间皮素靶向的双特异性抗体构建及其介导的NK细胞抗肿瘤作用研究
Construction of a Bispecific Antibody Targeting Mesothelin with Anti-tumor Activity via NK Cell Activation
余聪 1朱建伟1
作者信息
- 1. 上海交通大学药学院,细胞工程及抗体药物教育部工程研究中心,上海 200240
- 折叠
摘要
CD16分子可以强效介导NK细胞激活而不需要其他受体的共同参与,在基于自然杀伤(NK)细胞重导向的双特异性抗体(BsAbs)中被广泛选择.间皮素(MSLN)在多种实体瘤中显著过度表达,能促进肿瘤细胞的黏附、迁移、增殖和存活.该研究构建了1种靶向CD16和MSLN的双特异性抗体16MSLN,通过Expi293F细胞表达抗体,经Protein L纯化后即能获得高纯度的16MSLN.细胞试验结果显示,16MSLN能促进NK细胞与靶细胞交联,并特异性增强NK细胞对MSLN+肿瘤细胞的杀伤作用.该研究为实体瘤治疗和MSLN靶点药物开发提供了参考.
Abstract
CD 16 has the capacity to effectively mediate natural killer(NK)cell activation without the necessity for co-engagement of other receptors,making it a widely selected target in bispecific antibodies(BsAbs)based on NK cell redirection.Mesothelin(MSLN)is significantly overexpressed in various solid tumors and can promote tumor cell adhesion,migration,proliferation,and survival.In this study,a bispecific antibody,16MSLN,targeting both CD 16 and MSLN was constructed.The antibody was expressed in Expi293F cells and purified using Protein L to obtain highly pure target antibody.The results of cell experiments indicated that 16MSLN could promote the crosslinking of NK cells with target cells and specifically enhance the killing effect of NK cells on MSLN+tumor cells.This study provides a reference for the development of NK cell-redirected BsAbs.
关键词
双特异性抗体/NK细胞/间皮素/CD16Key words
bispecific antibody/natural killer cell/mesothelin/CD16引用本文复制引用
出版年
2024
NETL
NSTL
万方数据