Amor, Corina (December 2024) PROPHYLACTIC AND LONG-LASTING THERAPEUTIC EFFICACY OF SENOLYTIC CAR T CELLS AGAINST AGE-RELATED PHENOTYPES. In: GSA 2024 Annual Scientific Meeting, “The Fortitude Factor”, November 13 to 16, 2024, Seattle, Washington.
Abstract
Senescent cells accumulate in organisms over their lifespan and play a key role in age-related tissue decline and the development of chronic aging pathologies. Thus, effective strategies to eliminate senescent cells (senolytics) could have broad therapeutic implications. In a departure from conventional chemical approaches we developed the first cell-based senolytic therapy based on chimeric antigen receptor (CAR) T cells targeting uPAR, a cell-surface protein upregulated on senescent cells. Our initial proof of concept showed their efficiency in young animal models of liver fibrosis and cancer. We now show that uPAR-positive senescent cells accumulate during physiological aging and characterize their cell types and expression profiles. Importantly, we find that they can be safely targeted with senolytic CAR T cells in aged animals where they result in significant improvements in both tissue regeneration and metabolic function. Of note, we find that the beneficial effects of senolytic CAR T cells are long lasting; single administration of a low dose is sufficient to safely achieve long-term therapeutic and preventive effects in healthspan.
| Item Type: | Conference or Workshop Item (Paper) |
|---|---|
| Subjects: | organs, tissues, organelles, cell types and functions > cell types and functions > cell functions organs, tissues, organelles, cell types and functions > cell types and functions organs, tissues, organelles, cell types and functions organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > senescence |
| CSHL Authors: | |
| Communities: | CSHL labs > Amor lab |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 31 December 2024 |
| Date Deposited: | 21 Jan 2025 13:37 |
| Last Modified: | 21 Jan 2025 13:37 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/41772 |
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