Antibody targeting of cathepsin S inhibits angiogenesis and synergistically enhances anti-VEGF.

Antibody targeting of cathepsin S inhibits angiogenesis and synergistically enhances anti-VEGF.

Blog Article

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 surfboard 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 microenvironment and facilitates endothelial invasion.The cathepsin S inhibitory antibody, Fsn0503, blocks extracellular proteolysis, inhibiting endothelial invasion and tube formation in cell-based assays.The anti-angiogenic effects of Fsn0503 were also shown in vivo where it significantly retarded the development of vasculature in human xenograft models.Furthermore, when Fsn0503 was combined with an anti-VEGF antibody, a synergistic inhibition of microvascular development was observed.CONCLUSIONS/SIGNIFICANCE: Taken together, this data demonstrates that the Faber Daisy B EG6 A55 55cm Angled Cooker Hood Black Glass 330 0529 664 antibody-mediated targeting of cathepsin S represents a novel method of inhibiting angiogenesis.

Furthermore, when used in combination with anti-VEGF therapies, Fsn0503 has the potential to significantly enhance current treatments of tumour neovascularisation and may also be of use in the treatment of other conditions associated with inappropriate angiogenesis.