BioE Seminar Series: Fade-Away Swish for Glioblastoma Treatment: Chemotherapy and Immunotherapy Delivery with Acetalated Dextran Scaffolds

Presenter: Kristy Ainslie, PhD is a Eshelman Distinguished Professor and Chair of the Division of Pharmacoengineering and Molecular Pharmaceutics at the UNC Eshelman School of Pharmacy

Glioblastoma (GBM) is an aggressive form of primary brain cancer with a dismal prognosis despite therapeutic intervention. With standard of care, patients with GBM have a median survival of less than one year with only 2% of patients surviving to three years. With this poor prognosis, there is a desperate need for new therapies for this fatal disease. Interstitial therapy, delivered at the time of surgical resection, can be a transformational option to deliver chemotherapy or immunotherapy. For this purpose we use acetalated dextran (Ace-DEX) nanofibrous scaffolds which have important advantages over the current FDA approved interstitial therapy (Gliadel). Ace-DEX scaffolds have uniquely tunable degradation rates that significantly impact therapeutic efficacy and they offer facile scalability between pre-clinical and clinical models. To explore this therapy in a clinically relevant model, we used an image guided mouse model of GBM resection and recurrence. Our studies show that Ace-DEX scaffolds degrade across a wide range of rates to release the chemotherapeutic paclitaxel from 7 days to more than 35 days, based on the cyclic acetal coverage (CAC) of the polymer. The effect of release is evident with a 78% long term survival observed for mice treated with combined fast and slow-release scaffolds, in comparison to a survival of 20% when the same dose is delivered at a medium release rate. By incorporating the immune adjuvant resiquimod into the scaffold instead of chemotherapy, we show that Ace-DEX scaffolds can modulate the immunosuppressive environment of the cancer to enhance clearance of the tumor and illustrate long-term memory and protection against subsequent tumor challenges out past 100 days after initial tumor inoculation. Our preclinical results indicate that we can enhance delivery of chemotherapeutics or immunotherapy with the application of Ace-DEX nanofibrous scaffolds to develop translational therapies to better treat this devastating cancer.