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

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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.

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Acknowledgements

The authors thank Gwendolyn Halford, FDA Library, for curating the literature search queries. We would like to thank Joanne Berger and Daniel Sloper, FDA Library, for editing the manuscript.

Funding

This project was supported in part by an appointment to the Research Participation Program at OBE/CBER, U.S. Food and Drug Administration, administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the FDA.

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Authors and Affiliations

  1. Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research, US FDA, Silver Spring, Maryland, USA

    Ujwani Nukala, Marisabel Rodriguez Messan, Osman N. Yogurtcu & Hong Yang

  2. Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, US FDA, Silver Spring, Maryland, USA

    Xiaofei Wang

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  1. Ujwani Nukala
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  2. Marisabel Rodriguez Messan
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  4. Xiaofei Wang
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  5. Hong Yang
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Contributions

Conceptualization: UN, MRM, ONY, HY

Data curation: UN, ONY

Formal analysis: UN, MRM, ONY, XW

Funding acquisition: HY

Investigation: UN, MRM, ONY, XW

Methodology: UN, ONY

Project administration: ONY, HY

Resources: HY

Supervision: HY

Visualization: UN, MRM

Writing—original draft: UN, MRM, ONY, XW, HY

Writing—review and editing: UN, MRM, ONY, XW, HY

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Correspondence to Hong Yang.

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Nukala, U., Rodriguez Messan, M., Yogurtcu, O.N. et al. A Systematic Review of the Efforts and Hindrances of Modeling and Simulation of CAR T-cell Therapy. AAPS J 23, 52 (2021). https://doi.org/10.1208/s12248-021-00579-9

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