Title:Modified Asparaginase for Treatment of Cancer Historical Appraisal and
Future Perspectives
Volume: 6
Issue: 1
Author(s): Luis Peña Icart*, Talita Stelling de Araújo, Marcius da Silva Almeida and Luís Maurício Trambaioli da Rocha e Lima*
Affiliation:
- Laboratory for Pharmaceutical Biotechnology - pbiotech, Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil
- Laboratory for Pharmaceutical Biotechnology - pbiotech, Faculty of Pharmacy, Federal University of Rio de Janeiro,
Rio de Janeiro, RJ, 21941-902, Brazil
- National Institute for Metrology, Quality and Technology (INMETRO), INMETRO, Duque de Caxias, RJ, 25250-020,
Brazil
Keywords:
Asparaginase, bioconjugation, mutation, PEGylated, encapsulated humanized, acute lymphoblastic leukemia (ALL).
Abstract: Asparaginase (ASNase) is widely used as an important component of first-line treatment
for acute lymphoblastic leukemia (ALL). Although it is associated with a high rate of complete remission
(~93%), challenges remain due to several side effects ranging from immune reactions to
severe toxicity, largely associated with its higher immunogenicity and glutamine coactivity. Innovative
products have therefore been devised to minimise these adverse reactions while increasing the
enzymes’ pharmacokinetic properties, stability, and efficacy. This review focuses on commercially
available formulations and others that remain in development, discussing the most recent strategies
for preparing alternative formulations of the enzyme to be less immunogenic and have low glutaminase
coactivity by using site-specific mutagenesis, PEGylation, and encapsulation techniques.
