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Engineering cytokine therapeutics
Nature Reviews Bioengineering Pub Date : 2023-02-16 , DOI: 10.1038/s44222-023-00030-y
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.



中文翻译:

工程细胞因子疗法

细胞因子在免疫中起着关键作用,这使得它们作为多种免疫相关疾病的治疗剂具有吸引力。然而,细胞因子的广泛临床应用受到其较短的血液半衰期和由低特异性和不利的生物分布引起的严重副作用的限制。生物工程的创新有助于提高我们对细胞因子生物学的认识,并产生了细胞因子工程的新技术。在这篇综述中,我们讨论了生物分析方法(例如测序和高分辨率成像与遗传技术相结合)的发展如何促进了对细胞因子生物学的更好理解。然后,我们概述了由细胞因子重新设计、靶向和递送、mRNA 疗法和细胞疗法引起的疗法。我们还强调了这些策略在调整不同免疫介导疾病(包括癌症、感染和自身免疫性疾病)中的免疫失衡中的应用。最后,我们展望了在细胞因子疗法发挥其全部潜力之前必须克服的障碍。

更新日期:2023-02-16
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