Arginine decomposing enzyme therapeutic composition

Abstract

A therapeutic composition and method for the treatment of cancer comprising an arginine decomposing enzyme, particularly an arginine decarboxylase that is a biosynthetic arginine decarboxylase of E. Coli and modifications thereof, and may be PEG-ilated. The therapeutic composition may contain essential co-factors of said arginine decomposing enzyme, protein breakdown inhibitors such as insulin, insulin-like growth factors, IGF-I, IGF-II, growth hormones, protein breakdown inhibiting peptide aldehydes such as Cbz-Leu-Leu-Leucinal, or lactacystin, and glucose, all of which can be admixed with the arginine decomposing enzyme or may be maintained apart from and separately administered from the arginine decomposing enzyme. The therapeutic composition can be administered intravenously, intraperitoneally, intramuscularly, intraventricularly, nasally, extracorporeally or orally.

1 . A method of treating cancer in a mammal comprising administering to said mammal a therapeutically effective amount of an arginine decomposing enzyme.  
     
     
         2 . The method of  claim 1  wherein said arginine decomposing enzyme is administered intravenously, intraperitoneally, intramuscularly, intraventricularly, nasally, extracorporeally or orally.  
     
     
         3 . The method of  claim 2  wherein said arginine decomposing enzyme is arginine decarboxylase.  
     
     
         4 . The method of  claim 3  wherein said arginine decarboxylase is selected from the group consisting of biosynthetic arginine decarboxylase of  E. Coli  and modifications thereof.  
     
     
         5 . The method of  claim 4  wherein said arginine decarboxylase is administered intravenously.  
     
     
         6 . The method of  claim 4  wherein said arginine decarboxylase is administered to the lungs by means of an aerosol spray.  
     
     
         7 . The method of  claim 4  wherein said arginine decarboxylase is administered extracorporeally.  
     
     
         8 . The method of  claim 1 , further comprising administering essential co-factors of said arginine decomposing enzyme.  
     
     
         9 . The method of  claim 8 , wherein said arginine decomposing enzyme is biosynthetic arginine decarboxylase of  E. Coli , and said essential co-factor is a magnesium ion.  
     
     
         10 . The method of  claim 8 , wherein said arginine decomposing enzyme is biosynthetic arginine decarboxylase of  E. Coli , and said essential co-factor is pyridoxal 5-phosphate.  
     
     
         11 . The method of  claim 1 , wherein said arginine decomposing enzyme is PEG-ilated.  
     
     
         12 . The method of  claim 1 , further comprising administering a protein breakdown inhibitor.  
     
     
         13 . The method of  claim 12 , wherein said protein breakdown inhibitor is selected from the group consisting of insulin, insulin-like growth factors, IGF-I, IGF-II, growth hormones, protein breakdown inhibiting peptide aldehydes such as Cbz-Leu-Leu-Leucinal, and lactacystin.  
     
     
         14 . The method of  claim 12 , further comprising administering glucose.  
     
     
         15 . A therapeutic composition for the treatment of cancer comprising an arginine decomposing enzyme.  
     
     
         16 . A therapeutic composition of  claim 15 , wherein said arginine decomposing enzyme is arginine decarboxylase.  
     
     
         17 . The therapeutic composition of  claim 16 , wherein said arginine decarboxylase is selected from the group consisting of biosynthetic arginine decarboxylase of  E. Coli  and modifications thereof.  
     
     
         18 . The therapeutic composition of  claim 15 , wherein said composition further contains essential co-factors of said arginine decomposing enzyme.  
     
     
         19 . The therapeutic composition of  claim 18 , wherein said co-factors of said enzyme are administered separately from said arginine decomposing enzyme.  
     
     
         20 . The therapeutic composition of  claim 18 , wherein said enzyme is biosynthetic arginine decarboxylase of  E. Coli , and said essential co-factor is a magnesium ion.  
     
     
         21 . The therapeutic composition of  claim 18 , wherein said enzyme is biosynthetic arginine decarboxylase of  E. Coli , and said essential co-factor is pyridoxal 5-phosphate.  
     
     
         22 . The therapeutic composition of  claim 1 , wherein said arginine decomposing enzyme is PEG-ilated.  
     
     
         23 . The therapeutic composition of  claim 1 , wherein said composition further contains a protein breakdown inhibitor.  
     
     
         24 . The therapeutic composition of  claim 23 , wherein said protein breakdown inhibitor is selected from the group consisting of insulin, insulin-like growth factors, IGF-I, IGF-II, growth hormones, protein breakdown inhibiting peptide aldehydes such as Cbz-Leu-Leu-Leucinal, or lactacystin.  
     
     
         25 . The therapeutic composition of  claim 23 , wherein said protein breakdown inhibitor is admixed with said arginine decomposing enzyme.  
     
     
         26 . The therapeutic composition of  claim 23 , wherein said protein breakdown inhibitor is maintained and administered separately from said arginine decomposing enzyme.  
     
     
         27 . The therapeutic composition of  claim 23 , wherein said composition further contains glucose.  
     
     
         28 . The therapeutic composition of  claim 27 , wherein said glucose is maintained and administered separately from said arginine decomposing enzyme and said protein breakdown inhibitor.  
     
     
         29 . The therapeutic composition of  claim 15  wherein said arginine decomposing enzyme is administered intravenously, intraperitoneally, intramuscularly, intraventricularly, nasally, extracorporeally or orally.