Jinan University, China
Ning Deng has his expertise in antibody drug and tumor polypeptide vaccine around tumor angiogenesis inhibition. He has established antibody design and construction system, included the phage antibody library, affinity maturation and improvement based on antibody structural simulation, evaluation system for tumor peptide vaccine. He also researched on the mechanism of tumor angiogenesis in ovarian cancer and stem cell evaluation.
Angiogenesis plays a critical role in tumor growth. Fibroblast growth factor-2 (FGF-2) is one of the most important angiogenic factors. The over-expression of bFGF plays a crucial role 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 our lab, we scanned human anti-bFGF antibody from the phage antibody library. The results showed that the human anti-bFGF antibody could significantly inhibit the tumor angiogenesis and inhibit the tumor growth and migration. Based on this antibody, a newly small molecular antibody of disulfide-stabilized diabody (ds-Diabody) against bFGF was constructed by site-directed mutation and overlap extension PCR (SOE-PCR) at the position of VH44 and VL100 in the scFv. The ds-Diabody was expressed in Pichia pastoris system. We found that the ds-Diabody against bFGF could maintain good antigen binding activity and stability in vitro and in vivo. The ds-Diabody against bFGF could efficiently suppress the proliferation, migration and invasion of human lung cancer (A549 cells) and breast cancer (MCF-7 cells), inhibit bFGF-induced activation of downstream signaling regulators, phospho-Akt and phospho- MAPK. In the nude mouse xenograft model, the ds-Diabody against bFGF could significantly inhibit tumor growth, tumor angiogenesis and lymphangiogenesis. The ds-Diabody against bFGF showed stability in vivo and could more effectively suppress the tumor growth through blockade of bFGF signaling pathway and inhibition of tumor angiogenesis, which may make it a potential therapeutic candidate antibody drug for human lung cancer therapy.