Introduction to Antibody Humanization-Special topic on antibody modification and modification-Tekbiotech-Yeast Display Service,Phage display technology

Introduction to Antibody Humanization

一．What is Antibody Humanization?

Humanized antibodies mainly refer to antibodies that are re-expressed by mouse monoclonal antibodies through gene cloning and DNA recombination technology. Most of their amino acid sequences are replaced by human sequences, which basically retains the affinity and specificity of the parent mouse monoclonal antibody and reduces its heterology, which is conducive to the application of antibodies in humans.

Humanized antibodies refer to the constant region of antibodies (i.e., CH and CL regions) or all antibodies encoded by human antibody genes. Humanized antibodies can greatly reduce the immune side effects caused by heterologous antibodies to the human body. Humanized antibodies include chimeric antibodies, modified antibodies, and fully humanized antibodies.

二．Principles of Antibody Humanization

1. Chimeric Antibodies: Chimeric antibodies use DNA recombination technology to insert the light and heavy chain variable region genes of heterologous monoclonal antibodies into expression vectors containing human antibody constant regions, and transform mammalian cells to express chimeric antibodies. In this way, the V regions of the light and heavy chains in the expressed antibody molecules are heterologous, while the C regions are human, so that nearly 2/3 of the entire antibody molecule is human. The antibodies produced in this way reduce the immunogenicity of heterologous antibodies while retaining the ability of the parent antibody to specifically bind to antigens.

2. Modified Antibodies: Modified antibodies are also called CDR grafted antibodies. The CDR of the antibody variable region is the region where the antibody recognizes and binds to antigens, which directly determines the specificity of the antibody. The CDR of the mouse monoclonal antibody is transplanted into the variable region of the human antibody to replace the human antibody CDR, so that the human antibody obtains the antigen binding specificity of the mouse monoclonal antibody and reduces its heterology.

3. Surface Remodeling Antibodies: Surface remodeling antibodies refer to humanization of the amino acid residues on the surface of heterologous antibodies. The principle of this method is to replace only the regions that are significantly different from the SAR of human antibodies, and to select amino acids similar to the surface residues of human antibodies for replacement while maintaining the antibody activity and reducing heterology; in addition, the replaced segments should not be too many, and residues that affect the size, charge, hydrophobicity of the side chain, or that may form hydrogen bonds and thus affect the conformation of the antibody complementary determining region (CDR) should not be replaced as much as possible.

4. Fully Humanized Antibodies: Fully humanized antibodies refer to the transfer of all human antibody-encoding genes to genetically engineered antibody gene-deficient animals through transgenic or transchromosomal technology, so that the animals express human antibodies and achieve the purpose of fully humanizing antibodies.

三．Application of Humanized Antibodies:

1. In tumor treatment: Monoclonal antibody tumor drugs can effectively reduce the adverse reactions of traditional tumor drug treatment. The development of these humanized monoclonal antibodies is mainly aimed at target molecules related to tumor occurrence and development. Some humanized monoclonal antibodies also work by carrying anticancer drugs such as toxins, cytotoxic drugs, radionuclides, enzymes, chemotherapy drugs and other molecules. In this way, the "biological missile" is coupled to achieve the effect of specifically killing cancer cells.

2. Application in organ transplantation: The use of antibody drugs as induction therapy for solid organ transplantation is gradually increasing.

3. Application in autoimmune diseases: In the treatment of autoimmune diseases, monoclonal antibody drugs inhibit excessive immunopathological reactions by removing activated cells, blocking their functions, or reducing elevated pro-inflammatory cytokine levels to normal levels.

Tek Biotech has mature antibody humanization technology, which can humanize antibody sequences and ensure that the affinity of the modified humanized antibodies remains at the same order of magnitude. We provide guaranteed humanization services to facilitate your experiments. We are committed to building a complete one-stop technical service platform, which can provide a series of services from bioinformatics analysis, humanized antibody design, antibody expression and purification, to affinity determination, antibody affinity maturation, etc. to meet the needs of different customers.

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