Red blood cell-encapsulated L-asparaginase: potential therapy of patients with asparagine synthetase deficient acute myeloid leukemia

• Published in: Protein and peptide letters Vol. 20; no. 4; p. 392
• Main Authors: Agrawal, Vaidehi, Woo, Jung Hee, Borthakur, Gautham, Kantarjian, Hagop, Frankel, Arthur E
• Format: Journal Article
• Language: English
• Published: Netherlands 01-04-2013
• Subjects: Asparaginase - administration & dosage; Asparaginase - adverse effects; Asparaginase - genetics; Asparaginase - pharmacology; Asparaginase - therapeutic use; Asparagine - metabolism; Aspartate-Ammonia Ligase - deficiency; Aspartate-Ammonia Ligase - genetics; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug Discovery; Epigenesis, Genetic; Erythrocytes - enzymology; Humans; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - enzymology; Polymorphism, Single Nucleotide; Treatment Outcome
• ISSN: 1875-5305
• DOI: 10.2174/092986613805290426

Red blood cell (RBC) encapsulated L-asparaginase is a novel therapeutic for the treatment of asparagine auxotrophic malignancies. The enzyme-loaded red blood cells function as bioreactors to deplete bloodstream substrate. This delivery system provides improved pharmacodynamics with protection from circulating proteolytic enzymes and avoidance of early liver or renal clearance. The "drug" is manufactured with ABO and Rh compatible donor blood when a prescription is received. Because of the industrial scale manufacturing, the "drug" is transfused the day of receipt at the clinical site. Preliminary clinical studies show utility in childhood and adult acute lymphoblastic leukemia. Based on previous studies of applications in different diseases and assessment of different biomarkers, we propose this agent offers a safe and potentially effective treatment for a subset of chemotherapy refractory acute myeloid leukemia patients. The history, chemistry, biology, pharmacology, and relevant clinical experiences with L-asparaginase as well as the properties and proposed protocols with the red cell-encapsulated enzyme are reviewed.