ArticleCPT: pharmacometrics & systems pharmacology2021
Bench-to-bedside translation of chimeric antigen receptor (CAR) T cells using a multiscale systems pharmacokinetic-pharmacodynamic model: A case study with anti-BCMA CAR-T.
Article in CPT: pharmacometrics & systems pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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
38 citing papers in PubMed, 48 citations in OpenAlex.
- Cell-delivered CD3×CD19 T-cell engager by STAb-T19 cells mediates leukemia clearance with limited systemic exposure.Journal for immunotherapy of cancer · 2026Article
- Patient-Specific Determinants of Response to BCMA- and GPRC5D-Targeted CAR T-Cell Therapy in Multiple Myeloma: A QSP Analysis of Clinical Trial and Real-World Data.Clinical pharmacology and therapeutics · 2026Article
- Model-Based Analysis with Mechanistic Insights to CAR-T-Cell Therapy Kinetics: Case Study with Axicabtagene Ciloleucel and Brexucabtagene Autoleucel.Clinical pharmacology and therapeutics · 2026Article
- Quantitative Characterization of Innate and Adaptive Pharmacology of Allogeneic anti-CD20 Chimeric Antigen Receptor (CAR) Vδ1 γδ T cells using Multiscale Mechanistic Modeling.The AAPS journal · 2026Article
- Optimizing Clinical Study Designs for CAR-T Cell Therapy: Development of an Efficient Sampling Strategy Through Optimal Experimental Design.CPT: pharmacometrics & systems pharmacology · 2026Article
- A hybrid multiscale model for predicting CAR-T therapy outcomes in solid tumors.Scientific reports · 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
- Emerging Multimodal Strategies for Bacterial Biofilm Eradication: A Comprehensive Review.Microorganisms · 2025Review
- Mechanistic data-informed multiscale quantitative systems pharmacology modeling framework enables the clinical translation and efficacy assessment of CAR-T therapy in solid tumors.Journal for immunotherapy of cancer · 2025Article
- Discovery of BMS-986408, a First-In-Class Dual DGKα and DGKζ Inhibitor that Unleashes PD-1 Checkpoint and CAR T-cell Immunotherapies.Cancer immunology research · 2025Article
- Bench to Bedside Modeling of mRNA Encoding IgG Using a Multiscale Mechanistic Pharmacokinetic-Toxicokinetic (PK-TK) Model: A Case Study With Anti-Claudin 18.2.Clinical and translational science · 2025Article
- Mathematical modeling unveils the timeline of CAR-T cell therapy and macrophage-mediated cytokine release syndrome.PLoS computational biology · 2025Article
- A Multiple-Model-Informed Drug-Development Approach for Optimal Regimen Selection of an Oncolytic Virus in Combination With Pembrolizumab.CPT: pharmacometrics & systems pharmacology · 2025Article
- Computational modelling of CAR T-cell therapy: from cellular kinetics to patient-level predictions.EBioMedicine · 2025Review
- Quantitative pharmacology of dual-targeted bicistronic CAR-T-cell therapy using multiscale mechanistic modeling.CPT: pharmacometrics & systems pharmacology · 2025Article
- Mechanistic Evaluation of Anti-CD19 CAR-T Cell Therapy Repurposed in Systemic Lupus Erythematosus Using a Quantitative Systems Pharmacology Model.Clinical and translational science · 2025Article
- Multi-physiology modeling of the immune system in the era of precision immunotherapy.Frontiers in immunology · 2025Review
- Applying population mechanistic modelling to find determinants of chimeric antigen receptor T-cells dynamics in month-one lymphoma patients.Immunotherapy advances · 2025Article
- In vivo gene editing and in situ generation of chimeric antigen receptor cells for next-generation cancer immunotherapy.Journal of hematology & oncology · 2024Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Despite tremendous success of chimeric antigen receptor (CAR) T cell therapy in clinical oncology, the dose-exposure-response relationship of CAR-T cells in patients is poorly understood. Moreover, the key drug-specific and system-specific determinants leading to favorable clinical outcomes are also unknown. Here we have developed a multiscale mechanistic pharmacokinetic (PK)-pharmacodynamic (PD) model for anti-B-cell maturation antigen (BCMA) CAR-T cell therapy (bb2121) to characterize (i) in vitro target cell killing in multiple BCMA expressing tumor cell lines at varying effector to target cell ratios, (ii) preclinical in vivo tumor growth inhibition and blood CAR-T cell expansion in xenograft mice, and (iii) clinical PK and PD biomarkers in patients with multiple myeloma. Our translational PK-PD relationship was able to effectively describe the commonly observed multiphasic CAR-T cell PK profile in the clinic, consisting of the rapid distribution, expansion, contraction, and persistent phases, and accounted for the categorical individual responses in multiple myeloma to effectively calculate progression-free survival rates. Preclinical and clinical data analysis revealed comparable parameter estimates pertaining to CAR-T cell functionality and suggested that patient baseline tumor burden could be more sensitive than dose levels toward overall extent of exposure after CAR-T cell infusion. Virtual patient simulations also suggested a very steep dose-exposure-response relationship with CAR-T cell therapy and indicated the presence of a "threshold" dose, beyond which a flat dose-response curve could be observed. Our simulations were concordant with multiple clinical observations discussed in this article. Moving forward, this framework could be leveraged a priori to explore multiple infusions and support the preclinical/clinical development of future CAR-T cell therapies.
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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.