ArticleThe AAPS journal2017
Optimal Affinity of a Monoclonal Antibody: Guiding Principles Using Mechanistic Modeling.
Article in The AAPS journal, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.
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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
15 citing papers in PubMed.
- Article
- Simultaneous Affinity Maturation and Liability Removal from Antibodies.Methods in molecular biology (Clifton, N.J.) · 2026Article
- The Anti-EMMPRIN Monoclonal Antibody hMR18-mAb Induces Tumor Dormancy and Inhibits the EMT Process in Human Carcinoma Cell Lines Co-Cultured with Macrophages.Biomedicines · 2025Article
- Leveraging quantitative systems pharmacology modeling for elranatamab regimen optimization in relapsed or refractory multiple myeloma.NPJ systems biology and applications · 2025Article
- Minimally sufficient experimental design using identifiability analysis.NPJ systems biology and applications · 2024Article
- Leveraging a physiologically-based quantitative translational modeling platform for designing B cell maturation antigen-targeting bispecific T cell engagers for treatment of multiple myeloma.PLoS computational biology · 2022Article
- Identifying Safety Thresholds for Immunosuppressive Drugs: Applying Insights from Primary Antibody Deficiencies to Mitigate Adverse Events in Secondary Antibody Deficiencies Using Mathematical Modeling of Preclinical and Early Clinical Data.European journal of drug metabolism and pharmacokinetics · 2021Review
- Article
- Modeling Pharmacokinetics and Pharmacodynamics of Therapeutic Antibodies: Progress, Challenges, and Future Directions.Pharmaceutics · 2021Review
- A Mechanistic Site-Of-Action Model: A Tool for Informing Right Target, Right Compound, And Right Dose for Therapeutic Antagonistic Antibody Programs.Frontiers in bioinformatics · 2021Article
- Guiding dose selection of monoclonal antibodies using a new parameter (AFTIR) for characterizing ligand binding systems.Journal of pharmacokinetics and pharmacodynamics · 2019Article
- Role of Interstitial Fluid Turnover on Target Suppression by Therapeutic Biologics Using a Minimal Physiologically Based Pharmacokinetic Model.The Journal of pharmacology and experimental therapeutics · 2018Article
- Model-Based Discovery and Development of Biopharmaceuticals: A Case Study of Mavrilimumab.CPT: pharmacometrics & systems pharmacology · 2018Article
- Review
- Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Affinity optimization of monoclonal antibodies (mAbs) is essential for developing drug candidates with the highest likelihood of clinical success; however, a quantitative approach for setting affinity requirements is often lacking. In this study, we computationally analyzed the in vivo mAb-target binding kinetics to delineate general principles for defining optimal equilibrium dissociation constant ([Formula: see text]) of mAbs against soluble and membrane-bound targets. Our analysis shows that in general [Formula: see text] to achieve 90% coverage for a soluble target is one tenth of its baseline concentration ([Formula: see text]), and is independent of the dosing interval, target turnover rate or the presence of competing ligands. For membrane-bound internalizing targets, it is equal to the ratio of internalization rate of mAb-target complex and association rate constant ([Formula: see text]). In cases where soluble and membrane-bound forms of the target co-exist, [Formula: see text] lies within a range determined by the internalization rate ([Formula: see text]) of the mAb-membrane target complex and the ratio of baseline concentrations of soluble and membrane-bound forms ([Formula: see text]). Finally, to demonstrate practical application of these general rules, we collected target expression and turnover data to project [Formula: see text] for a number of marketed mAbs against soluble (TNFα, RANKL, and VEGF) and membrane-bound targets (CD20, EGFR, and HER2).
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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.