ArticlemAbs
Engineering multivalent antibodies to target heregulin-induced HER3 signaling in breast cancer cells.
Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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.
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Who cites it
22 citing papers in PubMed, 28 citations in OpenAlex.
- Detection of phosphatidylserine-positive exosomes as a diagnostic marker for ovarian malignancies: a proof of concept study.Oncotarget · 2017Trial
- DB-1310, a HER3-targeting antibody-drug conjugate, has synergistic anti-tumor activity with trastuzumab in HER2- and HER3-expressing breast cancer.Cancer biology & medicine · 2025Article
- Advances in Personalized Oncology.Cancers · 2024Review
- HER3 receptor and its role in the therapeutic management of metastatic breast cancer.Journal of translational medicine · 2024Review
- HER3 in cancer: from the bench to the bedside.Journal of experimental & clinical cancer research : CR · 2022Review
- A feed-forward loop between SorLA and HER3 determines heregulin response and neratinib resistance.Oncogene · 2021Article
- Golden Gate assembly with a bi-directional promoter (GBid): A simple, scalable method for phage display Fab library creation.Scientific reports · 2020Article
- The pharmacology and therapeutic applications of monoclonal antibodies.Pharmacology research & perspectives · 2019Review
- Clinical significance of overexpression of NRG1 and its receptors, HER3 and HER4, in gastric cancer patients.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2018Article
- Targeting Phosphatidylserine with Calcium-Dependent Protein-Drug Conjugates for the Treatment of Cancer.Molecular cancer therapeutics · 2018Article
- Recombinant Antibodies to Arm Cytotoxic Lymphocytes in Cancer Immunotherapy.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2017Review
- Engineered Multivalency Enhances Affibody-Based HER3 Inhibition and Downregulation in Cancer Cells.Molecular pharmaceutics · 2017Article
- Lapatinib resistance in HER2+ cancers: latest findings and new concepts on molecular mechanisms.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- Review
- Heregulin/ErbB3 Signaling Enhances CXCR4-Driven Rac1 Activation and Breast Cancer Cell Motility via Hypoxia-Inducible Factor 1α.Molecular and cellular biology · 2016Article
- Macrophage-Mediated Trogocytosis Leads to Death of Antibody-Opsonized Tumor Cells.Molecular cancer therapeutics · 2016Article
- A Modeling and Experimental Investigation of the Effects of Antigen Density, Binding Affinity, and Antigen Expression Ratio on Bispecific Antibody Binding to Cell Surface Targets.The Journal of biological chemistry · 2016Article
- Emerging anti-cancer antibodies and combination therapies targeting HER3/ERBB3.Human vaccines & immunotherapeutics · 2016Review
- HER-3 targeting alters the dimerization pattern of ErbB protein family members in breast carcinomas.Oncotarget · 2016Article
- Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The use of antibodies in therapy and diagnosis has undergone an unprecedented expansion during the past two decades. This is due in part to innovations in antibody engineering that now offer opportunities for the production of "second generation" antibodies with multiple specificities or altered valencies. The targeting of individual components of the human epidermal growth factor receptor (HER)3-PI3K signaling axis, including the preferred heterodimerization partner HER2, is known to have limited anti-tumor effects. The efficacy of antibodies or small molecule tyrosine kinase inhibitors (TKIs) in targeting this axis is further reduced by the presence of the HER3 ligand, heregulin. To address these shortcomings, we performed a comparative analysis of two distinct approaches toward reducing the proliferation and signaling in HER2 overexpressing tumor cells in the presence of heregulin. These strategies both involve the use of engineered antibodies in combination with the epidermal growth factor receptor (EGFR)/HER2 specific TKI, lapatinib. In the first approach, we generated a bispecific anti-HER2/HER3 antibody that, in the presence of lapatinib, is designed to sequester HER3 into inactive HER2-HER3 dimers that restrain HER3 interactions with other possible dimerization partners. The second approach involves the use of a tetravalent anti-HER3 antibody with the goal of inducing efficient HER3 internalization and degradation. In combination with lapatinib, we demonstrate that although the multivalent HER3 antibody is more effective than its bivalent counterpart in reducing heregulin-mediated signaling and growth, the bispecific HER2/HER3 antibody has increased inhibitory activity. Collectively, these observations provide support for the therapeutic use of bispecifics in combination with TKIs to recruit HER3 into complexes that are functionally inert.
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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.