Respiratory, Inflammatory and Autoimmune Diseases, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Gothenburg, Sweden.
Laboratory of Molecular Immunology and the Immunology Center, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland, USA.
J Leukoc Biol. 2018 Apr;103(4):643-655. doi: 10.1002/JLB.2RI0717-278R. Epub 2018 Mar 9.
Cytokines signal through specific cell surface receptors to broadly regulate immune development, differentiation, proliferation, and survival, thereby influencing cellular fate and function. Accordingly, cytokines are potential therapeutic targets for modulation of immune responses. Indeed, over the last several decades, an increasing number of cytokine-based clinical trials have been performed, collectively using either recombinant forms of cytokines or blocking agents that modulate the actions of cytokines. The pleiotropic actions of cytokines, including their abilities to mediate both inflammatory and protective immune responses, indicate that using or targeting cytokines can have desired but also potentially undesirable effects. Here, we focus on the immunomodulatory cytokine, IL-2. We review the underlying basic science related to IL-2 and its biologic actions, discuss the current state of IL-2-based immunotherapy, and focus on emerging concepts of modulating the activities of this cytokine, including the generation of novel partial cytokine agonists as new potential therapeutics.
细胞因子通过特定的细胞表面受体信号转导，广泛调节免疫发育、分化、增殖和存活，从而影响细胞命运和功能。因此，细胞因子是调节免疫反应的潜在治疗靶点。事实上，在过去几十年中，已经进行了越来越多的基于细胞因子的临床试验，这些试验要么使用细胞因子的重组形式，要么使用调节细胞因子作用的阻断剂。细胞因子的多效性作用，包括它们介导炎症和保护性免疫反应的能力，表明使用或针对细胞因子可能具有理想的但也可能是不理想的效果。在这里，我们专注于免疫调节细胞因子 IL-2。我们回顾了与 IL-2 及其生物学作用相关的基础科学，讨论了基于 IL-2 的免疫治疗的现状，并重点介绍了调节这种细胞因子活性的新出现的概念，包括作为新的潜在治疗药物生成新型部分细胞因子激动剂。
