Dashwood Amy, Ghodsinia Arman Ali, Dooley James, Liston Adrian
Department of Pathology, University of Cambridge, Cambridge, UK.
Immunology Programme, Babraham Institute, Cambridge, UK.
Immunotargets Ther. 2025 Apr 4;14:403-431. doi: 10.2147/ITT.S500229. eCollection 2025.
Interleukin 2 (IL2) is a dual-acting cytokine, playing important roles in both immune activation and regulation. The role IL2 plays as a potent activator of CD8 T cells saw IL2 become one of the earliest immunotherapies, used for the treatment of cancer. In more recent years refined understanding of IL2, and the potent capacity it has for Treg stimulation, has seen low-dose IL2 therapy trialled for the treatment of auto-immune and inflammatory conditions. However, despite clinical successes, IL2 therapy is not without its caveats. The complicated receptor biology of IL2 gives rise to a narrow therapeutic window, made problematic by its short half-life. Armed with a better understanding of the structure of IL2 in complex with its receptors, many attempts have been made to create designer IL2 molecules which overcome these problems. A wide range of approaches have been used, resulting in >100 designer IL2 molecules. These include antibody complexes, fusion proteins, mutant IL2 molecules and PEGylation, each uniquely modifying the biological activity in an effort to enhance its therapeutic potential. Collectively, designer IL2 molecules form a blueprint outlining modification pathways available to other immunotherapeutics, paving the way for the next generation of immunotherapy.
白细胞介素2（IL2）是一种具有双重作用的细胞因子，在免疫激活和调节中均发挥着重要作用。IL2作为CD8 T细胞的强效激活剂，使其成为最早用于癌症治疗的免疫疗法之一。近年来，随着对IL2及其刺激调节性T细胞（Treg）强大能力的深入了解，低剂量IL2疗法已被用于自身免疫性疾病和炎症性疾病的试验治疗。然而，尽管临床取得了成功，但IL2疗法并非没有问题。IL2复杂的受体生物学特性导致其治疗窗口狭窄，而其半衰期短更是加剧了这一问题。基于对IL2与其受体复合物结构的更深入了解，人们进行了许多尝试来设计新型IL2分子，以克服这些问题。目前已采用了多种方法，产生了100多种新型IL2分子。这些方法包括抗体复合物、融合蛋白、突变型IL2分子和聚乙二醇化，每种方法都以独特的方式改变生物学活性，以增强其治疗潜力。总的来说，新型IL2分子形成了一个蓝图，勾勒出其他免疫疗法可用的修饰途径，为下一代免疫疗法铺平了道路。
