Compositions and methods for the diagnosis and treatment of tumors of glial origin

Abstract

The present invention is directed to compositions of matter useful for the diagnosis and treatment of tumor in mammals and to methods of using those compositions of matter for the same.

1 . A method of therapeutically treating a mammal having a tumor of glial origin comprising cells that express a type A glial tumor antigen, said method comprising contacting said cells with a composition comprising a first binding agent and a second binding agent, wherein said first binding agent is a first antibody, first oligopeptide or first organic molecule that binds to a type A glial tumor antigen and wherein said second binding agent is a second antibody, second oligopeptide or second organic molecule that binds to a type B glial tumor antigen, the binding of said first antibody, first oligopeptide or first organic molecule to said type A glial tumor antigen and the binding of said second antibody, second oligopeptide or second organic molecule to said type B glial tumor antigen thereby effectively treating said mammal.  
     
     
         2 . The method of  claim 1 , wherein said first or second antibody is a monoclonal antibody.  
     
     
         3 . The method of  claim 1 , wherein said first or second antibody is an antibody fragment.  
     
     
         4 . The method of  claim 1 , wherein said first or second antibody is a chimeric or a humanized antibody.  
     
     
         5 . The method of  claim 1 , wherein said first or second antibody, first or second oligopeptide or first or second organic molecule is conjugated to a growth inhibitory agent.  
     
     
         6 . The method of  claim 1 , wherein said first or second antibody, first or second oligopeptide or first or second organic molecule is conjugated to a cytotoxic agent.  
     
     
         7 . The method of  claim 6 , wherein said cytotoxic agent is selected from the group consisting of toxins, antibiotics, radioactive isotopes and nucleolytic enzymes.  
     
     
         8 . The method of  claim 6 , wherein the cytotoxic agent is a toxin.  
     
     
         9 . The method of  claim 8 , wherein the toxin is selected from the group consisting of maytansinoid and calicheamicin.  
     
     
         10 . The method of  claim 8 , wherein the toxin is a maytansinoid or an auristatin.  
     
     
         11 . The method of  claim 1 , wherein said first or second antibody is produced in bacteria.  
     
     
         12 . The method of  claim 1 , wherein said first or second antibody is produced in CHO cells.  
     
     
         13 . The method of  claim 1 , wherein said cells are further exposed to radiation treatment or a chemotherapeutic agent.  
     
     
         14 . The method of  claim 1  which causes the death of said cells.  
     
     
         15 . The method of  claim 1 , wherein said first binding agent and said second binding agent are linked.  
     
     
         16 . The method of  claim 15 , wherein said first binding agent and said second binding agent are contained within a bispecific antibody.  
     
     
         17 . The method of  claim 1 , further comprising contacting said cells with a third binding agent which is a third antibody, third oligopeptide or third organic molecule that binds to a type C glial tumor antigen.  
     
     
         18 . A method of therapeutically treating a mammal having a tumor of glial origin comprising cells that express a type B glial tumor antigen, said method comprising contacting said cells with a composition comprising a first binding agent and a second binding agent, wherein said first binding agent is a first antibody, first oligopeptide or first organic molecule that binds to a type A glial tumor antigen and wherein said second binding agent is a second antibody, second oligopeptide or second organic molecule that binds to a type B glial tumor antigen, the binding of said first antibody, first oligopeptide or first organic molecule to said type A glial tumor antigen and the binding of said second antibody, second oligopeptide or second organic molecule to said type B glial tumor antigen thereby effectively treating said mammal.  
     
     
         19 . The method of  claim 18 , wherein said first or second antibody is a monoclonal antibody.  
     
     
         20 . The method of  claim 18 , wherein said first or second antibody is an antibody fragment.  
     
     
         21 . The method of  claim 18 , wherein said first or second antibody is a chimeric or a humanized antibody.  
     
     
         22 . The method of  claim 18 , wherein said first or second antibody, first or second oligopeptide or first or second organic molecule is conjugated to a growth inhibitory agent.  
     
     
         23 . The method of  claim 18 , wherein said first or second antibody, first or second oligopeptide or first or second organic molecule is conjugated to a cytotoxic agent.  
     
     
         24 . The method of  claim 23 , wherein said cytotoxic agent is selected from the group consisting of toxins, antibiotics, radioactive isotopes and nucleolytic enzymes.  
     
     
         25 . The method of  claim 23 , wherein the cytotoxic agent is a toxin.  
     
     
         26 . The method of  claim 25 , wherein the toxin is selected from the group consisting of maytansinoid and calicheamicin.  
     
     
         27 . The method of  claim 25 , wherein the toxin is a maytansinoid or an auristatin.  
     
     
         28 . The method of  claim 18 , wherein said first or second antibody is produced in bacteria.  
     
     
         29 . The method of  claim 18 , wherein said first or second antibody is produced in CHO cells.  
     
     
         30 . The method of  claim 18 , wherein said cells are further exposed to radiation treatment or a chemotherapeutic agent.  
     
     
         31 . The method of  claim 18  which causes the death of said cells.  
     
     
         32 . The method of  claim 18 , wherein said first binding agent and said second binding agent are linked.  
     
     
         33 . The method of  claim 32 , wherein said first binding agent and said second binding agent are contained within a bispecific antibody.  
     
     
         34 . The method of  claim 18 , further comprising contacting said cells with a third binding agent which is a third antibody, third oligopeptide or third organic molecule that binds to a type C glial tumor antigen.  
     
     
         35 . A method of determining the presence of a type A glial tumor in a mammal, said method comprising: 
 (a) obtaining a test tissue sample from said mammal, wherein said test tissue sample is suspected of being a glial cell-derived tumor; and    (b) detecting at least a 5 fold increase in the amount of at least 3 different type A glial tumor antigens in said test sample as compared to normal adult brain, wherein said detection is indicative of said test tissue sample being a type A glial tumor.    
     
     
         36 . The method according to  claim 35 , wherein said increased expression of said type A glial tumor antigens is at the mRNA level.  
     
     
         37 . The method according to  claim 35 , wherein said increased expression of said type A glial tumor antigens is at the protein level.  
     
     
         38 . A method of determining the presence of a type B glial tumor in a mammal, said method comprising: 
 (a) obtaining a test tissue sample from said mammal, wherein said test tissue sample is suspected of being a glial cell-derived tumor; and    (b) detecting (i) at least a 10 fold increase in the amount of at least 3 different type B glial tumor antigens in said test sample as compared to normal adult brain and (ii) that no group of three type A antigens are expressed at least 5-fold above the level of expression of that group in normal adult brain, wherein said detection is indicative of said test tissue sample being a type B glial tumor.    
     
     
         39 . The method according to  claim 38 , wherein said increased expression of said type B glial tumor antigens is at the mRNA level.  
     
     
         40 . The method according to  claim 38 , wherein said increased expression of said type B glial tumor antigens is at the protein level.