Characterization and evaluation of the antitumour activity of a dual-targeting monoclonal antibody against claudin-3 and claudin-4.

Background: Because human claudin-3 and claudin-4 (CLDN3 and CLDN4) are overexpressed in a variety of carcinomas, they are promising targets for cancer therapy. The aim of the present study was to generate a dual-targeting monoclonal antibody against CLDN3 and CLDN4 and evaluate its antitumour activity. Materials and Methods: BALB/c mice were immunised with CLDN4-expressing Chinese hamster ovary cells and cell-based screening was performed. The antibody-binding epitope of CLDN3 and CLDN4 and the antitumour activity of the antibody were evaluated. Results: A monoclonal antibody, KM3907 (IgG2a), which recognised CLDN3 and CLDN4, but not CLDN5, CLDN6 and CLDN9, was successfully isolated. The binding assay of KM3907 revealed that KM3907 recognised the extracellular loop 1 of CLDN3 and CLDN4. Mouse human chimeric IgG1 induced antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity in vitro, and treatment with murine KM3907 significantly inhibited tumour formation in SCID mice in vivo. Conclusion: A dual-targeting monoclonal antibody against CLDN3 and CLDN4 is a promising strategy for cancer immunotherapy.