通过RAY121进行长期补充中和,这是一种具有C1q位移功能的工程抗C1s抗体
Adrian W S Ho1, Taku Fukuzawa2, Hikaru Koga2
1Chugai Pharmabody Research, Singapore, 138623, Singapore.
EBioMedicine
|November 8, 2025
概括
RAY121是一种新型抗体药物,通过皮下注射提供延长补体通路中和,改善患者对自身免疫性疾病治疗的遵从性.
科学领域:
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
- 生物化学 生物化学
背景情况:
- 针对补体经典通路 (CP) 的抗体药物通常需要频繁的静脉注射.
- 高水平的补充蛋白和快速的周转需要繁重的治疗方案.
- 这限制了患者的遵从性和治疗疗效.
研究的目的:
- 识别和设计具有长期CP中和的抗体.
- 开发一种皮下注射的抗体,以提高患者的方便性.
- 为了研究长期CP抑制的作用机制.
主要方法:
- 查具有CP中和功能的抗C1s抗体,重点关注CUB域.
- 工程抗体用于pH依赖的C1s结合和增强新生儿Fc受体 (FcRn) 相互作用.
- 使用冷电子显微镜来阐明抗体-抗原相互作用和机制.
主要成果:
- 工程抗体RAY121实现了延长循环半衰期和持续的CP中和.
- 在Cynomolgus子中,单次皮下注射抑制了CP活动超过一个月.
- RAY121通过独特的固体阻碍机制将C1q从C1复合体中移除.
结论:
- RAY121表现出扩展的CP中和,方便地进行皮下注射.
- 这种工程抗体对治疗补体驱动的自身免疫性疾病充满了希望.
- RAY121提供了潜在的治疗效果和治疗效果的改善.
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