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Cited by 328

The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.

Oncolytic HSV-1 G207 Immunovirotherapy for Pediatric High-Grade Gliomas

Open access
Friedman, Gregory K., Johnston, James M., Bag, Asim K., Bernstock, Joshua D., Li, Rong, Aban, Inmaculada, Kachurak, Kara, Nan, Li, Kang, Kyung-Don, Totsch, Stacie, Schlappi, Charles, Martin, Allison M., Pastakia, Devang, McNall-Knapp, Rene, Farouk Sait, Sameer, Khakoo, Yasmin, Karajannis, Matthias A., Woodling, Karina, Palmer, Joshua D., Osorio, Diana S., Leonard, Jeffrey, Abdelbaki, Mohamed S., Madan-Swain, Avi, Atkinson, T. Prescott, Whitley, Richard J., Fiveash, John B., Markert, James M., Gillespie, G. Yancey·2021·New England Journal of Medicine
DOI 10.1056/nejmoa2024947
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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. G207 converted immunologically "cold" tumors to "hot." (Supported by the Food and Drug Administration and others; ClinicalTrials.gov number, NCT02457845.).

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Metadata

Authors
Friedman, G. K., Johnston, J. M., Bag, A. K., Bernstock, J. D., Li, R., Aban, I., Kachurak, K., Nan, L., Kang, K.-D., Totsch, S., Schlappi, C., Martin, A. M., Pastakia, D., McNall-Knapp, R., Farouk Sait, S., Khakoo, Y., Karajannis, M. A., Woodling, K., Palmer, J. D., Osorio, D. S., Leonard, J., Abdelbaki, M. S., Madan-Swain, A., Atkinson, T. P., Whitley, R. J., Fiveash, J. B., Markert, J. M., & Gillespie, G. Y.
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2021-04-29
Volume
384
Issue
17
Pages
1613-1622
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa2024947
OpenAlex
W3142013426
Cited by
328
References
27
FWCI
29.71
Type
journal article
Language
en
Open access
bronze

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