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Cell senescence

Goodbye, senescent cells: CAR-T cells unleashed to fight ageing

Nature Reviews Molecular Cell Biology volume 25, page 955 (2024)Cite this article

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Senescent cells accumulate in various ageing-associated diseases. Numerous studies using genetically engineered mouse models or chemical inhibitors that target pathways induced in senescent cells have indicated that the clearance of senescent cells can alleviate some of these diseases and promote healthy ageing. Amor et al. proposed a therapeutic approach for the removal of senescent cells that exploits the adaptive immune system by using chimeric antigen receptor (CAR)-T cell therapy, referred to as ‘senolytic CAR-T cells’.

Although the study by Amor et al. presents promising results, further optimization of the CAR may be necessary to ensure maximal therapeutic efficacy while limiting potential side effects. For example, UPAR is detectable, albeit at low levels, in the lungs, in a subset of myocytes and innate immune cells, raising important concerns about the off-target effects of senolytic CAR-T cells on healthy tissues. Furthermore, before this innovative therapy can be applied to the treatment of ageing-related diseases, its efficacy and long-term responses must be confirmed in humans, particularly in older individuals with compromised immune systems.

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  1. University School for Advanced Studies IUSS, Pavia, Italy

    Raffaella Di Micco

  2. Senescence in Stem Cell Aging, Differentiation, and Cancer Unit, San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), San Raffaele Scientific Institute, Milan, Italy

    Raffaella Di Micco

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  1. Raffaella Di Micco
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Correspondence to Raffaella Di Micco.

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Di Micco, R. Goodbye, senescent cells: CAR-T cells unleashed to fight ageing. Nat Rev Mol Cell Biol 25, 955 (2024). https://doi.org/10.1038/s41580-024-00792-2

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  • DOI: https://doi.org/10.1038/s41580-024-00792-2

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