ArticleThe Journal of biological chemistry2015
Generation and characterization of small single domain antibodies inhibiting human tumor necrosis factor receptor 1.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Research Progress and Applications of Multivalent, Multispecific and Modified Nanobodies for Disease Treatment.Frontiers in immunology · 2021Pooled it
- Soluble tumor necrosis factor receptors in diabetes: risk sensing and receptor-resolved targeting.Endocrine journal · 2026Review
- A simple and broadly applicable nanobody-based approach to generate potent TNFR agonists.Cell death & disease · 2026Article
- Article
- Osteoarthritis: molecular pathogenesis and potential therapeutic options.Signal transduction and targeted therapy · 2026Review
- Epitope mapping targeting the K205R protein of African swine fever virus using nanobody as a novel tool.Microbiology spectrum · 2025Article
- Paneth cell TNF signaling induces gut bacterial translocation and sepsis.Cell host & microbe · 2024Article
- Peptide-based allosteric inhibitor targets TNFR1 conformationally active region and disables receptor-ligand signaling complex.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A dual computational and experimental strategy to enhance TSLP antibody affinity for improved asthma treatment.PLoS computational biology · 2024Article
- Deciphering the Synthetic and Refolding Strategy of a Cysteine-Rich Domain in the Tumor Necrosis Factor Receptor (TNF-R) for Racemic Crystallography Analysis and d-Peptide Ligand Discovery.ACS bio & med chem Au · 2024Article
- Scrutiny of chimeric antigen receptor activation by the extracellular domain: experience with single domain antibodies targeting multiple myeloma cells highlights the need for case-by-case optimization.Frontiers in immunology · 2024Article
- Dual-targeting inhibition of TNFR1 for alleviating rheumatoid arthritis by a novel composite nucleic acid nanodrug.International journal of pharmaceutics: X · 2023Article
- TNF and TNF receptors as therapeutic targets for rheumatic diseases and beyond.Nature reviews. Rheumatology · 2023Review
- NANOBODYInternational journal of molecular sciences · 2023Review
- Zafirlukast Is a Promising Scaffold for Selectively Inhibiting TNFR1 Signaling.ACS bio & med chem Au · 2023Article
- Discovery of a Non-competitive TNFR1 Antagonist Affibody with Picomolar Monovalent Potency That Does Not Affect TNFR2 Function.Molecular pharmaceutics · 2023Article
- Development of a TNF-α-mediated Trojan Horse for bacteria-based cancer therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Immunosuppressant Therapies in COVID-19: Is the TNF Axis an Alternative?Pharmaceuticals (Basel, Switzerland) · 2022Review
- VInternational journal of molecular sciences · 2022Review
- Applications of nanobodies in brain diseases.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cytokine TNF is a well known drug target for several inflammatory diseases such as Crohn disease. Despite the great success of TNF blockers, therapy could be improved because of high costs and side effects. Selective inhibition of TNF receptor (TNFR) 1 signaling holds the potential to greatly reduce the pro-inflammatory activity of TNF, thereby preserving the advantageous immunomodulatory signals mediated by TNFR2. We generated a selective human TNFR1 inhibitor based on Nanobody (Nb) technology. Two anti-human TNFR1 Nbs were linked with an anti-albumin Nb to generate Nb Alb-70-96 named "TNF Receptor-One Silencer" (TROS). TROS selectively binds and inhibits TNF/TNFR1 and lymphotoxin-α/TNFR1 signaling with good affinity and IC50 values, both of which are in the nanomolar range. Surface plasmon resonance analysis reveals that TROS competes with TNF for binding to human TNFR1. In HEK293T cells, TROS strongly reduces TNF-induced gene expression, like IL8 and TNF, in a dose-dependent manner; and in ex vivo cultured colon biopsies of CD patients, TROS inhibits inflammation. Finally, in liver chimeric humanized mice, TROS antagonizes inflammation in a model of acute TNF-induced liver inflammation, reflected in reduced human IL8 expression in liver and reduced IL6 levels in serum. These results demonstrate the considerable potential of TROS and justify the evaluation of TROS in relevant disease animal models of both acute and chronic inflammation and eventually in patients.
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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.