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一个治疗策略,以针对不同的IgE来源,并持久地逆转过敏
Andre Limnander1, Navneet Kaur1, Seblewongel Asrat1
1Regeneron Pharmaceuticals, Tarrytown, New York, 10591, USA.
Science translational medicine
|December 13, 2023
概括
暂时耗尽IgE生成的血细胞,并阻止IL-4Rα信号传递,可长期消除致病性IgE,防止过敏反应,同时保留必要的抗体.
科学领域:
- 免疫学 免疫学 免疫学
- 过敏研究 研究过敏
- 治疗开发的治疗方法
背景情况:
- 全球范围内,由免疫球蛋白E (IgE) 驱动的过敏性疾病正在增加.
- 目前的治疗方法无法完全消除IgE的产生,因此需要新的策略.
- 长寿的IgE产生血细胞有助于持续的过敏记忆.
研究的目的:
- 研究一种新型组合疗法,以长期消除致病性IgE.
- 评估长寿IgE+血细胞在维持过敏记忆中的作用.
- 评估这种方法在预防过敏反应方面的潜力.
主要方法:
- 暂时使用B细胞成熟抗原xCD3 (BCMAxCD3) 双特异抗体,以消耗血细胞.
- 同时阻断介素-4受体α (IL-4Rα) 信号传递.
- 在小鼠模型中评估IgE水平,免疫球蛋白恢复和过敏反应预防,并提供支持的Cynomolgus和人类数据.
主要成果:
- BCMAxCD3抗体通过切除长寿血细胞,暂时减少IgE和其他免疫球蛋白,但IgE水平反弹了.
- 结合IL-4Rα阻断通过阻断类切换来特别且持久地防止IgE重新出现.
- 组合疗法在小鼠中预防了过敏反应,并在非人类灵长类动物和人类中显示出潜力.
结论:
- 过敏记忆是由非IgE+记忆B细胞和长寿IgE+血细胞维持的.
- 针对血细胞和IgE类切换的组合疗法为持久的IgE消除提供了一个策略.
- 这种方法有望治疗人类的过敏,同时保持保护性抗体介导免疫力.
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