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Engineered cellular immunotherapies in cancer and beyond

Abstract

This year marks the tenth anniversary of cell therapy with chimeric antigen receptor (CAR)-modified T cells for refractory leukemia. The widespread commercial approval of genetically engineered T cells for a variety of blood cancers offers hope for patients with other types of cancer, and the convergence of human genome engineering and cell therapy technology holds great potential for generation of a new class of cellular therapeutics. In this Review, we discuss the goals of cellular immunotherapy in cancer, key challenges facing the field and exciting strategies that are emerging to overcome these obstacles. Finally, we outline how developments in the cancer field are paving the way for cellular immunotherapeutics in other diseases.

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Fig. 1: Autologous and allogeneic engineered cell manufacturing.
Fig. 2: Mechanisms of tolerance.
Fig. 3: Innate and adaptive mechanisms of cell recognition and rejection.
Fig. 4: Permutations of cell therapies for cancer treatment.

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Acknowledgements

The authors would like to thank R. Young for insightful discussions, and the authors apologize to colleagues for work that we were unable to cite owing to space constraints. This was supported by 1P01CA214278, R01CA226983 and the Parker Institute for Cancer Immunotherapy (C.H.J.); the National Science Foundation Graduate Fellowship DGE-1321851 (A.V.F.); the National Institute of Health T32 CA009140 (T.B.); and the Go for IT Fondazione CRUI/MIUR (Italy) Fellowship 2020 (G.G.).

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C.H.J. has received grant support from Novartis, and has patents related to CAR therapy with royalties paid from Novartis to the University of Pennsylvania. C.H.J. is also a scientific co-founder and holds equity in Capstan Therapeutics and Tmunity Therapeutics. C.H.J. serves on the board of AC Immune and is a scientific advisor to Alaunos, BluesphereBio, Cabaletta, Carisma, Cartography, Cellares, Cellcarta, Celldex, Danaher, Decheng, ImmuneSensor, Poseida, Verismo, Viracta, and WIRB-Copernicus group.

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Finck, A.V., Blanchard, T., Roselle, C.P. et al. Engineered cellular immunotherapies in cancer and beyond. Nat Med 28, 678–689 (2022). https://doi.org/10.1038/s41591-022-01765-8

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