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Chimeric Antigen Receptor T Cell Therapies: A Review of Cellular Kinetic‐Pharmacodynamic Modeling Approaches

Chimeric antigen receptor T cell (CAR‐T cell) therapies have shown significant efficacy in CD19+ leukemias and lymphomas. There remain many challenges and questions for improving next‐generation CAR‐T cell therapies, and mathematical modeling of CAR‐T cells may play a role in supporting further deve...

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Bibliographic Details
Published in:Journal of clinical pharmacology 2020-10, Vol.60 (S1 Suppl 1), p.S147-S159
Main Authors: Chaudhury, Anwesha, Zhu, Xu, Chu, Lulu, Goliaei, Ardeshir, June, Carl H., Kearns, Jeffrey D., Stein, Andrew M.
Format: Article
Language:English
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Summary:Chimeric antigen receptor T cell (CAR‐T cell) therapies have shown significant efficacy in CD19+ leukemias and lymphomas. There remain many challenges and questions for improving next‐generation CAR‐T cell therapies, and mathematical modeling of CAR‐T cells may play a role in supporting further development. In this review, we introduce a mathematical modeling taxonomy for a set of relatively simple cellular kinetic‐pharmacodynamic models that describe the in vivo dynamics of CAR‐T cell and their interactions with cancer cells. We then discuss potential extensions of this model to include target binding, tumor distribution, cytokine‐release syndrome, immunophenotype differentiation, and genotypic heterogeneity.
ISSN:0091-2700
1552-4604
DOI:10.1002/jcph.1691