Fully human antibodies from transgenic animals play increasingly important role in new therapeutics. Creative Biolabs has developed the Magic™ Human Antibody Discovery Platform to produce fully human monoclonal antibodies in transgenic mice. As a leading provider in human antibody production field, Creative Biolabs can employ "humanized" transgenic mice to discover and produce human antibodies.
Human monoclonal antibodies (mAbs) can be produced by two parallel technologies: phage display, with selection of antigen-specific binders from blood lymphocyte libraries, and transgenic mice, with integrated human immunoglobulin (Ig) loci. The engineering of antibodies with a "humanized humoral immune" system in transgenic mice can be valuable for therapeutic uses since these antibody derivatives have been preselected in vivo. The advantage of the transgenic animal approach is that natural diversification and selection can be exploited under the control of the animal's immune system. The Ig loci can undergo normal processes of DNA rearrangement and hypermutation. Antibodies produced by other techniques, such as phage display, are derived from non-animal sources, which have very artificial antibody sequences that do not exist in nature. Maybe these non-nature-selected antibody sequences perform well in vitro, but their behaviors in vivo cannot be predicted. One of the common problems is that the artificial antibodies will disappear in vivo without disclosing their whereabouts. This problem may be caused by antibodies binding to unknown epitopes, or the antibodies may be captured by cells or simply degraded or sliced in vivo. Alternatively, antibodies derived from transgenic mice or other living animals have passed nature-selection and usually do not have such issues.
The first regulatory approved antibody produced by humanized mice is EGFR targeting antibody panitumumab (Vectibix). After that, dozens of additional transgenic mouse-derived mAbs have entered human clinical testing, i.e., CD20 (Ofatumumab), CD4 (Zanolimumab), CD70 (MDX-1411), etc. The transgenic mice can be developed by introducing human immunoglobulin loci into the germline of mice to generate human antibody production transgenic mice. Scientists can use oocytes microinjection technology and the embryonic stem (ES) cells to aid this process. In this process, human V, (D) and J segments are constructed on bacterial artificial chromosomes (BACs) or yeast artificial chromosomes (YACs) and then introduced to embryonic stem (ES) cells. Various Ig knockout (KO) lines are introduced to generate mouse line with a silenced IgH locus. Breeding regimes to combine H- and L-chain KOs with human IgH and IgL transloci can express considerable levels of diverse fully human Ig. Upon immunization, the immunoglobulin transgenes undergo V(D)J joining, random nucleotide (N region) addition, class switching, and somatic mutation to generate high-affinity monoclonal antibodies.
Creative Biolabs can employ "humanized" transgenic mice to directly generate high affinity, fully human antibodies, which avoid the subsequent costly and tedious in vitro affinity maturation and antibody humanization process. For more detailed information, please feel free to contact us or directly sent us an inquiry.
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