Oncolytic HSV-1 G207 immunotherapy for pediatric high-grade gliomas

Children and adolescents with recurrent or progressive high-grade gliomas have a poor prognosis, with a historical median overall survival of 5.6 months. Pediatric high-grade gliomas are largely immunologically ‘cold’, with few tumor-infiltrating lymphocytes. A multicenter phase 1 study evaluated genetically engineered HSV-1 G207, which lacks genes essential for replication in normal brain tissue, but can replicate in tumors. G207 was administered through up to four intratumoral catheters. Half of patients also received radiation to the gross tumor volume within 24 hours after G207 administation. Intratumoral G207 alone and with radiation resulted in median overall survival of 12.2 months (95% CI 8.0-16.4). Four of eleven patients with alive 18 months after G207 treatment. The authors conclude that G207 converted 'cold' tumors to 'hot'.