iXgene, a startup from Keio University, is currently developing suicide gene-transfected iPS cell-derived neural stem cells for the treatment of malignant brain tumors. The tNSCs contain suicide fusion genes from yeast cytosine deaminase (CD) and uracil phosphoribosyltransferase (UPRT), which are introduced into iPS cells derived from a healthy donor using genome editing technology. The cells are then induced to differentiate into neural stem cells.
Since tNSCs have the ability to migrate to tumors and brain injury sites, they can be administered directly after resection of malignant brain tumors or during stereotactic brain surgery to collect at the tumor site of glioblastoma or at the site of brain dysfunction damage and inflammation. On top of that, when flucytosine (5-FC), a prodrug and antifungal drug, is orally administered, the introduced cytosine deaminase (CD) and uracil phosphoribosyltransferase (UPRT) metabolize 5-FC into tumor-killing substances that inhibit DNA and RNA synthesis.
Malignant brain tumors are targeted to enter clinical trials in 2025, and iXgene will lead the development of tNSCs for glioblastoma, one of the most refractory malignant brain tumors.