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

Biochem Biophys Res Commun. 2009 Feb 6;379(2):314-8. doi: 10.1016/j.bbrc.2008.12.051. Epub 2008 Dec 25.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Catalytic / biosynthesis*
  • Antibodies, Catalytic / chemistry
  • Antibodies, Catalytic / immunology
  • Antibodies, Monoclonal / biosynthesis*
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology
  • Complementarity Determining Regions / biosynthesis*
  • Complementarity Determining Regions / chemistry
  • Complementarity Determining Regions / immunology
  • DNA / immunology*
  • Humans
  • Hydrolysis
  • Mice
  • Models, Molecular
  • Molecular Sequence Data

Substances

  • Antibodies, Catalytic
  • Antibodies, Monoclonal
  • Complementarity Determining Regions
  • DNA