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通过数学模型理解 B 细胞在白血病 CAR-T 细胞治疗中的作用

英文原题:Understanding the role of B cells in CAR T-cell therapy in leukemia through a mathematical model.

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

PubMed 2024/08/01(内容时间) Chaos Q1 · IF 3.3(JCR 2025)

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中文摘要

CAR-T(CAR-T)细胞疗法已被证明可成功治疗多种白血病和淋巴瘤。本文对描述CAR-T、白血病、肿瘤和B细胞竞争的数学模型进行了分析和数值研究。考虑到B细胞在维持抗CD19 CAR-T 细胞刺激中的重要性,模型中整合了一个B细胞来源项。通过稳定性和分岔分析,揭示了肿瘤清除的可能性依赖于B细胞的持续流入,并在临界B细胞输入处显示出跨临界分岔。此外,还识别出平衡点之间近乎异宿环的现象,为理解疾病复发提供了理论基础。通过分析系统的振荡行为,可以近似CAR-T 细胞和白血病细胞的时间依赖性动态,从而揭示初始肿瘤负荷对治疗结果的影响。总之,该研究为急性淋巴细胞白血病的CAR-T 细胞治疗动态提供了见解,为临床观察提供了理论基础,并为未来免疫治疗建模研究指明了方向。

展开英文摘要原文

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.

论文信息

作者
Serrano S、Barrio R、Martínez-Rubio Á、Belmonte-Beitia J、Pérez-García VM
第一作者单位
IUMA, CoDy and Department of Applied Mathematics, Universidad de Zaragoza, Zaragoza 50009, Spain.Spain
通讯作者单位
Mathematical Oncology Laboratory (MOLAB), Departament of Mathematics, Instituto de Matemática Aplicada a la Ciencia y la Ingeniería, Universidad de Castilla-La Mancha, Ciudad Real 13071, Spain.Spain
文献类型
非美国政府资助研究
期刊
Chaos (Woodbury, N.Y.)2024 Aug 1
原文标识
PubMed 39191245 · DOI 10.1063/5.0206341