Mathematical model for IL-2-based cancer immunotherapy

IF 1.9 4区 数学 Q2 BIOLOGY
Megan Dixon , Tuan Anh Phan , J.C. Dallon , Jianjun Paul Tian
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Abstract

A basic mathematical model for IL-2-based cancer immunotherapy is proposed and studied. Our analysis shows that the outcome of therapy is mainly determined by three parameters, the relative death rate of CD4+ T cells, the relative death rate of CD8+ T cells, and the dose of IL-2 treatment. Minimal equilibrium tumor size can be reached with a large dose of IL-2 in the case that CD4+ T cells die out. However, in cases where CD4+ and CD8+ T cells persist, the final tumor size is independent of the IL-2 dose and is given by the relative death rate of CD4+ T cells. Two groups of in silico clinical trials show some short-term behaviors of IL-2 treatment. IL-2 administration can slow the proliferation of CD4+ T cells, while high doses for a short period of time over several days transiently increase the population of CD8+ T cells during treatment before it recedes to its equilibrium. IL-2 administration for a short period of time over many days suppresses the tumor population for a longer time before approaching its steady-state levels. This implies that intermittent administration of IL-2 may be a good strategy for controlling tumor size.

基于 IL-2 的癌症免疫疗法数学模型
我们提出并研究了基于IL-2的癌症免疫疗法的基本数学模型。我们的分析表明,治疗结果主要由三个参数决定,即 CD4+ T 细胞的相对死亡率、CD8+ T 细胞的相对死亡率和 IL-2 治疗剂量。在 CD4+ T 细胞死亡的情况下,大剂量的 IL-2 可以达到最小平衡肿瘤大小。然而,在 CD4+ 和 CD8+ T 细胞持续存在的情况下,最终的肿瘤大小与 IL-2 剂量无关,而是由 CD4+ T 细胞的相对死亡率决定的。有两组硅学临床试验显示了 IL-2 治疗的一些短期行为。IL-2可以减缓CD4+ T细胞的增殖,而几天内短期大剂量的IL-2会在治疗期间短暂增加CD8+ T细胞的数量,然后再恢复到平衡状态。多天短期服用 IL-2 可在较长时间内抑制肿瘤细胞数量,然后再接近其稳态水平。这意味着间歇性给药 IL-2 可能是控制肿瘤大小的良好策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Mathematical Biosciences
Mathematical Biosciences 生物-生物学
CiteScore
7.50
自引率
2.30%
发文量
67
审稿时长
18 days
期刊介绍: Mathematical Biosciences publishes work providing new concepts or new understanding of biological systems using mathematical models, or methodological articles likely to find application to multiple biological systems. Papers are expected to present a major research finding of broad significance for the biological sciences, or mathematical biology. Mathematical Biosciences welcomes original research articles, letters, reviews and perspectives.
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