Construction of a Novel Bispecific Antibody to Enhance Antitumor Activity against Lung Cancer.

HER2 and VEGF are closely related to the progression of several tumors. The inhibitor simultaneously targeting these two proteins will effectively inhibit the progression of tumors. Here, a bispecific antibody, termed as YY0411, targeting both HER2 and VEGF as a potent anticancer therapeutic antibody is reported. YY0411 is the first bispecific antibody constructed in IgG-Decoy receptor format. It efficiently identifies and combines both HER2 and VEGF protein. YY0411 is believed to be a candidate tumor suppressor as it significantly inhibits the colony formation ability of human cancer cells (Calu-3, MDA-MB-453, and NCI-N87 cells). The phosphorylation of HER2 and VEGF downstream components are also decreased in these cells with the treatment of YY0411. Similar to other antibodies, YY0411 has the ability to promote the secretion of IFN-gamma by T lymphocytes. In addition, YY0411 significantly inhibits the growth of Calu-3 cells-induced xenograft in nude mice. This work demonstrates that YY0411 may be a potential anti-lung cancer drug.