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Humanization by Sequential Guided Selection

Guided selection provides a powerful tool for humanization of the preexisting animal-derived antibodies. Equipped with world-leading technology platforms and professional scientific staffs in phage display, Creative Biolabs has developed an advanced Phage Display Platform to provide a full range of innovative integrated services that are based on phage display technology. Based on this advanced platform, our scientists have developed a sequential guided selection method for the humanization of non-human antibodies. We are pleased to meet every unique requirement and provide the most suitable solution for our client’s satisfaction.

The Background of Guided Selection

Rodent monoclonal antibodies (mAbs) have limitations as therapeutic agents due to their immunogenicity and insufficient activation of human effector functions. This has driven diverse humanization approaches including initial chimeric antibody approach, humanization by CDR grafting, humanization by resurfacing, and deimmunization by the removal of the T-cell epitope. However, the resulting humanized antibodies still have potential to provoke an immune response in humans. As an alternative humanization method, guided selection has been successfully used since 1994. Its value was proved by HUMIRA, the world’s first human therapeutic antibody approved. The method is based on chain shuffling of V-genes by using phage display technology and enables conversion of the murine antibody into completely human antibody with similar binding characteristics. Mouse VH and VL domains are used as epitope template to guide the selection of a human antibody-partner and are replaced sequentially or in parallel with human VH and VL domains, respectively. The resulting human antibodies, therefore, bind to epitopes that are at least overlapping with that of original mouse mAb. Thus, guided selection provides a powerful tool for humanization of the preexisting nonhuman antibodies of which biological activities are demonstrated.

Humanization by Sequential Guided Selection in Creative Biolabs

Creative Biolabs has developed a sequential guided selection procedure to derive completely human antibody. Mouse VL and VH domains are replaced sequentially with human VL and VH, respectively. The humanization procedure of a Fab format is as follows. 1) to clone the variable regions of a mouse antibody to a phagemid vector containing human constant domains; 2) to construct a human VL shuffled library by replacing the mouse VL with human VL repertoires; 3) to select binders after panning against a target antigen; 4) to construct a human VH shuffled library by replacing the mouse VH. 5) To select fully-human Fab clones after panning. Based on sequential guided selection, we have successfully selected a series of human antibodies with similar characteristics to the original non-human antibody.

Key Features and Advantages Including but Not Limited to:


Creative Biolabs has more than ten years’ experience in antibody engineering for therapeutic and diagnostic development. We can offer our clients high-quality service of humanization of non-human antibodies by sequential guided selection at the most competitive price.

Please contact us for more information and a detailed quote.

Reference

  1. Kim, S.J.; Hong, H.J. Humanization by guided selections. Methods Mol Biol. 2012, 907:247-57.

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