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.

恶性神经胶质瘤几乎是中枢神经系统的致命癌症，在很大程度上对常规治疗方式难治性。一种有前途的新方法是使用经过基因工程的，有条件地复制单纯疱疹病毒（HSV），以杀死剩余的肿瘤细胞。 G207是一种重组HSV，缺乏正常脑细胞复制必不可少的基因。 在鼠模型中，G207在治疗人类和啮齿动物肿瘤方面具有有效性。 在Aotus Monkey（Nancymai Aotus）中颅内接种后，已经建立了安全性。我们假设G207是一种基因设计的HSV-1，对于治疗尽管经常手术和/或活检和外束辐射治疗的恶性神经胶质瘤患者，这些患者具有恶性神经胶质瘤患者，这些患者具有进行性疾病的迹象。 给药方式将是将病毒的立体定向接种到肿瘤的增强区域。