Abstract
Chimeric antigen receptor T‐cell (CART) therapy is a new and promising cancer therapy. However, severe toxicity due to cytokine release syndrome (CRS) in CART‐treated patients highlighted the possible danger of this new therapy. Disease burden and CART doses are the potential factors associated with CRS but the detail relationships between these factors and the severity of the CRS remain largely unknown. In this study, the quantitative systems pharmacology (QSP) approach is used to quantify the complex relationships among CART doses, disease burden, and pro inflammatory cytokines in human subjects and to gain relevant insights into the determinant of clinical toxicity/efficacy in development of CART therapy. The expansion of CART and elimination of B cells are more highly correlated with disease burden than the administered CART doses. To our best knowledge, this is the first QSP model that can describe the observed clinical data from CART‐treated patients with cancer. This QSP model is a valuable tool for deepening our understanding of how the mechanism of action connects to the clinical outcomes and, therefore, may serve as an important model‐based platform to guide the development and personalized dosing of the CART therapy.
Document Type
Article
Publication Date
7-2019
Digital Object Identifier (DOI)
https://doi.org/10.1111/cts.12636
Related Content
Supplementary information accompanies this paper on the Clinical and Translational Science website (www. cts-journal.com).
Repository Citation
Hardiansyah, Deni and Ng, Chee Meng, "Quantitative Systems Pharmacology Model of Chimeric Antigen Receptor T-Cell Therapy" (2019). Pharmaceutical Sciences Faculty Publications. 143.
https://uknowledge.uky.edu/ps_facpub/143
Supplementary Material, Tables and Figures.
Notes/Citation Information
Published in Clinical and Translational Science, v. 12, issue 4, p. 343-349.
© 2019 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.