Department of Chemical & Biomolecular Engineering, Johns Hopkins University School of Engineering, Baltimore, MD.
Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD.
J Immunol. 2024 Jan 15;212(2):225-234. doi: 10.4049/jimmunol.2300467.
The delicate balance of immune homeostasis is regulated by the interactions between cytokines and their cognate cell surface signaling receptors. There is intensive interest in harnessing cytokines as drugs for diseases such as cancer and autoimmune disorders. However, the multifarious and often contradictory activities of cytokines, coupled with their short serum half-lives, limit clinical performance and result in dangerous toxicities. There is thus growing emphasis on manipulating natural cytokines to enhance their selectivity, safety, and durability through various strategies. One strategy that has gained traction in recent years is the development of anticytokine Abs that not only extend the circulation half-life of cytokines but also specifically bias their immune activities through multilayered molecular mechanisms. Although Abs are notorious for their antagonistic activities, this review focuses on anticytokine Abs that selectively agonize the activity of the target protein. This approach has potential to help realize the clinical promise of cytokine-based therapies.
免疫稳态的微妙平衡由细胞因子与其细胞表面信号受体的相互作用来调节。人们对利用细胞因子作为癌症和自身免疫性疾病等疾病的药物产生了浓厚的兴趣。然而，细胞因子的多种且常常相互矛盾的活性，加上它们的血清半衰期短，限制了临床疗效并导致危险的毒性。因此，人们越来越关注通过各种策略来操纵天然细胞因子，以增强其选择性、安全性和耐久性。近年来，一种备受关注的策略是开发拮抗性细胞因子 Abs，这些 Abs 不仅延长了细胞因子的循环半衰期，而且还通过多层次的分子机制特异性地改变其免疫活性。尽管 Abs 以其拮抗活性而闻名，但本综述重点介绍了选择性激活靶蛋白活性的拮抗性细胞因子 Abs。这种方法有可能有助于实现基于细胞因子的治疗的临床承诺。
