TMIC-28. COMBINING INDUCED NEURAL STEM CELL THERAPY AND IMMUNOMODULATION IN GLIOBLASTOMA

Abstract Glioblastoma (GBM) is an aggressive malignant adult brain tumor and characterized by poor prognosis survival outcome. Insufficient drug accumulation to the site development of monotherapy resistance are critical challenges overcome in combating GBM. Human induced neural stem cells (hiNSC) therapy promising due cells’ innate capability migrate tumors deliver therapeutics. We previously have developed spheroidal iNSCs engineered them constitutively secrete pro-apoptotic protein TRAIL—hiNeuroS-TRAIL. However, investigating a combination along with hiNeuroS-TRAIL needed potentially avoid enhance overall treatment durability. One GBM hallmarks its immunosuppressed microenvironment (TME). GBM-associated macrophages microglia (GAMs) display pro-tumoral phenotypes TME—inhibiting their ability target or recruit other immune cells. In humans, higher glioma grade associated expression Mer Tyrosine Kinase Receptor (MerTK) both GAMs. Activation MerTK GAMs exacerbates immunosuppression progression respectively. Inhibiting activation via small molecule drug, MRX-2843 combining demonstrated robust synergistic killing effects vitro (CDI=0.22) ex vivo (CDI=0.18). Additionally, preliminary data for pilot study revealed that median treated group mice extended over 24 days whereas control, MRX-2843, groups were 16, 18, 21 think these two therapies could significantly extend our murine model Therefore, we will be optimizing dose concentration cell counts single agent therapies, then repeat y synergy optimized larger sample size fully uncover potential this therapy.