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

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.