From Tanabe Research Labs U.S.A. Inc., San Diego, California 92121 and.
Covagen AG, Wagistrasse 25, 8952 Schlieren, Switzerland.
J Biol Chem. 2018 Jun 15;293(24):9326-9334. doi: 10.1074/jbc.M117.818559. Epub 2018 Apr 20.
Despite the success of current biological therapeutics for rheumatoid arthritis, these therapies, targeting individual cytokines or pathways, produce beneficial responses in only about half of patients. Therefore, better therapeutics are needed. IL-6 and IL-17A are proinflammatory cytokines in many autoimmune and inflammatory diseases, and several therapeutics have been developed to specifically inhibit them. However, targeting both of these cytokines with a bispecific therapeutic agent could account for their nonoverlapping proinflammatory functions and for the fact that IL-6 and IL-17A act in a positive feedback loop. Here, we present the development of MT-6194, a bispecific antibody targeting both IL-6R and IL-17A that was developed with the FynomAb technology. We also present data from mouse inflammatory disease experiments, indicating that simultaneous inhibition of both IL-6 and IL-17A yields enhanced efficacy compared with inhibition of each cytokine alone.
尽管目前针对类风湿关节炎的生物疗法取得了成功,但这些针对单个细胞因子或途径的疗法仅能使约一半的患者受益。因此,需要更好的治疗方法。IL-6 和 IL-17A 是许多自身免疫性和炎症性疾病中的促炎细胞因子,已经开发出几种治疗方法来专门抑制它们。然而,使用双特异性治疗剂同时靶向这两种细胞因子可以解释它们非重叠的促炎功能,以及 IL-6 和 IL-17A 以正反馈环的方式起作用。在这里,我们介绍了 MT-6194 的开发,这是一种针对 IL-6R 和 IL-17A 的双特异性抗体,是使用 FynomAb 技术开发的。我们还提供了来自小鼠炎症性疾病实验的数据,表明同时抑制 IL-6 和 IL-17A 比单独抑制每种细胞因子产生更高的疗效。