The Oncolytic Virus Delta-24-RGD Elicits an Antitumor Effect in Pediatric Glioma and DIPG Mouse Models

Nat Commun. 2019 May 28;10(1):2235. doi: 10.1038/s41467-019-10043-0.

Abstract

Pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors in desperate need of a curative treatment. Oncolytic virotherapy is emerging as a solid therapeutic approach. Delta-24-RGD is a replication competent adenovirus engineered to replicate in tumor cells with an aberrant RB pathway. This virus has proven to be safe and effective in adult gliomas. Here we report that the administration of Delta-24-RGD is safe in mice and results in a significant increase in survival in immunodeficient and immunocompetent models of pHGG and DIPGs. Our results show that the Delta-24-RGD antiglioma effect is mediated by the oncolytic effect and the immune response elicited against the tumor. Altogether, our data highlight the potential of this virus as treatment for patients with these tumors. Of clinical significance, these data have led to the start of a phase I/II clinical trial at our institution for newly diagnosed DIPG (NCT03178032).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae*
  • Animals
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy
  • Brain Stem Neoplasms / pathology
  • Brain Stem Neoplasms / therapy*
  • Cell Line, Tumor
  • Cell Survival
  • Computer Simulation
  • Disease Models, Animal
  • Glioma / pathology
  • Glioma / therapy*
  • Humans
  • In Vitro Techniques
  • Mice
  • Neoplasm Grading
  • Oncolytic Virotherapy / methods*
  • Oncolytic Viruses*
  • Xenograft Model Antitumor Assays

Associated data

  • ClinicalTrials.gov/NCT03178032