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Engineering IL-2 for immunotherapy of autoimmunity and cancer.
Nature Reviews Immunology ( IF 100.3 ) Pub Date : 2022-02-25 , DOI: 10.1038/s41577-022-00680-w
Rosmely Hernandez 1 , Janika Põder 1 , Kathryn M LaPorte 1 , Thomas R Malek 1
Affiliation  

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 (Treg 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 Treg 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.

中文翻译:

工程化 IL-2 用于自身免疫和癌症的免疫治疗。

IL-2 的 T 细胞生长因子活性的临床前研究导致这种细胞因子成为近 30 年前美国食品和药物管理局批准用于治疗癌症的第一种免疫疗法。从那时起,我们了解了 IL-2 在通过调节性 T 细胞(Treg 细胞)调节耐受性方面的重要作用,此外还通过其对效应 T 细胞和记忆 T 细胞的作用促进免疫。IL-2 研究史上的另一个关键事件是解决与其三方受体结合的 IL-2 的晶体结构,这促进了细胞类型选择性工程化 IL-2 产品的开发。这些新的 IL-2 类似物靶向 Treg 细胞以抵消自身免疫和炎症性疾病或靶向效应 T 细胞背景下失调的免疫系统,记忆 T 细胞和自然杀伤细胞以增强其抗肿瘤反应。IL-2 生物制剂已被证明在临床前研究中是有效的,目前正在对一些生物制剂进行临床评估。这些研究将很快揭示工程化的 IL-2 生物制剂是否真正能够利用 IL-2-IL-2 受体途径作为自身免疫和癌症的有效单一疗法或联合疗法。
更新日期:2022-02-25
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