Antibody-mediated delivery of VEGF-C potently reduces chronic skin inflammation

Abstract

Conflict of interest: DN is a cofounder and shareholder of Philogen, a biotech company that owns and is developing derivatives of F8 antibodies for clinical applications. MD, CH, TH, DN, SR, and SS are inventors on a pending patent for F8-VEGF-C (PCT/EP2018/064900).

Vascular endothelial growth factor‐A as a promising therapeutic target for the management of psoriasis

“…[87] In mouse models of psoriasis, activation and expansion of the lymphatic vasculature promoted the resolution of inflammation including oedema reduction and downregulation of the inflammatory cell infiltrate. [88] VEGFR-3 and its ligands, VEGF-C and VEGF-D, constitute the main signalling pathway involved in lymphatic development. While angiogenesis enhances skin inflammation, lymphangiogenesis resolves skin inflammation and activation of the lymphatic vasculature could present a novel therapeutic strategy for the management of psoriasis.…”

The Role of Lymphatic Vascular Function in Metabolic Disorders

“…Although the development of targeted therapeutics for tissue specific activation of VEGFR-3 is currently a limitation, increasing evidence has shown that targeting this pathway to improve lymphatic function within this pathological context warrants further investigation. Thus, strategies to specifically stimulate adiposespecific lymphangiogenesis may be viable options for therapy to improve inflammatory cell clearance, similar to strategies targeting lymphatic expansion in an inflammatory site-specific manner within the context of a model of chronic skin inflammation (Schwager et al, 2018).…”

The lymphatic system in alcohol-associated liver disease

“…Delivery of lymphangiogenic factors, such as VEGF-C, to targeted organs has been shown to reduce inflammation in a variety of disease models. 6,[14][15][16][17][18] For example, virus-mediated delivery of VEGF-C alleviated chronic skin inflammation, 15 inflammatory bowel disease, 16 tubulointerstitial nephritis 17 and hepatic encephalopathy 33 in experimental models using mice or rats. In a mouse model of psoriasis-like skin inflammation, targeted delivery of VEGF-C to sites of inflammation led to a significant increase of lymphatic vessels in inflamed skin and improved lymphatic drainage function.…”

“…At the same time, this treatment significantly reduced infiltration of inflammatory cells in inflamed skin. 18 These studies suggest that promoting lymphangiogenesis may be a novel potential therapeutic strategy, particularly for diseases where inflammation plays a key role in their pathogenesis.…”

“…It can increase collection of interstitial fluid and migration of inflammatory cells out of affected tissues, interfere with recruitment of inflammatory cells, and enhance clearance of antigens and proinflammatory mediators, leading to mitigation of inflammation. [14][15][16][17][18]…”