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Critical overview of the main features and techniques used for the evaluation of the clinical applicability of L-asparaginase as a biopharmaceutical to treat blood cancer.
Blood Reviews ( IF 6.9 ) Pub Date : 2020-01-13 , DOI: 10.1016/j.blre.2020.100651
T A Costa-Silva 1 , I M Costa 1 , H P Biasoto 1 , G M Lima 1 , C Silva 1 , A Pessoa 1 , G Monteiro 1
Affiliation  

L-asparaginase is an enzyme used as a biopharmaceutical to treat acute lymphoblastic leukemia. Several adverse effects have been related to L-asparaginase use, so the scientific community has searched for novel proteoforms of L-ASNase. However, some critical characteristics must be considered for a novel L-ASNase source to be effective as an antitumour drug. Accordingly, this article provides a critical analysis of the parameters and methods applied to estimate L-ASNase concentration, measure the L-ASNase and GLNase activities and kinetics, evaluate the enzyme preparations purity and define the antitumour activity against leukemic cells in vitro. Among the main features, the proposed new enzyme needs to present high affinity for L-asparagine; low percentage of glutaminase activity in relation to L-ASNase; high enzyme stability and half-life and mainly antileukemic activity when a low protein amount is applied. These parameters are discussed in an attempt to guide the consideration of an enzyme as a promising biopharmaceutical against ALL.



中文翻译:

关键概述和主要特征和技术,用于评估L-天冬酰胺酶作为治疗血液癌的生物药物的临床适用性。

L-天冬酰胺酶是一种用作治疗急性淋巴细胞白血病的生物药物的酶。与L-天冬酰胺酶的使用相关的一些不良影响,因此科学界已经在寻找L-ASNase的新型蛋白形式。但是,必须考虑一些关键特征,才能使新型L-ASNase来源有效用作抗肿瘤药。因此,本文对用于估计L-ASNase浓度,测量L-ASNase和GLNase的活性和动力学,评估酶制剂的纯度以及确定体外抗白血病细胞的抗肿瘤活性的参数和方法进行了严格的分析。在主要特征中,提出的新酶需要对L-天冬酰胺具有高亲和力。与L-ASNase相比,谷氨酰胺酶活性的百分比低;高酶稳定性和半衰期,主要是抗贫血活性(当应用少量蛋白质时)。讨论这些参数是为了指导人们考虑将酶作为对抗ALL的有前途的生物药物。

更新日期:2020-01-13
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