A novel human Fab antibody for Trop2 inhibits breast cancer growth in vitro and in vivo

Human trophoblastic cell surface antigen 2 (Trop2) has been suggested as an oncogene, which is associated with the different types of tumors. In this study, a human Fab antibody against Trop2 extracellular domain was isolated from phage library by phage display technology, and characterized by ELISA, FACS, fluorescence staining and Western blotting analysis. MTT, apoptosis assay and wound healing assay were employed to evaluate the inhibitory effects of Trop2 Fab on breast cancer cell growth in vitro, while tumor‐xenograft model was employed to evaluate the inhibitory effects on breast cancer growth in vivo. The results showed that Trop2 Fab inhibited the proliferation, induced the apoptosis and suspended the migration of MDA‐MB‐231 cells in a dose dependent manner. The expression caspase‐3 was activated, and the expression of Bcl‐2 was reduced while that of Bax was elevated in MDA‐MB‐231 cells by treating with Trop2 Fab. In addition, Trop2 Fab inhibited the growth of breast cancer xenografts and the expression of Bcl‐2 was reduced while that of Bax was elevated in xenografts. Trop2 Fab, which was isolated successfully in this research, is a promising therapeutic agent for the treatment of Trop2 expressing breast cancer. What's new? Human trophoblastic cell surface antigen 2 (Trop2) is a calcium signaling molecule with oncogenic activity linked to tumor development, progression, and metastasis. Previous studies have indicated that it may be a valuable therapeutic target, as well as a prognostic or diagnostic marker. Here, a fully human Fab antibody targeting Trop2 was cloned and expressed. In breast cancer cell lines, Trop2 Fab inhibited growth, induced apoptosis, and suppressed migration, while in breast cancer xenografts, it successfully suppressed tumor growth and induced changes in the expression of cell death signaling molecules.