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CAR T cells for T-cell leukemias: Insights from mathematical models
Communications in Nonlinear Science and Numerical Simulation ( IF 3.9 ) Pub Date : 2020-12-23 , DOI: 10.1016/j.cnsns.2020.105684
Víctor M. Pérez-García , Odelaisy León-Triana , María Rosa , Antonio Pérez-Martínez

Immunotherapy has the potential to change the way all cancer types are treated and cured. Cancer immunotherapies use elements of the patient immune system to attack tumor cells. One of the most successful types of immunotherapy is CAR-T cells. This treatment works by extracting patient’s T-cells and adding to them an antigen receptor allowing tumor cells to be recognized and targeted. These new cells are called CAR-T cells and are re-infused back into the patient after expansion in-vitro. This approach has been successfully used to treat B-cell malignancies (B-cell leukemias and lymphomas). However, its application to the treatment of T-cell leukemias faces several problems. One of these is fratricide, since the CAR-T cells target both tumor and other CAR-T cells. This leads to nonlinear dynamical phenomena amenable to mathematical modeling. In this paper we construct a mathematical model describing the competition of CAR-T, tumor and normal T-cells and studied some basic properties of the model and its practical implications. Specifically, we found that the model reproduced the observed difficulties for in-vitro expansion of the therapeutic cells found in the laboratory. The mathematical model predicted that CAR-T cell expansion in the patient would be possible due to the initial presence of a large number of targets. We also show that, in the context of our mathematical approach, CAR-T cells could control tumor growth but not eradicate the disease.



中文翻译:

T细胞白血病的CAR T细胞:数学模型的见解

免疫疗法有可能改变所有癌症类型的治疗和治愈方式。癌症免疫疗法利用患者免疫系统的成分攻击肿瘤细胞。免疫疗法最成功的类型之一是CAR-T细胞。这种治疗方法是通过提取患者的T细胞并向其添加抗原受体,从而使肿瘤细胞得以识别和靶向。这些新细胞被称为CAR-T细胞,并在体外扩增后重新注入患者体内。该方法已成功用于治疗B细胞恶性肿瘤(B细胞白血病和淋巴瘤)。然而,将其用于治疗T细胞白血病面临若干问题。其中之一是杀人剂,因为CAR-T细胞同时靶向肿瘤和其他CAR-T细胞。这导致了适合于数学建模的非线性动力学现象。在本文中,我们构建了描述CAR-T,肿瘤和正常T细胞竞争的数学模型,并研究了该模型的一些基本特性及其实际意义。具体而言,我们发现该模型再现了在实验室中发现的治疗性细胞体外扩增的观察到的困难。数学模型预测,由于最初存在大量靶标,因此可能在患者体内扩增CAR-T细胞。我们还表明,在我们的数学方法的背景下,CAR-T细胞可以控制肿瘤的生长,但不能根除疾病。我们发现该模型再现了在实验室中发现的治疗性细胞体外扩增的观察到的困难。数学模型预测,由于最初存在大量靶标,因此可能在患者体内扩增CAR-T细胞。我们还表明,在我们的数学方法的背景下,CAR-T细胞可以控制肿瘤的生长,但不能根除疾病。我们发现该模型再现了在实验室中发现的治疗性细胞体外扩增的观察到的困难。数学模型预测,由于最初存在大量靶标,因此可能在患者体内扩增CAR-T细胞。我们还表明,在我们的数学方法的背景下,CAR-T细胞可以控制肿瘤的生长,但不能根除疾病。

更新日期:2020-12-29
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