Safety, Biodistribution and Viral Shedding of Oncolytic Vaccinia Virus TG6002 Administered Intravenously in Healthy Beagle Dogs

Oncolytic virotherapy is an emerging strategy that uses replication-competent viruses to kill tumor cells. We have previously reported the oncolytic effects of TG6002, a novel recombinant oncolytic vaccinia virus, in various 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 four immune-competent healthy dogs. Three dogs each received a single intravenous injection of TG6002 at 1 x 10 5 PFU/kg, 1 x 10 6 PFU/kg or 1 x 10 7 PFU/kg, and one dog received three intravenous injections at 1 x 10 7 PFU/kg. The injections were well tolerated without any clinical, hematological or biochemical adverse events. Viral genomes were only detected in blood one hour after injection. Post mortem analyses allowed detection of viral DNA in the spleen of one dog. Viral genomes were not detected in the urine, saliva or feces of any dogs. Seven days after the injections, a dose-dependent immune response was identified. In conclusion, intravenous administration of TG6002 shows a good safety profile, a finding that supports the initiation of clinical trials in canine cancer patients as well as further development of TG6002 as a human cancer therapy.