ArticleProceedings of the National Academy of Sciences of the United States of America2009
Antibodies specifically targeting a locally misfolded region of tumor associated EGFR.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 81 citations in OpenAlex.
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- Characterization of mAb104, a mAb Targeting a Conformationally Exposed, Tumor-Specific Epitope of HER2.Molecular cancer therapeutics · 2025Article
- Design of immunogens to present a tumor-specific cryptic epitope.Scientific reports · 2025Article
- T330M Substitution in the Sodium-Dependent Phosphate Transporter NaPi2b Abolishes the Efficacy of Monoclonal Antibodies Against MX35 Epitope.Antibodies (Basel, Switzerland) · 2025Article
- Potent and durable control of mesothelin-expressing tumors by a novel T cell-secreted bi-specific engager.Journal for immunotherapy of cancer · 2025Article
- Structural insights into the role and targeting of EGFRvIII.Structure (London, England : 1993) · 2024Article
- An anion exchange membrane sensor detects EGFR and its activity state in plasma CD63 extracellular vesicles from patients with glioblastoma.Communications biology · 2024Article
- Confinement of unliganded EGFR by tetraspanin nanodomains gates EGFR ligand binding and signaling.Nature communications · 2023Article
- Modeling of Protein Complexes.Methods in molecular biology (Clifton, N.J.) · 2023Article
- A cross-reactive pH-dependent EGFR antibody with improved tumor selectivity and penetration obtained by structure-guided engineering.Molecular therapy oncolytics · 2022Article
- EGFR, the Lazarus target for precision oncology in glioblastoma.Neuro-oncology · 2022Review
- Locally secreted BiTEs complement CAR T cells by enhancing killing of antigen heterogeneous solid tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Antitumor Efficacy of EGFR-Targeted Recombinant Immunotoxin in Human Head and Neck Squamous Cell Carcinoma.Biology · 2022Article
- Challenges in the Treatment of Glioblastoma by Chimeric Antigen Receptor T-Cell Immunotherapy and Possible Solutions.Frontiers in immunology · 2022Review
- Mechanisms of EGFR Resistance in Glioblastoma.International journal of molecular sciences · 2020Review
- Characterizing Epitope Binding Regions of Entire Antibody Panels by Combining Experimental and Computational Analysis of Antibody: Antigen Binding Competition.Molecules (Basel, Switzerland) · 2020Article
- Computer-guided binding mode identification and affinity improvement of an LRR protein binder without structure determination.PLoS computational biology · 2020Article
- Finding the Keys to the CAR: Identifying Novel Target Antigens for T Cell Redirection Immunotherapies.International journal of molecular sciences · 2020Review
- 'Characterization of monoclonal antibodies generated to the 287-302 amino acid loop of the human epidermal growth factor receptor'.Antibody therapeutics · 2019Article
Corrections and comments
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Authors and funding
28 authors at 5 institutions in 2 countries.
Funding
Abstract
Epidermal Growth Factor Receptor (EGFR) is involved in stimulating the growth of many human tumors, but the success of therapeutic agents has been limited in part by interference from the EGFR on normal tissues. Previously, we reported an antibody (mab806) against a truncated form of EGFR found commonly in gliomas. Remarkably, it also recognizes full-length EGFR on tumor cells but not on normal cells. However, the mechanism for this activity was unclear. Crystallographic structures for Fab:EGFR(287-302) complexes of mAb806 (and a second, related antibody, mAb175) show that this peptide epitope adopts conformations similar to those found in the wtEGFR. However, in both conformations observed for wtEGFR, tethered and untethered, antibody binding would be prohibited by significant steric clashes with the CR1 domain. Thus, these antibodies must recognize a cryptic epitope in EGFR. Structurally, it appeared that breaking the disulfide bond preceding the epitope might allow the CR1 domain to open up sufficiently for antibody binding. The EGFR(C271A/C283A) mutant not only binds mAb806, but binds with 1:1 stoichiometry, which is significantly greater than wtEGFR binding. Although mAb806 and mAb175 decrease tumor growth in xenografts displaying mutant, overexpressed, or autocrine stimulated EGFR, neither antibody inhibits the in vitro growth of cells expressing wtEGFR. In contrast, mAb806 completely inhibits the ligand-associated stimulation of cells expressing EGFR(C271A/C283A). Clearly, the binding of mAb806 and mAb175 to the wtEGFR requires the epitope to be exposed either during receptor activation, mutation, or overexpression. This mechanism suggests the possibility of generating antibodies to target other wild-type receptors on tumor cells.
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