Antibody Humanization

Antibody humanization aims to reduce the immunogenicity of monoclonal antibodies from xenogeneic origin by replacing non-human framework regions, (FR), with human ones. It is a crucial step in therapeutic antibody development.

Process:

  • Sequencing of the VH and VL genes
  • Modelling of the parent VH and VL domains
  • Alignment with a range of preferred human germline sequences
  • Assessment of conflicts between non-human CDRs and human FRs and design of back mutations to prevent a loss of affinity in the final products.
  • CDR grafting onto preferred germline backbones
  • ~8 different humanized sequences generated
  • Synthesis, cloning and small-scale production of all humanized variants, original parent and chimeric controls in our mammalian expression system
  • Characterization of the variants by ELISA or SPR
  • Detailed report
Timeline:
  • ~14 weeks from reception of the VH and VL sequences
Reference:

Robert R, Streltsov VA, Newman J, Pearce LA, Wark KL, Dolezal O. Germline humanization of a murine Abeta antibody and crystal structure of the humanized recombinant Fab fragment. Protein Sci. 2010: 19:299-308.