Virotherapy for Brain Tumors — Defining the Path to Success

Most high-grade gliomas are associated with dismal survival in both adults and children, even after aggressive treatment. Despite initial promise, immunotherapy with immune checkpoint inhibitors or peptide vaccines has failed to show efficacy in phase 3, randomized trials involving patients with glioblastoma,1,2 the most common World Health Organization grade IV glioma in adults. The lack of progress in developing effective immunotherapies for adult and pediatric high-grade glioma can be explained by several factors, including scarcity of tumor infiltrating lymphocytes, T-cell exhaustion, low somatic mutational load with decreased burden of tumor-specific antigens, and systemic immunosuppression, both tumor- and treatment-induced. In the . . .