IR@PKUHSC  > 北京大学第三临床医学院
学科主题临床医学
Active immunization with Tocilizumab mimotopes induces specific immune responses
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
2015-06-02
DOI10.1186/s12896-015-0161-9
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
WOS记录号WOS:000355393100003
项目编号81260461 ; 81273293
资助机构National Nature Science Foundation of China
引用统计
被引频次:2[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/62220
专题北京大学第三临床医学院
北京大学第二临床医学院_图书馆
北京大学第三临床医学院_风湿免疫科
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
推荐引用方式
GB/T 7714
Yang, Lin,Xing, Rui,Li, Changhong,et al. Active immunization with Tocilizumab mimotopes induces specific immune responses[J]. BMC BIOTECHNOLOGY,2015,15.
APA Yang, Lin.,Xing, Rui.,Li, Changhong.,Liu, Yuan.,Sun, Lin.,...&Wang, Yongfu.(2015).Active immunization with Tocilizumab mimotopes induces specific immune responses.BMC BIOTECHNOLOGY,15.
MLA Yang, Lin,et al."Active immunization with Tocilizumab mimotopes induces specific immune responses".BMC BIOTECHNOLOGY 15(2015).
条目包含的文件
条目无相关文件。
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Yang, Lin]的文章
[Xing, Rui]的文章
[Li, Changhong]的文章
百度学术
百度学术中相似的文章
[Yang, Lin]的文章
[Xing, Rui]的文章
[Li, Changhong]的文章
必应学术
必应学术中相似的文章
[Yang, Lin]的文章
[Xing, Rui]的文章
[Li, Changhong]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。