A single-domain antibody-linked Fab bispecific antibody Her2-S-Fab has potent cytotoxicity against Her2-expressing tumor cells.
Her2, which is frequently overexpressed in breast cancer, is one of the most studied tumor-associated antigens for cancer therapy. Anti-HER2 monoclonal antibody, trastuzumab, has achieved significant clinical benefits in metastatic breast cancer. In this study, we describe a novel bispecific antibody Her2-S-Fab targeting Her2 by linking a single domain anti-CD16 VHH to the trastuzumab Fab. The Her2-S-Fab antibody can be efficiently expressed and purified from Escherichia coli, and drive potent cancer cell killing in HER2-overexpressing cancer cells. In xenograft model, the Her2-S-Fab suppresses tumor growth in the presence of human immune cells. Our results suggest that the bispecific Her2-S-Fab may provide a valid alternative to Her2 positive cancer therapy.
School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.|Center for Cellular and Structural Biology, Sun Yat-Sen University, Guangzhou, China.
Aifen
A
Li
School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.|Center for Cellular and Structural Biology, Sun Yat-Sen University, Guangzhou, China.
Jieyu
J
Xing
School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.|Center for Cellular and Structural Biology, Sun Yat-Sen University, Guangzhou, China.
Li
L
Li
School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.|Center for Cellular and Structural Biology, Sun Yat-Sen University, Guangzhou, China.
Changhua
C
Zhou
School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.|Center for Cellular and Structural Biology, Sun Yat-Sen University, Guangzhou, China.
Bin
B
Dong
School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.|Center for Cellular and Structural Biology, Sun Yat-Sen University, Guangzhou, China.
Ping
P
He
School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China. liqing66@mail.sysu.edu.cn.|Center for Cellular and Structural Biology, Sun Yat-Sen University, Guangzhou, China. liqing66@mail.sysu.edu.cn.
Qing
Q
Li
School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China. wangzh357@mail.sysu.edu.cn.|Center for Cellular and Structural Biology, Sun Yat-Sen University, Guangzhou, China. wangzh357@mail.sysu.edu.cn.
Zhong
Z
Wang
Bacterial expression; Bispecific antibody; CD16; Fab; Her2; Single domain antibody