ArticleCPT: pharmacometrics & systems pharmacology2019
Target-Mediated Drug Disposition Model for Bispecific Antibodies: Properties, Approximation, and Optimal Dosing Strategy.
Article in CPT: pharmacometrics & systems pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Population Pharmacokinetic and Pharmacokinetic-Pharmacodynamic Modeling of Serum M-Protein Response for Modakafusp Alfa in a Phase 1/2 Study of Patients With Relapsed or Refractory Multiple Myeloma.Clinical and translational science · 2025Trial
- A randomized phase-I pharmacokinetic trial comparing the potential biosimilar tocilizumab (QX003S) with the reference product (ActemraAnnals of medicine · 2021Trial
- Elranatamab Population Pharmacokinetics and Exposure-Response for Cytokine Release Syndrome in Patients with Relapsed or Refractory Multiple Myeloma.Clinical pharmacokinetics · 2026Article
- A Generalized Minimal PBPK-PD Model of Bispecific Antibodies: Case Studies and Applications in Drug Development.CPT: pharmacometrics & systems pharmacology · 2026Article
- Overview of Quantitative Clinical Pharmacology for T-Cell Engaging Bispecific Antibodies.Methods in molecular biology (Clifton, N.J.) · 2026Review
- An Overview on T-Cell Engagers: The Current Position in Both the Biological and Mathematical Context.Computational and structural biotechnology journal · 2026Review
- Impacts of Antibody Structure and Mixtures on Receptor Signaling for Antibody-Dependent Cellular Cytotoxicity.The AAPS journal · 2025Article
- Next-generation T cell engagers in oncology: Pharmacologic evolution from bispecific to trispecific antibodies.The Journal of pharmacology and experimental therapeutics · 2025Review
- Predicting the Pharmacokinetics of T-Cell Engagers as a Function of Target-Mediated Drug Disposition.Clinical and translational science · 2025Article
- Whole-Body Physiologically Based Pharmacokinetic Modeling Framework for Tissue Target Engagement of CD3 Bispecific Antibodies.Pharmaceutics · 2025Article
- Quantitative pharmacology of dual-targeted bicistronic CAR-T-cell therapy using multiscale mechanistic modeling.CPT: pharmacometrics & systems pharmacology · 2025Article
- 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
- Population pharmacokinetics and CD20 binding dynamics for mosunetuzumab in relapsed/refractory B-cell non-Hodgkin lymphoma.Clinical and translational science · 2024Article
- Combining mathematical modeling,Frontiers in pharmacology · 2024Article
- Article
- Using quantitative systems pharmacology modeling to optimize combination therapy of anti-PD-L1 checkpoint inhibitor and T cell engager.Frontiers in pharmacology · 2023Article
- Quantitative systems pharmacology modeling sheds light into the dose response relationship of a trispecific T cell engager in multiple myeloma.Scientific reports · 2022Article
- Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Bispecific antibodies (BsAbs) bind to two different targets, and create two binary and one ternary complex (TC). These molecules have shown promise as immuno-oncology drugs, and the TC is considered the pharmacologically active species that drives their pharmacodynamic effect. Here, we have presented a general target-mediated drug disposition (TMDD) model for these BsAbs, which bind to two different targets on different cell membranes. The model includes four different binding events for BsAbs, turnover of the targets, and internalization of the complexes. In addition, a quasi-equilibrium (QE) approximation with decreased number of binding parameters and, if necessary, reduced internalization parameters is presented. The model is further used to investigate the kinetics of BsAb and TC concentrations. Our analysis shows that larger doses of BsAbs may delay the build-up of the TC. Consequently, a method to compute the optimal dosing strategy of BsAbs, which will immediately create and maintain maximal possible TC concentration, is presented.
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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.