首页|Regnase-1敲除对脐血CAR-T细胞分泌细胞因子的影响

Regnase-1敲除对脐血CAR-T细胞分泌细胞因子的影响

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在不断改造嵌合抗原受体T(chimeric antigen receptor T,CAR-T)细胞药物以增强其抗肿瘤能力的同时,也需要关注该细胞药物激活后分泌的系列细胞因子谱.这些细胞因子可引起细胞因子风暴(cytokine release syndrome,CRS),而CRS与细胞药物的临床安全性密切相关.Re-gnase-1 具有核糖核酸酶作用,负向调控免疫应答.利用CRISPR/Cas9基因编辑技术成功制备了Regnase-1缺陷型脐血CAR-T细胞,发现虽然Regnase-1-CAR-T的杀伤能力显著比CAR-T细胞强,但Regnase-1-CAR-T细胞分泌促炎因子的能力也显著增强,提示Regnase-1-CAR-T细胞在安全性方面存在潜在风险.
The Effect of Regnase-1 Knockout on the Cytokine Secretion from Cord Blood Derived CAR-T Cells
As CAR-T(chimeric antigen receptor T)cells are continually modified to enhance their anti-tu-mor efficacy,attention must also be paid to the cytokine profiles secreted by activated CAR-T cells.These cytokines are important factors in causing the CRS(cytokine release syndrome),which is closely related to the clinical safety of CAR-T.Regnase-1 is a ribonuclease that negatively regulates the immune response.Using CRISPR/Cas9 gene editing technology,Regnase-1-deficient CAR-T cells derived from CB(cord blood)were successfully prepared.It was found that although the specific killing ability of Regnase-1-CAR-T cells was significantly stronger than that of CAR-T cells,the secretion of pro-inflammatory cytokines by Regnase-1-CAR-T cells was also significantly in-creased,indicating that Regnase-1-CAR-T cells were potentially risky in terms of clinical safety.

Regnase-1cord blood(CB)CAR-Tcytokine

刘佳慧、冉凤萍、毛娟、蒙露、赵日、李华

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成都中医药大学基础医学院,成都 610075

西部战区总医院肿瘤科,成都 610083

成都京东方医院妇产科,成都 610200

成都市第五人民医院血液科,成都 611130

成都医学院基础医学院,成都 610500

西南交通大学医学院,成都 610031

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Regnase-1 脐血 CAR-T 细胞因子

四川省科技厅应用基础研究项目国家自然科学基金青年项目

19YYJC024231900643

2024

中国细胞生物学学报
中国科学院上海生命科学研究院,生物化学与细胞生物学研究所,中国细胞生物学学会

中国细胞生物学学报

CSTPCD
影响因子:0.554
ISSN:1674-7666
年,卷(期):2024.46(2)
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