Mathematical Model of Leukemia Treatment with Chimeric Antigen Receptor (CAR) T Cell Therapy

Mia Siti Khumaeroh, Mar Atus Shalehah, F. Ilahi
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Abstract

Leukemia, a type of blood cancer that originates in the bone marrow, is characterized by the uncontrolled growth of abnormal blood cells, which disrupt the normal functioning of blood cells. Chimeric antigen receptor (CAR) T-cell treatment, a form of immunotherapy, utilizes genetically modified T cells to specifically target and eliminate cancer cells. This treatment has shown promising results for leukemia patients who are unresponsive to chemotherapy or other therapies, as well as those who experience relapses.  In this study, we develop a mathematical model of leukemia that incorporates chimeric antigen receptor (CAR) T-cell therapy. The model takes into account the logistic intrinsic growth rate of leukemia cells, which gradually declines over time due to limited resources within the body. There are four compartments in this model: susceptible blood cells, infected blood cells, leukemia cells, and immune cells. We have analyzed the equilibrium points and their local stability, determined the basic reproduction number, and conducted a sensitivity analysis.  Through numerical simulations, we observed that prior to treatment, the number of leukemia cells in the blood escalated rapidly towards endemic conditions. However, after receiving CAR T-cell therapy through external infusion, the leukemia cells either became extinct or took a significant amount of time to reach endemic levels in the blood. Sensitivity analysis revealed that the growth rate of cancer cells (r) and the death rate of immune cells (significantly contribute to the increase in the basic reproduction number (.
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CAR - T细胞治疗白血病的数学模型
白血病是一种起源于骨髓的血癌,其特点是异常血细胞不受控制地生长,从而破坏血细胞的正常功能。嵌合抗原受体(CAR) T细胞治疗是免疫治疗的一种形式,利用基因修饰的T细胞特异性靶向和消除癌细胞。对于那些对化疗或其他疗法没有反应的白血病患者,以及那些经历复发的患者,这种治疗已经显示出令人鼓舞的结果。在这项研究中,我们开发了一个白血病的数学模型,结合嵌合抗原受体(CAR) t细胞治疗。该模型考虑了白血病细胞的逻辑固有生长速率,由于体内资源有限,随着时间的推移,白血病细胞的生长速率逐渐下降。这个模型中有四个区室:易感血细胞、感染血细胞、白血病细胞和免疫细胞。分析了平衡点及其局部稳定性,确定了基本繁殖数,并进行了灵敏度分析。通过数值模拟,我们观察到,在治疗之前,血液中的白血病细胞数量迅速升级到地方性条件。然而,在通过外部输注接受CAR - t细胞治疗后,白血病细胞要么灭绝,要么需要很长时间才能达到血液中的地方性水平。敏感性分析显示,癌细胞的生长率(r)和免疫细胞的死亡率(r)对基本繁殖数(r)的增加有显著贡献。
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