TY - JOUR T1 - Selective Activity Against Proliferating Tumor Endothelial Cells by CVX-22, A Thrombospondin-1 Mimetic CovX-Body™ JF - Anticancer Research JO - Anticancer Res SP - 2243 LP - 2252 VL - 29 IS - 6 AU - JULIA CORONELLA AU - LINGNA LI AU - KIMBERLY JOHNSON AU - STEVEN PIRIE-SHEPHERD AU - GIOVANNI ROXAS AU - NANCY LEVIN Y1 - 2009/06/01 UR - http://ar.iiarjournals.org/content/29/6/2243.abstract N2 - CVX-22 is a CovX-Body™, produced by covalently attaching a thrombospondin-1 (TSP-1) type 1 repeat peptide mimetic to a humanized IgG1 molecule. To dissect the antiangiogenic mechanism of CVX-22, the numbers and proliferative status of defined tumor endothelial cell (TEC) subsets from the B16 and C32 melanoma models were examined. CVX-22 treatment reduced the numbers of activated, vascular endothelial growth factor receptor 2 (VEGFR2)-positive TECs. Because the vast majority of mitotically active TECs reside in the VEGFR2 subset, a reduction in numbers of this compartment resulted in an 82% overall decrease in BrdU labeling of TEC. However, the rate of proliferation and VEGFR2 receptor density of this VEGFR2-positive subpopulation were unaffected. Instead, CVX-22 induced endothelial cell apoptosis both in vitro and in vivo, indicating that CVX-22 acts by selective deletion of activated, VEGFR2-positive TEC. The overrepresentation of activated cells in sites of tumor angiogenesis may confer a unique specificity of CVX-22 for tumor vasculature. ER -