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

• Published in: Chaos (Woodbury, N.Y.) N.Y.), 2024-08, Vol.34 (8)
• Main Authors: Serrano, Sergio, Barrio, Roberto, Martínez-Rubio, Álvaro, Belmonte-Beitia, Juan, Pérez-García, Víctor M.
• Format: Article
• Language: English
• Subjects: B-Lymphocytes - immunology; Bifurcations; Humans; Immunotherapy, Adoptive - methods; Impact analysis; Leukemia; Leukemia - immunology; Leukemia - therapy; Lymphocytes; Mathematical models; Models, Biological; Receptors, Chimeric Antigen - immunology; T-Lymphocytes - immunology; Therapy; Tumors
• ISSN: 1054-1500; 1089-7682; 1089-7682
• DOI: 10.1063/5.0206341

Chimeric antigen receptor T (CAR T) cell therapy has been proven to be successful against a variety of leukemias and lymphomas. This paper undertakes an analytical and numerical study of a mathematical model describing the competition of CAR T, leukemia, tumor, and B cells. Considering its significance in sustaining anti-CD19 CAR T-cell stimulation, a B-cell source term is integrated into the model. Through stability and bifurcation analyses, the potential for tumor eradication, contingent on the continuous influx of B cells, has been revealed, showing a transcritical bifurcation at a critical B-cell input. Additionally, an almost heteroclinic cycle between equilibrium points is identified, providing a theoretical basis for understanding disease relapse. Analyzing the oscillatory behavior of the system, the time-dependent dynamics of CAR T cells and leukemic cells can be approximated, shedding light on the impact of initial tumor burden on therapeutic outcomes. In conclusion, the 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.