Next generation chimeric antigen receptor T cells: safety strategies to overcome toxicity

被引：213
|
作者：
Yu, Shengnan [1 ]
Yi, Ming [1 ]
Qin, Shuang [1 ]
Wu, Kongming [1 ]
机构：
[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Oncol, 1095 Jiefang Ave, Wuhan 430030, Hubei, Peoples R China
来源：
MOLECULAR CANCER | 2019年 / 18卷 / 01期
基金：
中国国家自然科学基金;
关键词：
Chimeric antigen receptor; Toxicity; Immunotherapy; Suicide gene; Synthetic notch receptor; CYTOKINE RELEASE SYNDROME; ENGINEERED DONOR LYMPHOCYTES; THYMIDINE KINASE GENES; I CLINICAL-TRIAL; SUICIDE-GENE; IMMUNE-RESPONSES; SOLID TUMORS; CANCER; CAR; THERAPY;
D O I：
10.1186/s12943-019-1057-4
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Chimeric antigen receptor T (CAR-T) cell therapy is an emerging and effective cancer immunotherapy. Especially in hematological malignancies, CAR-T cells have achieved exciting results. Two Anti-CD19 CAR-T therapies have been approved for the treatment of CD19-positive leukemia or lymphoma. However, the application of CAR-T cells is obviously hampered by the adverse effects, such as cytokines release syndrome and on-target off-tumor toxicity. In some clinical trials, patients quitted the treatment of CAR-T cells due to life-threatening toxicity. Seeking to alleviate these toxicities or prevent the occurrence, researchers have developed a number of safety strategies of CAR-T cells, including suicide genes, synthetic Notch receptor, on-switch CAR, combinatorial target-antigen recognition, bispecific T cell engager and inhibitory CAR. This review summarized the preclinical studies and clinical trials of the safety strategies of CAR-T cells and their respective strengths and weaknesses.
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页数：13
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