Nagahira K, Fukuda Y, Oyama Y, Kurihara T, Nasu T, Kawashima H, Noguchi C, Oikawa S, Nakanishi T
Suntory Institute for Biomedical Research, Osaka, Japan.
J Immunol Methods. 1999 Jan 1;222(1-2):83-92. doi: 10.1016/s0022-1759(98)00184-7.
An anti-human tumor necrosis factor-alpha (TNF-alpha) monoclonal antibody, designated as 3B10, inhibits the biological activity of human TNF-alpha. In the present study, we constructed humanized version of the antibody by grafting its complementarity-determining regions (CDRs) onto a human antibody, HBS-1. Using a molecular model of mouse 3B10, framework residues affecting the CDR conformation were identified. Thus, these residues were also introduced into the framework together with the CDRs in a stepwise manner, depending on the degree of the possible importance of the residues. As a result, one humanized version (h3B10-9) which possesses nine mouse framework residues showed the same binding activity as that of the chimeric version. This humanized anti-TNF-alpha antibody is expected to be less immunogenic and thus more suitable for possible clinical use.
一种名为3B10的抗人肿瘤坏死因子-α（TNF-α）单克隆抗体可抑制人TNF-α的生物活性。在本研究中，我们通过将其互补决定区（CDR）嫁接到人抗体HBS-1上构建了该抗体的人源化版本。利用小鼠3B10的分子模型，确定了影响CDR构象的框架残基。因此，根据这些残基可能的重要程度，这些残基也与CDR一起逐步引入框架中。结果，一种含有九个小鼠框架残基的人源化版本（h3B10-9）表现出与嵌合版本相同的结合活性。这种人源化抗TNF-α抗体预计免疫原性较低，因此更适合临床应用。
