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鉴定和优化抑制剂以阻止VISTA/PSGL-1相互作用,用于癌症免疫治疗

Xiaoshuang Niu^1,2, Menghan Wu¹, Guodong Li¹

¹School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.

Acta pharmaceutica Sinica. B

|November 16, 2023

概括

研究人员开发了新型来阻断VISTA免疫检查点,通过增强T细胞功能和减少抑制性髓状细胞来显示癌症免疫治疗的前景.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
药物发现药物发现药物发现

背景情况:

癌症免疫疗法面临的挑战是,PD-1/PD-L1阻塞的响应率很低.
免疫检查点VISTA在瘤透的免疫细胞上高度表达,包括髓质衍生抑制细胞 (MDSC) 和CD8+ T细胞.

研究的目的:

开发针对癌症免疫治疗的VISTA免疫检查点的新型类药物.
研究VISTA阻断的抗瘤活性和机制.

主要方法:

用体显示生物分析来开发具有VISTA结合亲和力的C1.
分子对接引导突变产生VS3,该结合VISTA,并在酸性条件下阻止PSGL-1相互作用.
DVS3-Pal是用d-氨基酸替代和脂肪酸修饰进行工程设计的,以提高稳定性和有效性.

主要成果:

体VS3表现出与VISTA结合的高亲和力,并抑制了VISTA/PSGL-1相互作用.
在体内,VS3引起了抗瘤活性.
改性DVS3-Pal通过促进CD8+T细胞功能和减少MDSC透,显示出增强的蛋白质分解稳定性和显著的抗瘤作用.

结论:

这项研究介绍了第一个旨在阻止VISTA/PSGL-1相互作用的.
这些,特别是DVS3-Pal,代表了增强癌症免疫疗法的有希望的治疗候选者.

关键词:

癌症免疫疗法癌症免疫疗法免疫检查站检查站在MDSC中,MDSC是MDSC.在PSGL-1中,它是PSGL-1.这是一种类.菌体显示生物扫描.一个T细胞细胞.在视野中看到的.

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