ArticleNeuro-oncology2024
The oncolytic adenovirus Delta-24-RGD in combination with ONC201 induces a potent antitumor response in pediatric high-grade and diffuse midline glioma models.
Article in Neuro-oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
11 citing papers in PubMed, 7 citations in OpenAlex.
- ONC201/dordaviprone for H3 K27M-mutant tumors: Discovery, mechanisms, therapeutic potential, and future directions.Genes & diseases · 2027Review
- Murine modeling of IDH-mutant 1p/19q-codeleted oligodendroglioma reveals genotype specific phenotypes.bioRxiv : the preprint server for biology · 2026Article
- Review
- Enhancing Oncolytic Adenovirus Replication by Early Region 1A Protein-Mediated Degradation of E1A Binding Protein p300.MedComm · 2026Article
- Targeted therapies in pediatric oncology: A start.Molecular therapy. Oncology · 2026Review
- Oncolytic Viruses in Glioblastoma: Clinical Progress, Mechanistic Insights, and Future Therapeutic Directions.Cancers · 2025Review
- Article
- Review
- Connecting Innovation and Trust through Translational Sciences - A Need for a Community Focus and Effective Education Strategiess.Puerto Rico health sciences journal · 2025Article
- Turning the tide: harnessing vaccines and viruses to fight cancer.Immunotherapy advances · 2025Review
- Overcoming the blood-brain barrier: targeted delivery strategies for gliomas.Frontiers in pharmacology · 2025Review
Corrections and comments
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Authors and funding
32 authors at 10 institutions in 6 countries.
Funding
Abstract
backgroundPediatric high-grade gliomas (pHGGs), including diffuse midline gliomas (DMGs), are aggressive pediatric tumors with one of the poorest prognoses. Delta-24-RGD and ONC201 have shown promising efficacy as single agents for these tumors. However, the combination of both agents has not been evaluated.
methodsThe production of functional viruses was assessed by immunoblotting and replication assays. The antitumor effect was evaluated in a panel of human and murine pHGG and DMG cell lines. RNAseq, the seahorse stress test, mitochondrial DNA content, and γH2A.X immunofluorescence were used to perform mechanistic studies. Mouse models of both diseases were used to assess the efficacy of the combination in vivo. The tumor immune microenvironment was evaluated using flow cytometry, RNAseq, and multiplexed immunofluorescence staining.
resultsThe Delta-24-RGD/ONC201 combination did not affect the virus replication capability in human pHGG and DMG models in vitro. Cytotoxicity analysis showed that the combination treatment was either synergistic or additive. Mechanistically, the combination treatment increased nuclear DNA damage and maintained the metabolic perturbation and mitochondrial damage caused by each agent alone. Delta-24-RGD/ONC201 cotreatment extended the overall survival of mice implanted with human and murine pHGG and DMG cells, independent of H3 mutation status and location. Finally, combination treatment in murine DMG models revealed a reshaping of the tumor microenvironment to a proinflammatory phenotype.
conclusionsThe Delta-24-RGD/ONC201 combination improved the efficacy compared to each agent alone in in vitro and in vivo models by potentiating nuclear DNA damage and in turn improving the antitumor (immune) response to each agent alone.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.