Potent Pleiotropic Anti-angiogenic Effects of TM601, a Synthetic Chlorotoxin Peptide

Chemically synthesized chlorotoxin (TM601) has been studied as a tumor targeting peptide. In this study, the anti-angiogenic properties of TM601 are reported. Materials and Methods: In vitro and in vivo models of angiogenesis and tumor growth were used to characterize the anti-angiogenic effects of TM601. Results: TM601 bound to proliferating vascular endothelial cells, decreased human umbilical vein endothelial cell (HUVEC) invasion, and reduced secretion of bioactive matrix metalloproteinase-2 (MMP-2). Using the chick chorioallantoic membrane assay (CAM), TM601 inhibited angiogenesis stimulated by any of eight pro-angiogenic factors, and when TM601 was co-administered with bevacizumab, the combination was significantly more potent than a ten-fold increase in bevacizumab dose. TM601 did not alter tumor or vascular endothelial cell growth in vitro, but TM601 treatment of tumors grown on the CAM decreased tumor growth and intra-tumoral hemoglobin levels. Intravenously injected TM601 was also shown to significantly decrease new blood vessel growth in mice. Conclusion: TM601 inhibits angiogenesis stimulated by many factors and potentiates the anti-angiogenic effect of bevacizumab.