ArticleCommunications biology2021
TNF receptor agonists induce distinct receptor clusters to mediate differential agonistic activity.
Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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Who cites it
39 citing papers in PubMed, 52 citations in OpenAlex.
- Intra-cluster receptor density (IRD): A molecular switch for TNFR1 clusters' signaling.Science advances · 2026Article
- Realizing the potential of agonistic antibody immunotherapy.Nature reviews. Drug discovery · 2026Review
- Soluble tumor necrosis factor receptors in diabetes: risk sensing and receptor-resolved targeting.Endocrine journal · 2026Review
- Gas-phase unfolding assay rapidly predicts structure-function relationships in engineered antibodies with tuned flexibilities.Nature communications · 2026Article
- A simple and broadly applicable nanobody-based approach to generate potent TNFR agonists.Cell death & disease · 2026Article
- OX40 signaling in cancer immunotherapy: mechanisms of action, translational applications, and therapeutic perspectives.Frontiers in immunology · 2026Review
- Article
- Nanomechanical binding mechanism of ligands drives agonistic activity.Nature communications · 2025Article
- Integrating AI/ML and multi-omics approaches to investigate the role of TNFRSF10A/TRAILR1 and its potential targets in pancreatic cancer.Computers in biology and medicine · 2025Article
- Inducing Cancer Cell Killing Using DNA Nanostructure-Mediated Superclustering of Death Receptors.Nano letters · 2025Article
- Structure-guided disulfide engineering restricts antibody conformation to elicit TNFR agonism.Nature communications · 2025Article
- Target-conditioned diffusion generates potent TNFR superfamily antagonists and agonists.Science (New York, N.Y.) · 2024Article
- Genetically engineered IgG1 and nanobody oligomers acquire strong intrinsic CD40 agonism.Bioengineered · 2024Article
- The novel and potent CD40 agonist KHK2840 augments the antitumor efficacy of anti-PD-1 antibody and paclitaxel.Cancer science · 2024Article
- Discovery of Cyclic Peptide Inhibitors Targeted on TNFα-TNFR1 from Computational Design and Bioactivity Verification.Molecules (Basel, Switzerland) · 2024Article
- Extracellular vesicle surface display enhances the therapeutic efficacy and safety profile of cancer immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Targeting TNFRSF25 by agonistic antibodies and multimeric TL1A proteins co-stimulated CD8Journal for immunotherapy of cancer · 2024Article
- Impact of isotype on the mechanism of action of agonist anti-OX40 antibodies in cancer: implications for therapeutic combinations.Journal for immunotherapy of cancer · 2024Article
- Reversible Chemical Modification of Antibody Effector Function Mitigates Unwanted Systemic Immune Activation.Bioconjugate chemistry · 2024Article
- Agonist Antibodies for Cancer Immunotherapy: History, Hopes, and Challenges.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
Monoclonal antibodies (mAb) and natural ligands targeting costimulatory tumor necrosis factor receptors (TNFR) exhibit a wide range of agonistic activities and antitumor responses. The mechanisms underlying these differential agonistic activities remain poorly understood. Here, we employ a panel of experimental and clinically-relevant molecules targeting human CD40, 4-1BB and OX40 to examine this issue. Confocal and STORM microscopy reveal that strongly agonistic reagents induce clusters characterized by small area and high receptor density. Using antibody pairs differing only in isotype we show that hIgG2 confers significantly more receptor clustering than hIgG1 across all three receptors, explaining its greater agonistic activity, with receptor clustering shielding the receptor-agonist complex from further molecular access. Nevertheless, discrete receptor clustering patterns are observed with different hIgG2 mAb, with a unique rod-shaped assembly observed with the most agonistic mAb. These findings dispel the notion that larger receptor clusters elicit greater agonism, and instead point to receptor density and subsequent super-structure as key determinants.
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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.