GENETICALLY ENGINEERED HSV 1 IN MALIGNANT GLIOMA

恶性胶质瘤中的基因工程 HSV 1

• 批准号: 6263442
• 负责人: JAMES M MARKERT
• 金额: $ 2.95万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6263442
• 关键词: clinical research; gene therapy; genetic manipulation; glioma; herpes simplex virus 1; human subject; human therapy evaluation; magnetic resonance imaging; neoplastic growth; transfection /expression vector

Malignant glioma is a nearly uniformly lethal cancer of the central nervous system that is largely refractory to conventional modalities of therapy. One promising new approach is the use of a genetically engineered, conditionally replicating herpes simplex virus (HSV) following conventional therapy to kill remaining tumor cells. G207 is a recombinant HSV lacking genes essential for replication in normal brain cells. G207 has been shown to be efficacious in the treatment of both human and rodent tumors in murine models. Safety has been established following intracranial inoculation in the Aotus monkey (Aotus nancymai). We hypothesize that G207, a genetically-engineered HSV-1, will be safe and potentially useful for the treatment of patients with malignant gliomas who have evidence of progressive disease on MRI despite treatment with conventional surgery and/or biopsy and external beam radiation. The mode of administration will be stereotactic inoculation of virus into an enhancing region of the tumor.

恶性神经胶质瘤是一种几乎一致致命的中枢神经系统癌症，在很大程度上对传统的治疗方式是难治的。一种很有希望的新方法是使用一种基因工程，在常规治疗后有条件地复制单纯疱疹病毒（HSV）来杀死剩余的肿瘤细胞。G207是一种重组HSV，缺乏在正常脑细胞中复制所必需的基因。在小鼠模型中，G207已被证明对人类和啮齿动物的肿瘤都有效。经颅内接种后，在南脉猕猴（Aotus nancymai）中建立了安全性。我们假设G207（一种基因工程HSV-1）将是安全的，并且可能用于治疗MRI显示疾病进展的恶性胶质瘤患者，尽管接受了常规手术和/或活检和外部束辐射治疗。给药方式将是立体定向接种病毒到肿瘤的增强区。