Abstract
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.
Keywords: Red blood cell encapsulation, L-asparaginase and AML, Red blood cell (RBC), novel therapeutic, bloodstream, pharmacodynamics, proteolytic enzyme, leukemia, chemotherapy, pharmacology, encapsulated enzyme
Protein & Peptide Letters
Title:Red Blood Cell-Encapsulated L-Asparaginase: Potential Therapy of Patients with Asparagine Synthetase Deficient Acute Myeloid Leukemia
Volume: 20 Issue: 4
Author(s): Vaidehi Agrawal, Jung Hee Woo, Gautham Borthakur, Hagop Kantarjian and Arthur E. Frankel
Affiliation:
Keywords: Red blood cell encapsulation, L-asparaginase and AML, Red blood cell (RBC), novel therapeutic, bloodstream, pharmacodynamics, proteolytic enzyme, leukemia, chemotherapy, pharmacology, encapsulated enzyme
Abstract: 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.
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Cite this article as:
Agrawal Vaidehi, Hee Woo Jung, Borthakur Gautham, Kantarjian Hagop and E. Frankel Arthur, Red Blood Cell-Encapsulated L-Asparaginase: Potential Therapy of Patients with Asparagine Synthetase Deficient Acute Myeloid Leukemia, Protein & Peptide Letters 2013; 20 (4) . https://dx.doi.org/10.2174/0929866511320040003
DOI https://dx.doi.org/10.2174/0929866511320040003 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
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