|
KMID : 0624620090420100636
|
|
BMB Reports
2009 Volume.42 No. 10 p.636 ~ p.641
|
|
|
Development and characterization of a fully functional small anti-HER2 antibody
|
|
Gao Jie
Li Bohua
Li Huimei
Zhang Xunmin
Zhang Dapeng
Zhao Lei
Wang Chong
Fang Chen
Qian Weizhu
Hou Sheng
Kou Geng
Wei Huafeng
Shi Shu
Wang Hao
Guo Yajun
|
|
|
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.
|
|
|
KEYWORD
|
|
|
Breast cancer, Complementarity-determining regions, Monoclonal antibody, Rational design, Trastuzumab
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|