Speaker
Description
Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable clinical success in the treatment of B-cell malignancies. Numerous mathematical models have been developed to describe the interactions between CAR T cells and malignant B cells at the tumor site \cite{LT21, S25}; however, these approaches often neglect the systemic trafficking of CAR T cells across physiological compartments, which plays a crucial role in linking intravenously administered doses to quantitative measurements at the tumor site \cite{Z96}. In this work, we develop a physiologically based pharmacokinetic (PBPK) framework for CAR T-cell trafficking in humans, comprising both a full whole-body model and a sensitivity-analysis-based minimal PBPK model. The full model describes organ-level transport processes, intra-tissue kinetics, and interactions with malignant B cells within lymph nodes \cite{S25}, and is used for parameter calibration and validation against clinical data from more than 100 patients. The minimal model is used to perform equilibria and stability analyses, providing insight into biologically uncertain mechanisms such as organ uptake. Our results highlight the importance of migration dynamics for a quantitative understanding of CAR T-cell therapy and support the use of mechanistic whole-body models for dose optimization and personalized treatment planning through simulation-guided approaches.
Bibliography
@article{LT21,
title = {{CAR} {T} cell therapy in {B}-cell acute lymphoblastic leukaemia: {Insights} from mathematical models},
volume = {94},
issn = {10075704},
shorttitle = {{CAR} {T} cell therapy in {B}-cell acute lymphoblastic leukaemia},
url = {https://linkinghub.elsevier.com/retrieve/pii/S1007570420304007},
doi = {10.1016/j.cnsns.2020.105570},
language = {en},
urldate = {2026-03-16},
journal = {Communications in Nonlinear Science and Numerical Simulation},
author = {León-Triana, Odelaisy and Sabir, Soukaina and Calvo, Gabriel F. and Belmonte-Beitia, Juan and Chulián, Salvador and Martínez-Rubio, Álvaro and Rosa, María and Pérez-Martínez, Antonio and Ramirez-Orellana, Manuel and Pérez-García, Víctor M.},
month = mar,
year = {2021},
pages = {105570},
}
@article{S25,
title = {Mathematical {Model} of {CAR} {T}-{Cell} {Therapy} for a {B}-{Cell} {Lymphoma} {Lymph} {Node}},
volume = {87},
issn = {0092-8240, 1522-9602},
url = {https://link.springer.com/10.1007/s11538-025-01417-1},
doi = {10.1007/s11538-025-01417-1},
language = {en},
number = {3},
urldate = {2026-03-16},
journal = {Bulletin of Mathematical Biology},
author = {Sabir, Soukaina and León-Triana, Odelaisy and Serrano, Sergio and Barrio, Roberto and Pérez-García, Victor M.},
month = mar,
year = {2025},
pages = {40},
}
@article{Z96,
title={Physiologically based kinetic model of effector cell biodistribution in mammals: implications for adoptive immunotherapy.},
author={Hui Zhu and Robert J. Melder and Laurence T. Baxter and Rakesh K. Jain},
journal={Cancer research},
year={1996},
volume={56 16},
pages={3771-81},
url={https://api.semanticscholar.org/CorpusID:25569522}
}
