药学学报, 2019, 54(12): 2209-2213
引用本文:
王秋霞, 时丽丽. 开关型嵌合抗原受体T细胞的研究进展[J]. 药学学报, 2019, 54(12): 2209-2213.
WANG Qiu-xia, SHI Li-li. Progress in research of switchable chimeric antigen receptor T cells[J]. Acta Pharmaceutica Sinica, 2019, 54(12): 2209-2213.

开关型嵌合抗原受体T细胞的研究进展
王秋霞1, 时丽丽2
1. 西安交通大学医学部药学院, 陕西 西安 710061;
2. 启德医药科技(苏州)有限公司, 江苏 苏州 215000
摘要:
近两年,嵌合抗原受体T细胞(chimeric antigen receptor T cell,CAR-T)在血液瘤治疗方面取得了巨大成就。但传统型CAR-T细胞治疗时伴随的不良反应如细胞因子风暴、脱靶效应及神经毒性,严重威胁患者生命安全。而且传统型CAR-T细胞胞外区为固定的某类单链抗体可变区(single-chain variable fragment,scFv),因此只能靶向一种固定的靶点,若肿瘤靶抗原突变或消失,CAR-T细胞也将失效。近年来,领域前沿涌现了一批开关型CAR-T(switchable CAR-T,sCAR-T)设计,用以解决上述问题。此类设计将传统的CAR-T细胞分解为CAR-T细胞和分子开关,使得CAR-T的激活完全依赖于分子开关,不仅拓展了CAR-T细胞的通用性,还可以通过开关控制CAR-T细胞生物学活性,从而降低传统型CAR-T细胞带来的不良反应。本文就现有报道的sCAR-T进行分类总结,目的是为更多的CAR-T设计及优化提供思路,为sCAR-T进入临床治疗奠定基础。
关键词:    嵌合抗原受体T细胞      开关型嵌合抗原受体T细胞      抗体偶联物型开关      药物偶联物型开关      药物型开关     
Progress in research of switchable chimeric antigen receptor T cells
WANG Qiu-xia1, SHI Li-li2
1. School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China;
2. GeneQuantum Healthcare(Suzhou) Co., Ltd., Suzhou 215000, China
Abstract:
In recent years, chimeric antigen receptor T cells (CAR-T) have been viewed as a target for successful treatment of hematologic malignancies. However, targeting conventional CAR-T cell has a series of side effects, such as cytokine storm, on-target off-tumor effect and neurotoxicity during treatment, and these side effects threatened patients' life. The extracellular domain of conventional CAR-T is a fixed single-chain variable fragment (scFv) that only targets one specific antigen, and once the tumor antigen is mutated or disappears, the CAR-T cell will fail. In recent years, a number of different switchable CAR-T cells have emerged. The design of switchable CAR-T cells is divided into two aspects:CAR-T cell and molecular switch respectively, and the activation of CAR-T is completely dependent on the switch. It is not only universal, but also decreases the side effect of conventional CAR-T through controlling the molecular switch. We summarized the existing sCAR-T to provide an idea for CAR-T design and optimization, and lay a foundation for entering sCAR-T into clinical practice.
Key words:    conventional chimeric antigen receptor T cell    switchable chimeric antigen receptor T cell    Ab-tag switch    drug-tag switch    drug switch   
收稿日期: 2019-05-17
DOI: 10.16438/j.0513-4870.2019-0389
基金项目: 江苏省自然科学基金资助项目(BK20160367).
通讯作者: 时丽丽,Tel:17397937671,E-mail:shill@genequantum.com
Email: shill@genequantum.com
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