High-grade gliomas, including glioblastoma, are among the most lethal brain cancers with very limited treatment options. This completed phase I clinical trial explored whether adding Gene Mediated Cytotoxic Immunotherapy (GMCI) — a gene therapy approach using aglatimagene besadenovec injected into the tumor followed by oral valacyclovir — alongside the PD-1 immune checkpoint inhibitor nivolumab could safely complement standard radiation and temozolomide chemotherapy. GMCI works by killing tumor cells and simultaneously activating an immune response against remaining cancer cells. Nivolumab blocks a pathway that tumors exploit to suppress the immune system. Enrolling 41 patients, the trial aimed to establish the safety profile of this four-pronged attack on one of the most treatment-resistant cancers. Results could inform future combination immunotherapy strategies for brain cancer.
