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通过下一代测序增强挖掘新型免疫VNAR图书馆发现的针对FAP的发明

Gihan S Gunaratne¹, Joseph P Gallant¹, Kendahl L Ott^1,2

¹Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA.

bioRxiv : the preprint server for biology

|January 27, 2025

概括

鱼抗体碎片 (VNARs) 针对纤维细胞激活蛋白 (FAP) 显示出癌症治疗的希望. 这些新的VNAR-Fc构造有效地准FAP阳性瘤,并为光学发展提供了一个新的平台.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
生物技术是生物技术.

背景情况:

与癌症相关的纤维细胞 (CAF) 创造了一个免疫抑制性瘤微环境 (TME),阻碍了癌症治疗.
由CAFs表达的纤维细胞激活蛋白 (FAP) 是调节TME的治疗点.
现有的针对FAP的生物药物无法利用可变新抗原受体 (VNAR) 的独特特性.

研究的目的:

使用鱼抗体技术开发新的抗FAP VNAR.
评估针对FAP的VNAR-Fc融合蛋白的治疗潜力.
建立VNAR-Fc构建为癌症治疗学的多功能平台.

主要方法:

通过免疫护士鱼生成了一个反FAP VNAR菌体显示库.
通过in vitro生物扫描和in silico方法确定了抗FAP的VNAR.
研究了四种VNAR-Fc融合蛋白用于FAP结合,内化和体内瘤局部化.

主要成果:

开发了一个庞大的反FAP VNARs图书馆.
确定了对FAP有很高亲和力的VNAR.
VNAR-Fc结构证明了有效的FAP向,FAP阳性细胞的快速内化,以及体外抗体-药物结合活性.
在活体中,VNAR-Fc结构局部化到FAP阳性异种移植.

结论:

VNAR-Fc融合蛋白是有效的针对FAP的治疗剂.
VNAR技术为开发向癌症治疗和诊断提供了一种新的方法.
VNAR-Fc结构代表了调节瘤微环境和改善治疗结果的多功能平台.

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