A Systematic Review of the Efforts and Hindrances of Modeling and Simulation of CAR T-cell Therapy

Abstract

Chimeric antigen receptor (CAR) T-cell therapy is an immunotherapy that has recently become highly instrumental in the fight against life-threatening diseases. A variety of modeling and computational simulation efforts have addressed different aspects of CAR T-cell therapy, including T-cell activation, T- and malignant cell population dynamics, therapeutic cost-effectiveness strategies, and patient survival. In this article, we present a systematic review of those efforts, including mathematical, statistical, and stochastic models employing a wide range of algorithms, from differential equations to machine learning. To the best of our knowledge, this is the first review of all such models studying CAR T-cell therapy. In this review, we provide a detailed summary of the strengths, limitations, methodology, data used, and data gap in currently published models. This information may help in designing and building better models for enhanced prediction and assessment of the benefit-risk balance associated with novel CAR T-cell therapies, as well as with the data need for building such models.

Keywords: CAR T-cell therapy; cost-effectiveness; modeling and simulation; pharmacokinetics-pharmacodynamics; survival analysis.