{"doi":"10.1056/nejmoa2024947","title":"Oncolytic HSV-1 G207 Immunovirotherapy for Pediatric High-Grade Gliomas","abstract":"BACKGROUND: Outcomes in children and adolescents with recurrent or progressive high-grade glioma are poor, with a historical median overall survival of 5.6 months. Pediatric high-grade gliomas are largely immunologically silent or \"cold,\" with few tumor-infiltrating lymphocytes. Preclinically, pediatric brain tumors are highly sensitive to oncolytic virotherapy with genetically engineered herpes simplex virus type 1 (HSV-1) G207, which lacks genes essential for replication in normal brain tissue. METHODS: plaque-forming units) by controlled-rate infusion over a period of 6 hours. Cohorts 3 and 4 received radiation (5 Gy) to the gross tumor volume within 24 hours after G207 administration. Viral shedding from saliva, conjunctiva, and blood was assessed by culture and polymerase-chain-reaction assay. Matched pre- and post-treatment tissue samples were examined for tumor-infiltrating lymphocytes by immunohistologic analysis. RESULTS: Twelve patients 7 to 18 years of age with high-grade glioma received G207. No dose-limiting toxic effects or serious adverse events were attributed to G207 by the investigators. Twenty grade 1 adverse events were possibly related to G207. No virus shedding was detected. Radiographic, neuropathological, or clinical responses were seen in 11 patients. The median overall survival was 12.2 months (95% confidence interval, 8.0 to 16.4); as of June 5, 2020, a total of 4 of 11 patients were still alive 18 months after G207 treatment. G207 markedly increased the number of tumor-infiltrating lymphocytes. CONCLUSIONS: Intratumoral G207 alone and with radiation had an acceptable adverse-event profile with evidence of responses in patients with recurrent or progressive pediatric high-grade glioma. 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Totsch","orcid":"0000-0001-7340-7627","position":9,"is_corresponding":false},{"id":619742,"name":"Charles Schlappi","orcid":null,"position":10,"is_corresponding":false},{"id":618654,"name":"Allison Martin","orcid":"0000-0002-5984-4684","position":11,"is_corresponding":false},{"id":619743,"name":"Devang Pastakia","orcid":null,"position":12,"is_corresponding":false},{"id":341510,"name":"Rene McNall‐Knapp","orcid":"0000-0002-0416-7364","position":13,"is_corresponding":false},{"id":618655,"name":"Sameer Farouk Sait","orcid":"0000-0001-6715-2402","position":14,"is_corresponding":false},{"id":106425,"name":"Yasmin Khakoo","orcid":"0000-0003-1633-6759","position":15,"is_corresponding":false},{"id":236638,"name":"Matthias A. Karajannis","orcid":"0000-0002-7151-6528","position":16,"is_corresponding":false},{"id":619744,"name":"Karina Woodling","orcid":null,"position":17,"is_corresponding":false},{"id":286417,"name":"Joshua D. Palmer","orcid":"0000-0003-3311-0129","position":18,"is_corresponding":false},{"id":510409,"name":"Diana S. Osorio","orcid":"0000-0003-1082-7338","position":19,"is_corresponding":false},{"id":447437,"name":"Jeffrey R. Leonard","orcid":"0000-0002-4426-0037","position":20,"is_corresponding":false},{"id":618656,"name":"Mohamed S Abdelbaki","orcid":"0000-0002-8262-7469","position":21,"is_corresponding":false},{"id":539935,"name":"Avi Madan‐Swain","orcid":null,"position":22,"is_corresponding":false},{"id":495432,"name":"T. Prescott Atkinson","orcid":"0000-0003-2528-6976","position":23,"is_corresponding":false},{"id":409095,"name":"Richard J. Whitley","orcid":"0000-0001-9959-9276","position":24,"is_corresponding":false},{"id":443388,"name":"John B. Fiveash","orcid":"0000-0002-1129-2884","position":25,"is_corresponding":false},{"id":254082,"name":"James M. Markert","orcid":"0000-0001-7457-7329","position":26,"is_corresponding":false},{"id":242515,"name":"G. Yancey Gillespie","orcid":"0000-0001-6436-9542","position":27,"is_corresponding":false},{"id":242516,"name":"Gregory K. Friedman","orcid":"0000-0002-6653-7420","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-18T23:42:12.871665Z","pmid":"33838625","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}