Arginine deiminase, a potential anti-tumor drug.
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.
Ni
Ye
Y
Laboratory of Biocatalysis, School of Biotechnology, Jiangnan University, The Key Laboratory of Industrial Biotechnology, Ministry of Education, 1800 Lihu Road, Wuxi 214122, PR China.
Schwaneberg
Ulrich
U
Sun
Zhi-Hao
ZH
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D003001:Cloning, Molecular; D006801:Humans; D006867:Hydrolases / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy; D008545:Melanoma / Q000188:drug therapy*; D008958:Models, Molecular; D012878:Skin Neoplasms / Q000188:drug therapy
D000970:Antineoplastic Agents; D006867:Hydrolases; C019723:arginine deiminase