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广泛反应的抗VHH抗体用于表征,阻断或激活基于纳米体的CAR-T细胞

Scott McComb^1,2,3,4, Bianca Dupont², Alex Shepherd²

¹Human Health Therapeutics Research Centre, National Research Council Canada, Montreal, QC, H4P 2R2, and Ottawa, ON, K1A 0R6, Canada.

Antibody therapeutics

|September 24, 2025

概括

研究人员开发了新的抗VHH抗体,用于化学抗原受体T细胞 (CAR-T) 疗法. 这些抗体有效标记,激活和扩展VHH-CAR-T细胞,而不妨碍抗原结合,改善CAR-T细胞治疗的发展.

科学领域:

免疫学免疫学免疫学
生物技术是生物技术.
抗体工程抗体工程

背景情况:

化学抗原受体T细胞 (CAR-T) 疗法依赖于用于T细胞操纵的抗体.
在一些CAR设计中,仅使用重链抗体 (VHHs) 或纳米体的可变域.
开发针对VHHs的特定抗体工具对于推进CAR-T疗法至关重要.

研究的目的:

创建针对重链仅抗体 (VHHs) 的可变域的特定抗体工具.
评估这些抗VHH抗体在标记,调节和扩大VHH-CAR-T细胞中的实用性.
增强基于VHH的免疫疗法的理解和操纵.

主要方法:

用VHH免疫小鼠,并选择小鼠单克隆抗体 (mAbs).
使用ELISA,SPR和HDX-MS等技术对抗VHHmAbs进行表征.
对抗VHH mAbs进行细胞/组织标记和调节VHH-CAR-T细胞活性的测试.

主要成果:

一种双克隆抗VHH抗体产品对VHH蛋白具有高反应性 (>98%),对人类IgG没有交叉反应性.
抗VHH抗体不会干扰VHH/抗原结合,但可以阻止VHH-CAR-T细胞激活.
动不动的抗VHH抗体诱导了显著的VHH-CAR-T细胞扩张 (730倍) 和纯度 (> 94%),同时保持了功能.

结论:

新型抗VHH单克隆抗体已被确定为CAR-T细胞研究的宝贵工具.
这些抗体可用于VHH-CAR-T细胞的二次标记和功能调节.
开发的抗VHH抗体有助于更好地理解和操纵基于VHH的CAR-T细胞和免疫疗法.

关键词:

在CAR标签上,使用CAR标签.在CART-T中,我们可以使用CAR-T.化学抗原受体化学抗原受体纳米体是一种纳米体.这就是VHH VHH.

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