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Comment
. 2022 Jul;32(7):603-604.
doi: 10.1038/s41422-022-00682-2.

A SNIPpet of safety: a Goldilocks approach in CAR-T therapy

Mehdi Benzaoui  1   2 , Naomi Taylor  3   4 , Nirali N Shah  5
Affiliations
Comment

A SNIPpet of safety: a Goldilocks approach in CAR-T therapy

Mehdi Benzaoui et al. Cell Res. 2022 Jul.
No abstract available

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Figures

Fig. 1
Fig. 1. SNIP CARs as a druggable platform to enhance CAR T-cell efficacy and safety against solid tumors.
Left: Many constitutively expressed CARs exhibit tonic signaling in the absence of ligand, resulting in a pre-infused product that is enriched in exhausted CAR T-cells (top). In the SNIP CAR system, the trans expression of a hepatitis C protease together with inclusion of its cleavage site upstream of the CAR intracellular signaling domain abrogates tonic signaling (SNIP OFF), thus conferring a less exhausted T-cell phenotype. Middle: Upon encounter with malignant cells expressing the target antigen, constitutive CAR T-cells are less responsive because of their exhausted state. However, optimal signaling in non-exhausted SNIP CAR T-cells can be induced by inhibiting the protease with the FDA-approved grazoprevir (GPV) drug (SNIP ON), resulting in increased anti-tumor cytotoxicity. Right: While constitutive CAR T-cells can induce severe toxicities, secondary to CRS or targeting of healthy cells, the activity of SNIP CAR T-cells can be inhibited by pausing GPV administration, resulting in a reversal of toxicities. Figure made with permission from BioRender.com.
See this image and copyright information in PMC

Comment on

  • Enhanced safety and efficacy of protease-regulated CAR-T cell receptors.
    Labanieh L, Majzner RG, Klysz D, Sotillo E, Fisher CJ, Vilches-Moure JG, Pacheco KZB, Malipatlolla M, Xu P, Hui JH, Murty T, Theruvath J, Mehta N, Yamada-Hunter SA, Weber EW, Heitzeneder S, Parker KR, Satpathy AT, Chang HY, Lin MZ, Cochran JR, Mackall CL. Labanieh L, et al. Cell. 2022 May 12;185(10):1745-1763.e22. doi: 10.1016/j.cell.2022.03.041. Epub 2022 Apr 27. Cell. 2022. PMID: 35483375 Free PMC article.

References

    1. Maus MV, et al. J. Immunother. Cancer. 2020;8:e001511. doi: 10.1136/jitc-2020-001511. - DOI - PMC - PubMed
    1. Pulsipher MA, et al. Blood Cancer Discov. 2022;3:66–81. doi: 10.1158/2643-3230.BCD-21-0095. - DOI - PMC - PubMed
    1. Long AH, et al. Nat. Med. 2015;21:581–590. doi: 10.1038/nm.3838. - DOI - PMC - PubMed
    1. Fraietta JA, et al. Nat. Med. 2018;4:563–571. doi: 10.1038/s41591-018-0010-1. - DOI - PMC - PubMed
    1. Labanieh L, et al. Cell. 2022;185:1745–1763. doi: 10.1016/j.cell.2022.03.041. - DOI - PMC - PubMed

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