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

• Published in: European journal of pharmaceutical sciences 2024-01, Vol.192, p.106647-106647, Article 106647
• Main Authors: Zhao, Yuchen, Wang, Han, Jin, Lin, Zhang, Ziwei, Liu, Lianghu, Zhou, Mengqi, Zhang, Xianzheng, Zhang, Lingling
• Format: Article
• Language: English
• Subjects: Anti-inflammatories; Anti-Inflammatory Agents - therapeutic use; Autoinflammatory diseases; Cytokines; Cytokines - metabolism; Fusion protein; Hereditary Autoinflammatory Diseases; Humans; Inflammation - drug therapy; Inflammation - metabolism; Interleukins; Interleukins - genetics; Interleukins - metabolism
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2023.106647

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. [Display omitted]