Clinical translation of intravenous therapies to treat disseminated or metastatic cancer is imperative. Comparative oncology, the evaluation of novel cancer therapies in animals with spontaneous cancer, can be utilized to inform and accelerate clinical translation. Preclinical murine studies demonstrate that single-shot systemic therapy with a vesicular stomatitis virus (VSV)-IFNβ-NIS, a novel recombinant oncolytic VSV, can induce curative remission in tumor-bearing mice. Clinical translation of VSV-IFNβ-NIS therapy is dependent on comprehensive assessment of clinical toxicities, virus shedding, pharmacokinetics, and efficacy in clinically relevant models. Dogs spontaneously develop cancer with comparable etiology, clinical progression, and response to therapy as human malignancies. A comparative oncology study was carried out to investigate feasibility and tolerability of intravenous oncolytic VSV-IFNβ-NIS therapy in pet dogs with spontaneous cancer. Nine dogs with various malignancies were treated with a single intravenous dose of VSV-IFNβ-NIS. Two dogs with high-grade peripheral T-cell lymphoma had rapid but transient remission of disseminated disease and transient hepatotoxicity that resolved spontaneously. There was no shedding of infectious virus. Correlative pharmacokinetic studies revealed elevated levels of VSV RNA in blood in dogs with measurable disease remission. This is the first evaluation of intravenous oncolytic virus therapy for spontaneous canine cancer, demonstrating that VSV-IFNβ-NIS is well-tolerated and safe in dogs with advanced or metastatic disease. This approach has informed clinical translation, including dose and target indication selection, leading to a clinical investigation of intravenous VSV-IFNβ-NIS therapy, and provided preliminary evidence of clinical efficacy and potential biomarkers that correlate with therapeutic response. Mol Cancer Ther; 17(1); 316–26. ©2017 AACR.

中文翻译：

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静脉注射重组溶瘤性水泡性口炎病毒治疗自发性犬癌的比较肿瘤学评价

治疗播散性或转移性癌症的静脉疗法的临床转化势在必行。比较肿瘤学是对自发性癌症动物的新型癌症疗法的评估，可用于通知和加速临床转化。临床前小鼠研究表明，使用水泡性口炎病毒 (VSV)-IFNβ-NIS（一种新型重组溶瘤 VSV）进行单次全身治疗可以诱导荷瘤小鼠的治愈性缓解。VSV-IFNβ-NIS 治疗的临床转化取决于临床相关模型中临床毒性、病毒脱落、药代动力学和功效的综合评估。狗自发地患上癌症，其病因、临床进展和对治疗的反应与人类恶性肿瘤相当。进行了一项比较肿瘤学研究，以研究静脉溶瘤 VSV-IFNβ-NIS 治疗患有自发性癌症的宠物犬的可行性和耐受性。九只患有各种恶性肿瘤的狗接受了单次静脉注射 VSV-IFNβ-NIS 的治疗。两只患有高级别外周 T 细胞淋巴瘤的犬的播散性疾病和暂时性肝毒性迅速但暂时缓解，可自行消退。没有传染性病毒的脱落。相关的药代动力学研究表明，狗的血液中 VSV RNA 水平升高，可测量的疾病缓解。这是首次评估静脉溶瘤病毒治疗自发性犬癌，证明 VSV-IFNβ-NIS 在患有晚期或转移性疾病的犬中具有良好的耐受性和安全性。这种方法为临床翻译提供了信息，包括剂量和靶点适应症选择，导致对静脉内 VSV-IFNβ-NIS 治疗的临床研究，并提供了临床疗效和与治疗反应相关的潜在生物标志物的初步证据。摩尔癌症治疗; 17(1); 316-26。©2017 AACR。