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
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Immunotherapy Commons, Medical Genetics Commons, Medical Immunology Commons, Oncology Commons