ArticleThe Journal of biological chemistry2011
Structural insights into the down-regulation of overexpressed p185(her2/neu) protein of transformed cells by the antibody chA21.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 34 citations in OpenAlex.
- A humanized 4-1BB-targeting agonistic antibody exerts potent antitumor activity in colorectal cancer without systemic toxicity.Journal of translational medicine · 2022Article
- A Tetravalent Biparatopic Antibody Causes Strong HER2 Internalization and Inhibits Cellular Proliferation.Life (Basel, Switzerland) · 2021Article
- Structural and dynamic characterization of the C-terminal tail of ErbB2: Disordered but not random.Biophysical journal · 2021Article
- Molecular Application of Aptamers in the Diagnosis and Treatment of Cancer and Communicable Diseases.Pharmaceuticals (Basel, Switzerland) · 2018Review
- EVIR: chimeric receptors that enhance dendritic cell cross-dressing with tumor antigens.Nature methods · 2018Article
- Antitumor effects and persistence of a novel HER2 CAR T cells directed to gastric cancer in preclinical models.American journal of cancer research · 2018Article
- Epitope Mapping of Human HER2 Specific Mouse Monoclonal Antibodies Using Recombinant Extracellular SubdomainsAsian Pacific journal of cancer prevention : APJCP · 2017Article
- A Tri-part Protein Complementation System Using Antibody-Small Peptide Fusions Enables Homogeneous Immunoassays.Scientific reports · 2017Article
- Article
- Development and Characterization of a Humanized Anti-HER2 Antibody HuA21 with Potent Anti-Tumor Properties in Breast Cancer Cells.International journal of molecular sciences · 2016Article
- Recent advances in T-cell engineering for use in immunotherapy.F1000Research · 2016Review
- Predominant structural configuration of natural antibody repertoires enables potent antibody responses against protein antigens.Scientific reports · 2015Article
- Effective Optimization of Antibody Affinity by Phage Display Integrated with High-Throughput DNA Synthesis and Sequencing Technologies.PloS one · 2015Article
- Construction and evaluation of a novel humanized HER2-specific chimeric receptor.Breast cancer research : BCR · 2014Article
- Structural and functional characterization of MBS301, an afucosylated bispecific anti-HER2 antibody.mAbsArticle
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
p185(her2/neu) belongs to the ErbB receptor tyrosine kinase family, which has been associated with human breast, ovarian, and lung cancers. Targeted therapies employing ectodomain-specific p185(her2/neu) monoclonal antibodies (mAbs) have demonstrated clinical efficacy for breast cancer. Our previous studies have shown that p185(her2/neu) mAbs are able to disable the kinase activity of homomeric and heteromeric kinase complexes and induce the conversion of the malignant to normal phenotype. We previously developed a chimeric antibody chA21 that specifically inhibits the growth of p185(her2/neu)-overexpressing cancer cells in vitro and in vivo. Herein, we report the crystal structure of the single-chain Fv of chA21 in complex with an N-terminal fragment of p185(her2/neu), which reveals that chA21 binds a region opposite to the dimerization interface, indicating that chA21 does not directly disrupt the dimerization. In contrast, the bivalent chA21 leads to internalization and down-regulation of p185(her2/neu). We propose a structure-based model in which chA21 cross-links two p185(her2/neu) molecules on separate homo- or heterodimers to form a large oligomer in the cell membrane. This model reveals a mechanism for mAbs to drive the receptors into the internalization/degradation path from the inactive hypophosphorylated tetramers formed dynamically by active dimers during a "physiologic process."
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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.