Oncolytic reovirus therapy: Pilot study in dogs with spontaneously occurring tumours

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 × 10 to 5.0 × 10 TCID 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.

Oncolytic activity of canine distemper virus in canine mammary tubular adenocarcinoma cells

“…Oncolytic virotherapy has been recognized as a promising option for human cancer treatment particularly benefiting from the recent advances in molecular virology and oncology . However, application of oncolytic virotherapy within the field of veterinary medicine remains limited . Our studies have focused on the oncolytic feasibility and mechanism of oncolytic activity of CDV within CMTAC CIPp cells.…”

“…In human cancers, promising results have been obtained in clinical trials using oncolytic virotherapy . In the veterinary field, several viruses of different virus families including Adeno ‐, Pox ‐, Reo ‐, and Paramyxoviridae , have been reported as oncolytic agents before or after genetic engineering and exhibit anti‐tumour activities …”

“…8 In the veterinary field, several viruses of different virus families including Adeno-, Pox-, Reo-, and Paramyxoviridae, have been reported as oncolytic agents before or after genetic engineering and exhibit anti-tumour activities. [9][10][11][12][13][14][15] Canine distemper virus (CDV), an enveloped, negative-sense RNA virus with a single stranded genome, belongs to the family Paramyxoviridae, genus Morbillivirus. It closely resembles human measles virus (MV) including its clinical outcome, and that prompts its consideration for cancer treatment.…”

Anti‐tumour activity of oncolytic reovirus against canine histiocytic sarcoma cells

“…Oncolytic virotherapy is a novel treatment strategy for the treatment of canine and feline cancers, as well as those of humans . While many kinds of viruses have been proposed as candidates for virotherapy, our laboratory has been researching the use of a naturally occurring reovirus, the serotype‐3 Dearing strain, as a new approach for treating canine cancer in veterinary medicine . Reovirus is a ubiquitous and non‐enveloped mammalian virus with a genome that consists of 10 segments of double‐stranded RNA.…”

“…Moreover, those studies showed that there was no relationship between Ras activation and susceptibility to reoviral killing in canine cancers. To assess the efficacy of reovirus in a clinical setting, we conducted a pilot study of reovirus therapy in tumour‐bearing dogs . However, the pilot study did not include dogs with histiocytic sarcoma.…”