Generation of humanized anti-DNA hydrolyzing catalytic antibodies by complementarity determining region grafting

• Published in: Biochemical and biophysical research communications 2009-02, Vol.379 (2), p.314-318
• Main Authors: Kim, Dong-Sik, Lee, Seung-Hyun, Kim, Jeong-Sun, Lee, Suk-Chan, Kwon, Myung-Hee, Kim, Yong-Sung
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Anti-DNA hydrolyzing antibody; Antibodies, Catalytic - biosynthesis; Antibodies, Catalytic - chemistry; Antibodies, Catalytic - immunology; Antibodies, Monoclonal - biosynthesis; Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - immunology; Antibody humanization; Catalytic antibody; CDR grafting; Complementarity Determining Regions - biosynthesis; Complementarity Determining Regions - chemistry; Complementarity Determining Regions - immunology; DNA - immunology; Humans; Hydrolysis; Mice; Models, Molecular; Molecular modeling; Molecular Sequence Data
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2008.12.051

Humanization of nonhuman antibodies (Abs) has been carried out mainly for Abs which bind to antigen without catalytic activity. Here we report humanization of mouse-originated 3D8 (m3D8) mAbs (scFv, VH, and VL) with DNA hydrolyzing catalytic activity by grafting the complementarity determining regions (CDRs) into the corresponding regions of a fixed human framework scaffold, generating humanized 3D8 (h3D8) Abs in the respective format of scFv, VH, and VL. h3D8 Abs retained comparable DNA binding and hydrolyzing activities to those of the corresponding m3D8 Abs. Our results suggest that CDRs of anti-DNA hydrolyzing Abs might possess the intrinsic properties of DNA binding and hydrolyzing activities.