Prophylactic but not therapeutic activity of a monoclonal antibody that neutralizes the binding of VEGF-B to VEGFR-1 in a murine collagen-induced arthritis model.

Abstract

To assess the therapeutic potential of a mAb that neutralizes the binding of VEGF-B to VEGFR-1, to inhibit the pathogenesis of CIA in mice. CIA was induced in C57BL6/J and DBA-1 mice by intradermal injection of chick collagen type II (CII) in adjuvant. A neutralizing VEGF-B mAb or an isotype control mAb was then administered by intraperitoneal injection twice weekly beginning either post CII booster injection but prior to or immediately following clinical disease diagnosis. Neutralizing VEGF-B mAb inhibited the development of CIA in C57BL6/J mice in a dose-dependent manner when administered following the CII booster injection, but prior to clinical disease diagnosis. This result was also confirmed in DBA-1 strain mice. In contrast, the neutralizing VEGF-B mAb had no measurable effect on disease severity or progression when treatment commenced from the day of clinical disease diagnosis. Treatment with an mAb that neutralizes the binding of VEGF-B to VEGFR-1 exhibits prophylactic but not therapeutic actions in a mouse model of RA. These data indicate that while VEGF-B/VEGFR-1 signalling is involved in the early development of arthritis it may not be required for maintenance or progression of established disease.