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Comment
. 2020 Aug 6;27(2):192-194.
doi: 10.1016/j.stem.2020.07.010.

A Fresh Approach to Targeting Aging Cells: CAR-T Cells Enhance Senolytic Specificity

Joey H Li  1 , Yvonne Y Chen  2
Affiliations
Comment

A Fresh Approach to Targeting Aging Cells: CAR-T Cells Enhance Senolytic Specificity

Joey H Li et al. Cell Stem Cell. .

Abstract

Senescence is a critical factor in several diseases, yet senolytic therapies targeting senescent cells remain hindered by lack of specificity. In the June issue of Nature, Amor et al. (2020) develop chimeric antigen receptor (CAR)-T cells targeting uPAR, a novel senescent-cell marker, to treat liver adenocarcinoma and liver fibrosis.

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Conflict of interest statement

Declaration of Interests Y.Y.C. is the inventor of the following patents on technologies mentioned in this Preview: US15/772403, on TGF-b CARUS15/535972, on CD19/CD20 bispecific CAR for B-cell lymphoma. The patents are all assigned to the Regents of the University of California.

Figures

Figure 1:
Figure 1:
uPAR CAR-T cells specifically target cells displaying a classical senescent phenotype. (Right) Various internal and external cell stressors can induce a senescent state, marked by upregulated antiapoptotic pathways, cell-cycle arrest, and expression of SASP, accompanied by overexpression of uPAR. (Inset) A CAR consisting of an extracellular uPAR-specific scFv linked to intracellular CD28 costimulatory and CD3ζ T-cell activating domains is activated by uPAR binding, resulting in T-cell activation and degranulation. Lytic granule contents released into the immunological synapse are endocytosed by the target cell, where granzyme B (GrB) and other cytotoxic molecules enter the cytoplasm via perforin channels to activate apoptotic pathways.
See this image and copyright information in PMC

Comment on

  • Senolytic CAR T cells reverse senescence-associated pathologies.
    Amor C, Feucht J, Leibold J, Ho YJ, Zhu C, Alonso-Curbelo D, Mansilla-Soto J, Boyer JA, Li X, Giavridis T, Kulick A, Houlihan S, Peerschke E, Friedman SL, Ponomarev V, Piersigilli A, Sadelain M, Lowe SW. Amor C, et al. Nature. 2020 Jul;583(7814):127-132. doi: 10.1038/s41586-020-2403-9. Epub 2020 Jun 17. Nature. 2020. PMID: 32555459 Free PMC article.

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