A novel anti-angiogenic method for treating cancer

Cancer is the second leading cause of death in the United States and it is estimated that there will be approximately 600,000 deaths caused by cancer in 2006. A major drawback of the existing chemotherapies is the cytotoxic side-effects that are associated with them. Thus, there is a need to develop new therapeutic approaches with reduced side-effects. Anti-angiogenic therapy is a recent approach in cancer therapeutics targeting the formation of blood vessels that are necessary for tumor growth. Anti-angiogenic therapeutic agents are generally devoid of toxic side-effects, recently gaining attention as cancer therapeutics with tremendous promise. Recently, the anti-angiogenic molecule bevacizumab (Avastin), a monoclonal antibody against the vascular endothelial growth factor (VEGF), has gained approval from the FDA for the first-line treatment of metastatic colon cancer in combination with standard chemotherapy. This technology describes a novel anti-angiogenic method for treating cancer. The alpha(v)beta(3)-integrin is upregulated on tumor endothelial cells and can bind RGD (Arg-Gly-Asp) peptides. By tagging the RGD peptide with the normally non- cytotoxic eosinophil-derived neurotoxin (EDN), this RNase molecule can be targeted to human vascular endothelial cells where it becomes cytotoxic. These RGD-EDN molecules inhibit the adhesion of HUVEC cells in response to endothelial growth factors. These molecules have also been shown to inhibit tumor growth in mice with Kaposi's sarcoma. This technology has therapeutic potential for a broad spectrum of cancer related diseases alone, or in combination with existing therapies. Applications: - A novel therapeutic molecule, RGD tagged EDN (RGD- EDN) - An anti-angiogenic cancer therapy for targeting RGD-EDN to endothelial cells via binding to the RGD receptor alpha(v) beta(3) integrin Market: - 600,000 deaths from cancer related diseases estimated in 2006 - The technology platform involving novel anti-angiogenic cancer therapy technology has a potential market of more than 2 billion US dollars Development Status: The technology is currently in the pre-clinical stage of development. Publications: 1. A Dricu et al., "A synthetic peptide derived from the human eosinophil-derived neurotoxin induces apoptosis in Kaposi's sarcoma cells," Anticancer Res. 2004 May-Jun; 24 (3a):1427-1432. 2. M Fani et al, "Comparative evaluation of linear and cyclic 99mTc-RGD peptides for targeting of integrins in tumor angiogenesis," Anticancer Res. 2006 Jan-Feb; 26(1A):431- 434. 3. DL Newton et al., "Construction and characterization of RNase-based targeted therapeutics," Methods Mol Biol. 2003; 207:283-304. 4. A Capello et al., "Anticancer activity of targeted proapoptotic peptides," J Nucl Med. 2006 Jan; 47(1):122-129.

Preclinical

U.S. Provisional Application No. 60/782,968 filed 15 Mar 2006 (HHS Reference No. E-094-2006/0-US-01) Inventors: Dianne L. Newton, Zhongyu Zhu, and Susanna M. Rybak (NCI)

Licensees sought: Available for non-exclusive and exclusive licensing. Collaborative Research Opportunity: The National Cancer Institute, Biological Testing Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize Peptide Targeted Human RNases. Please contact Bjarne Gabrielsen at (301) 846-5465 or bjg@nih.gov for more information.