Antibody Humanization Technologies

The first monoclonal antibodies were typically made entirely from mouse cells. One problem with this is that the human immune system will see these antibodies as foreign (because they’re from a different species) and will mount a response against them. In the short term, this can sometimes cause an immune response. In the long term, it means that the antibodies may only work the first time they are given; after that, the body’s immune system is primed to destroy them before they can provide treatment. This study presents a technology that generates stable, soluble, ultra-humanized antibodies via single-step CDR redundancy minimization. Lead clones demonstrated high stability, with affinity and specificity equivalent to, or better than, the parental immunoglobulin. This significantly lowered non-human sequence content, minimized t- and b-cell epitope risk in the final molecules and provided a heat map for the essential non-human CDR residue content of antibodies from disparate sources. Antibody humanization uses multiple sequence segments derived from variable (V) regions of unrelated human antibodies, unlike other technologies that typically use a single human V region framework as acceptors for complementarity determining regions (CDRs) from starting antibodies (typically rodent). Through careful selection of human sequence segments and the application of in silico tools, CD4+ T cell epitopes are avoided so the risk of immunogenicity is reduced compared to standard humanized antibodies whilst antibody affinity and specificity is maintained. Immunogenicity assessment technology is used to confirm T cell epitopes have been removed.

  • Rapid Humanization and Affinity Improvement of a Murine Antibody
  • IMGT Databases and Tools for Antibody Engineering and Humanization
  • Immunogenicity Assessment Strategies to Support the Development of Biological Therapeutics
  • Therapeutic Antibody Discovery and Development Using Humanized RabMAbs
  • Humanized Antibodies and Their Therapeutic Value
  • Non-human Primate Immune Libraries Combined with Germline Humanization
  • A Novel Fully Human Monoclonal Antibody Platform Using Transgenic Rats

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