Selective activity against proliferating tumor endothelial cells by CVX-22, a thrombospondin-1 mimetic CovX-Body.

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.

Chemically programmed antibodies: endothelin receptor targeting CovX-Bodies.

Aryl sulfonamide-based endothelin antagonists were synthesized and covalently linked to the reactive lysine of the m38C2 antibody to create a series of CovX-Bodies. These chemically programmed antibodies behaved as potent endothelin receptor antagonists in vitro and had antitumor efficacy in a prostate cancer xenograft model which, on a molar basis, far exceeded the activity of the parent small molecule.