Abstract
L-asparaginases have been established components in the treatment of acute leukemias for nearly 40 years. Their antitumor effect results from the depletion of asparagine, an amino acid essential to leukemic cells, and subsequent inhibition of protein synthesis leading to considerable cytotoxicity. The efficacy of L-asparaginases has been limited by a high rate of hypersensitivity reactions and development of anti-asparaginase antibodies, which neutralize their activity. PEG-asparaginase, a form of Escherichia coli L-asparaginase covalently linked to polyethylene glycol, was rationally synthesized to decrease immunogenicity of the enzyme and prolong its half-life. In recent years, clinical trials have established the importance of intramuscular PEG-asparaginase in frontline pediatric and adult acute lymphoblastic leukemia therapy. Present studies are evaluating the feasibility of intravenous PEG-asparaginase administration.
Acknowledgement and disclosure
The authors would like to thank Dr. Vassilios Avramis for his review of this manuscript. The authors have no conflict of interest to declare. This article was independently commissioned and no fee was received for preparation of the manuscript.