Deckers Jeroen, Anbergen Tom, Hokke Ayla M, de Dreu Anne, Schrijver David P, de Bruin Koen, Toner Yohana C, Beldman Thijs J, Spangler Jamie B, de Greef Tom F A, Grisoni Francesca, van der Meel Roy, Joosten Leo A B, Merkx Maarten, Netea Mihai G, Mulder Willem J M
Department of Internal Medicine and Radboud Center for Infectious diseases (RCI), Radboud University Medical Centre, Nijmegen, Netherlands.
Laboratory of Chemical Biology, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands.
Nat Rev Bioeng. 2023;1(4):286-303. doi: 10.1038/s44222-023-00030-y. Epub 2023 Feb 16.
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.
细胞因子在免疫中发挥着关键作用，这使得它们作为多种免疫相关疾病的治疗手段具有吸引力。然而，细胞因子在临床上的广泛应用受到其血液半衰期短以及低特异性和不良生物分布所导致的严重副作用的限制。生物工程学的创新有助于推进我们对细胞因子生物学的认识，并产生了用于细胞因子工程的新技术。在本综述中，我们讨论了生物分析方法的发展，如测序和与基因技术相结合的高分辨率成像，如何促进了对细胞因子生物学的更好理解。然后，我们概述了细胞因子重新设计、靶向和递送、mRNA治疗和细胞治疗所产生的治疗方法。我们还强调了这些策略在调节不同免疫介导疾病（包括癌症、感染和自身免疫性疾病）中的免疫失衡方面的应用。最后，我们展望了细胞因子治疗充分发挥其潜力之前必须克服的障碍。
