antibody targeting of cathepsin s inhibits angiogenesis and synergistically enhances anti-vegf抗体针对的组织蛋白酶s抑制血管生成作用增强vegf.pdfVIP

Antibody Targeting of Cathepsin S Inhibits Angiogenesis and Synergistically Enhances Anti-VEGF 1 1 1,2 1 1 Claire Ward , Diana Kuehn , Roberta E. Burden , Julie A. Gormley , Thomas J. Jaquin , Mihaela 1 1,2 3 4 2 1 Gazdoiu , Donna Small , Roy Bicknell , James A. Johnston , Christopher J. Scott *, Shane A. Olwill * 1 Drug Discovery, Fusion Antibodies Ltd, Belfast, United Kingdom, 2 School of Pharmacy, Queens University Belfast, Belfast, United Kingdom, 3 Schools of Immunity and Infection and Cancer Studies, College of Medicine and Dentistry, University of Birmingham, Birmingham, United Kingdom, 4 Centre for Infection and Immunity, Queens University Belfast, Belfast, United Kingdom Abstract Background: Angiogenesis is a key hallmark of tumourigenesis and its inhibition is a proven strategy for the development of novel anti-cancer therapeutics. An important aspect of early angiogenesis is the co-ordinated migration and invasion of endothelial cells through the hypoxic tumour tissue. Cathepsin S has been shown to play an important role in angiogenesis as has vascular endothelial growth factor (VEGF). We sought to assess the anti-angiogenic effect of Fsn0503, a novel cathepsin S inhibitory antibody, when combined with anti-VEGF on vascular development. Methodology/Principal Findings: Cathepsin S expression and secretion from endothelial cells was characterised using RT- PCR and western blotting. We further show that cathepsin S promotes pericellular hydrolysis of extracellular matrix components in the tumour microenvironmen