文章：

溶瘤HSV-1 G207接种小鼠小脑的安全性和有效性

Safety and efficacy of oncolytic HSV-1 G207 inoculated into the cerebellum of mice 

原文发布日期：2019-03-28 

英文摘要：

Primary malignant central nervous system (CNS) tumors are the leading cause of childhood cancer-related death and morbidity. While advances in surgery, radiation, and chemotherapy have improved the survival rates in children with malignant brain tumors, mortality persists in certain subpopulations and current therapies are associated with extreme morbidity. This is especially true for children with malignant infratentorial tumors. Accordingly, G207, a genetically engineered herpes simplex virus (HSV-1) capable of selectively targeting cancer cells has emerged as a promising therapeutic option for this patient population. Herein, we demonstrate that cerebellar inoculation of G207 was systemically non-toxic in an immunocompetent, HSV-1 sensitive mouse strain (CBA/J). Mice had neither abnormal brain/organ pathology nor evidence of G207 replication by immunohistochemistry at days 7 and 30 after cerebellar G207 inoculation. While a minute amount viral DNA was recovered in the cerebellum and brainstem of mice at day 7, no viral DNA persisted at day 30. Critically, G207 delivered to the cerebellum was able to target/treat the highly aggressive MYC-overexpressed group 3 murine medulloblastoma increasing survival vs controls. These results provide critical safety and efficacy data to support the translation of G207 for pediatric clinical trials in intractable cerebellar malignancies. 

摘要翻译： 

原发性恶性中枢神经系统（CNS）肿瘤是儿童癌症相关死亡和致残的主要原因。尽管手术、放疗和化疗的进步已提高了儿童恶性脑肿瘤的生存率，但特定亚群患者仍面临持续死亡率，且现有治疗手段伴随严重并发症。这一现象在幕下恶性脑肿瘤患儿中尤为显著。因此，G207——一种能够选择性靶向癌细胞的基因工程改造单纯疱疹病毒（HSV-1）——已成为该患者群体极具前景的治疗选择。本研究证实，在免疫功能正常且对HSV-1敏感的CBA/J小鼠品系中，小脑接种G207未引发系统性毒性。小鼠在接种后第7天和第30天既未出现脑部/器官病理学异常，免疫组化检测也未发现G207病毒复制证据。尽管第7天时在小脑和脑干回收到微量病毒DNA，但第30天时所有病毒DNA均已被清除。关键的是，小脑递送的G207能够靶向治疗MYC过表达的高侵袭性第3组小鼠髓母细胞瘤，与对照组相比显著延长了生存期。这些数据为推进G207用于难治性小脑恶性肿瘤儿科临床试验提供了关键的安全性与有效性依据。

原文链接：

Safety and efficacy of oncolytic HSV-1 G207 inoculated into the cerebellum of mice