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Taking CAR T cells up a synthetic Notch

Nature Reviews Immunology volume 21, page 135 (2021)Cite this article

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Therapeutic T cell engineering has facilitated precise targeting of adoptively transferred T cells against cancer cells. The most notable of these are T cells expressing chimeric antigen receptors (CARs), antibody–T cell receptor hybrids that, upon recognition of a surface-expressed antigen, provide activation signals to mediate cell killing. CAR T cell therapy has offered complete and durable control of B cell malignancies by targeting a homogeneously expressed antigen, CD19. However, in solid tumours such as glioblastoma, tumour-specific candidate CAR targets are expressed by only a subset of malignant cells, leading to outgrowth of resistant clones after initial tumour regression. Other targets lack tumour specificity, which can lead to off-tumour effects. Furthermore, constitutive CAR expression can lead to T cell exhaustion and relapse after remission.

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  1. OxMS Preprint Journal Club, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Miriam Saffern & Robert Samstein

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  1. Miriam Saffern
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  2. Robert Samstein
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Correspondence to Miriam Saffern.

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Saffern, M., Samstein, R. Taking CAR T cells up a synthetic Notch. Nat Rev Immunol 21, 135 (2021). https://doi.org/10.1038/s41577-021-00514-1

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  • DOI: https://doi.org/10.1038/s41577-021-00514-1

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