Method of treating a mammal, including human, against cancer using methionine and asparagine depletion

Abstract

The invention is related to a new method for treating liquid and solid cancers, in a mammal, including human, wherein methioninase is administered before asparaginase. The invention also encompasses the use of a dietary methionine deprivation, possibly combined with methioninase administration, in advance of asparaginase treatment. Methioninase and asparaginase may be used in particular under free form, pegylated form or encapsulated into erythrocytes.

1 - 25 . (canceled) 
     
     
         26 . A pharmaceutical composition or kit for use in treating cancer in a mammal comprising an asparagine-reducing means and a methionine-reducing means, wherein the methionine-reducing means is administered before the asparagine-reducing means and wherein there is a delay between the administration of the methionine-reducing means and the asparagine-reducing means. 
     
     
         27 . The composition or kit of  claim 26 , wherein when the methionine-reducing means comprises or consists essentially of a methioninase and/or when the asparagine-reducing means comprises or consists essentially of an asparaginase, the methioninase and/or the asparaginase are under free form, pegylated form or encapsulated inside erythrocytes. 
     
     
         28 . The composition or kit of  claim 27 , wherein the methioninase is under free form or is pegylated and the delay between the end of the methioninase administration and the initiation of the asparaginase administration is between about 1 h and about 7 days, between about 3 h and about 6 days, or between about 1 day and about 5 days. 
     
     
         29 . The composition or kit of  claim 27 , wherein the methioninase is encapsulated into erythrocytes and the delay between the end of methioninase administration and the initiation of the asparaginase administration is between about 1 h and about 30 days, between about 1 day and about 20 days, or between about 1 day and about 10 days. 
     
     
         30 . The composition or kit  claim 29 , wherein the methioninase is administered once or more in an amount of between about 100 and about 100,000 IU, between about 500 and about 50,000 IU, or between about 500 and about 5,000 IU; and wherein the asparaginase is administered once or more in an amount of between about 500 and about 100,000 IU, between about 1,000 and about 50,000 IU, or between about 5,000 and about 30,000 IU. 
     
     
         31 . The composition or kit of  claim 30 , wherein
 (a) the methioninase is under free form or pegylated form and the delay between the methioninase and the asparaginase administration is between about 1 h and about 7 days, between about 3 h and about 6 days, or between about 1 day and about 5 days; or   (b) the methioninase is encapsulated inside erythrocytes and the delay between the end of the methioninase administration and the initiation of the asparaginase administration is between about 1 h and about 30 days, between about 1 day and about 20 days, or between about 1 day and about 10 days;   
       wherein the methioninase is administered once or more in an amount of between about 100 and about 100,000 IU, between about 500 and about 50,000 IU, or between about 500 and about 5,000 IU; and wherein the asparaginase is administered once or more in an amount of between about 500 and about 100,000 IU, between about 1,000 and about 50,000 IU, or between about 5,000 and about 30,000 IU. 
     
     
         32 . The composition or kit of  claim 31 , further comprising PLP or a PLP precursor for simultaneous, separate or sequential administration with the methioninase. 
     
     
         33 . The composition or kit of  claim 32 , comprising methioninase encapsulated inside erythrocytes and a non-phosphate precursor of PLP for separate or sequential administration. 
     
     
         34 . The composition or kit of  claim 31 , wherein the methioninase encapsulated inside erythrocytes is administered at least once or twice before the asparaginase encapsulated inside erythrocytes is administered, and each methioninase administration is followed by administration of a solution of non-phosphate precursor of PLP before asparaginase is administered. 
     
     
         35 . The composition or kit of  claim 26 , wherein the methionine-reducing means comprises or consists essentially of a methionine-restricted diet. 
     
     
         36 . The composition or kit of  claim 26 , wherein the asparagine-reducing means comprises or consists essentially of an asparagine-restricted diet. 
     
     
         37 . A method for treating a cancer in a mammal in need thereof, the method comprising administering to the mammal in need thereof, a composition comprising a methionine-reducing means, delaying for a period of time, and then administering a composition comprising an asparagine-reducing means, thereby treating the cancer. 
     
     
         38 . The method of  claim 37 , wherein the methionine-reducing means comprises or consists essentially of a methioninase and the asparagine-reducing means comprises or consists essentially of an asparaginase. 
     
     
         39 . The method of  claim 37 , wherein the delay comprises between about 1 h and about 30 days. 
     
     
         40 . The method of  claim 37 , wherein the methionine-reducing means comprises or consists essentially of a methionine-restricted diet. 
     
     
         41 . The method of  claim 37 , wherein the asparagine-reducing means comprises or consists essentially of an asparagine-restricted diet. 
     
     
         42 . The method of  claim 38 , wherein the methioninase is encapsulated inside erythrocytes and is administered at least once or twice before the asparaginase, which is also encapsulated inside erythrocytes, and each methioninase administration is accompanied by administration of PLP or a precursor of PLP before the asparaginase is administered. 
     
     
         43 . The method of  claim 38 , wherein a non-phosphate precursor of PLP is administered once or more after each administration of methioninase. 
     
     
         44 . The method of  claim 43 , wherein the non-phosphate precursor of PLP is administered once a day, or twice or more per day, during the time of methioninase administration. 
     
     
         45 . The method of  claim 37 , wherein the cancer is leukemia or gastric cancer.