THE CLINICAL EFFICACY OF POLY(ETHYLENE GLYCOL)-MODIFIED PROTEINS
THE CLINICAL EFFICACY OF POLY(ETHYLENE GLYCOL)-MODIFIED PROTEINS
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DOI：
10.1016/0168-3659(90)90127-f
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发表时间：
1990-01-01
影响因子：
10.8
通讯作者：
ABUCHOWSKI, A
中科院分区：
文献类型：
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作者：
FUERTGES, F;ABUCHOWSKI, A
用聚（乙二醇）（PEG）修饰蛋白质产生具有显著增加的循环寿命和降低的免疫原性和抗原性的缀合物。循环寿命的增加归因于细胞受体识别的配体或抗原决定簇的掩蔽。蛋白质上抗原决定簇的空间位阻被认为降低了免疫原性和抗原性。目前，四种PEG修饰的酶正在进行临床试验。PEG-1-天冬酰胺酶处于治疗急性淋巴细胞白血病的III期研究中; PEG-腺苷脱氨酶（PEG-ADA）处于III期试验中并用于ADA缺陷型严重联合免疫缺陷综合征; PEG-超氧化物歧化酶（PEG-SOD）处于治疗与肾移植相关的再灌注损伤的III期研究中; PEG-尿酸酶是一种I期试验中的尿酸溶解剂，用于治疗与化疗相关的高尿酸血症。PEG-过氧化氢酶已完成临床前试验，并显示出在创伤，烧伤和过氧化氢介导的损伤中的潜在治疗用途。所有这些酶都表现出增加的循环寿命和降低的免疫原性。临床研究表明，这些修饰的酶是安全的，并具有治疗价值。
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.