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

Vaidehi Agrawal, Jung Hee Woo, Gautham Borthakur, Hagop Kantarjian, Arthur E. Frankel

Research output: Contribution to journalArticle

32 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)392-402
Number of pages11
JournalProtein and Peptide Letters
Volume20
Issue number4
DOIs
Publication statusPublished - Apr 2013

    Fingerprint

Keywords

  • L-asparaginase and AML
  • Red blood cell encapsulation

ASJC Scopus subject areas

  • Biochemistry
  • Structural Biology

Cite this