An anti­TROP2 monoclonal antibody TrMab­6 exerts antitumor activity in breast cancer mouse xenograft models.

Trophoblast cell surface antigen 2 (TROP2), reported to be overexpressed in several types of cancer, is involved in cell proliferation, invasion, metastasis, and poor prognosis of many types of cancer. Previously, a highly sensitive anti­TROP2 monoclonal antibody (clone TrMab­6; mouse IgG2b, κ) was developed using a Cell­Based Immunization and Screening (CBIS) method. TrMab­6 was useful for investigations using flow cytometry, western blot, and immunohistochemistry. The aim of the present study was to investigate whether TrMab­6 possesses in vitro antibody­dependent cellular cytotoxicity (ADCC) or complement­dependent cytotoxicity (CDC) activities or in vivo antitumor activities using mouse xenograft models of TROP2­overexpressed CHO­K1 (CHO/TROP2) and breast cancer cell lines, including MCF7, MDA­MB­231, and MDA­MB­468. In vitro experiments revealed that TrMab­6 strongly induced ADCC and CDC activities against CHO/TROP2 and the three breast cancer cell lines, whereas it did not show those activities against parental CHO­K1 and MCF7/TROP2­knockout cells. Furthermore, in vivo experiments on CHO/TROP2 and MCF7 xenografts revealed that TrMab­6 significantly reduced tumor growth, whereas it did not show antitumor activities against parental CHO­K1 and MCF7/TROP2­knockout xenografts. The findings suggest that TrMab­6 is a promising treatment option for TROP2­expressing breast cancers.