Sensitivity of PEGylated interferon detection by anti-polyethylene glycol (PEG) antibodies depends on PEG length

Ta Chun Cheng, Kuo Hsiang Chuang, Michael Chen, Hsin Ell Wang, Shey Cherng Tzou, Yu Cheng Su, Chih Hung Chuang, Chien Han Kao, Bing Mae Chen, Long Sen Chang, Steve R. Roffler, Tian Lu Cheng

研究成果: 雜誌貢獻文章同行評審

13 引文 斯高帕斯(Scopus)

摘要

Attachment of poly(ethylene glycol) to proteins can mask immune epitopes to increase serum half-life, reduce immunogenicity, and enhance in vivo biological efficacy. However, PEGylation mediated epitope-masking may also limit sensitivity and accuracy of traditional ELISA. We previously described an anti-PEG-based sandwich ELISA for universal assay of PEGylated molecules. Here, we compared the quantitative assessment of PEGylated interferons by anti-PEG and traditional anti-interferon sandwich ELISA. The detection limits for PEG-Intron (12k-PEG) and Pegasys (40k-PEG) were 1.9 and 0.03 ng/mL for anti-PEG ELISA compared to 0.18 and 0.42 ng/mL for traditional anti-interferon sandwich ELISA. These results indicate that the anti-PEG sandwich ELISA was insensitive to PEGylation mediated epitope-masking and the sensitivity increased in proportion to the length of PEG. By contrast, PEG-masking interfered with detection by traditional anti-interferon sandwich ELISA. Human and mouse serum did not affect the sensitivity of anti-PEG ELISA but impeded traditional anti-interferon sandwich ELISA. The anti-PEG sandwich ELISA was comparable to anti-interferon sandwich ELISA and radioassay of 131I-Pegasys in pharmacokinetic studies in mice. The anti-PEG sandwich ELISA provides a sensitive, accurate, and convenient quantitative measurement of PEGylated protein drugs.

原文英語
頁(從 - 到)1408-1413
頁數6
期刊Bioconjugate Chemistry
24
發行號8
DOIs
出版狀態已發佈 - 8月 21 2013

ASJC Scopus subject areas

  • 生物技術
  • 生物工程
  • 有機化學
  • 藥學科學
  • 生物醫學工程
  • 藥理
  • 醫藥 (全部)

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