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学科主题: 临床医学
题名:
Active immunization with Tocilizumab mimotopes induces specific immune responses
作者: Yang, Lin1; Xing, Rui1; Li, Changhong1; Liu, Yuan2; Sun, Lin1; Liu, Xiangyuan1; Wang, Yongfu2
关键词: Rheumatoid arthritis ; Tocilizumab ; Mimotope ; IL-6 ; Phage display
刊名: BMC BIOTECHNOLOGY
发表日期: 2015-06-02
DOI: 10.1186/s12896-015-0161-9
卷: 15
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biotechnology & Applied Microbiology
研究领域[WOS]: Biotechnology & Applied Microbiology
关键词[WOS]: JUVENILE IDIOPATHIC ARTHRITIS ; PHAGE-DISPLAYED PEPTIDES ; DISCONTINUOUS EPITOPES ; INTERLEUKIN-6 RECEPTOR ; RHEUMATOID-ARTHRITIS ; ANTIBODY ; MIMICKING ; LIBRARY ; DISEASE ; GROWTH
英文摘要:

Background: Tocilizumab is a humanized monoclonal antibody showing high-affinity binding to both soluble interleukin-6 receptor (sIL-6R) and membrane bound IL-6R (mIL-6R), thereby preventing pro-inflammatory effects of IL-6. However, therapeutic antibodies still have practical limitations. To overcome these limitations, we generated Tocilizumab specific epitope mimics by using the phage display technology and tested whether the peptide mimics could induce similar humoral responses in mice immunized with the peptides.

Results: Seven phage mimics were obtained by using phage display peptide library. Four phage mimics (YHTTDKLFYMMR, YSAYEFEYILSS, KTMSAEEFDNWL and LTSHTYRSQADT) were shown to mimic Tocilizumab epitope using immunoassays. The mimotopes were conjugated to immunogenic carrier proteins and used to intraperitoneally immunize BALB/c mice. Sera from the mimotopes immunized mice not only showed specific binding to recombinant IL-6R, but can also IL-6R expressed in Hela, U-937, Jurkat cell lines and in fibroblast-like synoviocytes from patients with RA (FLS-RA). Furthermore, sera from mice immunized with mimotopes-KLH conjugate could reduce the level of phosphorylated-signal transducers and activator of transcription (STAT3), STAT3, phosphorylated-extracellular signal-regulated kinase (Erk) 1/2 and Erk1/2 in HeLa and Jurkat cells. Antibody-dependent cellular cytotoxicity (ADCC) assay showed that antibodies induced by mimotopes-KLH conjugate could elicit specific lysis in Hela and U-937 cells.

Conclusions: From phage display library, we successfully isolated four Tocilizumab mimotopes which induced specific humoral and cellular reponses in vitro and in vivo.

语种: 英语
所属项目编号: 81260461 ; 81273293
项目资助者: National Nature Science Foundation of China
WOS记录号: WOS:000355393100003
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62220
Appears in Collections:北京大学第三临床医学院_期刊论文

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作者单位: 1.Peking Univ, Hosp 3, Dept Rheumatol & Immunol, Beijing 100191, Peoples R China
2.Baotou Med Coll, Affiliated Hosp 1, Dept Rheumatol, Baotou 014010, Peoples R China

Recommended Citation:
Yang, Lin,Xing, Rui,Li, Changhong,et al. Active immunization with Tocilizumab mimotopes induces specific immune responses[J]. BMC BIOTECHNOLOGY,2015,15.
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