Biological coupling technology Chemical based specific in situ antibody modification
The natural structure of monoclonal antibodies provides a variety of possibilities for biological coupling. Chemical and specific natural (non engineering) antibody coupling has some advantages. It can avoid the complexity of antibody specific site mutation and the possible challenges in the amplification and optimization of cell culture.
Coupling sites according to the antibody sequence, the connection sites between disulfide bonds of endogenous amino acids such as lysine, histidine, tyrosine and cysteine are very attractive. All FDA approved ADCs use these endogenous amino acids for coupling until 2021. However, antibody scaffolds also contain glycans, which is caused by post-translational modification of Fc region during monoclonal antibody production. Some studies have reported new strategies for sugar engineering, which seems to be an interesting alternative to biological coupling.