Hwang C C, Igase M, Sakurai M, Haraguchi T, Tani K, Itamoto K, Shimokawa T, Nakaichi M, Nemoto Y, Noguchi S, Coffey M, Okuda M, Mizuno T
Laboratory of Molecular Diagnostics and Therapeutics, The United Graduate School of Veterinary Science, Yamaguchi University, Yamaguchi, Japan.
Laboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi, Japan.
Vet Comp Oncol. 2018 Jun;16(2):229-238. doi: 10.1111/vco.12361. Epub 2017 Oct 27.
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.
溶瘤病毒疗法是一种新型治疗方法，涉及使用具有复制能力的病毒来消除癌症。我们之前报道过呼肠孤病毒在多种犬癌细胞系中的溶瘤作用。本研究旨在确定呼肠孤病毒在患有自发性肿瘤的犬中的安全性，并确定推荐的给药方案。19只患有各种肿瘤（大多为晚期）的犬接受了呼肠孤病毒治疗，剂量范围为1.0×10至5.0×10组织培养感染剂量（TCID），通过瘤内注射（IT）或静脉输注（IV）给药，连续5天每日给药，共进行1个或多个治疗周期。不良事件（AE）根据兽医肿瘤协作组-不良事件通用术语标准（VCOG-CTCAE）v1.1指南进行分级。还评估了病毒脱落、中和抗呼肠孤病毒抗体（NARA）产生以及肿瘤中呼肠孤病毒蛋白的免疫组织化学（IHC）检测情况。大多数犬未观察到AE，事件仅限于I级或II级发热、呕吐、腹泻以及注射肿瘤部位的炎症。未检测到有传染性的病毒脱落，所有犬在治疗后NARA水平均升高。尽管仅6只犬有免疫组织化学结果，但4只犬检测到呼肠孤病毒蛋白呈阳性。总之，根据本研究中使用的给药方案，呼肠孤病毒耐受性良好，可安全地给予荷瘤犬，无需对病毒脱落有重大担忧。呼肠孤病毒在各种类型的犬肿瘤中也可能有效。
