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CAR-T 细胞的体内制备与调控以提升成药性

英文原题:In vivo manufacture and manipulation of CAR-T cells for better druggability.

查看英文原题

In vivo manufacture and manipulation of CAR-T cells for better druggability.

PubMed 2024/04/09(内容时间) Cancer Metastasis Rev Q1 · IF 12.7(JCR 2025)

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中文摘要

目前CAR-T 细胞治疗产品的药物开发潜力受到多方面制约,包括个体化制备需求、药代动力学特征不明确以及不良反应难以预测。实现标准化生产并明确疗效和药代动力学特征,是确保CAR-T 细胞疗法作为药物有效、切实应用的前提。本综述全面介绍了体内调控CAR-T 细胞行为的不同方法。利用基因修饰载体可在体内生成CAR-T 细胞,从而缩短或跳过漫长的体外扩增过程。通过为CAR-T 细胞装配精细设计的控制元件,并利用分子开关或小分子抑制剂,可调控CAR-T 细胞活性。此外,对CAR-T 细胞活性进行开关控制可能有助于其表型重塑。这些方法为未来开发安全、可控、便捷且适合标准化生产的CAR-T 细胞治疗产品提供了有益参考。

展开英文摘要原文

The current CAR-T cell therapy products have been hampered in their druggability due to the personalized preparation required, unclear pharmacokinetic characteristics, and unpredictable adverse reactions. Enabling standardized manufacturing and having clear efficacy and pharmacokinetic characteristics are prerequisites for ensuring the effective practicality of CAR-T cell therapy drugs.

This review provides a broad overview of the different approaches for controlling behaviors of CAR-T cells in vivo. The utilization of genetically modified vectors enables in vivo production of CAR-T cells, thereby abbreviating or skipping the lengthy in vitro expansion process. By equipping CAR-T cells with intricately designed control elements, using molecule switches or small-molecule inhibitors, the control of CAR-T cell activity can be achieved.

Moreover, the on-off control of CAR-T cell activity would yield potential gains in phenotypic remodeling. These methods provide beneficial references for the future development of safe, controllable, convenient, and suitable for standardized production of CAR-T cell therapy products.

论文信息

作者
Hou R、Zhang X、Wang X、Zhao X、Li S、Guan Z、Cao J、Liu D
第一作者单位
College of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, China.China
通讯作者单位
Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China. mingshi@xzhmu.edu.cn.China
文献类型
综述 · 非美国政府资助研究
期刊
Cancer metastasis reviews2024 Sep
原文标识
PubMed 38592427 · DOI 10.1007/s10555-024-10185-8