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Therapeutic T cell engineering

Abstract

Genetically engineered T cells are powerful new medicines, offering hope for curative responses in patients with cancer. Chimaeric antigen receptors (CARs) are a class of synthetic receptors that reprogram lymphocyte specificity and function. CARs targeting CD19 have demonstrated remarkable potency in B cell malignancies. Engineered T cells are applicable in principle to many cancers, pending further progress to identify suitable target antigens, overcome immunosuppressive tumour microenvironments, reduce toxicities, and prevent antigen escape. Advances in the selection of optimal T cells, genetic engineering, and cell manufacturing are poised to broaden T-cell-based therapies and foster new applications in infectious diseases and autoimmunity.

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Figure 1: Receptors for antigen.
Figure 2: Where to apply CAR therapy.
Figure 3: Therapeutic T cell design: goals and strategies.
Figure 4: Cell sources for T cell engineering.

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Acknowledgements

The authors thank the National Cancer Institute for supporting their research via grants R01 CA114536; R01 CA136551; P01 CA59350 and P30 CA008748.

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M.S., I.R. and S.R. co-authored the review.

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Correspondence to Michel Sadelain.

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S.R., I.R. and M.S. are consultants for Juno Therapeutics.

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Reviewer Information Nature thanks C. Melief, N. Restifo and the other anonymous reviewer(s) for their contribution to the peer review of this work.

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Sadelain, M., Rivière, I. & Riddell, S. Therapeutic T cell engineering. Nature 545, 423–431 (2017). https://doi.org/10.1038/nature22395

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