Nature Reviews Clinical Oncology | 2021
HSV-1 G207 is active in paediatric glioma
Abstract
0123456789();: Nature reviews | CliniCal OnCOlOgy HSV-1 G207 mounts an efficient antitumour immune response in the brain standard therapy for paediatric malignant high-grade gliomas involves radiotherapy and chemo therapy, and results in poor survival and high toxicity. Now, data from a phase i trial show durable antitumour activity with the modified neurotropic oncolytic virus Hsv-1 G207. Hsv-1 G207 can be inoculated into tumour resection cavities in the brain. in previous early phase trials, intratumoural administration of this virus followed by a single dose of radiation was deemed to be safe in adults with high-grade gliomas. in the current study, patients aged 7–18 years with progressive high-grade gliomas were allocated to four dose cohorts: 107 or 10 plaque-forming units with or without 5 Gy of radiation (n = 3 per cohort). two minor complications were attributed to neurosurgery. Grade 1 adverse events attributed to Hsv-1 G207 occurred in 11 of 12 patients. all patients receiving radiation had grade 1–2 adverse events. Median overall survival (Os) was 12.2 months (95% CI 8–16.4 months), a value in contrast with 5.6 months, the historical median Os at initial progression with other therapies in this setting. Of note, four patients in the trial were alive beyond 18 months from treatment. Matched tissue samples collected before and 2–9 months after treatment were available for four patients (one per dose cohort). The number of CD3+, CD4+ and CD8+ tumour-infiltrating lymphocytes increased substantially after treatment in all evaluated patients. the researchers hypothesized that the presence of neutralizing antibodies from a previous Hsv-1 infection might interfere with the activity of Hsv-1 G207. indeed, median Os was 5.1 months and 18.3 months in patients with anti-Hsv-1 igGs at baseline and those with seroconversion, respectively (both n = 3). Overall, these results suggest that HSV-1 G207 mounts an effici ent antitumour immune response in the brain. “we are currently designing a larger phase ii trial to confirm the safety and efficacy of these findings,” mentions lead invest igator Gregory Friedman, adding: “we have an ongo ing firstin-human trial to assess the safety and effectiveness of Hsv-1 G207 in recurrent paediatric malignant tumours, such as medulloblastoma”. the results of both trials are eagerly awaited.