ArticleThe Journal of biological chemistry2018
Structural insights into the mechanism of action of a biparatopic anti-HER2 antibody.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 71 citations in OpenAlex.
- Recent advances in function-enhanced antibody-drug conjugates: Antibody optimization and payload combination.Acta pharmacologica Sinica · 2026Article
- The conditional promise of dual-epitope HER2 antibody-drug conjugates in breast cancer.Cancer biology & medicine · 2026Article
- Analytical Ultracentrifugation for Biopharmaceutical Characterization and Quality Control.International journal of molecular sciences · 2026Review
- Review
- Recent advances in bispecific antibody-drug conjugates for breast cancer therapy.Cancer chemotherapy and pharmacology · 2026Review
- Innately Fluorescent Tetravalent Cytotoxic Conjugate TetraFJournal of medicinal chemistry · 2025Article
- Current advances in separation chemistry for antibody purification and analysis.Analytical sciences : the international journal of the Japan Society for Analytical Chemistry · 2025Review
- A novel anti-HER2/EGFR bispecific antibody-drug conjugate demonstrates promising antitumor efficacy and overcomes resistance to HER2- or EGFR-targeted ADCs.Investigational new drugs · 2025Article
- The Evolving Paradigm of Antibody-Drug Conjugates Targeting the ErbB/HER Family of Receptor Tyrosine Kinases.Pharmaceutics · 2024Review
- Characterization of a novel format scFv×VHH single-chain biparatopic antibody against metal binding protein MtsA.Protein science : a publication of the Protein Society · 2024Article
- Bispecific antibody drug conjugates: Making 1+1>2.Acta pharmaceutica Sinica. B · 2024Review
- The present and future of bispecific antibodies for cancer therapy.Nature reviews. Drug discovery · 2024Review
- SpyMask enables combinatorial assembly of bispecific binders.Nature communications · 2024Article
- Exploring the next generation of antibody-drug conjugates.Nature reviews. Clinical oncology · 2024Review
- Novel HER-2 Targeted Therapies in Breast Cancer.Cancers · 2023Review
- 'Targeting' Improved Outcomes with Antibody-Drug Conjugates in Non-Small Cell Lung Cancer-An Updated Review.Current oncology (Toronto, Ont.) · 2023Review
- An anti-HER2 biparatopic antibody that induces unique HER2 clustering and complement-dependent cytotoxicity.Nature communications · 2023Article
- Engineered Ultrasmall Nanoparticle Drug-Immune Conjugates with "Hit and Run" Tumor Delivery to Eradicate Gastric Cancer.Advanced therapeutics · 2023Article
- Innovative Therapeutic Approaches for Patients with HER2-Positive Breast Cancer.Cancer treatment and research · 2023Review
- Targeted Approaches to HER2-Low Breast Cancer: Current Practice and Future Directions.Cancers · 2022Review
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pathways of human epidermal growth factor (EGF) receptors are activated upon ligand-dependent or -independent homo- or heterodimerization and their subsequent transphosphorylation. Overexpression of these receptors positively correlates with transphosphorylation rates and increased tumor growth rates. MEDI4276, an anti-human epidermal growth factor receptor 2 (HER2) biparatopic antibody-drug conjugate, has two paratopes within each antibody arm. One, 39S, is aiming at the HER2 site involved in receptor dimerization and the second, single chain fragment (scFv), mimicking trastuzumab. Here we present the cocrystal structure of the 39S Fab-HER2 complex and, along with biophysical and functional assays, determine the corresponding epitope of MEDI4276 and its underlying mechanism of action. Our results reveal that MEDI4276's uniqueness is based first on the ability of its 39S paratope to block HER2 homo- or heterodimerization and second on its ability to cluster the receptors on the surface of receptor-overexpressing cells.
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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.