CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, 518055, Shenzhen, China.
Cell Mol Immunol. 2022 Feb;19(2):192-209. doi: 10.1038/s41423-021-00786-6. Epub 2022 Jan 4.
Cytokines exert powerful immunomodulatory effects that are critical to physiology and pathology in humans. The application of natural cytokines in clinical studies has not been clearly established, and there are often problems associated with toxicity or lack of efficacy. The key reasons can be attributed to the pleiotropy of cytokine receptors and undesired activation of off-target cells. With a deeper understanding of the structural principles and functional signals of cytokine-receptor interactions, artificial modification of cytokine signaling through protein engineering and synthetic immunology has become an increasingly feasible and powerful approach. Engineered cytokines are designed to selectively target cells. Herein, the theoretical and experimental evidence of cytokine engineering is reviewed, and the "supercytokines" resulting from structural enhancement and the "immunocytokines" generated by antibody fusion are described. Finally, the "engager cytokines" formed by the crosslinking of cytokines and bispecific immune engagers and other synthetic cytokines formed by nonnatural analogs are also discussed.
细胞因子发挥着强大的免疫调节作用，对人类的生理和病理至关重要。天然细胞因子在临床研究中的应用尚未明确确立，而且常常存在毒性或缺乏疗效的问题。其关键原因可归因于细胞因子受体的多效性和对非靶细胞的意外激活。随着对细胞因子-受体相互作用的结构原理和功能信号的深入了解，通过蛋白质工程和合成免疫学对细胞因子信号进行人工修饰已成为一种越来越可行和强大的方法。工程细胞因子被设计为选择性地靶向细胞。本文综述了细胞因子工程的理论和实验证据，并描述了结构增强产生的“超级细胞因子”和抗体融合产生的“免疫细胞因子”。最后，还讨论了细胞因子与双特异性免疫结合物交联形成的“交联细胞因子”以及其他非天然类似物形成的合成细胞因子。
