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. doi: 10.16438/j.0513-4870.2019-0389
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. doi: 10.16438/j.0513-4870.2019-0389
WANG Qiu-xia, SHI Li-li. Progress in research of switchable chimeric antigen receptor T cellsJ. Acta Pharmaceutica Sinica, 2019,54(12): 2209-2213. doi: 10.16438/j.0513-4870.2019-0389
Citation: WANG Qiu-xia, SHI Li-li. Progress in research of switchable chimeric antigen receptor T cellsJ. Acta Pharmaceutica Sinica, 2019,54(12): 2209-2213. doi: 10.16438/j.0513-4870.2019-0389

开关型嵌合抗原受体T细胞的研究进展

Progress in research of switchable chimeric antigen receptor T cells

  • 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。

     

    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.

     

/

返回文章
返回