动力学
计算生物学
化学
药理学
医学
生物
物理
量子力学
作者
Timothy Qi,Kyle McGrath,Raghuveer Ranganathan,Gianpietro Dotti,Yanguang Cao
标识
DOI:10.1016/j.addr.2022.114421
摘要
To the extent that pharmacokinetics influence the effectiveness of nonliving therapeutics, so too do cellular kinetics influence the efficacy of Chimeric Antigen Receptor (CAR) -T cell therapy. Like conventional therapeutics, CAR-T cell therapies undergo a distribution phase upon administration. Unlike other therapeutics, however, this distribution phase is followed by subsequent phases of expansion, contraction, and persistence. The magnitude and duration of these phases unequivocally influence clinical outcomes. Furthermore, the "pharmacodynamics" of CAR-T cells is truly dynamic, as cells can rapidly become exhausted and lose their therapeutic efficacy. Mathematical models are among the translational tools commonly applied to assess, characterize, and predict the complex cellular kinetics and dynamics of CAR-T cells. Here, we provide a focused review of the cellular kinetics of CAR-T cells, the mechanisms underpinning their complexity, and the mathematical modeling approaches used to interrogate them.
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