ArticleThe Journal of biological chemistry2016
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.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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.
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Who cites it
41 citing papers in PubMed, 72 citations in OpenAlex.
- Article
- Functional Characteristics Derived from the Structural Design of Bispecific Antibodies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- In Vivo Auto-tuning of Antibody-Drug Conjugate Delivery to Maximize Efficacy Using High-Avidity, Low-Affinity Antibodies.Molecular cancer therapeutics · 2026Article
- YMN-V115: a novel humanized BCMA/GPRC5D/CD3 trispecific antibody in relapsed/refractory multiple myeloma.Journal for immunotherapy of cancer · 2026Article
- Computational epitope heterogeneity analysis in immunostainings from antibody-dilution series.Communications biology · 2026Article
- An Overview on T-Cell Engagers: The Current Position in Both the Biological and Mathematical Context.Computational and structural biotechnology journal · 2026Review
- Exploring antibody-antigen binding affinity using degree-based topological indices: a graph-theoretical approach.Frontiers in chemistry · 2026Article
- Enhanced solid tumor cell targeting by a neoepitope-encoding oncolytic measles virus combined with CAR therapy.Molecular therapy. Oncology · 2025Article
- Article
- Article
- Review
- The structural basis for the selective antagonism of soluble TNF-alpha by shark variable new antigen receptors.Nature communications · 2025Article
- An Asymptotic Analysis of Bivalent Monoclonal Antibody-Antigen Binding.Bulletin of mathematical biology · 2025Article
- Understanding antibody-target antigen interactions and the avidity effect using mathematical modelling.Journal of the Royal Society, Interface · 2025Article
- Review
- General quasi-equilibrium multivalent binding model to study diverse and complex drug-receptor interactions of biologics.Journal of pharmacokinetics and pharmacodynamics · 2024Article
- Design of Crosslinking Antibodies For T-Cell Activation: Experimental and Computational Analysis of PD-1/CD137 Bispecific Agents.The AAPS journal · 2024Article
- Mechanistic computational modeling of monospecific and bispecific antibodies targeting interleukin-6/8 receptors.PLoS computational biology · 2024Article
- Revolutionizing cancer treatment: the emerging potential and potential challenges ofTheranostics · 2024Review
- Design and engineering of bispecific antibodies: insights and practical considerations.Frontiers in bioengineering and biotechnology · 2024Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the increasing number of multivalent antibodies, bispecific antibodies, fusion proteins, and targeted nanoparticles that have been generated and studied, the mechanism of multivalent binding to cell surface targets is not well understood. Here, we describe a conceptual and mathematical model of multivalent antibody binding to cell surface antigens. Our model predicts that properties beyond 1:1 antibody:antigen affinity to target antigens have a strong influence on multivalent binding. Predicted crucial properties include the structure and flexibility of the antibody construct, the target antigen(s) and binding epitope(s), and the density of antigens on the cell surface. For bispecific antibodies, the ratio of the expression levels of the two target antigens is predicted to be critical to target binding, particularly for the lower expressed of the antigens. Using bispecific antibodies of different valencies to cell surface antigens including MET and EGF receptor, we have experimentally validated our modeling approach and its predictions and observed several nonintuitive effects of avidity related to antigen density, target ratio, and antibody affinity. In some biological circumstances, the effect we have predicted and measured varied from the monovalent binding interaction by several orders of magnitude. Moreover, our mathematical framework affords us a mechanistic interpretation of our observations and suggests strategies to achieve the desired antibody-antigen binding goals. These mechanistic insights have implications in antibody engineering and structure/activity relationship determination in a variety of biological contexts.
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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.