ArticleNature communications2021
Directed evolution of and structural insights into antibody-mediated disruption of a stable receptor-ligand complex.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- Antibodies targeting a shared epitope exploit IgE allostery to drive distinct functional outcomes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Intravenous oncolytic vaccinia expressing transgenes for enhanced safety, inhibition of shedding, imaging, and systemic cancer immunotherapy.Molecular therapy. Oncology · 2026Article
- High-affinity omalizumab variants with optimized disruptive potency prevent anaphylaxis in vivo.The Journal of allergy and clinical immunology · 2025Article
- Article
- Structural and Functional Insights Into IgE Receptor Interactions and Disruptive Inhibition.Immunological reviews · 2025Review
- Emerging diagnostic and therapeutic opportunities in food allergy.Frontiers in immunology · 2025Review
- Therapeutic monoclonal antibodies in allergy: Targeting IgE, cytokine, and alarmin pathways.Immunological reviews · 2024Review
- Accelerating therapeutic protein design with computational approaches toward the clinical stage.Computational and structural biotechnology journal · 2023Review
- Cryomicroscopy reveals the structural basis for a flexible hinge motion in the immunoglobulin M pentamer.Nature communications · 2022Article
- Biologics as novel therapeutics for the treatment of allergy: Challenges and opportunities.Frontiers in allergy · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Antibody drugs exert therapeutic effects via a range of mechanisms, including competitive inhibition, allosteric modulation, and immune effector mechanisms. Facilitated dissociation is an additional mechanism where antibody-mediated "disruption" of stable high-affinity macromolecular complexes can potentially enhance therapeutic efficacy. However, this mechanism is not well understood or utilized therapeutically. Here, we investigate and engineer the weak disruptive activity of an existing therapeutic antibody, omalizumab, which targets IgE antibodies to block the allergic response. We develop a yeast display approach to select for and engineer antibody disruptive efficiency and generate potent omalizumab variants that dissociate receptor-bound IgE. We determine a low resolution cryo-EM structure of a transient disruption intermediate containing the IgE-Fc, its partially dissociated receptor and an antibody inhibitor. Our results provide a conceptual framework for engineering disruptive inhibitors for other targets, insights into the failure in clinical trials of the previous high affinity omalizumab HAE variant and anti-IgE antibodies that safely and rapidly disarm allergic effector cells.
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.