聚乙二醇化生物技术药物面临的免疫原性挑战

Immunogenicity challenges of PEGylated biomacromolecular drugs

聚乙二醇(PEG)化可有效延长药物半衰期,是目前生物技术药物变构化学中最重要最成熟的技术之一。在早期研究中,PEG并未表现出免疫原性及抗原性,一直被认为是生物惰性材料。然而随着越来越多的PEG化药物进入临床应用,关于患者体内产生抗PEG抗体造成药效损失的报道不断出现,有关PEG化蛋白药物重复给药后引发副反应的报道也逐渐增多。本文就PEG化生物技术药物面临的免疫原性问题及由此引发的加速血液清除(ABC)现象,综述了影响抗PEG抗体产生的关键因素及目前的应对策略。

PEGylation can effectively extend the half-life of bimolecular drugs,which is one of the most important and mature technologies in the allosteric chemistry of biological macromolecules. In early study,polyethylene glycol（PEG）did not show immunogenicity and antigenicity,so was considered as a bio-inert material. However,with more and more PEGylated drugs entering clinical practice,reports on the loss of pharmacodynamic effects caused by anti-PEG antibody and the side effects caused by PEGylated protein drugs after repeated administration have increasingly emerged. In this paper,the immunogenicity problems of PEGylated biomacromolecule drugs and the resulting accelerated blood clearance（ABC）phenomenon are reviewed. The key influencing factors of antipolyethylene glycol antibody production are analyzed and the current coping strategies are proposed.