Method of reducing proliferation of cells in a mammal

Abstract

Materials and methods for reducing cell proliferation or extracellular matrix production in a mammal are disclosed. The methods comprise administering to a mammal a composition comprising a therapeutically effective amount of a zvegf4 antagonist in combination with a pharmaceutically acceptable delivery vehicle. Exemplary zvegf4 antagonists include anti-zvegf4 antibodies, inhibitory polynucleotides, inhibitors of zvegf4 activation, and mitogenically inactive, receptor-binding variants of zvegf4. The materials and methods are useful in the treatment of, inter alia, fibroproliferative disorders of the kidney, liver, and bone.

1 . A method of reducing proliferation of cells in a mammal comprising administering to the mammal a composition comprising a therapeutically effective amount of a zvegf4 antagonist in combination with a pharmaceutically acceptable delivery vehicle, wherein the zvegf4 antagonist is an antibody that binds to an epitope of a protein as shown in SEQ ID NO:2 from amino acid residue 19 to amino acid residue 370.  
     
     
         2 . The method of  claim 1  wherein proliferation of mesangial, epithelial, endothelial, smooth muscle, fibroblast, osteoblast, osteoclast, tumor, stromal, stellate, or interstitial cells is reduced.  
     
     
         3 . The method of  claim 1  wherein proliferation of tumor cells is reduced.  
     
     
         4 . The method of  claim 3  wherein the tumor cells are prostate tumor cells.  
     
     
         5 . The method of  claim 1  wherein the antibody is a monoclonal antibody.  
     
     
         6 . The method of  claim 1  wherein the antibody is a humanized antibody.  
     
     
         7 . The method of  claim 1  wherein the antibody is a single-chain antibody.  
     
     
         8 . The method of  claim 1  wherein the antibody is an antigen binding fragment selected from the group consisting of F(ab′)2 and Fab fragments.  
     
     
         9 . The method of  claim 1  wherein the antibody binds to an epitope of a protein as shown in SEQ ID NO:2 from amino acid residue 258 to amino acid residue 370.  
     
     
         10 . A method of reducing proliferation of tumor cells in a mammal comprising administering to the mammal a composition comprising a therapeutically effective amount of a zvegf4 antagonist in combination with a pharmaceutically acceptable delivery vehicle, wherein the zvegf4 antagonist is an antibody that binds to an epitope of a protein as shown in SEQ ID NO:2 from amino acid residue 258 to amino acid residue 370.  
     
     
         11 . The method of  claim 10  wherein the tumor cells are prostate tumor cells.  
     
     
         12 . The method of  claim 10  wherein the antibody is a monoclonal antibody.  
     
     
         13 . The method of  claim 10  wherein the antibody is a humanized antibody.  
     
     
         14 . The method of  claim 10  wherein the antibody is a single-chain antibody.  
     
     
         15 . The method of  claim 10  wherein the antibody is an antigen binding fragment selected from the group consisting of F(ab′)2 and Fab fragments.