ArticleThe Journal of biological chemistry2011
Bispecific designed ankyrin repeat proteins (DARPins) targeting epidermal growth factor receptor inhibit A431 cell proliferation and receptor recycling.
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 45 papers.
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.
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Who cites it
45 citing papers in PubMed, 109 citations in OpenAlex.
- Evaluation of Site-Specific Radioiodination of Anti-EGFR-Targeted DARPin E01 Using (4-Hydroxyphenyl)ethyl Maleimide.International journal of molecular sciences · 2026Article
- Genetically Encoded SpyTag Enables Modular AAV Retargeting via SpyCatcher-Fused Ligands for Targeted Gene Delivery.ACS synthetic biology · 2026Article
- Steric disruption of EGFR oligomerization overcomes therapy resistance in non-small cell lung cancer.Science advances · 2025Article
- Comparative Preclinical Evaluation of the Tumor-Targeting Properties of Radioiodine and Technetium-Labeled Designed Ankyrin Repeat Proteins for Imaging of Epidermal Growth Factor Receptor Expression in Malignant Tumors.International journal of molecular sciences · 2025Article
- Selective targeting of TBXT with DARPins identifies regulatory networks and therapeutic vulnerabilities in chordoma.Science advances · 2025Article
- DARPins as a novel tool to detect and degrade p73.Cell death & disease · 2024Article
- Designed Ankyrin Repeat Proteins as Actin Labels of Distinct Cytoskeletal Structures in Living Cells.ACS nano · 2024Article
- DARPins detect the formation of hetero-tetramers of p63 and p73 in epithelial tissues and in squamous cell carcinoma.Cell death & disease · 2023Article
- A split, conditionally active mimetic of IL-2 reduces the toxicity of systemic cytokine therapy.Nature biotechnology · 2023Article
- Dimeric Ankyrin with Inverted Module Promotes Bifunctional Property in Capturing Capsid to Impede HIV-1 Replication.International journal of molecular sciences · 2023Article
- Designed Ankyrin Repeat Proteins as a tool box for analyzing p63.Cell death and differentiation · 2022Article
- The impact of AlphaFold2 on experimental structure solution.Faraday discussions · 2022Article
- Enzymatic Construction of DARPin-Based Targeted Delivery Systems Using Protein Farnesyltransferase and a Capture and Release Strategy.International journal of molecular sciences · 2022Article
- Bivalent EGFR-Targeting DARPin-MMAE Conjugates.International journal of molecular sciences · 2022Article
- Distinct conformations of the HIV-1 V3 loop crown are targetable for broad neutralization.Nature communications · 2021Article
- Performance of Affinity-Improved DARPin Targeting HIV Capsid Domain in Interference of Viral Progeny Production.Biomolecules · 2021Article
- Crystal structures of HER3 extracellular domain 4 in complex with the designed ankyrin-repeat protein D5.Acta crystallographica. Section F, Structural biology communications · 2021Article
- Bispecific antibodies with Fab-arms featuring exchanged antigen-binding constant domains.Biochemistry and biophysics reports · 2021Article
- Spatiotemporally confined red light-controlled gene delivery at single-cell resolution using adeno-associated viral vectors.Science advances · 2021Article
- Engineering mono- and multi-valent inhibitors on a modular scaffold.Chemical science · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The EGF receptor (EGFR) has been implicated in the development and progression of many tumors. Although monoclonal antibodies directed against EGFR have been approved for the treatment of cancer in combination with chemotherapy, there are limitations in their clinical efficacy, necessitating the search for robust targeting molecules that can be equipped with new effector functions or show a new mechanism of action. Designed ankyrin repeat proteins (DARPins) may provide the targeting component for such novel reagents. Previously, four DARPins were selected against EGFR with (sub)nanomolar affinity. As any targeting module should preferably be able to inhibit EGFR-mediated signaling, their effect on A431 cells overexpressing EGFR was examined: three of them were shown to inhibit proliferation by inducing G(1) arrest, as seen for the Food and Drug Administration-approved antibody cetuximab. To understand this inhibitory mechanism, we mapped the epitopes of the DARPins using yeast surface display. The epitopes for the biologically active DARPins overlapped with the EGF-binding site, whereas the fourth DARPin bound to a different domain, explaining the lack of a biological effect. To optimize the biological activity of the DARPins, we combined two DARPins binding to different epitopes with a flexible linker or with a leucine zipper, leading to a homodimer. The latter DARPin was able to reduce surface EGFR by inhibiting receptor recycling, leading to a dramatic decrease in cell viability. These results indicate that multispecific EGFR-specific DARPins are superior to cetuximab and may form the basis of new opportunities in tumor targeting and tumor therapy.
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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.