TMIC-79. MYELOID-DIRECTED TREATMENT USING THE TLR7/8 AGONIST RESIQUIMOD IMPROVES THE SURVIVAL OF MICE WITH MEDULLOBLASTOMA AND ENHANCES EFFICACY OF RADIOTHERAPY

Abstract We show the therapeutic potential of myeloid-directed immunomodulatory treatment for medulloblastoma. Patients with medulloblastoma, most common malignant pediatric brain tumor, need new treatments, as standard therapy produces disabling neurotoxicities and fails 20% patients. About 30% medulloblastomas hyperactivation SHH (Sonic Hedgehog) signaling pathway, these tumors have large myeloid populations in tumor microenvironment (TME). analyzed whether activating toll-like receptors on cells would slow growth. Our prior single-cell RNA sequencing studies both patient samples mouse models showed that 10% medulloblastoma are uniquely express TLR7 TLR8. treated mice genetically engineered to develop TLR7/8 agonist resiquimod, administered systemically either free drug or polyoxazoline nanoparticles (POx-resiquimod), compared POx-resiquimod+radiotherapy radiotherapy alone. found POx-resiquimod extended survival time while failed benefit. PK increased exposure, consistent efficacy. Mechanistically, increases decreased fraction expressed IGF1. plus radiation therapy, moreover, was superior alone, Together our data delivered nanoparticle formulation, a significant anti-tumor effect efficacy radiotherapy. As is mainstay current treatment, we propose TLR7/8-agonist such resiquimod may be added regimens reduce dose needed efficacy, increase successfully