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Currently, there are about 100 types of antibody drugs approved in Japan, and there are many products under development. These are produced by cell culture methods and depend on the endogenous glycosylation mechanism of the cells, so they are produced as glycoproteins with heterogeneous glycan. The Fc region of the antibody has N-glycans, and it has been found that these glycans play an important role in antibody-dependent cellular cytotoxicity (ADCC activity), complement-dependent cytotoxicity (CDC activity), protein metabolism, anaphylactic shock, and other pharmacological effects. Therefore, in the quality evaluation of antibody drugs, it is necessary to confirm the ratio of core fucose, the proportion of nonreducing terminal galactose, and the presence of nonhuman type glycosylation such as Galα1-3Gal and NeuGc. In order to investigate the function of specific glycan that exists in a heterogeneous manner, it is necessary to prepare antibodies with homogeneous glycan, and approaches such as total synthetic methods by chemical synthesis, chemoenzymatic methods, and cell engineering methods by controlling the biosynthetic pathway have been attempted. In the total synthetic method, it is very difficult to produce antibodies that maintain the activity of antibodies with large molecular weight. Cell engineering requires control of all glycan-related proteins involved in the endogenous glycosylation mechanism, and it is difficult to prepare antibodies with only arbitrary glycan. The chemoenzymatic method is a glycoengineering technique in which the heterogeneous glycans on antibodies are cleaved with an enzyme (endo-β-N-acetylglucosaminidase, ENGase), and then the chemically prepared glycans are incorporated into the antibodies using an enzyme (glycosynthase) [1]. Therefore, the chemoenzymatic method is widely applied to prepare antibodies with homogeneous glycan. This technology has enabled the preparation of antibodies with various types of homogeneous glycan, and important glycan functions such as ADCC activity and CDC activity have been elucidated.

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Homogenization Technology of Antibody Glycans and ADCC Activity

  • 章节

  • 发表日期：

    2026年

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  • Masaki Kurogochi

摘要

Currently, there are about 100 types of antibody drugs approved in Japan, and there are many products under development. These are produced by cell culture methods and depend on the endogenous glycosylation mechanism of the cells, so they are produced as glycoproteins with heterogeneous glycan. The Fc region of the antibody has N-glycans, and it has been found that these glycans play an important role in antibody-dependent cellular cytotoxicity (ADCC activity), complement-dependent cytotoxicity (CDC activity), protein metabolism, anaphylactic shock, and other pharmacological effects. Therefore, in the quality evaluation of antibody drugs, it is necessary to confirm the ratio of core fucose, the proportion of nonreducing terminal galactose, and the presence of nonhuman type glycosylation such as Galα1-3Gal and NeuGc. In order to investigate the function of specific glycan that exists in a heterogeneous manner, it is necessary to prepare antibodies with homogeneous glycan, and approaches such as total synthetic methods by chemical synthesis, chemoenzymatic methods, and cell engineering methods by controlling the biosynthetic pathway have been attempted. In the total synthetic method, it is very difficult to produce antibodies that maintain the activity of antibodies with large molecular weight. Cell engineering requires control of all glycan-related proteins involved in the endogenous glycosylation mechanism, and it is difficult to prepare antibodies with only arbitrary glycan. The chemoenzymatic method is a glycoengineering technique in which the heterogeneous glycans on antibodies are cleaved with an enzyme (endo-β-N-acetylglucosaminidase, ENGase), and then the chemically prepared glycans are incorporated into the antibodies using an enzyme (glycosynthase) [1]. Therefore, the chemoenzymatic method is widely applied to prepare antibodies with homogeneous glycan. This technology has enabled the preparation of antibodies with various types of homogeneous glycan, and important glycan functions such as ADCC activity and CDC activity have been elucidated.