嵌合抗原受体
脾脏
医学
信使核糖核酸
体内
纤维化
抗原
心脏纤维化
免疫学
癌症研究
细胞生物学
生物
T细胞
离体
药理学
炎症
免疫系统
病理
基因
生物技术
生物化学
作者
Joel G. Rurik,István Tombácz,Amir Yadegari,Pedro O Méndez Fernández,Swapnil V Shewale,Li Li,Toru Kimura,Ousamah Younoss Soliman,Tyler E. Papp,Ying K Tam,Barbara L Mui,Steven M. Albelda,Ellen Puré,Carl H. June,Haig Aghajanian,Drew Weissman,Hamideh Parhiz,Jonathan A. Epstein
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2022-01-07
卷期号:375 (6576): 91-96
被引量:93
标识
DOI:10.1126/science.abm0594
摘要
Fibrosis affects millions of people with cardiac disease. We developed a therapeutic approach to generate transient antifibrotic chimeric antigen receptor (CAR) T cells in vivo by delivering modified messenger RNA (mRNA) in T cell–targeted lipid nanoparticles (LNPs). The efficacy of these in vivo–reprogrammed CAR T cells was evaluated by injecting CD5-targeted LNPs into a mouse model of heart failure. Efficient delivery of modified mRNA encoding the CAR to T lymphocytes was observed, which produced transient, effective CAR T cells in vivo. Antifibrotic CAR T cells exhibited trogocytosis and retained the target antigen as they accumulated in the spleen. Treatment with modified mRNA-targeted LNPs reduced fibrosis and restored cardiac function after injury. In vivo generation of CAR T cells may hold promise as a therapeutic platform to treat various diseases.
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