Bendich A, Kafkewitz D, Abuchowski A, Davis F F
Clin Exp Immunol. 1982 Apr;48(1):273-8.
The immunosuppressive effects of polyethylene glycol-modified asparaginases from Vibrio succinogenes (PEG-asparaginase VS) and Escherichia coli (PEG-asparaginase EC) have been investigated in mice. Measurements of the mitogen-induced blastogenic responses of splenocytes, harvested 5 days after in vivo administration of the PEG-enzymes, show that PEG-asparaginase VS is not immunosuppressive, whereas PEG-asparaginase EC does cause immunosuppression. Both enzymes cause the spleen to be smaller than the control mice. In mice carrying the L5178Y tumour and its associated LDH-elevating virus, which causes the circulation life of asparaginase VS to be comparable to that of PEG-asparaginase VS, tumour regression and its attendant immunological changes are identical in animals treated with either the native or the modified enzyme. The data presented in this paper, along with independent immunological evidence presented by other workers strongly suggest that PEG-asparaginase VS may be the enzyme of choice for clinical use.
已在小鼠中研究了来自琥珀酸弧菌(聚乙二醇化天冬酰胺酶VS)和大肠杆菌(聚乙二醇化天冬酰胺酶EC)的聚乙二醇化天冬酰胺酶的免疫抑制作用。在体内给予聚乙二醇化酶5天后收获脾细胞,对丝裂原诱导的脾细胞增殖反应进行测量,结果显示聚乙二醇化天冬酰胺酶VS没有免疫抑制作用,而聚乙二醇化天冬酰胺酶EC确实会引起免疫抑制。两种酶都会使脾脏比对照小鼠的小。在携带L5178Y肿瘤及其相关的乳酸脱氢酶升高病毒(这使得天冬酰胺酶VS的循环寿命与聚乙二醇化天冬酰胺酶VS相当)的小鼠中,用天然酶或修饰酶处理的动物的肿瘤消退及其伴随的免疫变化是相同的。本文提供的数据,以及其他研究人员提供的独立免疫学证据,强烈表明聚乙二醇化天冬酰胺酶VS可能是临床使用的首选酶。