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E. coli CD-expressing genetically modified neural stem cells (specifically the HB1.F3.CD line) is an investigational cell-based gene therapy developed by City of Hope National Medical Center for the treatment of recurrent high-grade gliomas. The therapy utilizes a clonal human neural stem cell (NSC) line that has been immortalized and retrovirally transduced to stably express the Escherichia coli enzyme cytosine deaminase (CD). These NSCs exhibit inherent tumor tropism, allowing them to migrate through the brain parenchyma toward invasive glioma cells. The therapeutic strategy involves the intracranial administration of these engineered NSCs into the tumor resection cavity or biopsy site, followed by the systemic administration of the prodrug 5-fluorocytosine (5-FC). The CD enzyme expressed by the NSCs locally converts 5-FC into the potent chemotherapeutic agent 5-fluorouracil (5-FU), thereby achieving high local concentrations of chemotherapy within the tumor microenvironment while minimizing systemic toxicity.
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