Grant: Project Grant

This proposal advances cancer survivorship by developing ImmunoGel, an injectable granular hydrogel designed to enhance CAR-T cell therapy targeting B7-H3 in glioblastoma (GBM), an aggressive brain tumor with a median survival of approximately 15 months under standard care. Key challenges in GBM-including infiltrative growth, tumor heterogeneity, blood-brain barrier constraints, and resistance to temozolomide (TMZ)-are addressed through locoregional delivery, which bypasses systemic toxicity and enables sustained CAR-T activation, expansion, and infiltration via ImmunoGel's porous architecture and immunostimulatory components (anti-CD3/CD28 antibodies, IL-2, and gemcitabine). Using patient-derived GBM-on-a-chip platforms (Tumoroid-on-a-Plate), the project will optimize treatment regimens for MGMT-methylated (TMZ-sensitive) and unmethylated (resistant) tumors while incorporating key elements of the tumor microenvironment, including microglia and fibroblasts. In resistant GBM models, combinatorial strategies incorporating tocilizumab will target IL-6-mediated immunosuppression, reduce T-cell exhaustion, and enhance therapeutic efficacy. This personalized, platform-driven approach aims to minimize neurotoxicity and cytokine-release syndrome, predict patient-specific responses, reduce recurrence, and ultimately extend survival and quality of life for patients.