%0 Journal Article
%A Deng, Yushuang
%A Kumar, Avadh
%A Xie, Kan
%A Schaaf, Kristina
%A Scifo, Enzo
%A Morsy, Sarah
%A Li, Tao
%A Ehninger, Armin
%A Bano, Daniele
%A Ehninger, Dan
%T Targeting senescent cells with NKG2D-CAR T cells.
%J Cell death discovery
%V 10
%N 1
%@ 2058-7716
%C London
%I Nature Publishing Group
%M DZNE-2024-00538
%P 217
%D 2024
%X This study investigates the efficacy of NKG2D chimeric antigen receptor (CAR) engineered T cells in targeting and eliminating stress-induced senescent cells in vitro. Cellular senescence contributes to age-related tissue decline and is characterized by permanent cell cycle arrest and the senescence-associated secretory phenotype (SASP). Immunotherapy, particularly CAR-T cell therapy, emerges as a promising approach to selectively eliminate senescent cells. Our focus is on the NKG2D receptor, which binds to ligands (NKG2DLs) upregulated in senescent cells, offering a target for CAR-T cells. Using mouse embryonic fibroblasts (MEFs) and astrocytes (AST) as senescence models, we demonstrate the elevated expression of NKG2DLs in response to genotoxic and oxidative stress. NKG2D-CAR T cells displayed potent cytotoxicity against these senescent cells, with minimal effects on non-senescent cells, suggesting their potential as targeted senolytics. In conclusion, our research presents the first evidence of NKG2D-CAR T cells' ability to target senescent brain cells, offering a novel approach to manage senescence-associated diseases. The findings pave the way for future investigations into the therapeutic applicability of NKG2D-targeting CAR-T cells in naturally aged organisms and models of aging-associated brain diseases in vivo.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:38704364
%2 pmc:PMC11069534
%R 10.1038/s41420-024-01976-7
%U https://pub.dzne.de/record/269441