A single-domain antibody-linked Fab bispecific antibody Her2-S-Fab has potent cytotoxicity against Her2-expressing tumor cells

AMB Express - Tập 6 - Trang 1-8 - 2016
Aifen Li1,2, Jieyu Xing1,2, Li Li1,2, Changhua Zhou1,2, Bin Dong1,2, Ping He1,2, Qing Li1,2, Zhong Wang1,2
1School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China
2Center for Cellular and Structural Biology, Sun Yat-Sen University, Guangzhou, China

Tóm tắt

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.

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