Han Xiao, Wang Yao, Han Wei-Dong
Molecular & Immunological Department, Bio-therapeutic Department, The General Hospital of People's Liberation Army, Beijing 100853, China.
Chronic Dis Transl Med. 2018 Sep 18;4(4):225-243. doi: 10.1016/j.cdtm.2018.08.002. eCollection 2018 Dec.
T cells engineered with the chimeric antigen receptor (CAR) are rapidly emerging as an important immunotherapy for hematologic malignancies. The anti-cluster of differentiation (CD)19 CAR-T cell therapy has been remarkably successful against refractory/relapsed acute lymphoblastic leukemia (ALL), and a complete remission rate as high as 90% was observed, in both children and adults. Although the achievement of clinical efficacy using CAR-T cell therapy for solid tumors has encountered several obstacles that were associated with the multiple mechanisms contributing to an immunosuppressive microenvironment, investigators are exploring more optimized approaches to improve the efficiency of CAR-T in solid tumors. In addition, cytokine release syndrome (CRS) and neurotoxicity following CAR-T cell therapy can be severe or even fatal; therefore, the management of these toxicities is significant. Herein, we briefly review the structure of CAR-T and some novel CAR designs, the clinical application of CAR-T cell therapies, as well as the assessment and management of toxicities.
嵌合抗原受体(CAR)工程化的T细胞正迅速成为血液系统恶性肿瘤的一种重要免疫疗法。抗分化簇(CD)19 CAR-T细胞疗法在治疗难治性/复发性急性淋巴细胞白血病(ALL)方面取得了显著成功,在儿童和成人中均观察到高达90%的完全缓解率。尽管使用CAR-T细胞疗法治疗实体瘤在实现临床疗效方面遇到了几个与导致免疫抑制微环境的多种机制相关的障碍,但研究人员正在探索更优化的方法来提高CAR-T在实体瘤中的效率。此外,CAR-T细胞疗法后的细胞因子释放综合征(CRS)和神经毒性可能很严重甚至致命;因此,对这些毒性的管理至关重要。在此,我们简要回顾CAR-T的结构和一些新型CAR设计、CAR-T细胞疗法的临床应用以及毒性的评估和管理。
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