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一种针对VEGF和TNF-α的新型单一域双特异性抗体改善了类风湿性关节炎
Nanwen Zhang1, Ningning Zheng2, Dunxiong Luo3
1The School of Pharmacy, Fujian Medical University, Fuzhou, Fujian 350122, China; Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, Fuzhou 350122, Fujian, China.
International immunopharmacology
|November 22, 2023
概括
一种新型双特异性抗体V5-3针对瘤亡因子-α (TNF-α) 和血管内皮生长因子 (VEGF). 与现有治疗方法相比,这种新疗法在治疗类风湿性关节炎 (RA) 中表现出更高的疗效.
科学领域:
- 免疫学 免疫学 免疫学
- 生物技术是生物技术.
- 类风湿病学 类风湿病学
背景情况:
- 抗瘤亡因子-α (TNF-α) 疗法对约30%的类风湿性关节炎 (RA) 患者是无效的.
- 在没有反应的患者中,TNF-α可能不是RA的唯一驱动因素.
研究的目的:
- 开发和评估一种新的双特异单域抗体V5-3,针对TNF-α和血管内皮生长因子 (VEGF).
- 在自身免疫性关节炎的临床前模型中评估V5-3的治疗潜力.
主要方法:
- 在体外测试中评估了V5-3对类风湿性关节炎相关的纤维细胞样同胞细胞 (RA-FLS) 和人类静脉内皮细胞 (HUVEC) 的影响.
- 在体内研究中使用了原诱导性关节炎 (CIA) 鼠标模型来评估V5-3的抗关节炎活性,与Anbainuo相比.
- 机理学研究研究了V5-3对关键信号通路 (p65,AKT,VEGFR2) 和关节组织中的炎症因子产生的影响.
主要成果:
- 在实验室中,V5-3对RA-FLS和HUVEC表现出增殖和迁移作用,促进HUVEC管形成和炎症因子表达.
- 在体内,V5-3与Anbainuo相比,表现出优越的抗风湿性关节炎 (抗RA) 活性.
- 在CIA小鼠中,V5-3治疗减少了炎症因素,突炎和血管生成,减轻了自身免疫性关节炎的严重程度.
- 从机制上讲,V5-3抑制了p65,AKT和VEGFR2的酸化,以及关节组织中TNF-α和VEGF的产生.
结论:
- V5-3显示出显著的抗RA作用,提供了一个有前途的治疗策略.
- 这种双特异性抗体可以克服当前针对类风湿性关节炎的抗TNF-α单克隆抗体疗法的局限性.
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