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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Development and characterization of a fully functional small anti-HER2 antibody

  • Gao, Jie (International Joint Cancer Institute and Changhai Hospital Cancer Center, the Second Military Medical University) ;
  • Li, Bohua (International Joint Cancer Institute and Changhai Hospital Cancer Center, the Second Military Medical University) ;
  • Li, Huimei (International Joint Cancer Institute and Changhai Hospital Cancer Center, the Second Military Medical University) ;
  • Zhang, Xunmin (International Joint Cancer Institute and Changhai Hospital Cancer Center, the Second Military Medical University) ;
  • Zhang, Dapeng (International Joint Cancer Institute and Changhai Hospital Cancer Center, the Second Military Medical University) ;
  • Zhao, Lei (International Joint Cancer Institute and Changhai Hospital Cancer Center, the Second Military Medical University) ;
  • Wang, Chong (School of Medicine and School of Pharmacy, Shanghai Jiao Tong University) ;
  • Fang, Chen (International Joint Cancer Institute and Changhai Hospital Cancer Center, the Second Military Medical University) ;
  • Qian, Weizhu (International Joint Cancer Institute and Changhai Hospital Cancer Center, the Second Military Medical University) ;
  • Hou, Sheng (International Joint Cancer Institute and Changhai Hospital Cancer Center, the Second Military Medical University) ;
  • Kou, Geng (International Joint Cancer Institute and Changhai Hospital Cancer Center, the Second Military Medical University) ;
  • Wei, Huafeng (International Joint Cancer Institute and Changhai Hospital Cancer Center, the Second Military Medical University) ;
  • Shi, Shu (International Joint Cancer Institute and Changhai Hospital Cancer Center, the Second Military Medical University) ;
  • Wang, Hao (International Joint Cancer Institute and Changhai Hospital Cancer Center, the Second Military Medical University) ;
  • Guo, Yajun (International Joint Cancer Institute and Changhai Hospital Cancer Center, the Second Military Medical University)
  • Published : 2009.10.31
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Abstract

The penetrating of monoclonal antibodies (mAbs) into solid tumor may be hampered by their large size. The antibody mimetics, composed of two complementarity-determining regions (CDRs) through a cognate framework region (FR), have been demonstrated to have the capacity to penetrate tumors superior to its parental intact IgG. In this study, we used CDR and FR sequences from the humanized anti-HER2 monoclonal antibody trastuzumab to design four antibody mimetics. Then these antibody mimetics were fused to human IgG Fc to generate mimetics-Fc small antibodies. One of the four mimetics-Fc antibodies binds well to HER2-overexpressing SK-BR3 cells and effectively inhibits the binding of trastuzumab. This mimetics-Fc, denoted as HMTI-Fc, was shown to be effective in mediating antibody-dependent cellular cytotoxicity and exhibit an antiproliferative effect in SK-BR3 cells. To our knowledge, the HMTI-Fc antibody shown here is the smallest fully functional antibody and may have a potential for treatment of cancer.

Keywords

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