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

J Clin Pharmacol. 2020 Oct:60 Suppl 1:S147-S159. doi: 10.1002/jcph.1691.

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.

Keywords: cellular kinetic-pharmacodynamic model; chimeric antigen receptor-T cell (CAR-T cell) therapy; model-informed drug development (MIDD); quantitative systems pharmacology (QSP).

Publication types

  • Review

MeSH terms

  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / metabolism
  • Hematologic Neoplasms / therapy
  • Humans
  • Immunotherapy, Adoptive*
  • Kinetics
  • Models, Biological*
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Chimeric Antigen / immunology
  • Receptors, Chimeric Antigen / metabolism*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen