Adenosine deaminase anticancer therapy
What is provided is a method of treating a patient having a tumor comprising administering an effective amount of adenosine deaminase, preferably polyalkylene oxide conjugated, to a patient in need thereof.
1. A method of treating a patient having a tumor or cancer of the prostate or ovaries comprising administering an effective amount of adenosine deaminase to the patient in need thereof, wherein the adenosine deaminase is adenosine deaminase purified from a bovine source or is a recombinant bovine adenosine deaminase according to SEQ ID NO: 5 or SEQ ID NO: 1, or
is a recombinant bovine adenosine deaminase according to SEQ ID NO: 1 or SEQ ID NO: 5, with an amino acid substitution selected from the group consisting of Gln in place of Lys 198 ; Ala in place of Thr 245 ; Arg in place of Gly 351 and combinations thereof;
wherein the adenosine deaminase is conjugated to polyethylene glycol; and wherein the polyethylene glycol ranges in size from about 4,000 to about 45,000 Daltons.
2. The method of claim 1 , wherein the tumor or cancer is malignant.
3. The method of claim 1 , wherein the amount of conjugated adenosine deaminase administered is effective to substantially reduce tissue levels of adenosine or deoxyadenosine in said patient, and wherein growth or spread of the tumor is inhibited by reduced tissue levels of adenosine in said patient.
4. The method of claim 1 , wherein the tumor or cancer is a solid tumor or cancer.
5. The method of claim 1 , wherein the conjugated adenosine deaminase is administered in a dose ranging from about 10 U to about 30 U of adenosine deaminase per kg.
6. The method of claim 1 , wherein the conjugated adenosine deaminase is administered for a sufficient period of time to maintain inhibition of the tumor.
7. The method of claim 1 , wherein the conjugated adenosine deaminase is administered for a time period ranging from 1 to about 20 days.
8. The method of claim 1 , wherein the conjugated adenosine deaminase comprises two or more molecules of adenosine deaminase per polyethylene glycol.
9. The method of claim 1 , wherein the conjugated adenosine deaminase comprises from about 11 to about 18 polyethylene glycol strands attached to epsilon amino groups of one or more Lys residues of the adenosine deaminase.
10. The method of claim 1 , wherein the adenosine deaminase is conjugated to the polyethylene glycol via a urethane linkage.
11. The method of claim 1 , wherein the conjugated adenosine deaminase is administered by a route selected from the group consisting of subcutaneous, intravenous, intramuscular, intrathecal, intraperitoneal, inhalation and transurethral.
12. The method of claim 1 , wherein the recombinant adenosine deaminase comprises the sequence of SEQ ID NO: 5.
13. The method of claim 1 , wherein the recombinant bovine adenosine deaminase comprising SEQ ID NO: 5 further comprises a Cys74 that is capped to prevent oxidation in an aqueous medium.
14. The method of claim 1 , wherein the tumor or cancer is a prostate tumor or cancer.
15. The method of claim 1 , wherein the tumor or cancer is an ovarian tumor or cancer.
16. The method of claim 1 , wherein the conjugated adenosine deaminase is ADAGEN®.
17. The method of claim 1 , wherein the polyethylene glycol is about 5,000 Daltons.
18. The method of claim 1 , wherein the recombinant adenosine deaminase comprises the sequence of SEQ ID NO: 1.
19. The method of claim 1 , wherein the recombinant adenosine deaminase is according to SEQ ID NO: 1 or SEQ ID NO: 5, with an amino acid substitution selected from the group consisting of Gln in place of Lys 198 ; Ala in place of Thr 245 ; Arg in place of Gly 351 and combinations thereof.