A humanized chimeric antibody Hai178 targeted to the β subunit of F1F0 ATP synthase.

Abstract

Inhibition of tumor vasculature is an effective strategy for cancer therapy. Angiostatin could suppress tumor growth and metastasis by binding and inhibiting F1F0 ATP synthase on the endothelial cell surface. We previously screened a monoclonal antibody (McAb, McAb178-5G10), which specifically bound to ATPase on the surface of cells and showed an angiostatin-like activity. Here, we further generated a panel of CHO-mAb subclone stable expressing a humanized chimeric antibody from hybridoma cell McAb178-5G10 by gene engineer. And then, we successfully expressed the humanized antibody Hai178 at high level in a 5-L wave bioreactor. The vitro results showed that Hai178 retained the specific binding and antitumor activity of murine antibody. Furthermore, Hai178 also had a tumor therapeutic effect in tumor xenografts. These results paved the way for Hai178 as a therapeutic antibody in clinic.