Antibody humanization transformation method

Abstract

The invention discloses an antibody humanization transformation method. The antibody humanization transformation method comprises the following steps: analyzing an antibody gene sequence; starting antibody Fab isogeny modeling and optimization; ascertaining humanization mutation locus by epitope scanning, simulating virtual mutation molecular dynamics, and confirming key amino acid; the antibody humanization transformation method designs reasonable humanization antibody through the analysis, and further uses the epitope to scan and authenticate antibody humanization degree; and finally authenticates the appetency of the humanization antibody in a biological experiment. The antibody humanization transformation method has the advantages that the antibody humanization transformation method can be used for humanization transformation of mouse sources or source antibodies of other animals, only needs to provide the gene sequence of the antibody Fab, and is not dependent on information of antigen epitope. The humanization antibody designed by the antibody humanization transformation method has higher appetency maintenance, higher humanization degree, is capable of solving a contradiction between antibody appetency and humanization degree to a maximum degree.

Description

technical field [0001] The invention belongs to the fields of immunology, molecular biology and bioinformatics, and in particular relates to an antibody humanization transformation method. [0002] Background technique [0003] Monoclonal antibody drugs have the advantages of strong specificity, small side effects, and significant curative effect, and have become important tools for fighting tumors, infectious diseases, autoimmune diseases and other patients. At present, cell fusion and hybridoma technology are still the most reliable methods for preparing monoclonal antibodies. Animals commonly used for immunization include mice, rats, sheep, rabbits and other animals, and the most commonly used ones are mice including rats and mice. The monoclonal antibody obtained by this method is of animal origin, and the development of animal-derived monoclonal antibody as an antibody drug for use in the human body must be humanized to reduce the human-anti-animal antibody response c...

AI Technical Summary

Problems solved by technology

Studies have proved that among all the amino acids in the FRs region, the humanized substitution of most amino acids has only a slight impact on the conformation of the CDRs region, and will not seriously affect the antibody affinity product, but there are also a few key amino acids, Once these key amino acids are replaced by the corresponding amino acids of adults, it will cause a great change in the conformation of the CDRs region, which will cause a serious drop in antibody affinity. The existing traditional humanization methods are unable to dynamically grasp these key amino acids. It will make it in the humanization experiment often lead to the decrease or disappearance of the antibody affinity after humanization transformation

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