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

页码：S147 / S159

页数：13

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