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Julia Tietz¹, Tea Gunde¹, Stefan Warmuth¹

¹Numab Therapeutics AG, Zürich, Switzerland.

JID innovations : skin science from molecules to population health

|February 20, 2024

概括

一种新的双特异性抗体,NM26-2198,有效地阻断了IL-4/IL-13和IL-31通路. 这种双重抑制表明,当单一途径抑制不足时,它有望用于治疗亚托皮炎 (AD).

科学领域:

免疫学免疫学免疫学
皮肤病学皮肤病学
药理学药理学是指药理学的学科.

背景情况:

目前针对IL-4/IL-13信号的亚托皮性皮肤炎 (AD) 治疗方法在某些患者中显示出有限的疗效.
阿尔茨海默病的症状也由IL-31调解,这种途径并未完全被IL-4/IL-13抑制剂解决.
需要同时针对IL-4/IL-13和IL-31通路的疗法,以改善AD管理.

研究的目的:

设计和评估NM26-2198,一种新型双特异抗体,旨在同时抑制IL-4/IL-13和IL-31信号传递.
评估NM26-2198在体外和体内疗效和安全性,用于潜在的亚托皮炎治疗.

主要方法:

在记者细胞系中测试了NM26-2198对IL-4/IL-13和IL-31信号的抑制.
通过测量IL-4诱导的CD23上调在人类PBMCs和胸腺和激活调节的化学激素 (TARC) 分泌物来评估功能活性.
药理动力学,疗效 (IL-31诱导的) 和毒理学均在Cynomolgus子模型中进行了评估.

主要成果:

在实验室中,NM26-2198显示出强大的同时抑制IL-4/IL-13和IL-31信号传递.
该抗体显示功能结合并抑制了AD生物标志物TARC分泌.
在体内研究显示出有利的药理动力学,显著减少IL-31诱导的,并在毒理学研究中没有观察到不良影响.

结论:

NM26-2198是一种有前途的双特异性抗体候选人,用于治疗中度至重度的亚托皮炎.
它同时阻断IL-4/IL-13和IL-31通路的能力解决了当前治疗方法的局限性.
这些临床前发现支持对AD的NM26-2198的临床研究.

关键词:

亚托邦性皮肤炎 (Atopic Dermatitis) 是一种不良的疾病.细胞因子 (cytokines) 是一种细胞因子.炎症性皮肤疾病是一种炎症性皮肤疾病.和刺痛 (Puritus Pruritus) 是一种令人发的疾病.

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