Endostatin Peptides with Anti-Tumor Properties
Inventors: M. Folkman, Kashi Javaherian, Robert Tjin Tham Sjin
Invention Types: Therapeutics
Research Areas: Oncology/Hematology
Keywords: Anti-angiogenesis, Composition of Matter, Peptide, Gene Therapy
Related Cases: 474, 1318For More Information Contact: Wong, Adrienne
Endostatin is a cleavage fragment from the C-terminal domain of collagen XVIII (see CMCC technology # 474) that has been developed as a clinical therapeutic, reaching phase II clinical trials with a very favorable safety profile. Endostatin and has been found to possess anti-angiogenic properties, including inhibition of endothelial cell proliferation, migration, and tube formation, as well as VEGF induced vascular permeability.
|Investigators at Children's Hospital Boston have identified a novel 27 amino acid fragment at the N terminus of endostatin that has anti-tumor, anto-angiogenic and anti-endothelial cell proliferation activity comparable to that of the full length protein. The peptide could be used as a therapeutic or the nucleic acid sequence that encodes it could be used as a gene therapy agent. The peptides have also been demonstrated to have activity against endometriosis (see CMCC technology # 1318).
The short synthetic endostatin peptides described here would be easier and cheaper to manufacture than the original form of endostatin, while anticipated to have a similar favorable safety and efficacy profile. The peptides represent new composition of matter with patents allowed as of early 2009 in the US and Europe.
Key Publications: Sunshine SB, et al. 2012. Endostatin lowers blood pressure via nitric oxide and prevents hypertension associated with VEGF inhibition. PNAS. 109(28):11306-11
Javaherian K, et al., 2011. Two endogenous antiangiogenic inhibitors, endostatin and angiostatin, demonstrate biphasic curves in their antitumor profiles. Dose Response 9(3):369-76
Lee TY, et al., 2008. Linking antibody Fc domain to endostatin significantly improves endostatin half-life and efficacy. Clin Cancer Res.14(5):1487-93
Tjin Tham Sjin RM, et al. 2006. Endostatin therapy reveals a U-shaped curve for antitumor activity. Cancer Gene Ther. 13(6):619-27
Related Publications: Yoshida J, et al., 2015. Inhibition of corneal neovascularization by subconjunctival injection of Fc-endostatin, a novel inhibitor of angiogenesis. J Ophthalmol. 2015:137136