Modified Asparaginase for Treatment of Cancer Historical Appraisal and Future Perspectives

Author:

Icart Luis Peña1ORCID,de Araújo Talita Stelling23,Almeida Marcius da Silva34,Trambaioli da Rocha e Lima Luís Maurício25

Affiliation:

1. Laboratory for Pharmaceutical Biotechnology - pbiotech, Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil

2. Laboratory for Pharmaceutical Biotechnology - pbiotech, Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil

3. Protein Advanced Biochemistry - PAB, National Center for Structural Biology and Bioimaging - CENABIO, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil

4. Institute for Medical Biochemistry Leopoldo De Meis, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil

5. National Institute for Metrology, Quality and Technology (INMETRO), INMETRO, Duque de Caxias, RJ, 25250-020, Brazil

Abstract

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.

Funder

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro Carlos Chagas Filho

Programa Nacional de ApoioaoDesenvolvimento da Metrologia, Qualidade e Tecnologia

Publisher

Bentham Science Publishers Ltd.

Subject

General Medicine

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