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Engineering and characterization of a humanized antibody targeting TNF-alpha and RANKL
Wang, Jun1,2; Du, Yuxuan1; Qian, Hongyan3; Yu, Haitao1; Li, Shentao1; Zhang, Xulong1; Li, Zhanguo4; Yuan, Huihui1; Zhao, Wenming1
关键词Humanized antibody Tumor necrosis factor-alpha (TNF-alpha) Receptor activator of NF-kappa B ligand (RANKL) Dual targets
刊名BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
2014-07-18
DOI10.1016/j.bbrc.2014.06.046
450期:1页:717-722
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Biophysics
研究领域[WOS]Biochemistry & Molecular Biology ; Biophysics
关键词[WOS]COLLAGEN-INDUCED ARTHRITIS ; RHEUMATOID-ARTHRITIS ; MONOCLONAL-ANTIBODY ; DISEASE
英文摘要

To neutralize the pathological activities of tumor necrosis factor-a (TNF-alpha) and receptor activator of NF-kappa B ligand (RANKL), we engineered and characterized a humanized 8G12 (h8G12) antibody that targeted TNF-alpha and RANKL. Standard molecular biological and complementarity determining region (CDR)-grafting techniques were used to engineer the h8G12 antibody, and enzyme-linked immunosorbent assays (ELISAs) and Western blotting were employed to determine its binding activation and specificity. TNF-alpha-mediated cytotoxicity and RANKL-induced osteoclastogenesis assays were used to evaluate the neutralizing effects of the antibody. The cDNA sequences were established by grafting the murine monoclonal antibody (mAb) 8G12 CDRs into the heavy and light chain (HC and LC) variable regions (VH and VL) of the human mAbs 3DGG_B and 1I9R_L, respectively. The recombinant plasmids were transfected into Chinese hamster ovary (CHO) cells to produce the h8G12 antibody, which could simultaneously recognize TNF-alpha and RANKL. In addition, the h8G12 antibody reduced the TNF-alpha-mediated apoptosis of L929 cells by 25.84%. Furthermore, the h8G12 antibody significantly inhibited leukocyte infiltration in a murine allergic contact inflammation model. Concurrent with the inhibition of apoptosis, the h8G12 antibody significantly reduced the number of osteoclast-like cells in a dose-dependent manner. These results demonstrated that the h8G12 antibody neutralized the activities of TNF-alpha and RANKL and that it might be a potential candidate for the treatment of inflammatory bone diseases, such as rheumatoid arthritis (RA). (C) 2014 Elsevier Inc. All rights reserved.

语种英语
WOS记录号WOS:000343641000117
引用统计
被引频次:1[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/400002259/65445
专题北京大学第二临床医学院
北京大学第二临床医学院_风湿免疫科
作者单位1.Capital Med Univ, Sch Basic Med Sci, Dept Immunol, Beijing 100069, Peoples R China
2.Inner Mongolia Med Univ, Sch Basic Med Sci, Dept Pathogeny Biol & Immunol, Hohhot 010110, Inner Mongolia, Peoples R China
3.Xiamen Univ, Affiliated Hosp 1, Dept Rheumatol & Clin Immunol, Xiamen 361003, Fujian, Peoples R China
4.Peking Univ, Peoples Hosp, Clin Immunol Ctr, Dept Rheumatol & Immunol, Beijing 100044, Peoples R China
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GB/T 7714
Wang, Jun,Du, Yuxuan,Qian, Hongyan,et al. Engineering and characterization of a humanized antibody targeting TNF-alpha and RANKL[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2014,450(1):717-722.
APA Wang, Jun.,Du, Yuxuan.,Qian, Hongyan.,Yu, Haitao.,Li, Shentao.,...&Zhao, Wenming.(2014).Engineering and characterization of a humanized antibody targeting TNF-alpha and RANKL.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,450(1),717-722.
MLA Wang, Jun,et al."Engineering and characterization of a humanized antibody targeting TNF-alpha and RANKL".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 450.1(2014):717-722.
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