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Vaccinia Virus Shuffling: deVV5, a Novel Chimeric Poxvirus with Improved Oncolytic Potency

Transgene SA, 400 Bld Gonthier d’Andernach, 67400 Illkirch-Graffenstaden, France
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Current address: Polyplus-Transfection SA, 850 Bld Sébastien Brant, 67400 Illkirch-Graffenstaden, France.
Cancers 2018, 10(7), 231;
Received: 2 May 2018 / Revised: 31 May 2018 / Accepted: 1 June 2018 / Published: 10 July 2018
(This article belongs to the Special Issue Oncolytic Virotherapy)
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. View Full-Text
Keywords: vaccinia virus; directed evolution; genome shuffling; deVV5-fcu1 vaccinia virus; directed evolution; genome shuffling; deVV5-fcu1
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Ricordel, M.; Foloppe, J.; Antoine, D.; Findeli, A.; Kempf, J.; Cordier, P.; Gerbaud, A.; Grellier, B.; Lusky, M.; Quemeneur, E.; Erbs, P. Vaccinia Virus Shuffling: deVV5, a Novel Chimeric Poxvirus with Improved Oncolytic Potency. Cancers 2018, 10, 231.

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