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[成人急性淋巴细胞白血病治疗中天然L-天冬酰胺酶的治疗替代方案]

[Therapeutic alternatives to native L-asparaginase in the treatment of adult acute lymphoblastic leukemia].

作者信息

Thomas X, Cannas G, Chelghoum Y, Gougounon A

机构信息

Hôpital Edouard-Herriot, Lyon, France.

出版信息

Bull Cancer. 2010 Sep;97(9):1105-17. doi: 10.1684/bdc.2010.1168.

Abstract

L-asparaginase is an effective antineoplastic agent, which is an integral part of combination chemotherapy protocols for adult acute lymphoblastic leukemia. Its antitumor effect results from the depletion of asparagine, an amino acid essential to leukemia cells, and subsequent inhibition of protein synthesis leading to cytotoxicity. However, its use has been limited by a high rate of hypersensitivity reactions and development of neutrolizing anti-asparaginase antibodies, and by the need of frequent administration. To overcome these limitations modified versions of L-asparaginase (such as asparaginase from other sources, pegylated formulations, and asparaginase loaded into erythrocytes) have been recently proposed. Advantages of these therapeutic alternatives to native L-asparaginase and their results as part of preliminary clinical trials in adults have been outlined in this review.

摘要

L-天冬酰胺酶是一种有效的抗肿瘤药物,是成人急性淋巴细胞白血病联合化疗方案的一个组成部分。其抗肿瘤作用源于白血病细胞必需的氨基酸天冬酰胺的消耗,以及随后对蛋白质合成的抑制,从而导致细胞毒性。然而,其应用受到高敏反应发生率高、中和性抗天冬酰胺酶抗体的产生以及需要频繁给药的限制。为克服这些局限性,最近有人提出了L-天冬酰胺酶的改良版本(如来自其他来源的天冬酰胺酶、聚乙二醇化制剂以及装载到红细胞中的天冬酰胺酶)。本综述概述了这些天然L-天冬酰胺酶治疗替代方案的优势及其作为成人初步临床试验一部分的结果。

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