Department of Pharmaceutical and Biochemical Technology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
Blood Rev. 2020 Sep;43:100651. doi: 10.1016/j.blre.2020.100651. Epub 2020 Jan 13.
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.
L-天冬酰胺酶是一种用于治疗急性淋巴细胞白血病的生物制药酶。已有多种不良反应与 L-天冬酰胺酶的使用有关，因此科学界一直在寻找 L-ASNase 的新型蛋白形式。然而，要使新型 L-ASNase 成为有效的抗肿瘤药物，还必须考虑一些关键特性。因此，本文对用于估计 L-ASNase 浓度、测量 L-ASNase 和 GLNase 活性和动力学、评估酶制剂纯度以及定义体外抗白血病细胞活性的参数和方法进行了批判性分析。在主要特性中，所提出的新酶需要对 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要低；酶稳定性和半衰期要高，并且在应用低蛋白量时主要具有抗白血病活性。本文讨论了这些参数，以期为将酶作为一种有前途的针对 ALL 的生物制药提供指导。
