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Oncolytic Viral Injections Tested in Pediatric Diffuse Intrinsic Pontine Glioma
Diffuse intrinsic pontine glioma (DIPG) is a deadly childhood brain cancer; patients survive an average of less than 1 year following diagnosis. Given the tumors' location, surgical resection is nearly impossible, and the only known efficacious treatment is radiation, without clear benefit from chemotherapy or immunotherapy. An emerging treatment for brain cancers is oncolytic viruses, which are injected directly into the tumor and can replicate within tumor cells, causing tumor-specific cell death. While early-phase clinical trials of oncolytic virus therapy have been encouraging, late-stage trials have yet to demonstrate improved survival, due in part to the complexity and cost. Here, researchers evaluated the safety of a single injection of the oncolytic virus DNX-2401 into DIPG tumors. Twelve children with newly diagnosed DIPG underwent biopsy and viral injection into the biopsy site, followed (in 11 children) by standard irradiation starting 10 to 20 days after surgery.
Although adverse events were frequent — most often headache, vomiting, neurologic decline, or fatigue) — only two patients had a serious adverse event that may have been related to the treatment. While the primary objective of this study was safety, median overall survival of these carefully selected participants was 17.8 months, longer than historical populations. Three patients survived at least 2 years following treatment. Correlative studies showed that all patients developed higher levels of adenoviral neutralizing antibodies following treatment, and patients with lower serum levels of adenoviral neutralizing antibodies lived longer (21.2 vs. 12.5 months).
In pediatric DIPG, a deadly cancer, a single infusion of DNX-2401 followed by irradiation carries some risk of toxicity but may offer improved survival. Further studies in a larger patient population are needed to confirm this finding given the small, carefully selected study population and the cost and difficulty of intra-tumoral viral injections.
Dr. Schreck is Assistant Professor of Neurology and Oncology, Johns Hopkins University School of Medicine, Baltimore.
Gállego Pérez-Larraya J et al.
Title: Oncolytic DNX-2401 virus for pediatric diffuse intrinsic pontine glioma.
Source: N Engl J Med 2022 Jun 30; [e-pub]. (Abstract/FREE Full Text)