Local acting Sticky‐trap inhibits vascular endothelial growth factor dependent pathological angiogenesis in the eye

Abstract

Current therapeutic antiangiogenic biologics used for the treatment of pathological ocular angiogenesis could have serious side effects due to their interference with normal blood vessel physiology. Here, we report the generation of novel antivascular endothelial growth factor-A (VEGF) biologics, termed VEGF “Sticky-traps,” with unique properties that allow for local inhibition of angiogenesis without detectable systemic side effects. Using genetic and pharmacological approaches, we demonstrated that Sticky-traps could locally inhibit angiogenesis to at least the same extent as the original VEGF-trap that also gains whole-body access. Sticky-traps did not cause systemic effects, as shown by uncompromised wound healing and normal tracheal vessel density. Moreover, if injected intravitreally, recombinant Sticky-trap remained localized to various regions of the eye, such as the inner-limiting membrane and ciliary body, for prolonged time periods, without gaining access either to the photoreceptors/choriocapillaris area or the circulation. These unique pharmacological characteristics of Sticky-trap could allow for safe treatment of pathological angiogenesis in patients with diabetic retinopathy and retinopathy of pre-maturity.

Novel Glycosylated VEGF Decoy Receptor Fusion Protein, VEGF-Grab, Efficiently Suppresses Tumor Angiogenesis and Progression

“…However, adverse effects of systemic anti-VEGF therapy have been reported, including delayed wound healing and hemorrhage (39). Recently, Sticky-trap, which locally inhibits angiogenesis, has been developed and confirmed to have no systemic side effects (40). Although the potential side effects of G3 in clinics should be carefully studied at varying dosages, time points, and after long-term treatment, it could be further improved by adopting the Sticky-trap concept.…”

Induction of VEGFA mRNA translation by CoCl2 mediated by HuR

“…These alterations are followed by microvascular occlusions that lead to progressive retinal ischemia, which in turn causes hypoxia and induces VEGFA synthesis and release. 7 Given the pivotal role of VEGF in such pathologies, different approaches have been developed to inhibit VEGF signaling, such as the recombinant protein VEGF-trap, 8 and monoclonal antibodies. 9 VEGFA expression in pathophysiological states can be induced by post-transcriptional mechanisms directed at the VEGFA mRNA.…”

Antisenescence effect of mouse embryonic stem cell conditioned medium through a PDGF/FGF pathway

“…Therefore, we examined whether H‐CM treatment had beneficial effects on the skin wound‐healing process. To accomplish this, we conducted an in vitro cell migration assay (37) and an in vivo skin wound‐healing analysis (38, 39). H‐CM treatment enhanced cellular migration in a dose‐dependent manner (Fig.…”