Lenalidomide improves NKG2D-based CAR-T cell activity against colorectal cancer cells invitro

Zarei, Mahdi; Abdoli, Shahriyar; Farazmandfar, Touraj; Shahbazi, Majid

doi:10.1016/j.heliyon.2023.e20460

Cited by 3 publications

(1 citation statement)

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“…NKG2D-CAR T cells targeting NKG2DLs have shown anticancer effects against various tumor types, such as T-cell lymphoma [ 39 ], glioblastoma [ 52 ], osteosarcoma [ 65 ], and colorectal cancer [ 66 ]. To assess the effectiveness of NKz-CAR T cells against in vitro models of NKG2DLs-expressing senescent cells, we conducted a Calcein-AM-based cytotoxicity assay using the IncuCyte platform.…”

Section: Discussionmentioning

confidence: 99%

Targeting senescent cells with NKG2D-CAR T cells

Deng,

Kumar,

Xie

et al. 2024

Cell Death Discov.

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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.

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Section: Discussionmentioning

confidence: 99%