ArticleNature communications2021
Engineering an anti-HER2 biparatopic antibody with a multimodal mechanism of action.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
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Who cites it
38 citing papers in PubMed, 59 citations in OpenAlex.
- Emerging organoids and organoids-on-chip platforms for translational development of antibody‒drug conjugates and next-generation bioconjugates.Acta pharmaceutica Sinica. B · 2026Review
- Multiparatopic antibodies overcome tyrosine kinase inhibitor resistance by inducing lysosomal degradation of EGFR mutants.Oncogene · 2026Article
- Plant-Produced Viral Nanoparticles Decorated with Nanobodies Against HER2 Improve Retention and Recruitment of Immune Cells in Solid Tumors.Advanced healthcare materials · 2026Article
- Spatial molecular analyses reveal key features associated with response to KN026 in advanced HER2-positive breast cancer.British journal of cancer · 2026Article
- Multimodal Physicochemical Characterization of Cross-Linking Activities of Biparatopic Antibodies.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Inhibition of HER2 signaling and breast cancer cell growth with a novel antibody targeting HER2 ECD III/IV.PloS one · 2026Article
- Gastrointestinal cancer: molecular pathogenesis and targeted therapy.Molecular biomedicine · 2025Review
- Antibody-drug conjugates in breast cancer: mechanisms of resistance and future therapeutic perspectives.NPJ breast cancer · 2025Review
- Structural analysis of HER2-trastuzumab complex reveals receptor conformational adaptation.Science advances · 2025Article
- Identification of potent biparatopic antibodies targeting FGFR2 fusion-driven cholangiocarcinoma.The Journal of clinical investigation · 2025Article
- The Evolving Applications of Bispecific Antibodies: Reaping the Harvest of Early Sowing and Planting New Seeds.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Biparatopic HER2-targeted nanobody binder synergizes with trastuzumab in resistant tumor cells.Frontiers in immunology · 2025Article
- Engineering HER2-targeted biparatopic antibodies to promote receptor internalization and restore antitumor efficacy.Frontiers in immunology · 2025Article
- Antibody drug conjugates in the clinic.Bioengineering & translational medicine · 2024Review
- Multiparatopic antibodies induce targeted downregulation of programmed death-ligand 1.Cell chemical biology · 2024Article
- 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
- Design and engineering of bispecific antibodies: insights and practical considerations.Frontiers in bioengineering and biotechnology · 2024Review
- Development of antibody-drug conjugates in cancer: Overview and prospects.Cancer communications (London, England) · 2024Review
- Key considerations based on pharmacokinetic/pharmacodynamic in the design of antibody-drug conjugates.Frontiers in oncology · 2024Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The receptor tyrosine kinase HER2 acts as oncogenic driver in numerous cancers. Usually, the gene is amplified, resulting in receptor overexpression, massively increased signaling and unchecked proliferation. However, tumors become frequently addicted to oncogenes and hence are druggable by targeted interventions. Here, we design an anti-HER2 biparatopic and tetravalent IgG fusion with a multimodal mechanism of action. The molecule first induces HER2 clustering into inactive complexes, evidenced by reduced mobility of surface HER2. However, in contrast to our earlier binders based on DARPins, clusters of HER2 are thereafter robustly internalized and quantitatively degraded. This multimodal mechanism of action is found only in few of the tetravalent constructs investigated, which must target specific epitopes on HER2 in a defined geometric arrangement. The inhibitory effect of our antibody as single agent surpasses the combination of trastuzumab and pertuzumab as well as its parental mAbs in vitro and it is effective in a xenograft model.
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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.