Revealing the Immunogenic Risk of Polymers

被引：108

作者：

Li, Bowen ^{[1
]}

Yuan, Zhefan ^{[2
]}

Hung, Hsiang-Chien ^{[2
]}

Ma, Jinrong ^{[2
]}

Jain, Priyesh ^{[2
]}

Tsao, Caroline ^{[2
]}

Xie, Jingyi ^{[1
]}

Zhang, Peng ^{[2
]}

Lin, Xiaojie ^{[2
]}

Wu, Kan ^{[2
]}

Jiang, Shaoyi ^{[1
,2
]}

机构：

[1] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA

[2] Univ Washington, Dept Chem Engn, Seattle, WA 98195 USA

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2018年 / 57卷 / 42期

关键词：

antibodies; immunochemistry; polymers; protein modifications; zwitterions; ACCELERATED BLOOD CLEARANCE; ANTI-PEG ANTIBODIES; POLYETHYLENE-GLYCOL; ZWITTERIONIC MATERIALS; DRUG-DELIVERY; PROTEINS; BIOPHARMACEUTICALS; PEGYLATION; STRATEGIES; RESISTANCE;

D O I：

10.1002/anie.201808615

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Poly(ethylene glycol) (PEG) conjugation has been the gold standard to ameliorate the pharmacokinetic (PK) and immunological profiles of proteins. PEG polymer does become immunogenic once attached to proteins, evoking PEG-specific antibody (Ab) responses. The anti-PEG Abs could cause PEGylated biologic treatments to fail and even result in lethal adverse reactions. Thus the zwitterionic poly(carboxybetaine) (PCB) has been introduced as a PEG substitute for protein modification. Addressed herein is anti-polymer Ab induction by conjugating PEG and PCB polymers to a series of carrier proteins with escalating immunogenicity. Results indicate that titers of PEG-specific Abs were quantitatively correlated to the immunogenicity of carrier proteins, whereas the generation of PCB-specific Abs was minimal and insensitive to increased protein immunogenicity. This work provides insight into the immunological properties of PEG and PCB and has far-reaching implications for the development of polymer-protein conjugates.

引用

页码：13873 / 13876

页数：4

共 39 条

[1]

[Anonymous], 2018, ANGEW CHEM INT EDIT, DOI [10.1002/ange.201710068, DOI 10.1002/ANGE.201710068]

[2] Roles of glycine betaine and proline in improving plant abiotic stress resistance [J].