Therapeutic Potential of Engineered Stem Cell Line with Chemokine Receptors and TRAIL/CD::UPRT in Glioblastoma Treatment

PurposeGlioblastoma (GBM) is an aggressive primary brain tumor marked by a poor prognosis and limited effectiveness of current therapies, which are often accompanied by substantial recurrence rates.To address this challenge, we developed BM03, an engineered mesenchymal stem cell (MSC) line specifically designed for glioblastoma therapy.BM03 is structured to enhance migration to GBM sites and deliver targeted, multimodal gene-based therapies. Materials and MethodsThis cell line was developed by transducing bone marrow-derived MSCs with lentiviral vectors to enable (1) continuous growth through immortalization, (2) tumor-targeted migration via GBMassociated chemokine receptors CCR2 and CXCR4, and (3) direct tumoricidal effects through TRAIL and CD::UPRT gene expression for apoptosis and prodrug activation. ResultsBM03 demonstrated strong chemotaxis toward GBM cells in both in vitro and in vivo models, facilitated by CCR2 and CXCR4 co-expression, which was maintained through tetracycline transactivator (tTA)-mediated transcriptional control.The combination of TRAIL and CD::UPRT showed significant cytotoxicity, effectively overcoming TRAIL resistance in GBM cells and exhibiting enhanced antitumor effects in a GBM mouse xenograft model.Moreover, repeated BM03 administration, particularly when combined with temozolomide (TMZ), resulted in sustained tumor regression and improved survival. ConclusionTo enhance clinical relevance, we evaluated intraventricular administration, which effectively