% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Deng:269441, author = {Deng, Yushuang and Kumar, Avadh and Xie, Kan and Schaaf, Kristina and Scifo, Enzo and Morsy, Sarah and Li, Tao and Ehninger, Armin and Bano, Daniele and Ehninger, Dan}, title = {{T}argeting senescent cells with {NKG}2{D}-{CAR} {T} cells.}, journal = {Cell death discovery}, volume = {10}, number = {1}, issn = {2058-7716}, address = {London}, publisher = {Nature Publishing Group}, reportid = {DZNE-2024-00538}, pages = {217}, year = {2024}, abstract = {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.}, cin = {AG Ehninger / AG Bano}, ddc = {610}, cid = {I:(DE-2719)1013005 / I:(DE-2719)1013003}, pnm = {352 - Disease Mechanisms (POF4-352) / 351 - Brain Function (POF4-351)}, pid = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-351}, typ = {PUB:(DE-HGF)16}, pubmed = {pmid:38704364}, pmc = {pmc:PMC11069534}, doi = {10.1038/s41420-024-01976-7}, url = {https://pub.dzne.de/record/269441}, }