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LPX-TI641,一个Tim3/4激动剂,在多发性硬化症模型中诱导长期免疫耐受性

Anas M Fathallah¹, Abdulraouf Ramadan¹, Basel Karzoun¹

¹LAPIX Therapeutics Inc., Cambridge, MA 021141, USA.

|November 27, 2025

概括

一种新型药物LPX-TI641通过扩大调节性T细胞 (Tregs) 来恢复免疫耐受性,对多发性硬化症 (MS) 显示出前景. 这种抗原独立的方法为MS提供了潜在的新治疗方法,克服了当前治疗方法的局限性.

科学领域:

免疫学免疫学免疫学
神经科学是一个神经科学.
药理学药理学是指药理学的学科.

背景情况:

目前的多发性硬化症 (MS) 治疗方法面临安全性和耐受性问题.
针对多发性硬化症的抗原特异性疗法受限于对已知的自身抗原的需求.
LPX-TI641是一种新的,口服可用的小分子 Tim-3/4 激动剂,通过调节性 T 细胞 (Treg) 扩张恢复免疫耐受性的抗原独立策略.

研究的目的:

评估LPX-TI641在体外诱导Treg群体的能力.
评估LPX-TI641在实验性自身免疫脑膜炎 (EAE) 鼠标模型中的治疗疗效.
分析Treg表型和功能,以响应LPX-TI641在外周血液单核细胞 (PBMCs) 来自MS患者 (PwMS).

主要方法:

在实验室中诱导Treg种群使用小鼠脊髓细胞.
在MOG35-55和PLP139-151诱导的EAE小鼠模型中的体内疗效评估.
来自PwMS的PBMCs的ex vivo分析用于对LPX-TI641.1.的Treg反应.

主要成果:

在实验室中,LPX-TI641证明了CD4+Foxp3+和CD4+Foxp3+Tim-3+Tregs的剂量依赖扩张.
在EAE模型中,LPX-TI641显著降低了疾病的严重程度,预防了复发,并在治疗后保持了临床益处.
LPX-TI641恢复了从PwMS中减少的Tim-3+Treg群体,并逆转了PBMC中的Treg功能障碍.
在动物模型中,治疗疗效与natalizumab相当或超过.

结论:

LPX-TI641通过激活Tim受体和扩展Tregs.促进抗原独立的免疫耐受性.
这些发现表明LPX-TI641是MS的潜在新疗法候选者.
LPX-TI641可能会解决与当前MS疾病修饰疗法相关的局限性.

关键词:

调控性T细胞 (Tregs) 是一种发现药物的发现.免疫调节免疫调节免疫耐受性免疫耐受性多发性硬化症多发性硬化症口服治疗是一种口服疗法.

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