用mRNA-LNP生成的CAR-NK细胞在体外和体外杀死瘤点细胞

用mRNA-LNP生成的CAR-NK细胞在体外和体外杀死瘤点细胞

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Updated: Jul 16, 2025

Advances in Human Induced Pluripotent Stem Cell-Derived Chimeric Antigen Receptor-Expressing Natural Killer Cells

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Vita Golubovskaya¹, John Sienkiewicz¹, Jinying Sun¹

¹Promab Biotechnologies, 2600 Hilltop Drive, Richmond, CA 94806, USA.

International journal of molecular sciences

|September 9, 2023

概括

新型脂质纳米粒子 (LNP) 技术有效地将仿真抗原受体 (CAR) mRNA传递给自然杀手 (NK) 细胞. 这产生具有强大的抗瘤活性的功能性CAR-NK细胞,提供了一个有前途的非病毒免疫疗法方法.

科学领域:

免疫学免疫学免疫学
细胞生物学细胞生物学
生物技术是生物技术.

背景情况:

自然杀手 (NK) 细胞是先天免疫系统的重要细胞毒性淋巴细胞.
工程NK细胞与仿真抗原受体 (CARs) 增强他们的瘤向能力.

研究的目的:

开发和评估一种新的CAR mRNA-脂质纳米粒子 (LNP) 传递系统,用于生成功能性的CAR-NK细胞.
评估通过这种非病毒方法产生的CAR-NK细胞的体外和体内抗瘤功效.

主要方法:

主要的外周血液单核细胞 (PBMCs) 被扩展并被LNP封装的CD19-CAR或BCMA-CARmRNA感染.
分析了CAR表达水平,体外对癌细胞系的细胞毒性和细胞因子分泌 (IFN-,Granzyme B).
在瘤外移植模型中评估了CD19-CAR-NK细胞的体内抗瘤疗效.

主要成果:

使用CAR mRNA-LNP技术实现了高CAR表达 (78%用于CD19-CAR,95%用于BCMA-CAR).
感染过的BCMA-CAR-NK和CD19-CAR-NK细胞表现出强大的剂量依赖性杀死多发性髓瘤和白血病细胞系.
与未被移植的NK细胞相比,CAR-NK细胞显著增强了细胞毒性和细胞因子分泌,CD19-CAR-NK细胞在体内显著抑制了瘤生长.

结论:

通过LNP传递CAR mRNA的非病毒传递是产生功能性CAR-NK细胞的有效方法.
这种方法产生具有高抗瘤活性的CAR-NK细胞,显示出高级癌症免疫疗法的潜力.

关键词:

仿制性抗原受体的复制性受体.免疫疗法免疫疗法这种白血病是白血病.脂质纳米颗粒的使用方法它们是mRNARNA.多发性骨髓瘤是多发性骨髓瘤的一种.自然杀手细胞是自然杀手细胞.瘤是一个瘤.

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