ArticleScience translational medicine2019
Regulatable interleukin-12 gene therapy in patients with recurrent high-grade glioma: Results of a phase 1 trial.
Article in Science translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02026271 (A Phase I Study of Ad-RTS-hIL-12, an Inducible Adenoviral Vector Engineered to Express hIL-12 in the Presence of the Activator Ligand Veledimex in Subjects With Recurrent or Progressive Glioblastoma or Grade III Malignant Glioma), which is not on this map. Cited by 180 papers, 2 of them syntheses that pooled it.
What it found
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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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase I Study of Ad-RTS-hIL-12, an Inducible Adenoviral Vector Engineered to Express hIL-12 in the Presence of the Activator Ligand Veledimex in Subjects With Recurrent or Progressive Glioblastoma or Grade III Malignant Glioma
Who cites it
180 citing papers in PubMed, 2 syntheses or guidelines pooled it, 257 citations in OpenAlex.
- Glioblastoma Immunotherapy: A Systematic Review of the Present Strategies and Prospects for Advancements.International journal of molecular sciences · 2023Pooled it
- A systematic review of ongoing clinical trials in optic pathway gliomas.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2020Pooled it
- Tumor-targeted interferon-α gene therapy for glioblastoma: a phase 1 trial.Nature medicine · 2026Trial
- Laser interstitial thermal therapy and adjuvant pembrolizumab in recurrent high-grade astrocytoma: a Phase 1/randomized Phase 2b trial.Nature communications · 2026Trial
- Shifting AAV9 tropism by binding moiety insertion enhances transduction of tumor cell lines and human glioblastoma explants.Scientific reports · 2026Article
- Next-generation programmable cell therapies for precision medicine.Nature reviews. Genetics · 2026Review
- Targeting immunosuppressive myeloid cells via implant-mediated slow release of small molecules to prevent glioblastoma recurrence.Nature biomedical engineering · 2026Article
- Engineering drug-responsive replication machinery for precise control of self-amplifying RNA.Nature biomedical engineering · 2026Article
- Dual-system engineered bacteria and dendritic cells enable precise intratumoral IL-12 delivery and potent antitumor immunity.Cell reports. Medicine · 2026Article
- Oncolytic viruses and cytokine-based gene therapies reprogram the tumor microenvironment.Nature cancer · 2026Review
- CCAAT/enhancer-binding protein delta regulates miRs-4257 and 3156 to attenuate the interleukin 12 through small extracellular vesicle transmission in glioblastoma.Cancer cell international · 2026Article
- Tropism Profiling of Lentiviral Vector Pseudotypes in Diverse Brain Tumor Models.Pharmaceutics · 2026Article
- Targeting myeloid cell polarization to prevent GBM recurrence.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Reconceptualizing glioblastoma immunotherapy: a four-pillar framework to overcome multidimensional resistance.Frontiers in medicine · 2026Review
- Recurrent Glioblastoma and the Tumor Immune Landscape: Emerging Immunotherapeutic Strategies.ImmunoTargets and therapy · 2026Review
- Multi-Omics Evidence Based on Spatial Transcriptomics Data Reveals the Therapeutic Value of Copper Death Genes in Glioblastoma.International journal of genomics · 2026Article
- Protein engineering to overcome limitations of key cytokines in cancer immunotherapy: current approaches and future perspectives.Immuno-oncology technology · 2025Review
- Retargeted oncolytic viruses engineered to remodel the tumor microenvironment for glioblastoma immunotherapy.Nature cancer · 2025Article
- A comprehensive review redefining viruses as therapeutic agents in cancer treatment.Discover oncology · 2025Review
- Natural products as therapeutic interventions for inflammation-mediated cancer.Discover oncology · 2025Review
120 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 7 institutions in 1 country.
Funding
Abstract
Human interleukin-12 (hIL-12) is a cytokine with anticancer activity, but its systemic application is limited by toxic inflammatory responses. We assessed the safety and biological effects of an hIL-12 gene, transcriptionally regulated by an oral activator. A multicenter phase 1 dose-escalation trial (NCT02026271) treated 31 patients undergoing resection of recurrent high-grade glioma. Resection cavity walls were injected (day 0) with a fixed dose of the hIL-12 vector (Ad-RTS-hIL-12). The oral activator for hIL-12, veledimex (VDX), was administered preoperatively (assaying blood-brain barrier penetration) and postoperatively (measuring hIL-12 transcriptional regulation). Cohorts received 10 to 40 mg of VDX before and after Ad-RTS-hIL-12. Dose-related increases in VDX, IL-12, and interferon-γ (IFN-γ) were observed in peripheral blood, with about 40% VDX tumor penetration. Frequency and severity of adverse events, including cytokine release syndrome, correlated with VDX dose, reversing promptly upon discontinuation. VDX (20 mg) had superior drug compliance and 12.7 months median overall survival (mOS) at mean follow-up of 13.1 months. Concurrent corticosteroids negatively affected survival: In patients cumulatively receiving >20 mg versus ≤20 mg of dexamethasone (days 0 to 14), mOS was 6.4 and 16.7 months, respectively, in all patients and 6.4 and 17.8 months, respectively, in the 20-mg VDX cohort. Re-resection in five of five patients with suspected recurrence after Ad-RTS-hIL-12 revealed mostly pseudoprogression with increased tumor-infiltrating lymphocytes producing IFN-γ and programmed cell death protein 1 (PD-1). These inflammatory infiltrates support an immunological antitumor effect of hIL-12. This phase 1 trial showed acceptable tolerability of regulated hIL-12 with encouraging preliminary results.
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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.