Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Modeling Patient-Specific CAR-T Cell Dynamics: Multiphasic Kinetics Via Phenotypic Differentiation

Version 1 : Received: 23 September 2022 / Approved: 23 September 2022 / Online: 23 September 2022 (05:33:24 CEST)

How to cite: Paixão, E.A.; Barros, L.R.C.; Fassoni, A.C.; Almeida, R.C.C.D. Modeling Patient-Specific CAR-T Cell Dynamics: Multiphasic Kinetics Via Phenotypic Differentiation. Preprints 2022, 2022090359 (doi: 10.20944/preprints202209.0359.v1). Paixão, E.A.; Barros, L.R.C.; Fassoni, A.C.; Almeida, R.C.C.D. Modeling Patient-Specific CAR-T Cell Dynamics: Multiphasic Kinetics Via Phenotypic Differentiation. Preprints 2022, 2022090359 (doi: 10.20944/preprints202209.0359.v1).

Abstract

Chimeric Antigen Receptor (CAR)-T cell immunotherapy revolutionized cancer treatment and consists of the genetic modification of T lymphocytes with a CAR gene, aiming to increase their ability to recognize and kill antigen-specific tumor cells. The dynamics of CAR-T cell responses in patients presents a multiphasic kinetics with distribution, expansion, contraction, and persistence phases. The characteristics and duration of each phase depend on the tumor type, the infused product, and on patient-specific characteristics. We present a mathematical model which describes the multiphasic CAR-T cell dynamics resulting from the interplay between CAR-T and tumor cells, considering patient and product heterogeneities. The CAR-T cell population is divided into functional (distributed and effector), memory, and exhausted CAR-T cell phenotypes. The model is able to describe the diversity of CAR-T cell dynamic behaviors in different patients and hematological cancers as well as their therapy outcomes. Our results indicate that the joint assessment of the area under the concentration-time curve in the first 28 days and the corresponding fraction of non-exhausted CAR-T cells may be considered as potential markers to classify therapy responses. Overall, the analysis of different CAR-T cell phenotypes can be a key aspect for a better understanding of the whole CAR-T cell dynamics.

Keywords

Hematological malignancies; treatment outcomes; CAR-T cell exhaustion; memory 22 pool, functional CAR-T cells; antigen dependent CAR-T expansion

Subject

MATHEMATICS & COMPUTER SCIENCE, Applied Mathematics

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.

We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.