Anti-VEGFR2 F(ab′)2 drug conjugate promotes renal accumulation and glomerular repair in diabetic nephropathy
Di Liu, Yanling Song, Hui Chen, Yuchan You, Luwen Zhu, Jucong Zhang, Xinyi Xu, Jiahao Hu, Xiajie Huang, Xiaochuan Wu, Xiaoling Xu, Saiping Jiang, Yongzhong Du, Saiping Jiang, Yongzhong Du
Abstract
Abstract Poor renal distribution of antibody-based drugs is the key factor contributing to low treatment efficiency for renal diseases and side effects. Here, we prepare F(ab′) 2 fragmented vascular endothelial growth factor receptor 2 antibody (anti-VEGFR2 (F(ab′) 2 ) to block VEGFR2 overactivation in diabetic nephropathy (DN). We find that the anti-VEGFR2 F(ab′) 2 has a higher accumulation in DN male mice kidneys than the intact VEGFR2 antibody, and simultaneously preserves the binding ability to VEGFR2. Furthermore, we develop an antibody fragment drug conjugate, anti-VEGFR2 F(ab′) 2 -SS31, comprising the anti-VEGFR2 F(ab′) 2 fragment linked to the mitochondria-targeted antioxidant peptide SS31. We find that introduction of SS31 potentiates the efficacy of anti-VEGFR2 F(ab′) 2 . These findings provide proof of concept for the premise that antibody fragment drug conjugate improves renal distribution and merits drug validation in renal disease therapy.