chaudhury, anwesha, Zhu, Xu, Chu, Lulu, Goliaei, Ardeshir, Kearns, Jeff and Stein, Andrew (2020) Chimeric Antigen Receptor T Cell Therapies: A Review of Cellular Kinetic-Pharmacodynamic Modeling Approaches. Journal of Clinical Pharmacology, 60 (S1). S147-S159. ISSN 15524604

Abstract

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.

Item Type:	Article
Keywords:	cellular kinetic-pharmacodynamic model chimeric antigen receptor-T cell (CAR-T cell) therapy model-informed drug development (MIDD) quantitative systems pharmacology (QSP)
Date Deposited:	07 Feb 2021 00:45
Last Modified:	07 Feb 2021 00:45
URI:	https://oak.novartis.com/id/eprint/42553