Chimeric Antigen Receptor T Cell Therapies: A Review of Cellular Kinetic‐Pharmacodynamic Modeling Approaches
Anwesha Chaudhury, Xu Zhu, Lulu Chu, Ardeshir Goliaei, Carl H. June, Jeffrey D. Kearns, Andrew M. Stein
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.