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

[1] Gregoriadis, Liposomes in therapeutic and preventive medicine: The development of the drug-carrier concept, Liposomes and their Uses in Biology and Medicine, (1978)
[2] Abuchowski, Davis, Soluble polymer-enzyme adducts. Enzymes, Enzymes as Drugs, (1981)
[3] Abuchowski, Kazo, Verhoest, van Es, Kafkewitz, Nucci, Viau, Davis, Cancer therapy with chemically modified enzymes. I. Antitumor properties of polyethylene glycol-aspara-ginase conjugates, Cancer Biochem. Biophys., 7, pp. 175-186, (1984)
[4] Abuchowski, McCoy, Palczuk, van Es, Davis, Effect of covalent attachment of polyethylene glycol on immunogenicity and circulating life of bovine liver catalase, J. Biol. Chem., 252, pp. 3582-3586, (1977)
[5] Ho, Brown, Yen, Holmes, Keating, Abuchowski, Newman, Krakoff, Clinical pharmacology of polyethylene glycol-asparaginase, Drug Metab. Disposit., 14, pp. 349-352, (1986)
[6] Scudiery, A review of the safety and tolerance of PEG-enzymes, Presented at Innovations in Protein Delivery: From Research to the Clinic, (1987)
[7] Muss, Spell, Capizzi, Cooper, Cruz, Jackson, Powell, Scudiery, Spurr, White, Zekan, PEG-l-asparaginase in non-Hodgin's lymphoma: A phase II trial, Presented at Innovations in Protein Therapeutics: From Research to the Clinic, (1987)
[8] Viau, Abuchowski, Greenspan, Davis, Safety evaluation of free radical scavengers PEG-catalase and PEG-superoxide dismutase, J. Free Radicals Biol. Med., 2, pp. 283-288, (1986)
[9] Nucci, Olejarczyk, Abuchowski, Immunogenicity of polyethylene glycol-modified super-oxide dismutase and catalase, J. Free Radicals Biol. Med., 2, pp. 321-325, (1986)
[10] Peroxinorm: Superoxide Dismutase, Specific enzyme therapy for the local treatment of inflammatory processes, (1988)

← 1 2 3 →