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Innovative Strategies for Antibody Humanization
Posted: Nov 19, 2014
Antibody humanization refers to modifying the protein sequences of antibodies from non-human species to increase their similarity to antibody variants produced naturally in humans. The development of biotechnology has witnessed the development and application of antibody humanization for years. Hybridoma technology, for example, makes a large number of rodent monoclonal antibodies with specificity for antigens of therapeutic interest being generated and characterized. However, rodent antibodies are highly immunogenic in humans, which limits their clinical applications, especially when repeated administration is required. Importantly, they are rapidly removed from circulation and can cause systemic inflammatory effects as well. Humanization is the key process for reducing the immunogenicity of monoclonal antibodies derived from xenogeneic sources (commonly rodent) and for improving their activation of the human immune system.
Creative BioLabs is a leading custom service provider in biotechnological reign that has extensive experience in antibody humanization. It developed three antibody humanization strategies of CDR Grafting & SDR Grafting,Chain Shuffling and Humanized IgG library screening that can preserve the specificity and affinity of the antibody toward the antigen whereas significantly or completely eliminate the immunogenicity of the antibody in humans.
=>CDR Grafting & SDR Grafting
Based on phage display of humanized scfv variants and selection of high-affinity humanized binders through bio-panning, Creative Biolabs established a CDR grafting platform, which is featured with randomization of a small set of framework residues using phage display technology and computer modeling. This approach allows the epitope specificity of the original antibody to be retained. Of note, humanization by this approach is not 100% since the CDR regions are still of a rodent origin. To reduce the immunogenicity of CDR-grafted humanized antibodies, the murine content in the CDR-grafted humanized antibodies is minimized through SDR grafting,which is developed to further update this system.
=>Chain Shuffling
Creative Biolabs has also optimized a chain shuffling strategy that is an entirely selective humanization strategy, which can result in humanized antibodies whose affinities are higher than that of the original antibody. In addition, this sequential chain shuffling procedure can generate several versions of humanized antibodies with different sequences.
=>Humanized IgG library screening
Humanized IgG library screening is an inventively designed technology because researchers will make a library of humanized whole IgG to be displayed on the surface of mammalian cells and then high-affinity binders will be sorted by FACS. In comparison with the bacterial phage display based methods, it allows selection of high affinity humanized antibodies in a dimeric IgG format while avoids time consuming conversion of scFv to IgG and codon optimization of converted IgG [for expression in mammalian cells], which sometime deselect some humanized scFvs.
Creative Biolabs’ antibody humanization service is viewed that two features single it from other leading biotechnological companies. First of all, antibody affinity maturation is an integrated step in its humanization procedure due to its complete research and development system, thus there is no need to improve the affinity after humanization. Secondly, in addition to the common computational and biochemical methods, it has developed a proprietary in vivo approach to evaluate the immunogenicity of the humanized antibodies in primates. The immunogenicity measured in primates is the closest one that may mimic the true immunogenicity of the humanized antibodies in humans.
With innovative technologies and years of experience, Creative Biolabs’ products and services are recognized world-wide as the benchmark for antibody production and engineering field. Creative Biolabs has been and will always be committed to delivering the top-notch quality products and services to customers all around the world.
Search here http://www.creative-biolabs.com/antibody-humanization.html to know more about antibody humanization now!
Creative Biolabs is a recognized service provider in converting small gene-engineered scFv or Fab human or mouse antibodies derived from phage display antibody library screening.