ArticleNature communications2023
An anti-HER2 biparatopic antibody that induces unique HER2 clustering and complement-dependent cytotoxicity.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers, 3 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
119 citing papers in PubMed, 3 syntheses or guidelines pooled it, 144 citations in OpenAlex.
- A Meta-Analysis on Outcomes of Zanidatamab Plus Chemotherapy in Patients with Advanced HER2-positive Gastroesophageal Adenocarcinoma.Journal of gastrointestinal cancer · 2026Pooled it
- Zanidatamab, a Dual HER2-Targeted Bispecific Antibody, in Patients with Unresectable Locally Advanced or Metastatic HER2-Positive Salivary Gland Cancer: A Combined Analysis of Early-Phase Studies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Pooled it
- Chinese guidelines for HER2-targeted therapy in gastric and gastroesophageal junction adenocarcinoma (2025 Edition).Journal of hematology & oncology · 2026Guideline
- Zanidatamab in patients with early stage HER2-positive breast cancer: the NeoZanHER phase 2 single-arm open-label trial.Nature communications · 2026Trial
- Phase Ib/II Study of Zanidatamab in Combination with Tislelizumab and Chemotherapy in First-Line HER2-Positive Gastric/Gastroesophageal Junction Adenocarcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Zanidatamab plus chemotherapy as first-line treatment for patients with HER2-positive advanced gastro-oesophageal adenocarcinoma: primary results of a multicentre, single-arm, phase 2 study.The Lancet. Oncology · 2025Trial
- A phase 2 trial of zanidatamab in HER2-overexpressed advanced endometrial carcinoma and carcinosarcoma (ZW25-IST-2).Gynecologic oncology · 2024Trial
- Article
- Review
- Article
- Advancing antibody drug conjugates in gastrointestinal cancers.British journal of cancer · 2026Review
- Lactylation-Mediated HER2 Stabilization Promotes Trastuzumab Resistance in Gastric Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Right-sizing treatment for HER2-positive breast cancer: evolving algorithms across the disease continuum.Nature reviews. Clinical oncology · 2026Review
- Advances in Bispecific Antibodies and Antibody-Drug Conjugates for Colorectal Cancer Treatment.Antibodies (Basel, Switzerland) · 2026Review
- Beyond trastuzumab: redefining first-line HER2-positive gastroesophageal cancer with bispecific HER2 targeting.Journal of gastrointestinal oncology · 2026Article
- A shark variable new antigen receptor recognizes an occluded epitope of fibroblast activation protein.bioRxiv : the preprint server for biology · 2026Article
- Bispecific antibodies for cancer therapy: evolution of structural formats and co-targeting strategies from wet-lab to AI-driven in silico modeling.Cancer letters · 2026Review
- Functional Characteristics Derived from the Structural Design of Bispecific Antibodies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Antibody-Drug Conjugates and Peptide-Drug Conjugates: Current Understandings and Future Perspectives.MedComm · 2026Review
- The next generation of antibody-drug conjugates.Nature medicine · 2026Review
59 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
39 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human epidermal growth factor receptor 2 (HER2) is a receptor tyrosine kinase that plays an oncogenic role in breast, gastric and other solid tumors. However, anti-HER2 therapies are only currently approved for the treatment of breast and gastric/gastric esophageal junction cancers and treatment resistance remains a problem. Here, we engineer an anti-HER2 IgG1 bispecific, biparatopic antibody (Ab), zanidatamab, with unique and enhanced functionalities compared to both trastuzumab and the combination of trastuzumab plus pertuzumab (tras + pert). Zanidatamab binds adjacent HER2 molecules in trans and initiates distinct HER2 reorganization, as shown by polarized cell surface HER2 caps and large HER2 clusters, not observed with trastuzumab or tras + pert. Moreover, zanidatamab, but not trastuzumab nor tras + pert, elicit potent complement-dependent cytotoxicity (CDC) against high HER2-expressing tumor cells in vitro. Zanidatamab also mediates HER2 internalization and downregulation, inhibition of both cell signaling and tumor growth, antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP), and also shows superior in vivo antitumor activity compared to tras + pert in a HER2-expressing xenograft model. Collectively, we show that zanidatamab has multiple and distinct mechanisms of action derived from the structural effects of biparatopic HER2 engagement.
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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.