Faculty, Staff and Student Publications

Publication Date

4-8-2022

Journal

JCI Insight

Abstract

Diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors, and patient survival has not changed despite many therapeutic efforts, emphasizing the urgent need for effective treatments. Here, we evaluated the anti-DIPG effect of the oncolytic adenovirus Delta-24-ACT, which was engineered to express the costimulatory ligand 4-1BBL to potentiate the antitumor immune response of the virus. Delta-24-ACT induced the expression of functional 4-1BBL on the membranes of infected DIPG cells, which enhanced the costimulation of CD8+ T lymphocytes. In vivo, Delta-24-ACT treatment of murine DIPG orthotopic tumors significantly improved the survival of treated mice, leading to long-term survivors that developed immunological memory against these tumors. In addition, Delta-24-ACT was safe and caused no local or systemic toxicity. Mechanistic studies showed that Delta-24-ACT modulated the tumor-immune content, not only increasing the number, but also improving the functionality of immune cells. All of these data highlight the safety and potential therapeutic benefit of Delta-24-ACT the treatment of patients with DIPG.

Keywords

Adenoviridae, Animals, Brain Stem Neoplasms, Diffuse Intrinsic Pontine Glioma, Humans, Mice, Oncolytic Virotherapy, Immunology, Oncology, Brain cancer, Cancer immunotherapy, Immunotherapy

DOI

10.1172/jci.insight.154812

PMID

35393952

PMCID

PMC9057625

PubMedCentral® Posted Date

4-8-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

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