Preclinical Efficacy and Safety of an Anti-Human VEGFA and Anti-Human NRP1 Dual-Targeting Bispecific Antibody (IDB0076).

摘要: Although bevacizumab (Avastin®) has been approved as an antiangiogenic agent against some cancers, the efficacy is transient and unsatisfactory in other cancers most likely owing to presence of alternative proangiogenic factors. Therefore, simultaneous blocking several factors may be a promising strategy for cancer therapeutics. Accordingly, neuropilin-1 (NRP1) attractive target because it serves multifunctional receptor vascular endothelial growth factor (VEGF) family. Here, we aimed generate test anti-VEGFA anti-NRP1 dual-targeting bispecific antibody (named IDB0076) by genetic fusion NRP1-targeting peptide C-terminus heavy chain. Similar parental (bevacizumab), IDB0076 suppressed VEGFA-induced migration human cells. In contrast, inhibited endothelial-cell induced angiogenesis manifested more potent antitumor activity than that murine tumor xenograft model. When toxicity was preliminarily evaluated cynomolgus monkeys, showed no substantial adverse effects, e.g., absence noticeable nephrotoxicity, which previously documented combination therapy antibody. Thus, VEGFA-and-NRP1 safe anticancer worthy further preclinical clinical studies.