Antibody Humanization & Maturation

Humanized antibodies are antibodies from non-human species whose amino acid sequences have been modified to increase their similarity to antibodies naturally produced in human.

The first generation of humanization refers to the creation of a mouse-human antibody chimera, in which the entire F_v domains of both heavy chain and light chain of a mouse antibody are grafted into a human antibody. Such a strategy of humanization is incomplete – because the majority of amino acid sequences in the F_v domain does not participate in the antibody-antigen interaction, these sequences, if carried over from mouse or other species, may still trigger a strong immune response in human.

The second generation of humanization refers to the grafting of the complementarity-determining regions (CDRs) within the F_v domain of a mouse antibody to a human antibody, which are responsible for the ability of the antibody to bind to its antigen. Such a strategy of humanization offers greatly improved safety. Nevertheless, the xenogenic grafting of mouse CDRs to human framework alters the overall 3D structure of the F_v domain, causing the humanized antibodies to either structurally collapse or significantly lose their binding affinities.

BiCell Scientific’s antibody humanization & maturation service utilizes a greater diversity of human antibody framework sequences that are from both human genome (germline) and single B cell RNA-seq database. BiCell Scientific Inc selects the framework sequences that resemble the original antibody’s structure using an inverse protein folding algorithm. BiCell Scientific Inc develops a unique and proprietary yeast display platform to incorporate the framework sequence variations and experimentally screen for the best human framework that is able to seamlessly fuse with the grafted CDRs from mouse or other species. BiCell Scientific Inc guarantees no loss of binding affinity or thermo stability in our humanized antibody.