Oncolytic properties of non-vaccinia poxviruses
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Marine Ricordel1,3, Johann Foloppe1, Christelle Pichon1, Annie Findeli1, Caroline Tosch1, Pascale Cordier1, Sandrine Cochin1, Eric Quémeneur1, Christelle Camus-Bouclainville2, Stéphane Bertagnoli2 and Philippe Erbs1
1Transgene SA, Illkirch-Graffenstaden 67405, France
2IHAP, INRA, Université de Toulouse, Toulouse 31058, France
3Current address: Polyplus-transfection SA, Illkirch-Graffenstaden 67400, France
Philippe Erbs, email: firstname.lastname@example.org
Keywords: non-vaccinia poxviruses; oncolytic properties; RCNtk-/gfp::fcu1
Received: June 26, 2018 Accepted: October 24, 2018 Published: November 13, 2018
Vaccinia virus, a member of the Poxviridae family, has been extensively used as an oncolytic agent and has entered late stage clinical development. In this study, we evaluated the potential oncolytic properties of other members of the Poxviridae family. Numerous tumor cell lines were infected with ten non-vaccinia poxviruses to identify which virus displayed the most potential as an oncolytic agent. Cell viability indicated that tumor cell lines were differentially susceptible to each virus. Raccoonpox virus was the most potent of the tested poxviruses and was highly effective in controlling cell growth in all tumor cell lines. To investigate further the oncolytic capacity of the Raccoonpox virus, we have generated a thymidine kinase (TK)-deleted recombinant Raccoonpox virus expressing the suicide gene FCU1. This TK-deleted Raccoonpox virus was notably attenuated in normal primary cells but replicated efficiently in numerous tumor cell lines. In human colon cancer xenograft model, a single intratumoral inoculation of the recombinant Raccoonpox virus, in combination with 5-fluorocytosine administration, produced relevant tumor growth control. The results demonstrated significant antitumoral activity of this new modified Raccoonpox virus armed with FCU1 and this virus could be considered to be included into the growing armamentarium of oncolytic virotherapy for cancer.
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