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Engineering cytokine therapeutics.

Nature reviews bioengineering

Authors: Jeroen Deckers, Tom Anbergen, Ayla M Hokke, Anne de Dreu, David P Schrijver, Koen de Bruin, Yohana C Toner, Thijs J Beldman, Jamie B Spangler, Tom F A de Greef, Francesca Grisoni, Roy van der Meel, Leo A B Joosten, Maarten Merkx, Mihai G Netea, Willem J M Mulder

Cytokines have pivotal roles in immunity, making them attractive as therapeutics for a variety of immune-related disorders. However, the widespread clinical use of cytokines has been limited by their short blood half-lives and severe side effects caused by low specificity and unfavourable biodistribution. Innovations in bioengineering have aided in advancing our knowledge of cytokine biology and yielded new technologies for cytokine engineering. In this Review, we discuss how the development of bioanalytical methods, such as sequencing and high-resolution imaging combined with genetic techniques, have facilitated a better understanding of cytokine biology. We then present an overview of therapeutics arising from cytokine re-engineering, targeting and delivery, mRNA therapeutics and cell therapy. We also highlight the application of these strategies to adjust the immunological imbalance in different immune-mediated disorders, including cancer, infection and autoimmune diseases. Finally, we look ahead to the hurdles that must be overcome before cytokine therapeutics can live up to their full potential.

© Springer Nature Limited 2023, corrected publication 2023Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

PMID: 37064653

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