HUMAN NEURAL STEM CELLS TARGET GENE THERAPY-BRAIN TUMORS

神经干细胞（NSC）显示出在移植后在整个CNS中迁移、与宿主细胞混合并表达外源转基因的显著能力。有趣的是，神经干细胞的这种固有迁移特性模仿了一些脑肿瘤的迁移模式，如神经胶质瘤，其特征在于侵入性单细胞迁移。潜在地，可以利用NSC的迁移特性将治疗基因产物传播到入侵的脑肿瘤细胞。作为实现这一目标的第一步，I期研究的结果表明，人类神经干细胞显示出显著的肿瘤靶向胶质瘤迁移行为，同时稳定表达报告基因。第二阶段需要对神经干细胞进行遗传修饰以表达一系列治疗基因，然后评估它们靶向肿瘤细胞并引发抗肿瘤反应的潜力。预期遗传修饰的NSC将渗入肿瘤块，追踪个体肿瘤细胞，并稳定表达可破坏啮齿动物模型中的癌细胞的溶瘤蛋白。这些研究将推动一种潜在的革命性治疗策略的发展，该策略使用人类神经干细胞作为一种新的，有效的递送载体，将治疗基因靶向难治性脑肿瘤。拟议的商业应用：神经干细胞代表了治疗神经系统疾病的一个引人注目的新技术平台。它们的自然迁移能力为治疗药物直接靶向难治性脑肿瘤提供了强大的工具。该项目将评估一系列治疗基因，以加快开发一种潜在的革命性癌症治疗策略，治疗致命的脑肿瘤。

Neural stem cells (NSCs) show a remarkable ability to migrate throughout the CNS, intermingle with host cells, and express foreign transgenes following transplantation. Intriguingly, this inherent migratory property of NSCs emulates the migratory pattern of some brain tumors, such as gliomas, characterized by invasive single cell migration. Potentially, the migratory properties of NSCs can be harnessed to disseminate therapeutic genes products to invading brain tumor cells. As the first step toward this goal, results from phase I studies demonstrated that human NSCs displayed significant tumor targeting migratory behavior toward gliomas while stable expressing a reporter gene. Phase II entails genetically modifying NSCs to express an array of therapeutic genes, and then assessing their potential to target tumor cells and elicit an anti-tumor response. It is anticipated that genetically modified NSCs will infiltrate the tumor mass, track individual tumor cells, and stably express oncolytic proteins that can destroy the cancerous cells in rodent models. These studies will advance the development of a potentially revolutionary treatment strategy using human NSCs as a novel, efficient delivery vehicle to target therapeutic genes to refractory brain tumors. PROPOSED COMMERCIAL APPLICATIONS: Neural stem cells represent a compelling new technology platform for the treatment of neurological diseases. Their natural migratory capacity provides a powerful vehicle to target therapeutic agents directly to refractory brain tumors. This project will evaluate an array of therapeutic genes to expedite the development of a potentially revolutionary cancer therapy strategy to treat deadly brain tumors.