ArticleProceedings of the National Academy of Sciences of the United States of America2013
Systemic administration of a bispecific antibody targeting EGFRvIII successfully treats intracerebral glioma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
82 citing papers in PubMed, 1 synthesis or guideline pooled it, 131 citations in OpenAlex.
- The Prognostic Significance of Epidermal Growth Factor Receptor Amplification and Epidermal Growth Factor Receptor Variant III Mutation in Glioblastoma: A Systematic Review and Meta-Analysis with Implications for Targeted Therapy.International journal of molecular sciences · 2025Pooled it
- Safety and efficacy of depatuxizumab mafodotin in Japanese patients with malignant glioma: A nonrandomized, phase 1/2 trial.Cancer science · 2021Trial
- Review
- The safety and efficacy of bispecific T-cell engagers (TCEs) in patients with glioma.Clinical and experimental medicine · 2026Review
- IL-7-mediated expansion of autologous lymphocytes increases CD8bioRxiv : the preprint server for biology · 2025Article
- CAR-T cell therapy for the treatment of adult high-grade gliomas.NPJ precision oncology · 2024Review
- CaCOHeliyon · 2024Article
- Intraventricular CARv3-TEAM-E T Cells in Recurrent Glioblastoma.The New England journal of medicine · 2024Article
- The present and future of bispecific antibodies for cancer therapy.Nature reviews. Drug discovery · 2024Review
- The Role of Antibody-Based Therapies in Neuro-Oncology.Antibodies (Basel, Switzerland) · 2023Review
- 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
- Tumor-associated macrophage-related strategies for glioma immunotherapy.NPJ precision oncology · 2023Review
- An Overview of EGFR Mechanisms and Their Implications in Targeted Therapies for Glioblastoma.International journal of molecular sciences · 2023Review
- Novel Immunotherapeutic Approaches for the Treatment of Glioblastoma.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- Activation of T Lymphocytes with Anti-PDL1-BiTE in the Presence of Adipose-Derived Mesenchymal Stem Cells (ASCs).BioMed research international · 2023Article
- Glioblastoma Multiforme Selective Nanomedicines for Improved Anti-Cancer Treatments.Pharmaceutics · 2022Article
- Pediatric brain tumors: a bibliometric analysis.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2022Article
- Controlling Cell Trafficking: Addressing Failures in CAR T and NK Cell Therapy of Solid Tumours.Cancers · 2022Review
- The current landscape of immunotherapy for pediatric brain tumors.Nature cancer · 2022Review
22 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Bispecific antibodies (bscAbs), particularly those of the bispecific T-cell engager (BiTE) subclass, have been shown to effectively redirect T cells against cancer. Previous efforts to target antigens expressed in both tumors and normal tissues have produced significant toxicity, however. Moreover, like other large molecules, bscAbs may be restricted from entry into the "immunologically privileged" CNS. A tumor-specific mutation of the epidermal growth factor receptor, EGFRvIII, is a constitutively activated tyrosine kinase not found in normal tissues but frequently expressed in glioblastomas and many other neoplasms. Because it is localized solely to tumor tissue, EGFRvIII presents an ideal target for immunotherapy. Here we report the preclinical evaluation of an EGFRvIII-targeted BiTE, bscEGFRvIIIxCD3. Our results show that bscEGFRvIIIxCD3 activates T cells to mediate potent and antigen-specific lysis of EGFRvIII-expressing gliomas in vitro (P < 0.001) at exceedingly low concentrations (10 ng/mL) and effector-to-target ratios (2.5:1). Treatment with i.v. bscEGFRvIIIxCD3 yielded extended survival in mice with well-established intracerebral tumors (P < 0.05) and achieved durable complete cure at rates up to 75%. Antitumor efficacy was significantly abrogated on blockade of EGFRvIII binding, demonstrating the need for target antigen specificity both in vitro and in vivo. These results demonstrate that BiTEs can be used to elicit functional antitumor immunity in the CNS, and that peptide blockade of BiTE-mediated activity may greatly enhance the safety profile for antibody-redirected T-cell therapies. Finally, bscEGFRvIIIxCD3 represents a unique advancement in BiTE technology given its exquisite tumor specificity, which enables precise elimination of cancer without the risk of autoimmune toxicity.
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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.