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在微流控肝内肿瘤模型中研究TCR T细胞的抗肿瘤活性。

Studying TCR T cell anti-tumor activity in a microfluidic intrahepatic tumor model.

作者信息

Adriani Giulia, Pavesi Andrea, Kamm Roger D

机构信息

BioSystems and Micromechanics IRG, Singapore-MIT Alliance for Research and Technology, Singapore, Singapore.

Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research, Singapore, Singapore.

出版信息

Methods Cell Biol. 2018;146:199-214. doi: 10.1016/bs.mcb.2018.05.009. Epub 2018 Jul 12.

Abstract

Adoptive cell therapy (ACT) is showing promising results in clinical trials but many challenges remain in understanding the key role of the tumor microenvironment. These challenges constitute a major barrier to advancing the field. Therefore, it is crucial to perform preclinical tests of the developed ACT strategies in a fast and reproducible way to assess the potential for patient therapy. Here, we describe the development of an intrahepatic tumor model in a microfluidic device for screening T cell-based immunotherapeutic strategies and the role of monocytes in these therapies. This system can be used to test also the effects of supporting cytokine administration and changes in oxygen level that are typically found in a liver tumor microenvironment. As a result, these 3D microfluidic assays provide a means to quantify T cell anti-tumor activity under different conditions to optimize existing therapeutic strategies or the design of new ones.

摘要

过继性细胞疗法(ACT)在临床试验中显示出了有前景的结果,但在理解肿瘤微环境的关键作用方面仍存在许多挑战。这些挑战构成了该领域发展的主要障碍。因此,以快速且可重复的方式对已开发的ACT策略进行临床前测试,以评估其用于患者治疗的潜力至关重要。在此,我们描述了一种用于筛选基于T细胞的免疫治疗策略以及单核细胞在这些治疗中的作用的微流控装置中的肝内肿瘤模型的开发。该系统还可用于测试支持性细胞因子给药的效果以及肝肿瘤微环境中常见的氧水平变化的影响。因此,这些三维微流控分析提供了一种手段,可在不同条件下量化T细胞的抗肿瘤活性,以优化现有治疗策略或设计新的治疗策略。

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