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Engineering cytokine therapeutics

Nature Reviews Bioengineering volume 1, pages 286–303 (2023)Cite this article

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An Author Correction to this article was published on 27 March 2023

This article has been updated

Abstract

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.

Key points

  • Cytokines are crucial regulators of the immune system and have important roles in health and disease.

  • Recombinant cytokine therapy is hampered by the short blood half-life and severe side effects of cytokines.

  • Increased knowledge of cytokine biology converges with new bioengineering approaches to develop engineered cytokine therapeutics.

  • Cytokine therapeutics can be applied to modulate dysregulated immune responses in disorders such as cancer or autoimmune diseases.

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Fig. 1: Cytokine biology and mechanisms.
Fig. 2: Re-engineering cytokines.
Fig. 3: Cytokine targeting and delivery.
Fig. 4: mRNA encoding cytokines and cell therapeutics.

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Author notes

  1. Roy van der Meel, Maarten Merkx & Willem J. M. Mulder

    Present address: Department of Biomedical Engineering, Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, Netherlands

  2. These authors contributed equally: Jeroen Deckers, Tom Anbergen, Ayla M. Hokke.

Authors and Affiliations

  1. Department of Internal Medicine and Radboud Center for Infectious diseases (RCI), Radboud University Medical Centre, Nijmegen, Netherlands

    Jeroen Deckers, Tom Anbergen, Yohana C. Toner, Thijs J. Beldman, Leo A. B. Joosten, Mihai G. Netea & Willem J. M. Mulder

  2. Laboratory of Chemical Biology, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands

    Ayla M. Hokke, Anne de Dreu, David P. Schrijver, Koen de Bruin, Tom F. A. de Greef, Roy van der Meel, Maarten Merkx & Willem J. M. Mulder

  3. Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Jamie B. Spangler

  4. Department of Chemical and Biomolecular Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, USA

    Jamie B. Spangler

  5. Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Jamie B. Spangler

  6. Department of Biomedical Engineering, Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, Netherlands

    Tom F. A. de Greef & Francesca Grisoni

  7. Institute for Molecules and Materials, Radboud University, Nijmegen, The Netherlands

    Tom F. A. de Greef

  8. Centre for Living Technologies, Alliance Eindhoven University of Technology, Wageningen University & Research, Utrecht University and University Medical Center Utrecht (EWUU), Utrecht, Netherlands

    Tom F. A. de Greef & Francesca Grisoni

  9. Radboud Institute for Molecular Life Sciences (RIMLS), Radboud University Medical Centre, Nijmegen, Netherlands

    Leo A. B. Joosten & Mihai G. Netea

  10. Department of Medical Genetics, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania

    Leo A. B. Joosten

  11. Department for Genomics and Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany

    Mihai G. Netea

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Contributions

J.D., T.A., A.M.H., M.G.N. and W.J.M.M. wrote the manuscript. All authors researched data for the article, provided substantial contributions to discussion of content and reviewed and edited the manuscript before submission.

Corresponding authors

Correspondence to Mihai G. Netea or Willem J. M. Mulder.

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Competing interests

W.J.M.M., L.A.B.J. and M.G.N. are scientific co-founders of and have equity in Trained Therapeutix Discovery. W.J.M.M. and M.G.N. have consulting agreements with Trained Therapeutix Discovery. The remaining authors declare no competing interests.

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Deckers, J., Anbergen, T., Hokke, A.M. et al. Engineering cytokine therapeutics. Nat Rev Bioeng 1, 286–303 (2023). https://doi.org/10.1038/s44222-023-00030-y

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