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Full Human Antibody from Humanized Mouse-derived Antibody Library

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HAIL Technology: Human Antibodies from Human Antibody Immune Libraries

Human Antibody from Humanized Mouse-derived Antibody Library
Creative Biolabs has built up HAIL (Human Antibody Immune Library) technology to develop full human monoclonal antibodies. In this technology, instead of immunizing humans (which is ethically impossible), strong immune responses and high affinity antibodies are generated by immunizing humanized mice. After that, a phage display human antibody library is constructed to select high affinity antibodies against the immunogens. The resultant antibodies are fully human that experience affinity maturation in vivo.

This unique technology combines our "humanized" transgenic mice (FHAT mice) with our unparalleled expertise in phage display human antibody library technology.

Being one of the most important means for generating full human antibodies, hybridoma generation using humanized transgenic mice has become an extremely powerful tool for antibody drug discovery. However, in comparison with hybridoma technology, phage display antibody library technology offers great advantages. Hybridoma based monoclonal antibody technology can only generate a small number of binders against a particular immunogenat a time; whereas phage display technology can present the entire antibody repertoire (e.g. 109) of an immunized animal, in which almost 10% of the antibodies are immunogen(s)-specific. With such a huge pool of potential binders, the chance is much better to use phage display technology to discover antibodies of the desired properties. In addition, using hybridoma technology, it is hard to incorporate an enriching step that can selectively isolate antibodies of desired functionality. In most cases, all the hybridoma clones are produced first and then validated one by one. In contrast, phage display technology allows various enriching strategies: antibodies of desired properties can be enriched thus those without the desired functionality can be excluded from further validation. For example, antibody library screening can be done using the target to capture strong binders while using the controls to block/deplete cross-reactive binders.

An immunized phage display human library can be constructed directly from the humanized mice that producing human antibodies. After immunization of a humanized transgenic mouse with specific target immunogen(s), mRNA and cDNA derived from PBMC, splenocytes or bone marrow cells are collected. Next, the cDNA (i.e. genes) of the human antibody repertories can be PCR amplified and cloned into our proprietary phage display vectors. Followed by several steps of iterative panning, human antibodies with high specificity and affinity can are produced. Of note, one unified antibody library is sufficient for multiple immunogen(s) even if multiple humanized mice are employed.

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