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arXiv · 2403.00340

Understanding the role of B-cells in CAR T-cell therapy in leukemia through a mathematical model

Sergio Serrano·Roberto Barrio·Álvaro Martínez-Rubio·Juan Belmonte-Beitia·Víctor M. Pérez-García
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Abstract

Chimeric Antigen Receptor T (CAR-T) cell therapy has been proven to be successful against different leukaemias and lymphomas. This paper makes an analytical and numerical study of a mathematical model describing the competition of CAR-T, leukaemias tumor and B cells. Considering its significance in sustaining anti-CD19 CAR T-cell stimulation, we integrate a B-cell source term into the model. Through stability and bifurcation analyses, we reveal the potential for tumor eradication contingent on the continuous influx of B-cells, uncovering a transcritical bifurcation at a critical B-cell input. Additionally, we identify an almost heteroclinic cycle between equilibrium points, providing a theoretical basis for understanding disease relapse. Analyzing the oscillatory behavior of the system, we approximate the time-dependent dynamics of CAR T-cells and leukemic cells, shedding light on the impact of initial tumor burden on therapeutic outcomes. In conclusion, our study provides insights into CAR T-cell therapy dynamics for acute lymphoblastic leukemias, offering a theoretical foundation for clinical observations and suggesting avenues for future immunotherapy modeling research.

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Sergio Serrano, Roberto Barrio, Álvaro Martínez-Rubio, Juan Belmonte-Beitia, Víctor M. Pérez-García. 2024-03-01. Understanding the role of B-cells in CAR T-cell therapy in leukemia through a mathematical model. https://arxiv.org/abs/2403.00340

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