ArticleNature communications2019
Human immunoglobulin G hinge regulates agonistic anti-CD40 immunostimulatory and antitumour activities through biophysical flexibility.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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.
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Who cites it
29 citing papers in PubMed, 39 citations in OpenAlex.
- Realizing the potential of agonistic antibody immunotherapy.Nature reviews. Drug discovery · 2026Review
- Similarity assessment of disulfide isoform profiles between the romosozumab biosimilar and the reference medicinal product.Scientific reports · 2026Article
- An antibody-drug conjugate designed through clone and isotype selection restricts the growth of CSPG4-expressing triple-negative breast cancer.NPJ precision oncology · 2026Article
- Designing and Evaluation of a Novel IL-1RA Fusion Cytokine to Enhance the Pharmacokinetics and Receptor Affinity for Better Therapeutic Intervention in Inflammatory Disorders.Current computer-aided drug design · 2026Article
- Article
- Diffusion, search and attack motions of antibodies.Communications biology · 2025Article
- Nanomechanical binding mechanism of ligands drives agonistic activity.Nature communications · 2025Article
- Structure-guided disulfide engineering restricts antibody conformation to elicit TNFR agonism.Nature communications · 2025Article
- Generation of antagonistic biparatopic anti-CD30 antibody from an agonistic antibody by precise epitope determination and utilization of structural characteristics of CD30 molecule.Antibody therapeutics · 2025Article
- Structural basis for antibody-mediated NMDA receptor clustering and endocytosis in autoimmune encephalitis.Nature structural & molecular biology · 2024Article
- Targeting TNFRSF25 by agonistic antibodies and multimeric TL1A proteins co-stimulated CD8Journal for immunotherapy of cancer · 2024Article
- Development of pharmacological immunoregulatory anti-cancer therapeutics: current mechanistic studies and clinical opportunities.Signal transduction and targeted therapy · 2024Review
- Agonist Antibodies for Cancer Immunotherapy: History, Hopes, and Challenges.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
- Rigid crosslinking of the CD3 complex leads to superior T cell stimulation.Frontiers in immunology · 2024Article
- Rituximab-IgG2 is a phagocytic enhancer in antibody-based immunotherapy of B-cell lymphoma by altering CD47 expression.Frontiers in immunology · 2024Article
- Effect of posttranslational modifications and subclass on IgG activity: from immunity to immunotherapy.Nature immunology · 2023Review
- Unlocking the potential of agonist antibodies for treating cancer using antibody engineering.Trends in molecular medicine · 2023Review
- Distinct impact of IgG subclass on autoantibody pathogenicity in different IgG4-mediated diseases.eLife · 2022Article
- Potent TRIM21 and complement-dependent intracellular antiviral immunity requires the IgG3 hinge.Science immunology · 2022Article
- Bispecific killer cell engager with high affinity and specificity toward CD16a on NK cells for cancer immunotherapy.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human immunoglobulin G (IgG) agonistic antibodies targeting costimulatory immunoreceptors represent promising cancer immunotherapies yet to be developed. Whether, and how, human IgG hinge and Fc impact on their agonistic functions have been disputed. Here, we show that different natural human IgGs confer divergent agonistic anti-CD40 immunostimulatory and antitumour activities in FcγR-humanized mice, including inactive IgG3 and superior IgG2. This divergence is primarily due to their CH1-hinges despite all human IgGs requiring Fc-FcγR binding for optimal agonistic activities. Unexpectedly, biophysical flexibility of these CH1-hinges inversely correlates with, and can modulate, their agonistic potency. Furthermore, IgG Fcs optimized for selective FcγR binding synergize with and still require IgG hinge, selected for rigidity, to confer improved anti-CD40 immunostimulatory and antitumour activities. These findings highlight the importance of both hinge rigidity and selective FcγR binding in antibody agonistic function, and the need for newer strategies to modulate antibody agonism for improved clinical application.
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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.