Low Bioavailability and High Immunogenicity of a New Brand of E. colil-Asparaginase with Active Host Contaminating Proteins.

Autor:	Zenatti PP; Centro Infantil Boldrini, Campinas, SP, Brazil., Migita NA; Centro Infantil Boldrini, Campinas, SP, Brazil., Cury NM; Centro Infantil Boldrini, Campinas, SP, Brazil., Mendes-Silva RA; Centro Infantil Boldrini, Campinas, SP, Brazil., Gozzo FC; Chemistry Institute, State University of Campinas, Campinas, SP, Brazil., de Campos-Lima PO; Centro Infantil Boldrini, Campinas, SP, Brazil., Yunes JA; Centro Infantil Boldrini, Campinas, SP, Brazil; Medical Genetics Department, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil. Electronic address: andres@boldrini.org.br., Brandalise SR; Centro Infantil Boldrini, Campinas, SP, Brazil. Electronic address: silvia@boldrini.org.br.
Jazyk:	angličtina
Zdroj:	EBioMedicine [EBioMedicine] 2018 Apr; Vol. 30, pp. 158-166. Date of Electronic Publication: 2018 Mar 09.
DOI:	10.1016/j.ebiom.2018.03.005
Abstrakt:	The drug l-asparaginase is a cornerstone in the treatment of acute lymphoblastic leukemia (ALL). The native E. colil-asparaginase used in Brazil until recently has been manufactured by Medac/Kyowa. Then a decision was taken by the Ministry of Health in 2017 to supply the National Health System with a cheaper alternative l-asparaginase manufactured by Beijing SL Pharmaceutical, called Leuginase®. As opposed to Medac, the asparaginase that has been in use in Brazil under the trade name of Aginasa®, it was not possible to find a single entry with the terms Leuginase in the Pubmed repository. The apparent lack of clinical studies and the scarcity of safety information provided to the hospitals by the drug distributor created a debate among Brazilian pediatric oncologists about issues of safety and efficacy that culminated eventually in a court decision to halt the distribution of the new drug all over the country. Boldrini Children's Center, a non-profit pediatric oncohematology hospital, has conducted its own evaluation of Leuginase®. Mass spectrometry analyses found at least 12 different contaminating host-cell proteins (HCP) in Leuginase®. The presence of two HCP (beta-lactamase and malate dehydrogenase) was confirmed by orthogonal methodologies. The relative number of HCP peptides ranged from 19 to 37% of the total peptides identified by mass spectrometry. In vivo studies in mice injected with Leuginase® revealed a 3 times lower plasma bioavailability and the development of higher antibody titres against l-asparaginase in comparison to Aginasa®-injected animals. The decision to buy a new drug based on its price alone is not safe. Developing countries are especially vulnerable to cheaper alternatives that lack solid quality assurance. (Copyright © 2018 German Center for Neurodegenerative Diseases (DZNE). Published by Elsevier B.V. All rights reserved.)
Databáze:	MEDLINE
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