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开发一种PD-1阻断,以重振T细胞活动并抑制瘤的进展

Yingzhou Qin¹, Xiangzhou Meng¹, Lin Li²

¹School of Nano Technology and Nano Bionics, University of Science and Technology of China, Hefei, 230026, China; CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China.

European journal of pharmacology

|October 22, 2023

概括

一种针对编程细胞死亡1 (PD-1) 途径的新型抑制剂有效抑制瘤生长. 这种可以重振T细胞,并显示出作为抗体基础癌症免疫疗法的替代品的潜力.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
生物技术是生物技术.

背景情况:

针对编程细胞死亡1 (PD-1) /编程细胞死亡-1 (PD-L1) 途径的单克隆抗体是有效的癌症免疫疗法.
抗体的局限性包括免疫性和薄弱的组织透,需要替代治疗策略.
类提供低分子量替代品,在临床应用中具有潜在的优势.

研究的目的:

确定和描述PD-1/PD-L1相互作用的新型抑制剂.
在临床前癌症模型中评估该的治疗潜力.

主要方法:

使用细菌表面显示技术发现了一种PD-1结合 (PBP).
进行了分子对接和竞争性结合试验,以阐明相互作用机制.
在体外测试中评估了T细胞功能,而在体内研究中使用了CT26瘤小鼠模型.

主要成果:

确定了一种,PBP,可以与人类和小鼠的PD-1结合,具有中等亲和力.
证明PBP会干扰PD-1/PD-L1相互作用,并重振PD-L1受抑制的T细胞.
在体内,PBP通过增强T细胞活性,抑制CT26小鼠模型中的瘤生长.

结论:

该PBP有效地阻断PD-1/PD-L1相互作用,并表现出抗瘤活性.
PBP显示出作为一种基于的新型治疗癌症免疫疗法的潜力.
这种为基于抗体的治疗提供了一个有希望的替代方案,解决了免疫性和透性等局限性.

关键词:

细菌表面显示器显示细菌的表面.检查点抑制剂检查点抑制剂在PD-1中使用PD-1.在PD-L1中.这是一种类.一个T细胞细胞.

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