ArticleJournal of pharmacokinetics and pharmacodynamics2023
A next generation mathematical model for the in vitro to clinical translation of T-cell engagers.
Article in Journal of pharmacokinetics and pharmacodynamics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Dose Selection for DuoBody®-CD40x4-1BB (GEN1042/BNT312) Using a mPBPK/RO Model Leveraging Preclinical and Clinical Data.Clinical pharmacology and therapeutics · 2025Trial
- An Overview on T-Cell Engagers: The Current Position in Both the Biological and Mathematical Context.Computational and structural biotechnology journal · 2026Review
- Foundational Principles for the Quantitative Translation of T-Cell Therapeutics for Hematologic Malignancies and Immunology.Clinical pharmacology and therapeutics · 2026Review
- Impacts of Antibody Structure and Mixtures on Receptor Signaling for Antibody-Dependent Cellular Cytotoxicity.The AAPS journal · 2025Article
- Predicting the Pharmacokinetics of T-Cell Engagers as a Function of Target-Mediated Drug Disposition.Clinical and translational science · 2025Article
- NI-3201 Is a Bispecific Antibody Mediating PD-L1-Dependent CD28 Co-stimulation on T Cells for Enhanced Tumor Control.Cancer immunology research · 2025Article
- Future Directions for Quantitative Systems Pharmacology.Handbook of experimental pharmacology · 2025Review
- General quasi-equilibrium multivalent binding model to study diverse and complex drug-receptor interactions of biologics.Journal of pharmacokinetics and pharmacodynamics · 2024Article
- Rapid Systematic Screening of Bispecific Antibody Surrogate Geometries for T-Cell Engagement Using DNA Nanotechnology.Journal of the American Chemical Society · 2024Article
- T-cell engagers: model interrogation as a tool to quantify the interplay of relative affinity and target expression on trimer formation.Frontiers in pharmacology · 2024Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
T-cell engager (TCE) molecules activate the immune system and direct it to kill tumor cells. The key mechanism of action of TCEs is to crosslink CD3 on T cells and tumor associated antigens (TAAs) on tumor cells. The formation of this trimolecular complex (i.e. trimer) mimics the immune synapse, leading to therapeutic-dependent T-cell activation and killing of tumor cells. Computational models supporting TCE development must predict trimer formation accurately. Here, we present a next-generation two-step binding mathematical model for TCEs to describe trimer formation. Specifically, we propose to model the second binding step with trans-avidity and as a two-dimensional (2D) process where the reactants are modeled as the cell-surface density. Compared to the 3D binding model where the reactants are described in terms of concentration, the 2D model predicts less sensitivity of trimer formation to varying cell densities, which better matches changes in EC
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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.