Oncolytic reovirus therapy: Pilot study in dogs with spontaneously occurring tumours |
| |
| Authors: | C C Hwang M Igase M Sakurai T Haraguchi K Tani K Itamoto T Shimokawa M Nakaichi Y Nemoto S Noguchi M Coffey M Okuda T Mizuno |
| |
| Affiliation: | 1. Laboratory of Molecular Diagnostics and Therapeutics, The United Graduate School of Veterinary Science, Yamaguchi University, Yamaguchi, Japan;2. Laboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan;3. Laboratory of Small Animal Clinical Science (Surgical Division), Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan;4. Laboratory of Veterinary Surgery, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan;5. Laboratory of Veterinary Internal Medicine, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan;6. Laboratory of Veterinary Radiology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan;7. Oncolytics Biotech Inc, Calgary, Canada;8. Biomedical Science Center for Translational Research, The United Graduate School of Veterinary Science, Yamaguchi University, Yamaguchi, Japan |
| |
| Abstract: | Oncolytic virotherapy is a novel treatment involving replication‐competent virus in the elimination of cancer. We have previously reported the oncolytic effects of reovirus in various canine cancer cell lines. This study aims to establish the safety profile of reovirus in dogs with spontaneously occurring tumours and to determine a recommended dosing regimen. Nineteen dogs with various tumours, mostly of advanced stages, were treated with reovirus, ranging from 1.0 × 108 to 5.0 × 109 TCID50 given as intratumour injection (IT) or intravenous infusion (IV) daily for up to 5 consecutive days in 1 or multiple treatment cycles. Adverse events (AEs) were graded according to the Veterinary Cooperative Oncology Group‐ Common Terminology Criteria for Adverse Events (VCOG‐CTCAE) v1.1 guidelines. Viral shedding, neutralizing anti‐reovirus antibody (NARA) production and immunohistochemical (IHC) detection of reovirus protein in the tumours were also assessed. AE was not observed in most dogs and events were limited to Grade I or II fever, vomiting, diarrhoea and inflammation of the injected tumour. No infectious virus was shed and all dogs had elevated NARA levels post‐treatment. Although IHC results were only available in 6 dogs, 4 were detected positive for reovirus protein. In conclusion, reovirus is well‐tolerated and can be given safely to tumour‐bearing dogs according to the dosing regimen used in this study without significant concerns of viral shedding. Reovirus is also potentially effective in various types of canine tumours. |
| |
| Keywords: | canine dosing regimen oncolytic virotherapy reovirus safety profile tumour |
|
|
