CAR T cells produced in vivo to treat cardiac injury.
Saved in:
| Title: | CAR T cells produced in vivo to treat cardiac injury. |
|---|---|
| Authors: | Rurik, Joel G., Tombácz, István, Yadegari, Amir, Fernández, Pedro O. Méndez, Shewale, Swapnil V., Li, Li, Kimura, Toru, Soliman, Ousamah Younoss, Papp, Tyler E., Tam, Ying K., Mui, Barbara L., Albelda, Steven M., Puré, Ellen, June, Carl H., Aghajanian, Haig, Weissman, Drew, Parhiz, Hamideh, Epstein, Jonathan A. |
| Source: | Science (pre-March 2025). 1/7/2022, Vol. 375 Issue 6576, p91-96. 6p. 4 Color Photographs. |
| Subjects: | Fibrosis, Heart diseases, Antigen receptors, Nanoparticles, Lymphocytes |
| 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. [ABSTRACT FROM AUTHOR] |
| Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
|
Full text is not displayed to guests.
Login for full access.
|
|
| 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. [ABSTRACT FROM AUTHOR] |
|---|---|
| ISSN: | 00368075 |
| DOI: | 10.1126/science.abm0594 |
