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一种pH敏感的结合方式可以使双价抗体的转移林受体介导的细胞转移成功地穿过大脑屏障

Philipp Kuhn¹, Sabrina Petralla², Fatemeh Dabbagh³

¹YUMAB GmbH, Braunschweig, Germany.

|September 22, 2025

概括

研究人员开发了一种针对转移素受体1 (TfR) 的pH敏感抗体,以增强跨大脑屏障的药物输送. 这种新的方法促进了受体介导细胞转移 (RMT) 治疗神经系统疾病.

科学领域:

神经科学是一个神经科学.
生物技术是生物技术.
药理学药理学是指药理学的学科.

背景情况:

由于生物障碍,有效的中枢神经系统 (CNS) 药物输送面临重大挑战.
受体介导细胞转移 (RMT) 是克服这些障碍的有希望的策略,但临床应用仍然有限.
针对转移素受体1 (TfR) 的双等抗体正在研究它们在RMT中的潜力.

研究的目的:

识别和描述针对TfR的双价抗体,以调解RMT.
调查pH敏感性在抗体结合和细胞转移中的作用.
为了证明这种方法在通过大脑屏障传递治疗载荷方面的潜力.

主要方法:

双价抗TfR抗体的鉴定和表征 (F06).
在脑屏障模型中对F06-介导的细胞转移进行体外评估.
在不同pH值下评估F06结合亲和力.
使用数学模型来预测RMT效率.
通过F06-介导的RMT进行货物交付 (scFvs针对TREM2或EGFRvIII) 的演示.

主要成果:

抗体F06在体外大脑屏障模型中表现出高效的细胞转移.
F06在细胞外pH值时表现出高亲和力结合,但在较低,酸性内体pH值时结合性降低.
假设这种pH敏感性可以防止 lysosomal 降解,这是高亲和度 TfR 结合剂的常见问题.
F06成功调解了针对TREM2和EGFRvIII的单链可变片段 (scFvs) 的转细胞分裂.

结论:

一种新型的,pH敏感的双价抗TfR抗体 (F06) 已被开发出来,作为增强中枢神经系统药物递送的概念验证.
在抗体结合中利用pH敏感性是一种可行的策略,可以提高RMT的效率并避免溶酶体降解.
这种方法有望为神经疾病开发有效的治疗方法,通过促进跨大脑屏障的向药物运输.

关键词:

抗体工程是一种抗体工程.通过CNS进行交付.这是一种双价两价的双价物.大脑屏障 - 大脑屏障对于pH值的敏感性通过细胞转化 (transcytosis).转移素受体的受体是转移素的受体.

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