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

被引：45
作者：
Chaudhury, Anwesha [1 ]
Zhu, Xu [2 ]
Chu, Lulu [3 ]
Goliaei, Ardeshir [3 ]
June, Carl H. [4 ]
Kearns, Jeffrey D. [3 ]
Stein, Andrew M. [1 ]
机构：
[1] Novartis Inst BioMed Res, Pharmacometr, 220 Massachusetts Ave, Cambridge, MA 02139 USA
[2] Novartis Inst BioMed Res, PK Sci Oncol, Cambridge, MA USA
[3] Novartis Inst BioMed Res, PK Sci Modeling & Simulat, Cambridge, MA USA
[4] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA 19104 USA
来源：
JOURNAL OF CLINICAL PHARMACOLOGY | 2020年 / 60卷
关键词：
cellular kinetic‐ pharmacodynamic model; chimeric antigen receptor‐ T cell (CAR‐ T cell) therapy; model‐ informed drug development (MIDD); quantitative systems pharmacology (QSP); MATHEMATICAL-MODEL; IMMUNOTHERAPY; STRATEGIES; RESPONSES; LEUKEMIA; AFFINITY; TUMORS;
D O I：
10.1002/jcph.1691
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
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.
引用
收藏
页码：S147 / S159
页数：13
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