Safety, biodistribution and viral shedding of oncolytic vaccinia virus TG6002 administered intravenously in healthy beagle dogs

Abstract Oncolytic virotherapy is an emerging strategy that uses replication-competent viruses to kill tumor cells. We have reported the oncolytic effects of TG6002, a recombinant oncolytic vaccinia virus, in preclinical human xenograft models and canine tumor explants. To assess the safety, biodist...

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Autores principales:	Jérémy Béguin, Murielle Gantzer, Isabelle Farine, Johann Foloppe, Bernard Klonjkowski, Christelle Maurey, Éric Quéméneur, Philippe Erbs
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/68a68d93323c4c66a8300f3d5dd7b61e
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spelling	oai:doaj.org-article:68a68d93323c4c66a8300f3d5dd7b61e2021-12-02T13:57:36ZSafety, biodistribution and viral shedding of oncolytic vaccinia virus TG6002 administered intravenously in healthy beagle dogs10.1038/s41598-021-81831-22045-2322https://doaj.org/article/68a68d93323c4c66a8300f3d5dd7b61e2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81831-2https://doaj.org/toc/2045-2322Abstract Oncolytic virotherapy is an emerging strategy that uses replication-competent viruses to kill tumor cells. We have reported the oncolytic effects of TG6002, a recombinant oncolytic vaccinia virus, in preclinical human xenograft models and canine tumor explants. To assess the safety, biodistribution and shedding of TG6002 administered by the intravenous route, we conducted a study in immune-competent healthy dogs. Three dogs each received a single intravenous injection of TG6002 at 105 PFU/kg, 106 PFU/kg or 107 PFU/kg, and one dog received three intravenous injections at 107 PFU/kg. The injections were well tolerated without any clinical, hematological or biochemical adverse events. Viral genomes were only detected in blood at the earliest sampling time point of one-hour post-injection at 107 PFU/kg. Post mortem analyses at day 35 allowed detection of viral DNA in the spleen of the dog which received three injections at 107 PFU/kg. Viral genomes were not detected in the urine, saliva or feces of any dogs. Seven days after the injections, a dose-dependent antibody mediated immune response was identified. In conclusion, intravenous administration of TG6002 shows a good safety profile, supporting the initiation of clinical trials in canine cancer patients as well as further development as a human cancer therapy.Jérémy BéguinMurielle GantzerIsabelle FarineJohann FoloppeBernard KlonjkowskiChristelle MaureyÉric QuéméneurPhilippe ErbsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jérémy Béguin Murielle Gantzer Isabelle Farine Johann Foloppe Bernard Klonjkowski Christelle Maurey Éric Quéméneur Philippe Erbs Safety, biodistribution and viral shedding of oncolytic vaccinia virus TG6002 administered intravenously in healthy beagle dogs
description	Abstract Oncolytic virotherapy is an emerging strategy that uses replication-competent viruses to kill tumor cells. We have reported the oncolytic effects of TG6002, a recombinant oncolytic vaccinia virus, in preclinical human xenograft models and canine tumor explants. To assess the safety, biodistribution and shedding of TG6002 administered by the intravenous route, we conducted a study in immune-competent healthy dogs. Three dogs each received a single intravenous injection of TG6002 at 105 PFU/kg, 106 PFU/kg or 107 PFU/kg, and one dog received three intravenous injections at 107 PFU/kg. The injections were well tolerated without any clinical, hematological or biochemical adverse events. Viral genomes were only detected in blood at the earliest sampling time point of one-hour post-injection at 107 PFU/kg. Post mortem analyses at day 35 allowed detection of viral DNA in the spleen of the dog which received three injections at 107 PFU/kg. Viral genomes were not detected in the urine, saliva or feces of any dogs. Seven days after the injections, a dose-dependent antibody mediated immune response was identified. In conclusion, intravenous administration of TG6002 shows a good safety profile, supporting the initiation of clinical trials in canine cancer patients as well as further development as a human cancer therapy.
format	article
author	Jérémy Béguin Murielle Gantzer Isabelle Farine Johann Foloppe Bernard Klonjkowski Christelle Maurey Éric Quéméneur Philippe Erbs
author_facet	Jérémy Béguin Murielle Gantzer Isabelle Farine Johann Foloppe Bernard Klonjkowski Christelle Maurey Éric Quéméneur Philippe Erbs
author_sort	Jérémy Béguin
title	Safety, biodistribution and viral shedding of oncolytic vaccinia virus TG6002 administered intravenously in healthy beagle dogs
title_short	Safety, biodistribution and viral shedding of oncolytic vaccinia virus TG6002 administered intravenously in healthy beagle dogs
title_full	Safety, biodistribution and viral shedding of oncolytic vaccinia virus TG6002 administered intravenously in healthy beagle dogs
title_fullStr	Safety, biodistribution and viral shedding of oncolytic vaccinia virus TG6002 administered intravenously in healthy beagle dogs
title_full_unstemmed	Safety, biodistribution and viral shedding of oncolytic vaccinia virus TG6002 administered intravenously in healthy beagle dogs
title_sort	safety, biodistribution and viral shedding of oncolytic vaccinia virus tg6002 administered intravenously in healthy beagle dogs
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/68a68d93323c4c66a8300f3d5dd7b61e
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Safety, biodistribution and viral shedding of oncolytic vaccinia virus TG6002 administered intravenously in healthy beagle dogs

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