ArticleScience translational medicine2015
Rational development and characterization of humanized anti-EGFR variant III chimeric antigen receptor T cells for glioblastoma.
Article in Science translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02209376 (Pilot Study of Autologous T Cells Redirected to EGFRVIII-With a Chimeric Antigen Receptor in Patients With EGFRVIII+ Glioblastoma), which is not on this map. Cited by 292 papers, 1 of them a synthesis 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.
Pilot Study of Autologous T Cells Redirected to EGFRVIII-With a Chimeric Antigen Receptor in Patients With EGFRVIII+ Glioblastoma
Who cites it
292 citing papers in PubMed, 1 synthesis or guideline pooled it, 448 citations in OpenAlex.
- Checkpoint inhibitor immunotherapy for glioblastoma: current progress, challenges and future outlook.Expert review of clinical pharmacology · 2020Pooled it
- Fine-tuning affinity and spacer design enhances T cell potency in DLL3 and BCMA CAR T cells.mAbs · 2026Article
- Co-expression of non-signaling CARs enhances EGFRvIII-specific CAR T-cell cytotoxicity against head and neck squamous cell carcinoma.BMC cancer · 2026Article
- Supramolecular immunomodulatory hydrogelator potentiates CAR-T therapy with long-lasting endogenous immunity toward solid tumor eradication.Science advances · 2026Article
- Drug-tolerant persisters and immunotherapy persister cells exhibit cross-resistance and share common survival mechanisms.Cell death and differentiation · 2026Article
- CAR T cells for pediatric CNS tumors: Clinical experience and reverse translational opportunities.Molecular therapy. Oncology · 2026Review
- The microenvironment of glioblastoma: in pursuit of universal multimodal immunotherapy.Acta neurologica Belgica · 2026Review
- Development of CAR Exosomes Targeting FAP for the Treatment of Intrauterine Adhesion.Journal of extracellular vesicles · 2026Article
- Review
- Developing a multimodal therapy for glioblastoma using oncolytic virus delivering CD19 and EGFRvIII antigens and bi-specific CARs.Nature communications · 2026Article
- Review
- Immune-Centered Cross-Talk Between Cancer Cells and the Tumor Microenvironment-Implications for Therapy.Cancers · 2026Review
- CAR-T Cell Therapy in Glioblastoma: Overcoming Immunological Barriers and Advancing Clinical Translation.Cancer management and research · 2026Review
- Measuring Chimeric Antigen Receptor T Cells (CAR T Cells) Activation by Coupling Intracellular Cytokine Staining with Flow Cytometry.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Cyclodextrin-Based Formulations as a Promising Strategy to Overcome the Blood-Brain Barrier: Historical Overview and Prospects in Glioblastoma Treatment.Pharmaceuticals (Basel, Switzerland) · 2025Review
- EnhancedScience advances · 2025Article
- Neoantigen-driven personalized tumor therapy: An update from discovery to clinical application.Chinese medical journal · 2025Review
- CAR-T cell therapy for glioblastoma: advances, challenges, and future directions.Annals of medicine and surgery (2012) · 2025Review
- IFN-γ-resistant CD28 CAR T cells demonstrate increased survival, efficacy, and durability in multiple murine tumor models.Science translational medicine · 2025Article
- Tonic signaling in CAR-T therapy: the lever long enough to move the planet.Frontiers of medicine · 2025Review
232 more citing papers are in PubMed but not listed here.
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Authors and funding
29 authors at 4 institutions in 1 country.
Funding
Abstract
Chimeric antigen receptors (CARs) are synthetic molecules designed to redirect T cells to specific antigens. CAR-modified T cells can mediate long-term durable remissions in B cell malignancies, but expanding this platform to solid tumors requires the discovery of surface targets with limited expression in normal tissues. The variant III mutation of the epidermal growth factor receptor (EGFRvIII) results from an in-frame deletion of a portion of the extracellular domain, creating a neoepitope. We chose a vector backbone encoding a second-generation CAR based on efficacy of a murine scFv-based CAR in a xenograft model of glioblastoma. Next, we generated a panel of humanized scFvs and tested their specificity and function as soluble proteins and in the form of CAR-transduced T cells; a low-affinity scFv was selected on the basis of its specificity for EGFRvIII over wild-type EGFR. The lead candidate scFv was tested in vitro for its ability to direct CAR-transduced T cells to specifically lyse, proliferate, and secrete cytokines in response to antigen-bearing targets. We further evaluated the specificity of the lead CAR candidate in vitro against EGFR-expressing keratinocytes and in vivo in a model of mice grafted with normal human skin. EGFRvIII-directed CAR T cells were also able to control tumor growth in xenogeneic subcutaneous and orthotopic models of human EGFRvIII(+) glioblastoma. On the basis of these results, we have designed a phase 1 clinical study of CAR T cells transduced with humanized scFv directed to EGFRvIII in patients with either residual or recurrent glioblastoma (NCT02209376).
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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.