| Literature DB >> 34990237 |
István Tombácz1, Amir Yadegari1, Joel G Rurik2,3,4, Pedro O Méndez Fernández2,3,4, Swapnil V Shewale3, Li Li2,3, Toru Kimura1, Ousamah Younoss Soliman1, Tyler E Papp1, Ying K Tam5, Barbara L Mui5, Steven M Albelda1,6, Ellen Puré7, Carl H June6, Haig Aghajanian2,3,4, Drew Weissman1, Hamideh Parhiz1, Jonathan A Epstein2,3,4,1.
Abstract
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.Entities:
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Year: 2022 PMID： 34990237 DOI： 10.1126/science.abm0594
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728