Li Bohua, Wang Hao, Zhang Dapeng, Qian Weizhu, Hou Sheng, Shi Shu, Zhao Lei, Kou Geng, Cao Zhiguo, Dai Jianxin, Guo Yajun
International Joint Cancer Institute, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China.
Biochem Biophys Res Commun. 2007 Jun 15;357(4):951-6. doi: 10.1016/j.bbrc.2007.04.039. Epub 2007 Apr 17.
SM5-1 is a mouse monoclonal antibody which has a high specificity for melanoma, hepatocellular carcinoma, and breast cancer, making it a promising candidate for cancer targeting therapy. We have therefore attempted to construct a humanized antibody of SM5-1 to minimize its immunogenicity for potential clinical use. Using a molecular model of SM5-1 built by computer-assisted homology modeling, framework region (FR) residues of potential importance to the antigen binding were identified. Then, a humanized version of SM5-1 was generated by transferring these mouse key FR residues onto a human framework that was selected based on homology to the mouse framework, together with the mouse complementarity-determining region (CDR) residues. This humanized antibody retained only six murine residues outside of the CDRs but was shown to possess affinity and specificity comparable to that of the parental antibody, suggesting that it might have the potential to be developed for future clinical use.
SM5-1是一种小鼠单克隆抗体，对黑色素瘤、肝细胞癌和乳腺癌具有高度特异性，使其成为癌症靶向治疗的一个有前景的候选药物。因此，我们试图构建SM5-1的人源化抗体，以将其免疫原性降至最低，用于潜在的临床应用。利用计算机辅助同源建模构建的SM5-1分子模型，确定了对抗原结合可能重要的框架区（FR）残基。然后，通过将这些小鼠关键FR残基转移到基于与小鼠框架的同源性选择的人框架上，连同小鼠互补决定区（CDR）残基，生成了SM5-1的人源化版本。这种人源化抗体在CDR之外仅保留了六个鼠源残基，但显示出与亲本抗体相当的亲和力和特异性，表明它可能有潜力用于未来的临床应用。
