Antibody methods for selectively inhibiting VEGF
AssigneeBoard of Regents, The University of Texas System
InventorsPhilip E. Thorpe, Rolf A. Brekken
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Abstract
Disclosed are antibodies that specifically inhibit VEGF binding to only one (VEGFR2) of the two VEGF receptors. The antibodies effectively inhibit angiogenesis and induce tumor regression, and yet have improved safety due to their specificity. The present invention thus provides new antibody-based compositions, methods and combined protocols for treating cancer and other angiogenic diseases. Advantageous immunoconjugate and prodrug compositions and methods using the new VEGF-specific antibodies are also provided.
Claims40
A method of inhibiting VEGF binding to the VEGF receptor VEGFR2, without significantly inhibiting VEGF binding to the VEGF receptor VEGFR1, the method comprising contacting a cell population including cells that express VEGFR2 (KDR/Flk-1) and cells that express VEGFR1 (Flt-1) with a composition comprising a biologically effective amount of at least a first anti-VEGF antibody that binds to substantially the same epitope as the monoclonal antibody 2C3 produced by hybridoma ATCC PTA 1595, or an antigen-binding fragment of said antibody.
A method of inhibiting VEGF-induced endothelial cell proliferation, comprising contacting a biological tissue comprising a population of endothelial cells with a composition comprising a biologically effective amount of at least a first anti-VEGF antibody that binds to substantially the same epitope as the monoclonal antibody 2C3 produced by hybridoma ATCC PTA 1595, or an antigen-binding fragment of said antibody.
A method of inhibiting VEGF-induced endothelial cell proliferation, without significantly inhibiting VEGF stimulation of macrophages, osteoclasts or chondroclasts, comprising contacting a tissue that contains endothelial cells and at least one of macrophages, osteoclasts or chondroclasts with a composition comprising a biologically effective amount of an anti-VEGF antibody that binds to substantially the same epitope as the monoclonal antibody 2C3 produced by hybridoma ATCC PTA 1595, or an antigen-binding fragment of said antibody.
A method of inhibiting angiogenesis, comprising contacting a population of potentially angiogenic blood vessels with at least a first anti-angiogenic composition comprising a biologically effective amount of at least a first anti-VEGF antibody, or antigen-binding fragment thereof, that binds to substantially the same epitope as the monoclonal antibody 2C3 produced by hybridoma ATCC PTA 1595.
A method for treating an animal that has, or is at risk for developing, a vascularized solid tumor, a metastatic tumor or metastases from a primary tumor, comprising administering to said animal at least a first pharmaceutical composition that comprises at least a first purified, unconjugated anti-VEGF antibody, or an antigen-binding fragment thereof, that binds to the same epitope as the monoclonal antibody 2C3 produced by hybridoma ATCC PTA 1595 and that significantly inhibits VEGF binding to the VEGF receptor VEGFR2 (KDR/Flk-1) without significantly inhibiting VEGF binding to the VEGF receptor VEGFR1 (Flt-1).
A method for treating cancer, comprising administering to an animal with a vascularized tumor a therapeutically effective amount of at least a first pharmaceutical composition that comprises at least a first unconjugated anti-VEGF antibody that binds to substantially the same epitope as the monoclonal antibody 2C3 produced by hybridoma ATCC PTA 1595, or an antigen-binding fragment thereof;
- wherein said anti-VEGF antibody substantially inhibits VEGF binding to the VEGF receptor VEGFR2 (KDR/Flk- 1) without significantly inhibiting VEGF binding to the VEGF receptor VEGFR1 (Flt-1), thereby inhibiting angiogenesis within said vascularized tumor without significantly impairing macrophage-mediated anti-tumor responses within said vascularized tumor.
A method for treating cancer, comprising administering to an animal with a vascularized tumor a therapeutically effective amount of at least a first pharmaceutical composition that comprises at least a first naked anti-VEGF antibody that binds to substantially the same epitope as the monoclonal antibody 2C3 produced by hybridoma ATCC PTA 1595, or an antigen-binding fragment thereof;
- wherein said anti-VEGF antibody substantially inhibits VEGF binding to the VEGF receptor VEGFR2 (KDR/Flk-1) without significantly inhibiting VEGF binding to the VEGF receptor VEGFR1 (Flt-1), thereby inhibiting angiogenesis within said vascularized tumor without significantly inhibiting VEGF stimulation of macrophages, osteoclasts or chondroclasts within said animal.
A method of inhibiting angiogenesis, comprising contacting a population of potentially angiogenic blood vessels with at least a first anti-angiogenic composition comprising a biologically effective amount of at least a first purified, unconjugated anti-VEGF antibody, or an antigen-binding fragment thereof, that binds to the same epitope as the monoclonal antibody 2C3 produced by hybridoma ATCC PTA 1595.
Dependencies are inferred from the claim text.