Antibody engineering refers to the engineering of transforming and reassembling antibody genes by recombinant DNA and protein engineering techniques, and transfecting appropriate recipient cells to express antibody molecules. It can also engineer antibody molecules by cell fusion, chemical modification, and other methods used to reduce the immunogenicity of drugs. With more than ten years of continuous knowledge expansion and experience accumulation, Creative Biolabs provides you with the latest antibody engineering tools and technical services with confidence to reduce the immune response of drugs in the body, thereby improving the efficacy of the drug.
The engineering form of antibody drugs is designed to minimize their immunogenicity. The methods include humanization and selection of fully human antibodies. The strategy of antibody engineering and process development was used to optimize the amino acid sequence of the molecule and its behavior under process conditions. It is worth noting that even fully human antibody therapy can be immunogenic due to the inherent sequence variability of antibody in the variable domain, so it can induce a significant immune response.
Fig.1 Schematic overview of antibody humanization from murine antibodies (red domains) to fully human antibodies (blue domains). (Santos, 2018)
At present, some studies have shown that CD4+ T cell epitopes only exist in the inclusion region of complementarity-determining residue (CDR) sequence, but not in framework regions (FRs). It can be concluded that in humanized antibodies and fully human antibodies:
I) CDRs are the only segments that may contain CD4+ T cell epitopes
II) Most CDRs are not immunogenic
III) Immunogenic CDRs can be de-immunized by site-specific engineering while maintaining complete biological function
Therefore, we propose a strategy based on antibody engineering to eliminate immunogenicity: reduce the immunogenicity potential by binding up to two amino acid substitutes in one epitope, while maintaining the natural binding characteristics.
This method has been successfully applied to the modification of mouse immunogenic antibody. Through a site-directed mutation of the immunogenic epitope gene of the variable region, it becomes a parent motif. In addition, the R3 region of the epidermal growth factor (EGF) receptor was blocked and 6 amino acids in the amphiphilic sequence were replaced by the expected residues of the homologous human sequence. This method has universal applicability and successfully reduces the immune response of non-human antibodies.
Creative Biolabs owns professional antibody sequencing and antibody engineering technology platforms to remove immunogenicity. If you are interested in antibody engineering, please contact us and we will provide you with technical service and support as soon as possible.
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