A HER2 bispecific antibody can be efficiently expressed in Escherichia coli with potent cytotoxicity.

Bispecific antibodies have been actively studied for cancer therapy due to their potent cytotoxicity against tumor cells. A number of bispecific antibody formats have exhibited strong tumor cytotoxicity in vitro and in vivo. However, effective production of bispecific antibodies remains challenging for the majority of bispecific antibody formats. In the present study, a bispecific antibody was designed that links a conventional antigen-binding fragment (Fab) against cluster of differentiation 3 antigen (CD3) to a camel single domain antibody (VHH) against human epidermal growth factor receptor 2 (HER2). This bispecific antibody may be secreted and purified efficiently from Escherichia coli culture medium. The purified bispecific antibody is able to trigger T cell-mediated HER2-specific cytotoxicity in vitro and in vivo. The data gathered in the present study suggest that this bispecific format may be applied to other tumor antigens to produce bispecific antibodies more efficiently.