Antibody Humanization

2020-07-08 Hits(1276)

Non-human antibodies enter into the human body will cause serious rejection of the body, which in turn affects the safety and therapeutic effect of the antibody in clinical application. Therefore, it is necessary to humanize the antibody, reducing the heterogeneity of the antibody and keeping its specificity and affinity unchanged. Antibody humanization is used for reducing the immunogenicity of animal monoclonal antibodies and for improving their activities in the human immune system. It is a very important step in therapeutic antibody discovery process.

 

1. Introduction to antibody humanization

Antibody humanization usually requires genetic engineering methods. According to the degree of antibody sequence changes, there are three antibody humanization strategies based on phage display technology , that can preserve the specificity and affinity of the antibody toward the antigen whereas significantly or completely eliminate the immunogenicity of the antibody in humans.

Chimeric Antibodies: Creation of chimeric antibodies (non-human variable regions with human constant regions) can partially alleviate immunogenic response. Transfected to mammalian cells for recombinant antibody expression using DNA recombination technology.

Fig. 1. Chimeric antibodies

CDR-Grafting Antibodies: This process involves transferring the antibody CDRs into a proper human antibody framework, while retaining its original affinity and specificity. Such as grafting of the murine CDRs into human frameworks.

Fig. 2. CDR grafting antibodies

Fully Humanized Antibodies: Using gene editing technology, the antibody gene in animal somatic cells were replaced by human, and the humanized antibodies was produced directly after animal immunization.

 

2. Characteristics for Nanobodies

 

With the development of antibody technology, the number of new antibody drugs entering the clinic has shown a significant increase. In 2015, more than 110 antibody drugs were approved. In the field of autoimmune diseases, monoclonal antibody drugs have clinical advantages such as strong specificity and small adverse reactions compared with small molecule drugs. Most antibody drugs are humanized antibodies and fully humanized antibodies. In recent years, the application of fully human antibodies has become more and more widespread, especially in the field of anti-tumor immune antibody drugs. Fully humanized antibody technology is commonly used phage antibody library technology and transgenic mouse technology. The first method is "phage display" technology, screening in a large-scale antibody library; the second method is a mouse immunization platform, allowing mice to express human antibody variable segments, diverse segments and connections VDJ antibody sequences, and immunize them. About 70% of the fully human antibodies that have been marketed are obtained from transgenic mice.

With many years of research and development, human antibody discovery technology and genetic engineering technology have reached maturity, with a variety of high-yield platforms available. A variety of fully humanized monoclonal antibodies that have been approved can be applied to the treatment of various diseases and inject new vitality into drug development. There are various high-yield platforms available for people. As the continuous advancement of technology, we will see more new monoclonal antibodies coming out in the future.

 

KMD Bioscience have developed three antibody humanization strategies based on our phage display technology and we can preserve the specificity and affinity of the antibody toward the antigen whereas significantly or completely eliminate the immunogenicity of the antibody in humans.

 

CDR-Grafting Antibodies: This process involves transferring the antibody CDRs into a proper human antibody framework, while retaining its original affinity and specificity. Such as grafting of the murine CDRs into human frameworks.

Chimeric Antibodies: Creation of chimeric antibodies (non-human variable regions with human constant regions) can partially alleviate immunogenic response. Transfected to mammalian cells for recombinant antibody expression using DNA recombination technology.

Fully Humanized Antibodies: Using gene editing technology, the antibody gene in animal somatic cells were replaced by human, and the humanized antibodies was produced directly after animal immunization.