Regnase-1敲除对脐血CAR-T细胞分泌细胞因子的影响
The Effect of Regnase-1 Knockout on the Cytokine Secretion from Cord Blood Derived CAR-T Cells
刘佳慧 1冉凤萍 2毛娟 3蒙露 4赵日 5李华6
作者信息
- 1. 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
- 2. 成都京东方医院妇产科,成都 610200
- 3. 成都市第五人民医院血液科,成都 611130
- 4. 成都医学院基础医学院,成都 610500
- 5. 西南交通大学医学院,成都 610031
- 6. 西部战区总医院肿瘤科,成都 610083
- 折叠
摘要
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.
Abstract
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.
关键词
Regnase-1/脐血/CAR-T/细胞因子Key words
Regnase-1/cord blood(CB)/CAR-T/cytokine引用本文复制引用
基金项目
四川省科技厅应用基础研究项目(19YYJC0242)
国家自然科学基金青年项目(31900643)
出版年
2024
NETL
NSTL
万方数据