ArticleFrontiers in systems biology2024
A multi-scale semi-mechanistic CK/PD model for CAR T-cell therapy.
Article in Frontiers in systems biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Cellular Heterogeneity in Drug Uptake Amplifies Pharmacodynamic Variability: A Stochastic PK-PD Analysis.CPT: pharmacometrics & systems pharmacology · 2026Article
- Anti-CD19 CAR T-cell therapy for autoimmune diseases: from exploratory clinical trials to quantitative pharmacodynamic modeling development.Frontiers in immunology · 2026Review
- Foundational Principles for the Quantitative Translation of T-Cell Therapeutics for Hematologic Malignancies and Immunology.Clinical pharmacology and therapeutics · 2026Review
- Immune effector cell-associated neurotoxicity syndrome: integrative mechanisms, predictive biomarkers, and translational pathways for prevention in CAR T-cell therapy.Frontiers in neurologyReview
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chimeric antigen receptor T (CAR T) cell therapy has shown remarkable success in treating various leukemias and lymphomas. Cellular kinetic (CK) and pharmacodynamic (PD) behavior of CAR T cell therapy is distinct from other therapies due to its living nature. CAR T CK is typically characterized by an exponential expansion driven by target binding, fast initial decline (contraction), and slow long-term decline (persistence). Due to the dependence of CK on target binding, CK and PD of CAR T therapies are inherently and bidirectionally linked. In this work, we develop a semi-mechanistic model of CAR T CK/PD, incorporating molecular-scale binding, T cell dynamics with multiple phenotypes, and tumor growth and killing. We calibrate this model to published CK and PD data for a CD19-targeting CAR T cell therapy. Using sensitivity analysis, we explore variability in response due to patient- and drug-specific properties. We further explore the impact of tumor characteristics on CAR T-cell expansion and efficacy through individual- and population-level parameter scans.
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Registered trials
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