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

Author:

Serrano Sergio1ORCID,Barrio Roberto1ORCID,Martínez-Rubio Álvaro23ORCID,Belmonte-Beitia Juan4ORCID,Pérez-García Víctor M.4ORCID

Affiliation:

1. IUMA, CoDy and Department of Applied Mathematics, Universidad de Zaragoza 1 , Zaragoza 50009, Spain

2. Department of Mathematics, Universidad de Cádiz 2 , Puerto Real, Cádiz 11510, Spain

3. Biomedical Research and Innovation Institute of Cádiz (INiBICA), Hospital Universitario Puerta del Mar 3 , Cádiz 11002, Spain

4. Mathematical Oncology Laboratory (MOLAB), Departament of Mathematics, Instituto de Matemática Aplicada a la Ciencia y la Ingeniería, Universidad de Castilla-La Mancha 4 , Ciudad Real 13071, Spain

Abstract

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.

Funder

Ministerio de Ciencia e Innovación

Junta de Comunidades de Castilla-La Mancha

Universidad de Castilla-La Mancha

Diputación General de Aragón

Publisher

AIP Publishing

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