A recombinant, fully human monoclonal antibody with antitumor activity constructed from phage-displayed antibody fragments

被引:80
作者
Huls, GA
Heijnen, IAFM
Cuomo, ME
Koningsberger, JC
Wiegman, L
Boel, E
de Vries, ARV
Loyson, SAJ
Helfrich, W
Henegouwen, GPV
van Meijer, M
de Kruif, J
Logtenberg, T [1 ]
机构
[1] Univ Utrecht Hosp, Dept Immunol, Utrecht, Netherlands
[2] Univ Utrecht Hosp, Dept Gastroenterol, Utrecht, Netherlands
[3] Univ Utrecht Hosp, Dept Pathol, Utrecht, Netherlands
[4] Univ Utrecht Hosp, Dept Microbiol, Utrecht, Netherlands
[5] Univ Utrecht Hosp, Utrecht Biotechnol Syst, Utrecht, Netherlands
[6] Univ Groningen Hosp, Dept Clin Immunol, NL-9713 EZ Groningen, Netherlands
关键词
phage display; Ep-CAM; single-chain Fv; immunotherapy; recombinant antibodies;
D O I
10.1038/7023
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
A single-chain Fv antibody fragment specific for the tumor-associated Ep-CAM molecule was isolated from a semisynthetic phage display library and converted into an intact, fully human IgG1 monoclonal antibody (huMab), The purified huMab had an affinity of 5 nM and effectively mediated tumor cell killing in: in vitro and in vivo assays. These experiments show that nonimmunized phage antibody display libraries can be used to obtain high-affinity, functional, and clinically applicable huMabs directed against a tumor-associated antigen.
引用
收藏
页码:276 / 281
页数:6
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