotherapy in some cancer models. Many different methods have been employed to improve the oncolytic potency of OVs. In this study, we used a directed evolution process, pooling different strains of VACV, including Copenhagen, Western Reserve and Wyeth strains and the attenuated modified vaccinia virus Ankara (MVA), to generate a new recombinant poxvirus with increased oncolytic properties. Through selective pressure, a chimeric VACV, deVV5, with increased cancer cell killing capacity and tumor selectivity in vitro was derived. The chimeric viral genome contains sequences of all parental strains. To further improve the tumor selectivity and anti-tumor activity of deVV5, we generated a thymidine kinase (TK)-deleted chimeric virus armed with the suicide gene FCU1. This TK-deleted virus, deVV5-fcu1 replicated efficiently in human tumor cells, and was notably attenuated in normal primary cells. These studies demonstrate the potential of directed evolution as an efficient way to generate recombinant poxviruses with increased oncolytic potency, and with high therapeutic index to improve cancer therapy. |
format | Online Article Text |
id | pubmed-6070928 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-60709282018-08-09 Vaccinia Virus Shuffling: deVV5, a Novel Chimeric Poxvirus with Improved Oncolytic Potency Ricordel, Marine Foloppe, Johann Antoine, Delphine Findeli, Annie Kempf, Juliette Cordier, Pascale Gerbaud, Aude Grellier, Benoit Lusky, Monika Quemeneur, Eric Erbs, Philippe Cancers (Basel) Article Oncolytic virus (OV) therapy has emerged as a promising approach for cancer treatment with the potential to be less toxic and more efficient than classic cancer therapies. Various types of OVs in clinical development, including Vaccinia virus (VACV)-derived OVs, have shown good safety profiles, but limited therapeutic efficacy as monotherapy in some cancer models. Many different methods have been employed to improve the oncolytic potency of OVs. In this study, we used a directed evolution process, pooling different strains of VACV, including Copenhagen, Western Reserve and Wyeth strains and the attenuated modified vaccinia virus Ankara (MVA), to generate a new recombinant poxvirus with increased oncolytic properties. Through selective pressure, a chimeric VACV, deVV5, with increased cancer cell killing capacity and tumor selectivity in vitro was derived. The chimeric viral genome contains sequences of all parental strains. To further improve the tumor selectivity and anti-tumor activity of deVV5, we generated a thymidine kinase (TK)-deleted chimeric virus armed with the suicide gene FCU1. This TK-deleted virus, deVV5-fcu1 replicated efficiently in human tumor cells, and was notably attenuated in normal primary cells. These studies demonstrate the potential of directed evolution as an efficient way to generate recombinant poxviruses with increased oncolytic potency, and with high therapeutic index to improve cancer therapy. MDPI 2018-07-10 /pmc/articles/PMC6070928/ /pubmed/29996551 http://dx.doi.org/10.3390/cancers10070231 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ricordel, Marine Foloppe, Johann Antoine, Delphine Findeli, Annie Kempf, Juliette Cordier, Pascale Gerbaud, Aude Grellier, Benoit Lusky, Monika Quemeneur, Eric Erbs, Philippe Vaccinia Virus Shuffling: deVV5, a Novel Chimeric Poxvirus with Improved Oncolytic Potency |
title | Vaccinia Virus Shuffling: deVV5, a Novel Chimeric Poxvirus with Improved Oncolytic Potency |
title_full | Vaccinia Virus Shuffling: deVV5, a Novel Chimeric Poxvirus with Improved Oncolytic Potency |
title_fullStr | Vaccinia Virus Shuffling: deVV5, a Novel Chimeric Poxvirus with Improved Oncolytic Potency |
title_full_unstemmed | Vaccinia Virus Shuffling: deVV5, a Novel Chimeric Poxvirus with Improved Oncolytic Potency |
title_short | Vaccinia Virus Shuffling: deVV5, a Novel Chimeric Poxvirus with Improved Oncolytic Potency |
title_sort | vaccinia virus shuffling: devv5, a novel chimeric poxvirus with improved oncolytic potency |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070928/ https://www.ncbi.nlm.nih.gov/pubmed/29996551 http://dx.doi.org/10.3390/cancers10070231 |
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