Hernandez Rosmely, Põder Janika, LaPorte Kathryn M, Malek Thomas R
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL, USA.
Nat Rev Immunol. 2022 Oct;22(10):614-628. doi: 10.1038/s41577-022-00680-w. Epub 2022 Feb 25.
Preclinical studies of the T cell growth factor activity of IL-2 resulted in this cytokine becoming the first immunotherapy to be approved nearly 30 years ago by the US Food and Drug Administration for the treatment of cancer. Since then, we have learnt the important role of IL-2 in regulating tolerance through regulatory T cells (T cells) besides promoting immunity through its action on effector T cells and memory T cells. Another pivotal event in the history of IL-2 research was solving the crystal structure of IL-2 bound to its tripartite receptor, which spurred the development of cell type-selective engineered IL-2 products. These new IL-2 analogues target T cells to counteract the dysregulated immune system in the context of autoimmunity and inflammatory disorders or target effector T cells, memory T cells and natural killer cells to enhance their antitumour responses. IL-2 biologics have proven to be effective in preclinical studies and clinical assessment of some is now underway. These studies will soon reveal whether engineered IL-2 biologics are truly capable of harnessing the IL-2-IL-2 receptor pathway as effective monotherapies or combination therapies for autoimmunity and cancer.
白细胞介素-2（IL-2）的T细胞生长因子活性的临床前研究，使这种细胞因子成为近30年前美国食品药品监督管理局批准用于治疗癌症的首个免疫疗法。从那时起，我们了解到IL-2除了通过对效应T细胞和记忆T细胞发挥作用来促进免疫外，在通过调节性T细胞（Tregs）调节免疫耐受方面也起着重要作用。IL-2研究史上的另一个关键事件是解析了与其三聚体受体结合的IL-2的晶体结构，这推动了细胞类型选择性工程化IL-2产品的开发。这些新型IL-2类似物靶向Tregs以对抗自身免疫和炎症性疾病背景下失调的免疫系统，或靶向效应T细胞、记忆T细胞和自然杀伤细胞以增强它们的抗肿瘤反应。IL-2生物制剂在临床前研究中已被证明是有效的，目前一些临床评估正在进行。这些研究很快将揭示工程化IL-2生物制剂是否真的能够利用IL-2-IL-2受体途径作为自身免疫和癌症的有效单药疗法或联合疗法。
