1. T cell immunotherapy for cardiac fibrosis: mRNA starts the CAR
- Author
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Ronald J. Vagnozzi and Timothy A. McKinsey
- Subjects
Mice ,T-Lymphocytes ,Genetics ,Molecular Medicine ,Animals ,Cell Biology ,Immunotherapy ,RNA, Messenger ,Fibroblasts ,Fibrosis ,Article - Abstract
Fibrosis affects millions of people with cardiac disease. We developed a therapeutic approach to generate transient anti-fibrotic chimeric antigen receptor (CAR) T cells in vivo by delivering modified mRNA in T cell targeted lipid nanoparticles. The efficacy of these in vivo reprogrammed CAR T cells was evaluated by injecting CD5-targeted lipid nanoparticles 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. Anti-fibrotic CAR T cells exhibited trogocytosis and retained the target antigen as they accumulated in the spleen. Treatment with modified mRNA targeted lipid nanoparticles reduced fibrosis and restored cardiac function after injury. In vivo generation of CAR T cells holds promise as a therapeutic platform to treat various diseases.
- Published
- 2022