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000269441 1001_ $$0P:(DE-2719)9001013$$aDeng, Yushuang$$b0$$eFirst author$$udzne
000269441 245__ $$aTargeting senescent cells with NKG2D-CAR T cells.
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000269441 520__ $$aThis study investigates the efficacy of NKG2D chimeric antigen receptor (CAR) engineered T cells in targeting and eliminating stress-induced senescent cells in vitro. Cellular senescence contributes to age-related tissue decline and is characterized by permanent cell cycle arrest and the senescence-associated secretory phenotype (SASP). Immunotherapy, particularly CAR-T cell therapy, emerges as a promising approach to selectively eliminate senescent cells. Our focus is on the NKG2D receptor, which binds to ligands (NKG2DLs) upregulated in senescent cells, offering a target for CAR-T cells. Using mouse embryonic fibroblasts (MEFs) and astrocytes (AST) as senescence models, we demonstrate the elevated expression of NKG2DLs in response to genotoxic and oxidative stress. NKG2D-CAR T cells displayed potent cytotoxicity against these senescent cells, with minimal effects on non-senescent cells, suggesting their potential as targeted senolytics. In conclusion, our research presents the first evidence of NKG2D-CAR T cells' ability to target senescent brain cells, offering a novel approach to manage senescence-associated diseases. The findings pave the way for future investigations into the therapeutic applicability of NKG2D-targeting CAR-T cells in naturally aged organisms and models of aging-associated brain diseases in vivo.
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000269441 7001_ $$0P:(DE-2719)2812452$$aKumar, Avadh$$b1$$udzne
000269441 7001_ $$0P:(DE-2719)2810906$$aXie, Kan$$b2$$udzne
000269441 7001_ $$0P:(DE-2719)2812495$$aSchaaf, Kristina$$b3$$udzne
000269441 7001_ $$0P:(DE-2719)2812562$$aScifo, Enzo$$b4
000269441 7001_ $$0P:(DE-2719)9002881$$aMorsy, Sarah$$b5$$udzne
000269441 7001_ $$aLi, Tao$$b6
000269441 7001_ $$aEhninger, Armin$$b7
000269441 7001_ $$0P:(DE-2719)2158358$$aBano, Daniele$$b8
000269441 7001_ $$0P:(DE-2719)2289209$$aEhninger, Dan$$b9$$eLast author
000269441 773__ $$0PERI:(DE-600)2842546-7$$a10.1038/s41420-024-01976-7$$gVol. 10, no. 1, p. 217$$n1$$p217$$tCell death discovery$$v10$$x2058-7716$$y2024
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