A fully chimeric IgG antibody for ROR1 suppresses ovarian cancer growth in vitro and in vivo

Abstract

BackgroundOver-expression of Receptor-tyrosine-kinase-like Orphan Receptor 1 (ROR1) in cancer cells has been reported in the context of several tumors (including ovarian cancer) and is associated with poor prognosis. The aim of this study was to construct a fully chimeric anti-ROR1 IgG antibody (ROR1-IgG) and investigate its antitumor activity against ovarian cancer cells, bothin vitro and in vivo. MethodsA fully chimeric anti-ROR1 IgG antibody (ROR1-IgG) eukaryotic expression vector was constructed and ROR1-IgG antibody was expressed in CHO cells. The characteristics of ROR1-IgG were investigated by ELISA, SPR, Western blotting, FACS and fluorescence staining analyses. CCK8 and wound healing assays were performed to determine inhibition and migration capacity of ovarian cancer cells after treatment with ROR1-IgGin vitro. Further, the antitumor activity of ROR1-IgG was assessed in vivo using tumor-mice xenograft model. ResultsThe results showed that ROR1-IgG could specifically bind to ROR1-positive cells (HO8910 and A2780) with a high affinity. Functional studies revealed that ROR1-IgG inhibited the malignant behavior of ROR1-positive cells (HO8910 and A2780) in a time- and dose-dependent manner. These effects were not observed in ROR1-negative lose386 cells. The tumor inhibition rates following treatment with low, medium, and high concentrations of ROR1-IgG were approximately 47.72%, 53.79%, and 60.51%, respectively. In addition, the expression of Bcl-2 was obviously reduced while that of Bax was distinctly elevated in xenografts. ConclusionsCollectively, our findings suggest that ROR1-IgG may be a novel therapeutic agent for patients with ROR1-positive ovarian cancer.