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Chimeric Antigen Receptor T Cell Therapies: A Review of Cellular Kinetic‐Pharmacodynamic Modeling Approaches
Author(s) -
Chaudhury Anwesha,
Zhu Xu,
Chu Lulu,
Goliaei Ardeshir,
June Carl H.,
Kearns Jeffrey D.,
Stein Andrew M.
Publication year - 2020
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.1691
Subject(s) - chimeric antigen receptor , immunophenotyping , cytokine release syndrome , cd19 , computational biology , antigen , t cell , biology , immunology , immune system
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.