Ni Ye, Schwaneberg Ulrich, Sun Zhi-Hao
Laboratory of Biocatalysis, School of Biotechnology, Jiangnan University, The Key Laboratory of Industrial Biotechnology, Ministry of Education, 1800 Lihu Road, Wuxi 214122, PR China.
Cancer Lett. 2008 Mar 8;261(1):1-11. doi: 10.1016/j.canlet.2007.11.038. Epub 2008 Jan 7.
Arginine deiminase (ADI; EC 3.5.3.6), an arginine-degrading enzyme, has been studied as a potential anti-tumor drug for the treatment of arginine-auxotrophic tumors, such as hepatocellular carcinomas (HCCs) and melanomas. Studies with human lymphatic leukemia cell lines further suggest that ADI is a potential anti-angiogenic agent and is effective in the treatment of leukemia. For instance ADI-PEG-20, patented by Pheonix Pharmacologic Inc., is currently in clinical trials for the treatment of HCC (Phase II/III) and melanoma (Phase I/II). This review summarizes results on recombinant expression, structural analysis, PEG (polyethylene glycerol) modification, in vivo anti-cancer activities, and clinical studies of ADI. Discussions on heterogeneous expression of ADI, directed evolution for improving enzymatic properties, and HSA-fusion for increased in vivo activity conclude this review.
精氨酸脱亚氨酶（ADI；EC 3.5.3.6）是一种降解精氨酸的酶，已被作为一种潜在的抗肿瘤药物进行研究，用于治疗精氨酸营养缺陷型肿瘤，如肝细胞癌（HCC）和黑色素瘤。对人淋巴白血病细胞系的研究进一步表明，ADI是一种潜在的抗血管生成剂，对白血病治疗有效。例如，由菲尼克斯制药公司申请专利的ADI-PEG-20目前正处于治疗HCC（II/III期）和黑色素瘤（I/II期）的临床试验中。本综述总结了关于ADI的重组表达、结构分析、聚乙二醇（PEG）修饰、体内抗癌活性及临床研究的结果。关于ADI的异源表达、改善酶学性质的定向进化以及提高体内活性的人血清白蛋白融合的讨论为本综述作结。
