Positioning hydrogels for next-generation immunovirotherapy in glioblastoma

High-grade gliomas, including Glioblastoma (GBM), are the most common primary malignant tumor of the central nervous system and confer a dismal clinical prognosis. Current standard-of-care consists of maximal safe resection followed by radiation, chemotherapy, and/or tumor treating fields. Immunovirotherapy is a novel treatment modality in which oncolytic viruses (OVs) are engineered to induce oncolysis and concurrently stimulate an antitumor immune response. Presently, effective OV delivery is challenged by the complex tumor microenvironment and the blood-brain barrier. Hydrogels have shown promise in overcoming such challenges; built of natural and synthetic polymers, hydrogels can effectively deliver therapeutic payloads over an extended period. Hydrogels may also help facilitate OV augmentation with immune adjuvants such as checkpoint inhibitors. In this review, we 1) summarize advances and challenges in OV therapy; 2) describe how hydrogels can improve delivery of viral therapies; and 3) highlight opportunities for hydrogel-mediated OV–immune adjuvant combinations in the treatment of GBM and other high-grade brain tumors. Glioblastoma is an aggressive brain tumor with poor prognosis; while treated with surgery and therapy, immunovirotherapy faces delivery barriers that hydrogels may help overcome. Here, the authors summarize progress in oncolytic virus therapy, hydrogels for delivery, and their combination with immune therapies.