EphA2 agonistic monoclonal antibodies and methods of use thereof
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A technology of antibodies and human antibodies, applied in the fields of antibodies, chemical instruments and methods, anti-receptors/cell surface antigens/cell surface determinant immunoglobulins, etc., can solve problems such as difficult standard chemotherapy for cancer
Inactive Publication Date: 2007-01-31
MEDIMMUNE LTD +1
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As a result, many cancers are refractory ...
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[0071] The present invention is based in part on the inventors' discovery that EphA2 monoclonal antibodies can suppress the phenotype of cancer cells. Reducing the activity of EphA2 selectively inhibits the growth of malignant cancer cells. EphA2 activity can be reduced with EphA2 agonistic monoclonal antibodies. While not wishing to be bound by any mechanism of action, this inhibition of cancer cell growth may be achieved by stimulating (ie, stimulating) EphA2 signaling to cause phosphorylation of EphA2 leading to its degradation. Reduced cancer cell growth was due to reduced EphA2 levels and ligand-independent EphA2 signaling.
[0072] Accordingly, the present invention relates to methods and compositions for the treatment, inhibition and management of cancer, particularly metastatic cancer. Particular aspects of the invention relate to methods and compositions comprising compounds that inhibit the proliferation and invasion of cancer cells, particularly those that overexp...
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Abstract
The present invention relates to methods and compositions designed to treat, control or prevent cancer, particularly metastatic cancer. The methods of the invention comprise administering an effective amount of one or more antibodies that bind and stimulate EphA2, thereby increasing the phosphorylation of EphA2 and reducing the level of stimulated EphA2 in the cell. The invention also includes antibodies that bind preferentially to EphA2 epitopes exposed on cancer cells rather than non-cancer cells. The present invention also provides pharmaceutical compositions comprising only one or more EphA2 antibodies of the present invention, or the antibodies in combination with one or more other drugs for the treatment of cancer.
Description
1. Field of invention [0001] This application claims priority to U.S. Patent Provisional Application No. 60 / 524,177, filed November 20, 2003, which is a continuation-in-part of U.S. Patent Nonprovisional Application No. 10 / 436,783, filed May 12, 2003, This non-provisional application claims priority to U.S. Patent Provisional Application Nos. 60 / 379,368, filed May 10, 2002, 60 / 418,204, filed October 14, 2002, and 60 / 460,358, filed April 3, 2003, The entire contents of these patent applications are incorporated herein by reference. [0002] The present invention relates to methods and compositions for treating, controlling or preventing cancer. The methods of the invention comprise administering an effective amount of one or more EphA2-specific antibodies, preferably monoclonal antibodies, which are agonists of EphA2 and / or are capable of preferentially and selectively binding to cancer cells rather than non-cancer cells EphA2 epitopes exposed or increased in number. The inv...
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