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Antibodies have been used for hundreds of years for the prevention, diagnosis, and treatment of diseases. Antibody drug research includes the development of mouse antibodies, chimeric antibodies, humanized antibodies, and fully human antibodies. Antibody drugs are exogenous proteins, which make it easy to activate the body's own immune response and induce the generation of drug-resistant antibodies. This can seriously affect the safety and effectiveness of antibody drugs. Therefore, it is very important to detect the immunogenicity of antibody drugs during drug development. Studies have shown that increasing the degree of antibody humanization can reduce its immunogenicity.
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The humanization of antibodies should follow two basic principles: to maintain or improve the affinity and specificity of antibodies and to greatly reduce or basically eliminate the immunogenicity of antibodies. Antibody humanization consists of three stages: human-mouse chimeric antibody, humanized antibody, and fully human antibody. According to different principles of action, humanized antibodies can be divided into four categories: human-mouse chimeric antibodies, CDR grafting antibodies, resurfacing antibodies, and fully human antibodies.
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| 1. Human-mouse Chimeric Antibody |
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2. CDR Grafting Antibody |
| The human-mouse chimeric antibody is the earliest humanized antibody. The variable region of the antibody is from the murine McAb, while the constant region is from the human antibody. Such antibodies not only retain the specificity and affinity of the original McAb, but also greatly reduce the immunogenicity in the human body. |
The CDR region can recognize and bind antigens,
which directly determines the specificity of the antibodies. The CDR of the mouse monoclonal antibody is grafted into the variable region of the human antibody to replace the human antibody’s CDR. Then, the human antibody can obtain the antigen-binding specificity of the mouse monoclonal antibody, and the heterology of mouse monoclonal antibodies is reduced as much as possible. |
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| 3. Resurfacing Antibody |
4. Fully Human Antibody |
| The resurfacing antibody humanizes amino acid residues on the surface of a heterologous antibody. The principle of this method is to replace only the region significantly different from human antibody SAR and select amino acids similar to human antibody surface residues in order to maintain antibody activity and reduce heterology. |
Fully human antibodies refer to the transfer of human antibody genes to genetically engineered animals with antibody gene deletion by transgenic or chromosomal technology. This is done so that the animals can express human antibodies and achieve the goal of full antibody humanization. Currently, several methods have been established to produce fully human antibodies, including phage display technology, transgenic mouse technology, ribosome display technology, and RNA-polypeptide technology. |
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Early "chimeric antibodies" contain the variable domain of mouse antibodies and the constant domain of human antibodies. However, the immunogenicity of these chimeric antibodies is still not low enough; humanized antibodies have lower immunogenicity than chimeric antibodies. The advent of humanization allowed the immunogenicity of mouse antibodies to be controlled by limiting the sequence in the complementary determinants of the variable region. Humanized antibodies are becoming more common as time passes. As of November 2019, the FDA has approved a total of 30 fully human antibody drugs, including 21 from transgenic mice and 9 from phage display technology. This may reflect the future development trend of monoclonal antibody drugs.
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In need of antibody humanization services for your research?
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| Synbio Technologies provides the following services (+ more!): |
| ● Chimeric antibody construction |
| ● Antigen-antibody binding analysis |
| ● Antibody model library construction |
| ● Phage/Yeast display antibody library construction |
| ● High-throughput antibody screening |
| ● Humanized antibody characterization and production |
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