Huls G A, Heijnen I A, Cuomo M E, Koningsberger J C, Wiegman L, Boel E, van der Vuurst de Vries A R, Loyson S A, Helfrich W, van Berge Henegouwen G P, van Meijer M, de Kruif J, Logtenberg T
Department of Immunology, University Hospital Utrecht, The Netherlands.
Nat Biotechnol. 1999 Mar;17(3):276-81. doi: 10.1038/7023.
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.
从一个半合成噬菌体展示文库中分离出一种对肿瘤相关上皮细胞黏附分子(Ep-CAM)具有特异性的单链Fv抗体片段,并将其转化为完整的、完全人源化的IgG1单克隆抗体(huMab)。纯化后的huMab亲和力为5 nM,在体外和体内实验中均能有效介导肿瘤细胞杀伤。这些实验表明,未免疫的噬菌体抗体展示文库可用于获得针对肿瘤相关抗原的高亲和力、功能性且临床适用的huMab。