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Journal of Biochemistry Advance Access originally published online on April 19, 2008
Journal of Biochemistry 2008 144(1):115-120; doi:10.1093/jb/mvn052
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© 2008 The Japanese Biochemical Society

Humanization of an Anti-CD34 Monoclonal Antibody by Complementarity-determining Region Grafting Based on Computer-assisted Molecular Modelling

Sheng Hou1,2,*, Bohua Li1,2,*, Ling Wang1,*, Weizhu Qian1,2, Dapeng Zhang1, Xueyu Hong1, Hao Wang1,2 and Yajun Guo1,2,{dagger}

1International Joint Cancer Institute, Second Military Medical University, Shanghai 200433, People's Republic of China; and 2Shanghai Center for Cell Engineering and Antibody, Shanghai 201203, People's Republic of China

{dagger}To whom correspondence should be addressed. Tel: +86-21-25070241, Fax: +86-21-25074349, E-mail: yjguo{at}smmu.edu.cn

Received January 25, 2008; Accepted March 26, 2008


  Abstract

4C8 is a new mouse anti-human CD34 monoclonal antibody (mAb), which recognizes class II CD34 epitopes and can be used for clinical hematopoietic stem/progenitor cell selection. In an attempt to improve its safety profiles, we have developed a humanized antibody of 4C8 by complementarity-determining region (CDR) grafting method in this study. Using a molecular model of 4C8 built by computer-assisted homology modelling, framework region (FR) residues of potential importance to the antigen binding were identified. A humanized version of 4C8, denoted as h4C8, was generated by transferring these key murine FR residues onto a human antibody framework that was selected based on homology to the mouse antibody framework, together with the mouse CDR residues. The resultant humanized antibody was shown to possess antigen-binding affinity and specificity similar to that of the original murine antibody, suggesting that it might be an alternative to mouse anti-CD34 antibodies routinely used clinically.

Key Words: CD34, hematopoietic stem cells, humanization, immunogenicity, monoclonal antibody

Abbreviations: CDR, complementarity-determining region; FR, framework region; HAMA, human antimouse antibody; HSC, hematopoietic stem cell

*These three authors contributed equally to this work.


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