Antiangiogenesis has become a promising pillar in modern
cancer therapy. This study investigates the antiangiogenic effects of the PEGylated Adnectin™,
CT-322, in a murine Colo-205 xenograft
tumor model.
CT-322 specifically binds to and blocks
vascular endothelial growth factor receptor (VEGFR-2). Adnectins are a novel class of targeted biologics engineered from the 10th domain of human
fibronectin.
CT-322 treated
tumors exhibited a significant reduction in
tumor growth of 69%, a 2.8 times lower
tumor surface area and fewer necrotic areas. Control
tumors showed a 2.36-fold higher microvessel density (MVD) and a 2.42 times higher vessel volume in corrosion casts. The vascular architecture in CT-322-treated
tumors was characterized by a strong normalization of vasculature. This was quantified in corrosion casts of
CT-322 treated
tumors in which the intervascular distance (a reciprocal parameter indicative of vessel density) and the distance between two consecutive branchings were assessed, with these distances being 2.21 times and 2.37 times greater than in controls, respectively. Fluorescence molecular tomography (FMT) equally affirmed the inhibitory effects of
CT-322 on
tumor vasculature as indicated by a 60% reduction of the vascular probe, AngioSense, accumulating in
tumor tissue, as a measurement of vascular permeability. Moreover, AngioSense accumulation was reduced as early as 24 h after starting treatment. The sum of these effects on
tumor vasculature illustrates the anti-angiogenic mechanism underlying the antitumor activity of
CT-322 and provides support for further evaluation of this Adnectin in combinatorial strategies with standard of care
therapies.