ArticleJournal of molecular biology2012
Triepitopic antibody fusions inhibit cetuximab-resistant BRAF and KRAS mutant tumors via EGFR signal repression.
Article in Journal of molecular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
22 citing papers in PubMed, 1 citations in OpenAlex.
- CD45 sequestration lowers the signaling threshold in lymphocytes and enhances anti-tumor immunity.bioRxiv : the preprint server for biology · 2025Article
- Multiparatopic antibodies induce targeted downregulation of programmed death-ligand 1.Cell chemical biology · 2024Article
- Revival of Bioengineered Proteins as Carriers for Nucleic Acids.Bioconjugate chemistry · 2024Article
- Bispecific antibody drug conjugates: Making 1+1>2.Acta pharmaceutica Sinica. B · 2024Review
- Engineered bispecific antibodies targeting the interleukin-6 and -8 receptors potently inhibit cancer cell migration and tumor metastasis.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Nanotechnology in the development of small and large molecule tyrosine kinase inhibitors and immunotherapy for the treatment of HER2-positive breast cancer.Journal of cancer & metastasis research · 2022Article
- MEK Inhibition Remodels the Immune Landscape of MutantCancer research · 2021Article
- A novel HER2-targeting antibody 5G9 identified by large-scale trastuzumab-based screening exhibits potent synergistic antitumor activity.EBioMedicine · 2020Article
- Targeting autophagy to modulate cell survival: a comparative analysis in cancer, normal and embryonic cells.Histochemistry and cell biology · 2017Article
- Emerging Strategies for Developing Next-Generation Protein Therapeutics for Cancer Treatment.Trends in pharmacological sciences · 2016Review
- 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
- Π-Clamp-mediated cysteine conjugation.Nature chemistry · 2016Article
- Antibody-mediated neutralization of perfringolysin o for intracellular protein delivery.Molecular pharmaceutics · 2015Article
- Engineering pH responsive fibronectin domains for biomedical applications.Journal of biological engineering · 2015Article
- A Nonpolycationic Fully Proteinaceous Multiagent System for Potent Targeted Delivery of siRNA.Molecular therapy. Nucleic acids · 2014Article
- Article
- Membrane domain formation-a key factor for targeted intracellular drug delivery.Frontiers in physiology · 2014Review
- Targeting the ERBB family in cancer: couples therapy.Nature reviews. Cancer · 2013Review
- Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Dysregulation of epidermal growth factor receptor (EGFR) is a hallmark of many epithelial cancers, rendering this receptor an attractive target for cancer therapy. Much effort has been focused on the development of EGFR-directed antibody-based therapeutics, culminating in the clinical approval of the drugs cetuximab and panitumumab. Unfortunately, the clinical efficacy of these drugs has been disappointingly low, and a particular challenge to targeting EGFR with antibody therapeutics has been resistance, resulting from mutations in the downstream raf and ras effector proteins. Recent work demonstrating antibody cocktail-induced synergistic downregulation of EGFR motivated our design of cetuximab-based antibody-fibronectin domain fusion proteins that exploit downregulation-based EGFR inhibition by simultaneously targeting multiple receptor epitopes. We establish that, among our engineered multiepitopic formats, trans-triepitopic antibody fusions demonstrate optimal efficacy, inducing rapid EGFR clustering and internalization and consequently ablating downstream signaling. The combined effects of EGFR downregulation, ligand competition, and immune effector function conspire to inhibit tumor growth in xenograft models of cetuximab-resistant BRAF and KRAS mutant cancers. Our designed triepitopic constructs have the potential to enhance the efficacy and expand the scope of EGFR-directed therapies, and our multiepitopic may be readily applied to other receptor targets to formulate a new class of antibody-based therapeutics.
Indexed as
Identifiers
What OpenQuestion holds
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.