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使用定量系统药理建模来优化抗PD-L1检查点抑制剂和T细胞参与者的联合治疗

Samira Anbari¹, Hanwen Wang¹, Yu Zhang¹

¹Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States.

Frontiers in pharmacology

|July 6, 2023

概括

一个新的定量系统药理学平台模型结直肠癌免疫疗法. 这种方法优化了与检查点抑制剂和双特异性T细胞参与剂的联合治疗,以改善患者的治疗结果.

科学领域:

免疫瘤学免疫瘤学
药理学药理学是指药理学的学科.
计算生物学是一种计算生物学.

背景情况:

免疫检查点抑制剂 (ICI) 在结直肠癌 (CRC) 中显示出有限的疗效.
双特异性T细胞参与剂 (TCEs) 增强T细胞激活和抗瘤反应.
结合ICI和TCE可能会改善CRC治疗结果,但尚不清楚最佳策略.

研究的目的:

开发一个模块化的定量系统药理学 (QSP) 平台用于CRC的免疫瘤学.
模拟PD-L1抑制剂 (阿特佐利祖马布) 和TCE (cibisatamab) 的联合治疗的虚拟临床试验.
优化剂量方案和评估药物协同作用,以改善CRC治疗.

主要方法:

开发了一种QSP模型,整合了CRC特有的免疫癌细胞相互作用.
为 *in silico* 临床试验创建了一个虚拟患者队列.
使用临床试验数据对模型进行校准.
进行虚拟试验,比较不同的阿特佐利祖马布和西比萨塔马布剂量和时间表.
对组合治疗的量化药物协同效应得分.

主要成果:

该QSP平台成功模拟了组合治疗的虚拟临床试验.
评估了阿特佐利祖马布和西比萨他马布的各种剂量方案和时间表.
药物协同效应得分被量化,提供了对组合疗效的见解.
该模型促进了治疗策略的*in silico*优化.

结论:

开发的QSP平台是优化CRC免疫瘤组合疗法的宝贵工具.
虚拟临床试验可以指导选择最佳剂量和时间表,以改善患者的反应.
了解药物协同作用对于最大化结合检查点抑制剂和TCEs在CRC治疗中的好处至关重要.

关键词:

双特异性T细胞参与者.剂量优化剂量优化免疫检查点抑制剂免疫检查点抑制剂免疫瘤学免疫瘤学定量系统药理学 (QSP) 是一种虚拟临床试验是虚拟的临床试验.

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