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靶向白细胞介素家族融合蛋白:治疗自身炎症性疾病的一种有前途的新策略。

Targeting fusion proteins of the interleukin family: A promising new strategy for the treatment of autoinflammatory diseases.

机构信息

Institute of Clinical Pharmacology, Anhui Medical University, Hefei, Anhui 230032, China; Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei, Anhui 230032, China; Anti-inflammatory Immune Drugs Collaborative Innovation Center, Hefei, Anhui 230032, China.

Institute of Clinical Pharmacology, Anhui Medical University, Hefei, Anhui 230032, China; Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Hefei, Anhui 230032, China; Anti-inflammatory Immune Drugs Collaborative Innovation Center, Hefei, Anhui 230032, China.

出版信息

Eur J Pharm Sci. 2024 Jan 1;192:106647. doi: 10.1016/j.ejps.2023.106647. Epub 2023 Nov 18.

Abstract

As a means of communication between immune cells and non-immune cells, Interleukins (ILs) has the main functions of stimulating the proliferation and activation of inflammatory immune cells such as dendritic cells and lymphocytes, promote the development of blood cells and so on. However, dysregulation of ILs expression is a major feature of autoinflammatory diseases. The drugs targeting ILs or IL-like biologics have played an important role in the clinical treatment of autoinflammatory diseases. Nevertheless, the widespread use of IL products may result in significant off-target adverse reactions. Thus, there is a clear need to develop next-generation ILs products in the biomedical field. Fusion proteins are proteins created through the joining of two or more genes that originally coded for separate proteins. Over the last 30 years, there has been increasing interest in the use of fusion protein technology for developing anti-inflammatory drugs. In comparison to single-target drugs, fusion proteins, as multiple targets drugs, have the ability to enhance the cytokine therapeutic index, resulting in improved efficacy over classical drugs. The strategy of preparing ILs or their receptors as fusion proteins is increasingly used in the treatment of autoimmune and chronic inflammation. This review focuses on the efficacy of several fusion protein drugs developed with ILs or their receptors in the treatment of autoinflammatory diseases, in order to illustrate the prospects of this new technology as an anti-inflammatory drug development protocol in the future.

摘要

作为免疫细胞和非免疫细胞之间的通讯手段,白细胞介素 (ILs) 具有刺激树突状细胞和淋巴细胞等炎症免疫细胞增殖和激活、促进血细胞发育等主要功能。然而,ILs 表达失调是自身炎症性疾病的主要特征。靶向 ILs 或类似 IL 的生物制剂的药物在自身炎症性疾病的临床治疗中发挥了重要作用。然而,IL 产品的广泛使用可能会导致明显的脱靶不良反应。因此,在生物医学领域开发下一代 ILs 产品是非常有必要的。融合蛋白是通过连接两个或多个原本编码不同蛋白质的基因而产生的蛋白质。在过去的 30 年中,人们越来越关注使用融合蛋白技术开发抗炎药物。与单靶标药物相比,融合蛋白作为多靶标药物,具有增强细胞因子治疗指数的能力,从而提高了经典药物的疗效。将 ILs 或其受体制备成融合蛋白的策略越来越多地用于治疗自身免疫性和慢性炎症。本综述重点介绍了几种以 ILs 或其受体为融合蛋白开发的融合蛋白药物在治疗自身炎症性疾病方面的疗效,以说明这项新技术作为未来抗炎药物开发方案的前景。

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