Safety, biodistribution and viral shedding of oncolytic vaccinia virus TG6002 administered intravenously in healthy beagle dogs - Archive ouverte HAL
Article Dans Une Revue Scientific Reports Année : 2021

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

Jérémy Béguin
  • Fonction : Auteur
Murielle Gantzer
  • Fonction : Auteur
Isabelle Farine
  • Fonction : Auteur
Johann Foloppe
  • Fonction : Auteur
Bernard Klonjkowski
Christelle Maurey
Éric Quéméneur
  • Fonction : Auteur
Philippe Erbs
  • Fonction : Auteur correspondant

Résumé

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 10 5 PFU/kg, 10 6 PFU/kg or 10 7 PFU/kg, and one dog received three intravenous injections at 10 7 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 10 7 PFU/kg. Post mortem analyses at day 35 allowed detection of viral DNA in the spleen of the dog which received three injections at 10 7 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.

Dates et versions

hal-03918521 , version 1 (02-01-2023)

Identifiants

Citer

Jérémy Béguin, Murielle Gantzer, Isabelle Farine, Johann Foloppe, Bernard Klonjkowski, et al.. Safety, biodistribution and viral shedding of oncolytic vaccinia virus TG6002 administered intravenously in healthy beagle dogs. Scientific Reports, 2021, 11 (1), pp.2209. ⟨10.1038/s41598-021-81831-2⟩. ⟨hal-03918521⟩
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