THE CLINICAL EFFICACY OF POLY(ETHYLENE GLYCOL)-MODIFIED PROTEINS

被引：200

作者：

FUERTGES, F

ABUCHOWSKI, A

机构：

[1] Enzon, Inc., Plainfield, NJ 07080, 300 C Corporate Ct., S

来源：

JOURNAL OF CONTROLLED RELEASE | 1990年 / 11卷 / 1-3期

关键词：

chemical modification; immunogenicity; pharmacokinetics; poly(ethylene glycol); proteins;

D O I：

10.1016/0168-3659(90)90127-F

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Modification of proteins with poly(ethylene glycol) (PEG) creates a conjugate with a dramatically increased circulating life and reduced immunogenicity and antigenicity. The increase in circulating life is attributed to the masking of ligands or antigenic determinants recognized by cellular receptors. Steric hindrance of the antigenic determinants on the protein is believed to reduce the immunogenicity and antigenicity. Currently four PEG-modified enzymes are undergoing clinical trials. PEG-l-asparaginase is in Phase III studies for treatment of acute lymphoblastic leukemia; PEG-adenosine deaminase (PEG-ADA) is in phase III trials and is used in ADA-deficient Severe Combined Immunodeficiency Syndrome; PEG-superoxide dismutase (PEG-SOD) is in Phase III studies for treatment of reperfusion injury associated with kidney transplantations; PEG-uricase is a uricolytic agent in Phase I trials for treatment of hyperuricemia associated with chemotherapy. PEG-catalase has completed preclinical trials and shows potential therapeutic use in trauma, burns and hydrogen peroxide-mediated injuries. All these enzymes demonstrate increased circulating lives and decreased immunogenicity. Clinical studies have shown these modified enzymes to be safe and have therapeutic value. © 1990.

引用

页码：139 / 148

页数：10

共 22 条

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