关于胶质母细胞瘤 CAR-T 细胞疗法数学模型的分析:数学模型的启示

M. Bodnar, U. Foryś, M. Piotrowska, Mariusz Bodzioch, J. A. Romero-Rosales, J. Belmonte-Beitia
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摘要

摘要 嵌合抗原受体 T(CAR-T)细胞疗法已被证明能成功治疗各种白血病和淋巴瘤。近年来,它的成功促使人们开始对不同的实体瘤进行试验,其中包括胶质母细胞瘤,这是一种以侵袭性和复发性为特征的原发性脑肿瘤。本文介绍了一个数学模型的分析研究,该模型描述了 CAR-T 与胶质母细胞瘤肿瘤细胞之间的竞争,同时考虑到了它们的免疫抑制能力。该模型以一般的方式制定,并对其基本特性进行了研究。不过,大部分分析考虑的是肿瘤指数增长模型,为简单起见,假设了这种增长类型。研究了稳态的存在和稳定性,随后重点讨论了两种不同类型的治疗:恒定治疗和周期治疗。最后,数值推导了胶质母细胞瘤的 CAR-T 细胞治疗方案;这些方案旨在防止肿瘤达到临界大小,并尽可能延长患者的生存时间。分析和数值结果为使用 CAR-T 细胞治疗胶质母细胞瘤提供了理论支持。
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On the Analysis of a Mathematical Model of CAR–T Cell Therapy for Glioblastoma: Insights from a Mathematical Model
Abstract Chimeric antigen receptor T (CAR-T) cell therapy has been proven to be successful against different leukaemias and lymphomas. Its success has led, in recent years, to its use being tested for different solid tumours, including glioblastoma, a type of primary brain tumour, characterised by aggressiveness and recurrence. This paper presents an analytical study of a mathematical model describing the competition of CAR-T and glioblastoma tumour cells, taking into account their immunosuppressive capacity. The model is formulated in a general way, and its basic properties are investigated. However, most of the analysis considers the model with exponential tumour growth, assuming this growth type for simplicity. The existence and stability of steady states are studied, and the subsequent focus is on two different types of treatment: constant and periodic. Finally, protocols for CAR-T cell therapy of glioblastoma are numerically derived; these are aimed at preventing the tumour from reaching a critical size and at prolonging the patients’ survival time as much as possible. The analytical and numerical results provide theoretical support for the treatment of glioblastoma using CAR-T cells.
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