Erythrocytes containing arginine deiminase
Use of erythrocytes containing arginine deirainase for the preparation of a medicinal product for lowering the plasma concentration of arginine in vivo. The use relates in particular to the treatment of arginine-dependent tumors, such as hepatocarcinoma and malignant melanoma, or inhibition of the synthesis of nitric oxide, and the prevention and/or treatment of septic shock.
1. A method for lowering the concentration of plasma arginine in vivo in a patient in need thereof comprising:
(a) providing a composition comprising a suspension of erythrocytes encapsulating arginine deiminase (ADI) having enzymatic activity, wherein said erythrocytes of said suspension are obtained from said patient or from one or more donors whose blood group is compatible with said patient, and wherein said encapsulation prolongs the half-life of the arginine deiminase; and
(b) intravenously administering to a patient in need thereof an effective amount of said composition, thereby lowering the plasma arginine concentration in said patient beyond 24 hours after administration of the composition; wherein (i) said erythrocytes encapsulating arginine deiminase having enzymatic activity are present in the patient's circulating blood, (ii) the patient's plasma arginine enters the inside of said erythrocytes encapsulating arginine deiminase having enzymatic activity, and (iii) the plasma arginine entered inside said erythrocytes is degraded by the arginine deiminase.
2. The method as claimed in claim 1 , wherein said administering is to a patient that requires treatment of an arginine-dependent tumor.
3. The method as claimed in claim 2 , wherein said administering is to a patient that requires treatment of hepatocarcinoma.
4. The method as claimed in claim 2 , wherein said administering is to a patient that requires treatment of malignant melanoma.
5. The method as claimed in claim 1 , wherein said administering is to a patient that requires inhibiting the synthesis of nitric oxide.
6. The method as claimed in claim 1 , wherein said administering is to a patient that requires treatment of septic shock.
7. The method as claimed in claim 2 , wherein said administering is to a patient that requires treatment of breast cancer, neuroblastoma or T-cell lymphoblastic leukemia.
8. The method as claimed in claim 1 , wherein said administering is to a patient that requires inhibition of angiogenesis or treatment for an angiogenesis associated disease.