Chimeric Antigen Receptor T Cell Therapies: A Review of Cellular Kinetic-Pharmacodynamic Modeling Approaches
Anwesha Chaudhury PhD
Pharmacometrics, Novartis Institutes of BioMedical Research, Cambridge, Massachusetts, USA
Search for more papers by this authorXu Zhu PhD
PK Sciences Oncology, Novartis Institutes of BioMedical Research, Cambridge, Massachusetts, USA
Search for more papers by this authorLulu Chu PhD
PK Sciences Modeling & Simulation, Novartis Institutes of BioMedical Research, Cambridge, Massachusetts, USA
Search for more papers by this authorArdeshir Goliaei PharmD, PhD
PK Sciences Modeling & Simulation, Novartis Institutes of BioMedical Research, Cambridge, Massachusetts, USA
Search for more papers by this authorCarl H. June MD
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Search for more papers by this authorJeffrey D. Kearns PhD
PK Sciences Modeling & Simulation, Novartis Institutes of BioMedical Research, Cambridge, Massachusetts, USA
Search for more papers by this authorCorresponding Author
Andrew M. Stein PhD
Pharmacometrics, Novartis Institutes of BioMedical Research, Cambridge, Massachusetts, USA
Corresponding Author:
Andrew M. Stein, PhD, Pharmacometrics, Novartis Institutes of BioMedical Research, 220 Massachusetts Avenue, Cambridge, MA 02139
Email: [email protected]
Search for more papers by this authorAnwesha Chaudhury PhD
Pharmacometrics, Novartis Institutes of BioMedical Research, Cambridge, Massachusetts, USA
Search for more papers by this authorXu Zhu PhD
PK Sciences Oncology, Novartis Institutes of BioMedical Research, Cambridge, Massachusetts, USA
Search for more papers by this authorLulu Chu PhD
PK Sciences Modeling & Simulation, Novartis Institutes of BioMedical Research, Cambridge, Massachusetts, USA
Search for more papers by this authorArdeshir Goliaei PharmD, PhD
PK Sciences Modeling & Simulation, Novartis Institutes of BioMedical Research, Cambridge, Massachusetts, USA
Search for more papers by this authorCarl H. June MD
Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Search for more papers by this authorJeffrey D. Kearns PhD
PK Sciences Modeling & Simulation, Novartis Institutes of BioMedical Research, Cambridge, Massachusetts, USA
Search for more papers by this authorCorresponding Author
Andrew M. Stein PhD
Pharmacometrics, Novartis Institutes of BioMedical Research, Cambridge, Massachusetts, USA
Corresponding Author:
Andrew M. Stein, PhD, Pharmacometrics, Novartis Institutes of BioMedical Research, 220 Massachusetts Avenue, Cambridge, MA 02139
Email: [email protected]
Search for more papers by this authorAbstract
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.
Conflicts of Interest
A.C., X.Z., L.C., A.G., J.D.K., and A.M.S. are current employees of Novartis. J.D.K. and A.M.S. hold equity interests in Novartis. C.H.J. received research support from Novartis Pharmaceuticals Corporation, received honoraria from and is a member of the board of directors or advisory committee for Western Institutional Review Board Copernicus Group and Celldex, owns equity in and is a member of a board of directors or advisory committee for Immune Design, has patents and royalties with Novartis Pharmaceuticals Corporation, and received research funding from Tmunity Therapeutics.
Supporting Information
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