Exth-13. enhancing induced neural stem cell-based trail therapy for glioblastoma through combination with the novel sensitizing agent tr-107

Abstract Tumor-homing neural stem cell therapy (tNSC) is emerging as a promising treatment for aggressive cancers of the brain. Despite their success, developing tNSC therapies that maintain durable tumor suppression remains a challenge. Here, we report a new synergistic combination regimen where the novel agent TR107 augments induced NSC-TRAIL therapy (hiNeuroS-TRAIL) in models of the incurable brain cancer glioblastoma (GBM). We found that the combination of hiNeuroS-TRAIL and TR-107 synergistically upregulated caspase markers and restored the sensitivity to the intrinsic apoptotic pathway by significantly downregulating inhibitory pathways associated with chemoresistance and radioresistance in GBM. This combination regimen showed dramatic tumor suppression and enhancement of survival of mice bearing human xenografts of both solid GBM and established invasive GBM. The combination also synergistically suppressed tumor growth in low-passage patient derived GBM cells established with an ex vivo brain slice platform. These findings elucidate a novel combination regimen and suggest combination of these clinically relevant agents may represent a new therapeutic option with increased potency for GBM patients.