Innovative Strategies for Antibody Humanization

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.
This is written by Victoria, the editor of Creative Biolabs, a leading custom service provider that is
professional in conducting in depth antibody humanization and affinity maturation using phage
display and DNA mutagenesis approaches and for more information kindly visit our website
www.creative-biolabs.com.