ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
BRD4 inhibition boosts the therapeutic effects of epidermal growth factor receptor-targeted chimeric antigen receptor T cells in glioblastoma.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29 citing papers in PubMed, 33 citations in OpenAlex.
- Chimeric antigen receptor (CAR)-T cell therapy for solid tumors in pediatric patients: current breakthroughs, dilemmas, and strategies.Experimental hematology & oncology · 2026Review
- Glucose and Glutamine Deprivation Promotes Breast Cancer Lung Metastasis via BRD4-Dependent Enhancer Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A spatially resolved implantable microdevice for multiplexed in situ screening of engineered cellular therapies in solid tumors.Science advances · 2026Article
- Targeting BRD4-A Promising Therapeutic Option for Glioblastoma?International journal of molecular sciences · 2026Review
- Integrating biocomputational techniques for vaccine development for glioblastoma multiforme: a possible way of enhancing precision.Frontiers in immunology · 2026Review
- PILRα on tumor cells interacts with the T cell surface protein CD99 to suppress antitumor immunity.Nature cancer · 2025Article
- Epigenetic Alterations in Glioblastoma Multiforme as Novel Therapeutic Targets: A Scoping Review.International journal of molecular sciences · 2025Article
- Epigenetic regulation of histone modifications in glioblastoma: recent advances and therapeutic insights.Biomarker research · 2025Review
- Recommended Tool Compounds: Thienotriazolodiazepines-Derivatized Chemical Probes to Target BET Bromodomains.ACS pharmacology & translational science · 2025Review
- Super-enhancers in tumors: unraveling recent advances in their role in Oncogenesis and the emergence of targeted therapies.Journal of translational medicine · 2025Review
- Accelerating CAR-T Cell Therapies with Small-Molecule Inhibitors.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Therapeutic advantage of combinatorial chimeric antigen receptor T cell and chemotherapies.Pharmacological reviews · 2025Review
- Adoptive T cell therapies for solid tumors: T(I)ME is of the essence.EBioMedicine · 2024Article
- A Review of the Bromodomain and Extraterminal Domain Epigenetic Reader Proteins: Function on Virus Infection and Cancer.Viruses · 2024Review
- Targeting BRD4: Potential therapeutic strategy for head and neck squamous cell carcinoma (Review).Oncology reports · 2024Article
- Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives.Journal of hematology & oncology · 2024Review
- Epigenetic regulation of tumor-immune symbiosis in glioma.Trends in molecular medicine · 2024Review
- Strategies to overcome tumor microenvironment immunosuppressive effect on the functioning of CAR-T cells in high-grade glioma.Therapeutic advances in medical oncology · 2024Review
- Optimizing CAR-T Therapy for Glioblastoma.Molecular diagnosis & therapy · 2023Review
- Bispecific T-Cell Engagers and Chimeric Antigen Receptor T-Cell Therapies in Glioblastoma: An Update.Current oncology (Toronto, Ont.) · 2023Review
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Authors and funding
9 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Glioblastoma (GBM) is the deadliest brain malignancy without effective treatments. Here, we reported that epidermal growth factor receptor-targeted chimeric antigen receptor T cells (EGFR CAR-T) were effective in suppressing the growth of GBM cells in vitro and xenografts derived from GBM cell lines and patients in mice. However, mice soon acquired resistance to EGFR CAR-T cell treatment, limiting its potential use in the clinic. To find ways to improve the efficacy of EGFR CAR-T cells, we performed genomics and transcriptomics analysis for GBM cells incubated with EGFR CAR-T cells and found that a large cohort of genes, including immunosuppressive genes, as well as enhancers in vicinity are activated. BRD4, an epigenetic modulator functioning on both promoters and enhancers, was required for the activation of these immunosuppressive genes. Accordingly, inhibition of BRD4 by JQ1 blocked the activation of these immunosuppressive genes. Combination therapy with EGFR CAR-T cells and JQ1 suppressed the growth and metastasis of GBM cells and prolonged survival in mice. We demonstrated that transcriptional modulation by targeting epigenetic regulators could improve the efficacy of immunotherapy including CAR-T, providing a therapeutic avenue for treating GBM in the clinic.
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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.