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首页> 外文期刊>Neurosurgical focus >Safety and interim survival data after intracranial administration of M032, a genetically engineered oncolytic HSV-1 expressing IL-12, in pet dogs with sporadic gliomas
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Safety and interim survival data after intracranial administration of M032, a genetically engineered oncolytic HSV-1 expressing IL-12, in pet dogs with sporadic gliomas

机译：M032颅内施用后的安全和临时存活数据，在散发性Gliomas的宠物狗中表达IL-12的遗传工程化溶血性HSV-1

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OBJECTIVE The diagnosis of glioma remains disheartening in the clinical realm. While a multitude of studies and trials have shown promise, improvements in overall survival have been disappointing. Modeling these tumors in the laboratory setting has become increasingly challenging, given their complex in situ behavior and interactions for therapeutic evasion. Dogs, particularly brachycephalic breeds, are known to spontaneously develop gliomas that resemble human gliomas both clinically and pathophysiologically, making canines with sporadic tumors promising candidates for study. Typically, survival among these dogs is approximately 2 months with palliation alone. METHODS The authors have completed the first stage of a unique phase I dose-escalating canine clinical trial in which the safety and tolerability of M032, a nonneurovirulent oncolytic herpes simplex virus–1 vector genetically engineered to express interleukin-12, are being studied in pet dogs with gliomas undergoing maximum safe tumor resection and inoculation of the cavity with the viral infusate. RESULTS Twenty-five canine patients were enrolled between January 2018 and August 2020. One patient was electively withdrawn from the trial by its owner, and 3 did not receive the virus. For the 21 dogs that remained, 13 had high-grade gliomas, 5 had low-grade gliomas, and 3 were undetermined. According to histopathological analysis, 62% of the tumors were oligodendrogliomas. At the time of this report, the median overall survival from the date of treatment was 151 days (± 78 days). No significant adverse events attributable to M032 or dose-limiting toxicities have been observed to date. CONCLUSIONS In this largest study of oncolytic viral therapy for canine brain tumors to date, treatment with M032 did not cause harm and the combination of surgery and oncolytic viral therapy may have contributed to prolonged survival in pet dogs with spontaneous gliomas. Forthcoming in-depth radiographic, immunohistochemical, and genetic analyses will afford a more advanced understanding of how this treatment impacts these tumors and the immune system. Our goal is to utilize these findings bitranslationally to inform human studies and refine therapies that will improve outcomes in both humans and pet dogs with gliomas.
机译：目的在临床领域诊断胶质瘤仍然令人意意。虽然众多的研究和试验表明了承诺，但整体生存的改善一直令人失望。在实验室环境中建模这些肿瘤已经变得越来越具有挑战性，鉴于他们的原位行为和治疗逃避的相互作用。众所周知，狗，特别是短暂的胸腺蛋白品种，可自发地发展脑胶质瘤，临床和病理生理学上的人胶质瘤，使犬类肿瘤的犬类患者有前途的研究候选者。通常，这些狗的生存率仅为2个月，仅粘合。方法采用作者完成了独特的I阶段升级犬临床试验的第一阶段，其中M032的安全性和耐受性，一种遗传地设计用于表达白细胞介素-12的单纯溶血性疱疹病毒-1载体。狗与胶质瘤进行最大的安全肿瘤切除，并用病毒输注接种腔体。结果二十五个犬患者于2018年1月至2020年代招募了一名患者。一名患者通过其所有者选出审判，3例未接受病毒。对于剩余的21只狗，13只有高级胶质瘤，5种低级胶质瘤，3个未确定。根据组织病理学分析，62％的肿瘤是少于寡糖。在本报告的时候，从治疗之日起，中位的整体生存率为151天（±78天）。迄今已观察到归因于M032或剂量限制毒性的显着不良事件。结论在这一最大的毒性病毒治疗毒性病毒治疗迄今为止的研究中，用M032的治疗没有造成伤害，手术和溶血性病毒治疗的结合可能导致宠物狗的延长生存在具有自发性胶质瘤的宠物犬。即将到来的深入射线照相，免疫组织化学和遗传分析将提供更高级的理解，对该治疗如何影响这些肿瘤和免疫系统。我们的目标是利用这些调查结果来告知人类研究，并细化疗法，这些疗法将改善具有胶质瘤的人类和宠物狗的结果。

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