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Use Of Calreticulin And Calreticulin Fragments To Inhibit Endothelial Cell Growth And Angiogenesis, And Suppress Tumor Growth

Posted Jun 09 2010 5:00pm

Description of Invention:
Tumor growth and invasion into normal tissues is dependent upon an adequate blood supply, and agents that target tumor blood supply have been shown to prevent or delay tumor formation and to promote the regression or dormancy of established tumors in preclinical models. It has been shown that EBV-immortalized cell lines can promote regression of experimental Burkitt's lymphoma, colon carcinoma and other human malignancies established in athymic mice through a vascular-based process. The inventors analyzed the cultured-media from EBV-immortalized cells and isolated a unique and potent factor which inhibits angiogenesis and tumor cell growth. This novel compound was named vasostatin. Vasostatin is an NH2-terminal fragment of human calreticulin, and it can inhibit endothelial cell proliferation in vitro, suppress neovascularization in vivo and prevent or reduce growth of experimental tumors while having minimal effect on other cell types. Vasostatin is the most conserved domain among calrecticulins so far cloned and has no homology to other protein sequences. Data suggests that the antitumor effects of vasostatin are related to inhibition of new vessel formation rather than to a toxic effect on established tumor vascular structures. Vasostatin has key differences from other inhibitors of angiogenesis. It is small and soluble, and it is stable for greater than 19 months in aqueous solution. It is easily produced and delivered. By comparison, angiostatin, endostatin and thrombospondin can be difficult to isolate, purify and deliver. Additionally, studies have shown that the effective dose of vasostatin is 4-10 fold lower than the effective doses of endostatin and angiostatin. Therefore, this new and potent anti-angiogenic molecule should prove highly useful for the prevention and treatment of human cancers.

Inventors:
Giovanna Tosato (FDA)
Sandra E Pike (NCI)
Lei Yao (NCI)


Patent Status:
HHS, Reference No. E-082-1998/0
PCT, Application No. PCT/US99/23240 filed 05 Oct 1999
US, , Patent No. 6,867,180, Issued 15 Mar 2005
US, , Patent No. 7,488,711, Issued 10 Feb 2009



Portfolios:
Cancer
Cancer - Therapeutics
In-vitro Data



For Additional Information Please Contact:
Whitney Hastings
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: hastingw@mail.nih.gov
Phone: 301-451-7337
Fax: 301-402-0220


Ref No: 52

Updated: 06/2010

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