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

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
Sandra Pike
Lei Yao

Intellectual Property:
U.S. Pat: No. 6,596,690 issued 2003-07-22
U.S. Pat: No. 6,867,180 issued 2005-03-15
U.S. Pat: No. 7,488,711 issued 2009-02-10
U.S. Pat: No. 7,812,117 issued 2009-06-11
PCT Application No. PCT/US1999/023240

Licensing Contact:
Bill Ronnenberg, JD-MIP, MS
FDA Technology Transfer Program
10903 New Hampshire Ave.
Building WO1, Rm 4214
Silver Spring, MD 20993
Email: FDAInventionlicensing@fda.hhs.gov
Phone: 240-402-4561

OTT Reference No: E-082-1998/0
Updated: August 9, 2015