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Published on: March 8, 2018
Potent pleiotropic anti-angiogenic effects of TM601, a synthetic chlorotoxin peptide
Douglas B Jacoby1, Evgeny Dyskin, Murat Yalcin
1TransMolecular, Inc., 840 Memorial Drive, Cambridge, MA 02139, USA. jacoby@transmolecular.com
Unlabelled:
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.
Insights
Chlorotoxin (TM601) exhibits anti-angiogenic properties, inhibiting new blood vessel formation. This tumor-targeting peptide enhances the effects of bevacizumab, offering a potent combination therapy.
Area of Science:
- Oncology
- Vascular Biology
- Biochemistry
Background:
- Chlorotoxin (TM601) is a chemically synthesized peptide investigated for tumor targeting.
- This study focuses on elucidating the anti-angiogenic potential of TM601.
Purpose of the Study:
- To characterize the anti-angiogenic properties of chlorotoxin (TM601).
- To evaluate TM601's efficacy in inhibiting angiogenesis and tumor growth in vitro and in vivo.
Main Methods:
- Utilized in vitro and in vivo models of angiogenesis and tumor growth.
- Assessed TM601's binding to vascular endothelial cells, invasion inhibition, and MMP-2 secretion.
- Employed the chick chorioallantoic membrane (CAM) assay and mouse models for in vivo evaluation.
Main Results:
- TM601 inhibited angiogenesis stimulated by multiple pro-angiogenic factors.
- TM601 reduced human umbilical vein endothelial cell (HUVEC) invasion and matrix metalloproteinase-2 (MMP-2) secretion.
- Co-administration of TM601 with bevacizumab showed enhanced anti-angiogenic potency; TM601 decreased tumor growth and intra-tumoral hemoglobin levels in CAM models and reduced neovascularization in mice.
Conclusions:
- TM601 demonstrates significant anti-angiogenic activity against various stimuli.
- TM601 potentiates the anti-angiogenic effects of bevacizumab, suggesting a synergistic therapeutic potential.
