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数学模型表明目前的CAR巨剂量对低注前瘤负担有效,但对高瘤负担耐火

Shilian Xu¹, Maoxuan Liu²

¹Department of Environment and Genetics, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, Australia; Department of Mathematics and Statistics, La Trobe University, Centre for Epidemiology and Biostatistics, Bundoora, Australia; Faculty of Biology, Technion-Israel Institute of Technology, Haifa, Israel.

Journal of theoretical biology

|September 6, 2025

概括

化学抗原受体 (CAR) - 巨细胞疗法对癌症治疗具有前景. 数学模型显示最佳剂量和瘤负担对于有效的CAR巨细胞治疗结果至关重要.

科学领域:

免疫疗法
数学生物学
癌症学

背景情况:

化学抗原受体 (CAR) - 巨细胞疗法提供了一种新的癌症治疗策略,通过利用抗原特异性细胞酶来清除瘤.
关键因素,如瘤负担和剂量策略对CAR巨细胞治疗的疗效的影响尚不充分理解.
了解这些参数对于优化治疗方案和改善患者的结果至关重要.

研究的目的:

研究瘤负担和剂量方案对CAR巨细胞治疗的有效性的影响.
开发一个数学模型来分析体外数据并预测治疗结果.
为各种瘤负担确定最佳的CAR巨剂量策略.

主要方法:

使用普通微分方程 (ODE) 数学建模来模拟CAR-巨细胞相互作用.
使用参数推断技术分析基于FACS的体外细胞测定数据.
模拟了各种剂量方案和瘤负担,以评估治疗效果.

主要成果:

随着细胞度的增加,CAR-巨的细胞效率会增加,但会达到和.
瘤细胞动力学表现出双稳定性,在某些CAR巨细胞度下,低负荷被清除,高负荷持续存在.
目前的临床试验剂量仅对较低的瘤负担有效;分割输液受益于较高的初始剂量.

结论:

瘤负担和服用时间表对CAR巨细胞治疗的疗效有显著影响.
减少瘤负担,最大限度地提高CAR巨细胞的初始剂量,并确保长时间的CAR巨细胞持续性是持久反应的关键.
不管最初的瘤负担如何,替代剂量方案,如每月或每两月输注,都显示出持续瘤抑制的潜力.

关键词:

B细胞急性淋巴细胞白血病双向性一个 CAR 巨剂量安排免疫疗法输液剂量淋巴瘤瘤负担

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