Understanding the role of B-cells in CAR T-cell therapy in leukemia through a mathematical model
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| Main Authors: | , , , , |
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| Format: | Preprint |
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2024
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| _version_ | 1866914700652969984 |
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| author | Serrano, Sergio Barrio, Roberto Martínez-Rubio, Álvaro Belmonte-Beitia, Juan Pérez-García, Víctor M. |
| author_facet | Serrano, Sergio Barrio, Roberto Martínez-Rubio, Álvaro Belmonte-Beitia, Juan Pérez-García, Víctor M. |
| contents | 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. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2403_00340 |
| institution | arXiv |
| publishDate | 2024 |
| record_format | arxiv |
| spellingShingle | Understanding the role of B-cells in CAR T-cell therapy in leukemia through a mathematical model Serrano, Sergio Barrio, Roberto Martínez-Rubio, Álvaro Belmonte-Beitia, Juan Pérez-García, Víctor M. Dynamical Systems Quantitative Methods 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. |
| title | Understanding the role of B-cells in CAR T-cell therapy in leukemia through a mathematical model |
| topic | Dynamical Systems Quantitative Methods |
| url | https://arxiv.org/abs/2403.00340 |