Modifying Post-Surgical Immunity: Controlled Release of TLR7/8 Agonist for Immune Mediated Clearance of Glioblastoma

Abstract Glioblastoma is an aggressive brain cancer with a dismal prognosis despite current therapeutic interventions. Tumor resection is standard-of-care for glioblastoma and has profound immunostimulatory effects. Resulting in a nadir in tumor burden, resection offers a unique opportunity to break local immune tolerance and mount an effective anti-tumor immune response. Here, we explore the effect of local and controlled release of TLR7/8 agonist from a polymer scaffold implanted at the time of tumor resection. We find that sustained release of TLR7/8 agonist leads to clearance of residual post-resection tumor, improved survival, and subsequent protection from tumor challenge in mice bearing orthotopic GL261 or CT2A gliomas. We show that scaffold therapy boosts resection-mediated disruption to the tumor microenvironment, leading to an early inflammatory innate immune response both in the brain and cervical lymph node. This is followed by an influx of activated NK cells in the brain and effector T cells in the lymph node and brain. In sum, sustained local TLR7/8 agonism within the context of tumor resection is a promising approach for glioblastoma.