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

Serrano, Sergio (Universidad de Zaragoza) ; Barrio, Roberto (Universidad de Zaragoza) ; Martínez-Rubio, Álvaro ; Belmonte-Beitia, Juan ; Pérez-García, Víctor M.

Resumen: 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.

Idioma: Inglés

DOI: 10.1063/5.0206341

Año: 2024

Publicado en: CHAOS 34, 8 (2024), [15 pp.]
ISSN: 1054-1500

Factor impacto JCR: 3.2 (2024)

Categ. JCR: PHYSICS, MATHEMATICAL rank: 5 / 61 = 0.082 (2024) - Q1 - T1
Categ. JCR: MATHEMATICS, APPLIED rank: 13 / 343 = 0.038 (2024) - Q1 - T1

Factor impacto CITESCORE: 4.8 - Engineering (all) (Q1) - Applied Mathematics (Q1) - Mathematical Physics (Q1) - Statistical and Nonlinear Physics (Q1) - Physics and Astronomy (all) (Q2)

Factor impacto SCIMAGO: 0.77 - Physics and Astronomy (miscellaneous) (Q1) - Mathematical Physics (Q2) - Statistical and Nonlinear Physics (Q2) - Applied Mathematics (Q2) - Medicine (miscellaneous) (Q2)

Financiación: info:eu-repo/grantAgreement/ES/AEI/PID2022-140341OB-I00
Financiación: info:eu-repo/grantAgreement/ES/AEI/PID2022-140451OB-I00
Financiación: info:eu-repo/grantAgreement/ES/DGA/E24-23R
Financiación: info:eu-repo/grantAgreement/ES/DGA/LMP 94-21

Tipo y forma: Article (PostPrint)

Área (Departamento): Área Matemática Aplicada (Dpto. Matemática Aplicada)