HUMAN NEURAL STEM CELLS TARGET GENE THERAPY-BRAIN TUMORS

神经干细胞（NSCs）在移植后表现出在整个中枢神经系统中迁移、与宿主细胞混合和表达外源转基因的显著能力。有趣的是，NSCs的这种固有迁移特性模拟了一些脑肿瘤（如胶质瘤）的迁移模式，其特征是侵袭性的单细胞迁移。潜在地，NSCs的迁移特性可以被利用来传播治疗基因产物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NSCs在稳定表达一个报告基因的同时，表现出向胶质瘤的显著肿瘤靶向迁移行为。II期需要对NSCs进行基因修饰以表达一系列治疗性基因，然后评估其靶向肿瘤细胞并引发抗肿瘤反应的潜力。在啮齿类动物模型中，基因修饰的NSCs有望浸润肿瘤肿块，追踪单个肿瘤细胞，并稳定表达能够破坏癌细胞的溶瘤蛋白。这些研究将推动一种潜在的革命性治疗策略的发展，利用人类NSCs作为一种新的、有效的递送载体，将治疗基因靶向治疗难治性脑肿瘤。建议的商业应用：神经干细胞为神经系统疾病的治疗提供了一个引人注目的新技术平台。它们的自然迁移能力为直接靶向治疗顽固性脑肿瘤提供了强有力的载体。该项目将评估一系列治疗基因，以加快潜在的革命性癌症治疗策略的发展，以治疗致命的脑肿瘤。

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.