Effect of protein immunogenicity and PEG size and branching on the anti-PEG immune response to PEGylated proteins
Effect of protein immunogenicity and PEG size and branching on the anti-PEG immune response to PEGylated proteins
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蛋白质免疫原性以及 PEG 大小和分支对聚乙二醇化蛋白质的抗 PEG 免疫反应的影响
DOI：
10.1016/j.procbio.2016.09.029
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发表时间：
2017-01-01
影响因子：
4.4
通讯作者：
Hu, Tao
中科院分区：
文献类型：
--
作者：
Wan, Xue;Zhang, Juankun;Hu, Tao
PEG化已成功地改善了治疗性蛋白质的药理学性质。然而，聚乙二醇（PEG）已被免疫原性所拖累，其对治疗性蛋白质产生负面临床效应。对PEG化蛋白质的抗PEG免疫应答可能取决于蛋白质的性质和缀合的甲氧基PEG（mPEG）。因此，有必要研究蛋白质免疫原性、PEG化程度、分子量（Mw）和mPEG的分支对抗PEG免疫应答的影响。卵清蛋白、破伤风类毒素cm、TT-TT偶联物和TT-牛血清白蛋白偶联物被用作靶蛋白。通过用尺寸排阻色谱分离PEG化的IT，获得具有不同PEG化程度的PEG化蛋白。通过用线性mPEG（5 kDa和20 kDa）和支化mPEG（20 kDa）修饰TT，获得具有不同Mw和支化mPEG的PEG化蛋白。聚乙二醇化蛋白引起高水平的抗PEG抗体（主要是IgM和IgG 1）。抗PEG免疫应答取决于蛋白质的免疫原性、PEG化程度和mPEG的分子量。相比之下，mPEG的分支对针对PEG化蛋白的抗PEG免疫应答具有不显著的影响。(C)2016爱思唯尔有限公司版权所有。
PEGylation has successfully improved the pharmacological properties of therapeutic proteins. However, polyethylene glycol (PEG) has been burdened by immunogenicity that renders a negative clinical effect on therapeutic proteins. The anti-PEG immune response to PEGylated proteins possibly depends on the nature of proteins and the conjugated methoxy PEG (mPEG). Thus, it is necessary to investigate the effects of protein immunogenicity, the extent of PEGylation, the molecular weight (Mw), and the branching of mPEG on the anti-PEG immune response. Ovalbumin, tetanus toxoid cm, TT-TT conjugate, and TT-bovine serum albumin conjugate were used as target proteins. PEGylated proteins with different extents of PEGylation were obtained by fractionation of the PEGylated IT with size exclusion chromatography. The PEGylated proteins with different Mw and branching of mPEG were obtained by modification of TT with linear mPEG (5 kDa and 20 kDa) and branched mPEG (20 kDa). The PEGylated proteins elicited high levels of anti-PEG antibodies (predominantly IgM and IgG1). The anti-PEG immune response depended on the immunogenicity of proteins, the extent of PEGylation, and the Mw of mPEG. In contrast, branching of mPEG had an insignificant effect on the anti-PEG immune response to the PEGylated proteins. (C) 2016 Elsevier Ltd. All rights reserved.