Construction and characterization of a high-affinity humanized SM5-1 monoclonal antibody

被引:23
作者
Li, Bohua
Wang, Hao
Zhang, Dapeng
Qian, Wezhu
Hou, Sheng
Shi, Shu
Zhao, Lei
Kou, Geng
Cao, Zhiguo
Dai, Jianxin
Guo, Yajun
机构
[1] Second Mil Med Univ, Int Joint Canc Inst, Shanghai 200433, Peoples R China
[2] Shanghai Ctr Cell Engn & Antibody, Shanghai 201203, Peoples R China
基金
中国国家自然科学基金;
关键词
humanization; immunogenicity; molecular modeling; monoclonal antibody; SM5-1;
D O I
10.1016/j.bbrc.2007.04.039
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (c) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:951 / 956
页数:6
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