Construction of a disulfide-stabilized diabody against fibroblast growth factor-2 and the inhibition activity in targeting breast cancer

Abstract

Fibroblast growth factor-2 (FGF-2) is one of the most important angiogenic factors to promote tumor growth, progression and metastasis. Neutralizing antibodies against FGF-2 may suppress the growth of tumor cells by blocking the FGF-2 signaling pathway. In this study, a disulfide-stabilized diabody (ds-Diabody) that specifically targets FGF-2 was designed. Compared to its parent antibody, the introduction of disulphide bonds in the diabody could significantly increase the stability of ds-Diabody and maintain its antigen binding activity. The ds-Diabody against FGF-2 could effectively inhibit the tube formation and migration of vascular endothelial cells and block the proliferation and invasion of human breast cancer cells. In the mouse model of breast cancer xenograft tumors, the ds-Diabody against FGF-2 could significantly inhibit the growth of tumor cells. Moreover, the densities of microvessels stained with CD31 and lymphatic vessels stained with LYVE1 in tumors showed a significant decrease following treatment with the ds-Diabody against FGF-2. Our data indicated that the ds-Diabody against FGF-2 could inhibit tumor angiogenesis, lymphangiogenesis and tumor growth.