Construction and characterization of a high-affinity humanized SM5-1 monoclonal antibody.
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.
Li
Bohua
B
International Joint Cancer Institute, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China.
Wang
Hao
H
Zhang
Dapeng
D
Qian
Weizhu
W
Hou
Sheng
S
Shi
Shu
S
Zhao
Lei
L
Kou
Geng
G
Cao
Zhiguo
Z
Dai
Jianxin
J
Guo
Yajun
Y
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000737:chemistry* / Q000276:immunology* / Q000648:ultrastructure; D006528:Carcinoma, Hepatocellular / Q000276:immunology*; D045744:Cell Line, Tumor; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology*; D051379:Mice; D008956:Models, Chemical; D018448:Models, Immunological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015202:Protein Engineering / Q000379:methods*
D000911:Antibodies, Monoclonal