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Optimization of the productive process of recombinant Erwinia carotovora's L-Asparaginase II in bioreactor and analysis of its antileukemic action

Grant number: 19/15376-2
Support type:Regular Research Grants
Duration: January 01, 2020 - December 31, 2021
Field of knowledge:Interdisciplinary Subjects
Cooperation agreement: CONFAP - National Council of State Research Support Foundations
Principal Investigator:José Andrés Yunes
Grantee:José Andrés Yunes
Home Institution: Centro Infantil de Investigações Hematológicas Dr Domingos A Boldrini (CIB). Campinas , SP, Brazil
Assoc. researchers:Bruna de Araujo Lima ; Pedro Otavio de Campos Lima ; Priscila Pini Zenatti
Associated scholarship(s):20/02144-3 - Optimization of the production process of recombinant L-Asparaginase II from Erwinia carotovora in a bioreactor and analysis of its anti-leukemic action, BP.TT

Abstract

The enzyme L-asparaginase II is one of the drugs of choice for the polychemotherapeutic treatment of acute lymphoblastic leukemia (ALL) in children and adults. Despite being a rare disease, ALL is the most common cancer in children and accounts for 25% of all cancers in children up to 15 years of age. Commonly, neoplastic cells use plasma asparagine for the synthesis of proteins. Asparaginase catalyzes the hydrolysis of asparagine in aspartic acid and ammonia. In absence of asparaginse leukemia cells interrupt protein synthesis and dye by apoptosis. This mechanism of action is relatively selective for leukemia cells, since normal cells are able to synthesize asparagine. The asparaginase used in the clinic is derived from Escherichia coli, and may or may not be conjugated to monomethoxy-polyethylene glycol, forming the variant known as Peg-asparaginase. Approximately 30% of patients develop an immune reaction against asparaginase, limiting its action and forcing a switch to a different asparaginase preparation. Alternative enzymes derived from Erwinia subspecies have shorter half-life than that obtained from E. coli, nevertheless they are associated with a reduced risk of hypersensitivity reactions due to their reduced glutaminase activity. Therefore, the objective of the present project is the optimization of the production of the recombinant enzyme L-asparaginase II from Erwinia carotovora in Escherichia coli for its industrial application and analysis of its purity, plasma half-life, immunogenicity and antileukemic action in mice. (AU)