治疗急性淋巴母细胞白血病和淋巴母细胞淋巴瘤的天冬酰胺酶。

Congying Gao, Xiang-Yu Ma, Zifan Zhang, Q. Lu, C. Ashby, Liuya Wei, Zhe S Chen
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引用次数: 2

摘要

急性淋巴细胞白血病(ALL)是一种以淋巴样细胞在血液和骨髓中的恶性增殖为特征的肿瘤疾病。它约占儿童白血病的75%。淋巴母细胞淋巴瘤(LBL)是一种以快速生长和高度侵袭性为特征的非霍奇金淋巴瘤,最常见于青少年和年轻人。天冬酰胺酶主要用于治疗ALL或LBL患者。由于使用细菌源性天冬酰胺酶治疗的患者会发生过敏反应,因此为对天冬酰胺酶过敏的患者开发替代性天冬酰胺酶制剂是很重要的。重组Erwinia chrysanthemi-rywn (JZP-458)是利用新型荧光假单胞菌表达平台生产的重组Erwinia天冬酰胺酶。JZP-458与菊花源性天冬酰胺酶(ERW)具有相同的氨基酸序列,其体外活性与ERW相似。JZP-458对天冬酰胺酶过敏患者疗效显著。一项I期临床试验的数据表明,志愿者肌肉或静脉注射JZP-458后,在给药72小时后,100%的志愿者血清天冬酰胺酶活性≥0.1 IU/mL。现就JZP-458治疗ALL或LBL的作用机制及相关研究资料进行综述。
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Asparaginase Erwinia chrysanthemi for acute lymphoblastic leukemia and lymphoblastic lymphoma.
Acute lymphoblastic leukemia (ALL) is a neoplastic disease characterized by the malignant proliferation of lymphoid cells in the blood and bone marrow. It accounts for approximately 75% of childhood leukemia. Lymphoblastic lymphoma (LBL) is a type of non-Hodgkin's lymphoma characterized by rapid growth and highly aggressive characteristics that occurs most commonly in adolescents and young adults. Asparaginase is primarily used to treat patients with ALL or LBL. Because allergic reactions occur in patients treated with bacterial-derived asparaginase, it is important to develop an alternative asparaginase preparation for patients allergic to asparaginase. Recombinant asparaginase Erwinia chrysanthemi-rywn (JZP-458) is a recombinant Erwinia asparaginase that uses a novel Pseudomonas fluorescens expression platform in the production process. JZP-458 has the same amino acid sequence as E. chrysanthemi-derived asparaginase (ERW) and its in vitro activity is similar to that of ERW. JZP-458 is highly efficacious in patients allergic to asparaginase. Data from a phase I clinical trial indicated that following the intramuscular or intravenous administration of JZP-458 to volunteers, serum asparaginase activity ≥ 0.1 IU/mL was observed in 100% of the volunteers 72 hours after administration. In this review, we summarize the mechanism of action and the related research data obtained with JZP-458 for the treatment of ALL or LBL.
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