开发基于高亲和性scFv异构体的双重VEGF/PDL1抑制剂,作为一种抗癌治疗策略

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Noam Tzuri¹, Ksenia M Yegodayev², Ofra Novoplansky²

¹Avram and Stella Goldstein-Goren Department of Biotechnology Engineering and The National Institute of Biotechnology in the Negev, Ben-Gurion University of the Negev, 8410501, Beer-Sheva, Israel.

Scientific reports

|July 24, 2023

概括

一种新的双特异蛋白,DuRan-Bis,同时准编程死亡连接体1 (PDL1) 和血管内皮生长因子 (VEGF). 这种双重抑制显示出对质母细胞瘤和头癌的优越抗癌作用.

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:

编程死亡配体1 (PDL1) 相互作用抑制了抗瘤免疫反应.
血管内皮生长因子 (VEGF) 促进瘤血管生成和增殖,同时抑制免疫细胞.
同时抑制PDL1和VEGF提供了潜在的协同抗癌疗法.

研究的目的:

开发一种新型治疗剂,可以同时结合并抑制PDL1和VEGF.
使用单个聚类链架设计双特异性蛋白质,以实现高亲和度双抑制.

主要方法:

产生一种双特异性蛋白质DuRan-Bis,该蛋白质由抗PDL1和抗VEGF单链可变片段 (scFv) 组成,并融为Fc片段.
评估Duran-Bis对PDL1和VEGF的结合亲和力.
评估DuRan-Bis在抑制质母细胞瘤细胞增殖和增强免疫细胞介导的头癌细胞杀死方面的疗效.

主要成果:

杜兰比斯证明了与PDL1和VEGF结合的高亲和度.
与单一特异性抑制剂相比,DuRan-Bis仿真体表现出较强的质母细胞瘤细胞增殖抑制.
与DuRan-Bis和免疫细胞的联合治疗比单独的免疫细胞更有效地降低了头癌细胞的活力.

结论:

该研究介绍了第一个单个多链scFv-scFv-Fc支架,用于设计一种高亲和度双特异性PDL1和VEGF抑制剂.
杜兰比斯 (DuRan-Bis) 代表了一种有前途的新型治疗策略,用于协同抗癌治疗,通过向免疫逃避和瘤生长途径.
这种方法有可能提高癌症免疫疗法的疗效.

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