Containing the virus.

Top Line: Treatment options are very limited for pediatric HGG (which includes GBM) that progress after first-line therapy.

The Study: In particular, these tumors are often immunologically “cold” and show limited benefit from immunotherapies. In this phase 1 study, pediatric and adolescent patients with progressive supratentorial HGG were treated with intratumoral inoculation of a genetically engineered herpes simplex virus (HSV-1), called G207. G207 was engineered so that Protein Kinase-R mediated translational arrest and minimized ribonucleotide reductase replication potential in normal cells. Tumor cells with dysfunctional Protein Kinase-R and upregulated ribonucleotide reductase sustain a selective infection that leads to tumor cell lysis. For treatment, intratumoral catheters (3-4) were placed and patients were inoculated over 6 hours followed (within 24 hours) by a single 5 Gy radiation treatment to gross disease. The radiation part was a result of preclinical studies showing it enhanced viral replication in tumor cells. A total of 12 patients were treated on trial—ten had GBM and two had grade 3 gliomas. All patients had two or more prior lines of therapy. There were no grade 3 or higher events, and there were no dose-limiting or serious adverse events related to G207 inoculation. G207 remained intratumoral with no patients having evidence of shedding or viremia. Eleven of twelve patients responded to G207 inoculation, and median survival among the small cohort was an encouraging 12.2 months. Histopathologically, there was a significant increase in tumor-infiltrating lymphocytes pre- and post-treatment, and this infiltrate persisted even after clearance of G207.

TBL: Intratumoral inoculation of the oncolytic virus, G207, has limited toxicity and produces a significantly higher and sustained immune cell infiltrate in pediatric and adolescent patients with HGG. | Friedman, N Engl J Med 2021