Abstract
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.
Highlights
The human epidermal growth factor receptors (HER) play important roles in cell growth and signaling
We describe a novel bispecific antibody Her2-S-Fab targeting Her2 by linking a single domain anti-CD16 VHH to the trastuzumab Fab
Our results suggest that the bispecific Her2-S-Fab may provide a valid alternative to Her2 positive cancer therapy
Summary
The human epidermal growth factor receptors (HER) play important roles in cell growth and signaling. Mutations of these receptors can lead to tumorgenesis (Cooke 2000). Among the members of HER, HER2 (human epidermal growth factor receptor 2), which is known as Her2/neu or ErbB2, has been extensively studied as activation of Her signaling pathways can lead to cell proliferation and tumorgenesis (Olayioye 2001; Yarden and Sliwkowski 2001; Citri and Yarden 2006). HER2 is amplified and overexpressed in 20~30 % of invasive breast carcinomas. Its overexpression can be found in various human cancers, such as gastric, lung, ovary, bladder and kidney carcinomas (Slamon et al 1987; Press et al 1994; Daniele and Sapino 2009). Trastuzumab (Herceptin®), which binds to the HER2 ectodomain, is the first clinical
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
