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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...

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Autores principales: Ricordel, Marine, Foloppe, Johann, Antoine, Delphine, Findeli, Annie, Kempf, Juliette, Cordier, Pascale, Gerbaud, Aude, Grellier, Benoit, Lusky, Monika, Quemeneur, Eric, Erbs, Philippe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
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.
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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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