Tag‐Free Enzymatic Modification for Antibody−Drug Conjugate Production

Abstract Currently, although >10 antibody−drug conjugates (ADCs) are available in the market, most of them (10 ADCs) have broad drug distribution, thereby potentially limiting their therapeutic index. The ADC industry is shifting from random conjugation technology to site‐specific conjugation technology to overcome this issue. Enzymatic site‐specific conjugation is a promising cutting‐edge technology owing to its mild conjugation conditions. This review discussed enzymatic conjugation strategies for producing ADCs via modifying native antibodies without using a tag moiety. We described the comparison of the three main conjugation technologies used to produce site‐specific ADCs. Each of the three enzymatic approaches described in this review differs in their advantages and disadvantages, providing pharmaceutical companies the option to select an approach suitable to their purpose and/or target protein.