Use of antibodies against the MUC18 antigen

Abstract

The present invention relates generally to the generation and characterization of anti-MUC18 monoclonal antibodies. The invention further relates to the use of such anti-MUC18 antibodies in the diagnosis and treatment of disorders associated with increased activity of MUC18, in particular, tumors, such as melanomas.

1 . A human monoclonal antibody, or binding fragment thereof, that binds MUC18 with a Kd of less than 0.69 nM.  
     
     
         2 . The monoclonal antibody of  claim 1 , wherein the antibody is mAb 3.19.1.  
     
     
         3 . A human monoclonal antibody, or binding fragment thereof, that binds MUC18, wherein the antibody, or binding fragment thereof, has one or more activity selected from: 
 (a) suppression of invasion of A375-SM and WM-2264 melanoma cells through matrigel-coated membrane in vitro;    (b) suppression of cell growth of WM-2264 tumor cells in vivo;    (c) suppression of formation of lung metastasis of melanoma A375-SM and WM-2264 cells in vivo; and    (d) prolongation of survival of mice bearing WM-2644 metastatic melanoma tumors in vivo.    
     
     
         4 . The monoclonal antibody, or binding fragment thereof, of  claim 3 , wherein the concentration of antibody necessary to suppress cell growth of WM-2264 tumor cells in vivo is about 1 mg of antibody per week in a mouse model.  
     
     
         5 . The monoclonal antibody, or binding fragment thereof, of  claim 4 , wherein the concentration of antibody necessary to suppress cell growth of WM-2264 tumor cells in vivo is about 100 μg of antibody per week in a mouse model.  
     
     
         6 . The monoclonal antibody of  claim 3 , wherein the antibody is mAb 3.19.1.  
     
     
         7 . The monoclonal antibody, or binding fragment thereof, of  claim 1  in association with a pharmaceutically acceptable carrier.  
     
     
         8 . A nucleic acid molecule encoding the monoclonal antibody, or binding fragment thereof, of  claim 1 .  
     
     
         9 . A vector comprising the nucleic acid molecule of  claim 8 .  
     
     
         10 . A host cell comprising the vector of  claim 9 .  
     
     
         11 . A method of inhibiting tumor growth associated with the expression of the MUC18 tumor antigen in an animal, comprising: 
 selecting an animal in need of treatment for a tumor, wherein the tumor comprises cells expressing MUC18;    administering to said animal a therapeutically effective dose of the antibody, or binding fragment thereof, of  claim 1 .    
     
     
         12 . The method of  claim 11 , wherein said antibody is conjugated to a therapeutic or cytotoxic agent.  
     
     
         13 . The method of  claim 12 , wherein the cytotoxic agent is ricin.  
     
     
         14 . The method of  claim 12 , wherein the therapeutic agent is a radioisotope.  
     
     
         15 . The method of  claim 11 , wherein said tumor is melanoma.  
     
     
         16 . The method of  claim 11 , wherein said tumor is a lung tumor.  
     
     
         17 . The method of  claim 11 , wherein said tumor growth is tumor metastasis.  
     
     
         18 . A method of inhibiting cell invasion associated with melanoma, comprising: 
 selecting an animal in need of treatment for melanoma;    administering to said animal a therapeutically effective dose of the antibody, or binding fragment thereof, of  claim 1 .    
     
     
         19 . A method of increasing survival of an animal having a metastatic tumor that expresses MUC18, comprising: 
 selecting an animal in need of treatment for a metastatic tumor, wherein the tumor comprises cells expressing MUC18;    administering to said animal a therapeutically effective dose of the antibody, or binding fragment thereof, of  claim 1.