ABSTRACT
The non-specific conjugation would result in more off-target side effects, leading to relatively low maximum tolerated dose. In contrast to the conventional conjugations through lysines or cysteines, which are abundant in an antibody, the site-specific conjugations couple the antibodies with cytotoxins through the unique and defined sites based on antibody engineering. There are four major categories of methods based on the conjugation sites in the antibody molecules: specific amino acids, unnatural amino acids, short peptide tags, or glycans. These approaches generated homogeneous antibody-drug conjugates with a high therapeutic index compared to the conventional conjugations. S. A. Kazane et al. developed a site-specific DNA-antibody conjugation method for specific and sensitive immuno-polymerase chain reaction used as diagnosis and imaging. The site-specific conjugation approaches have also been applied to other small-molecular-weight proteins or compounds in addition to cytotoxins or radioisotopes. The site-specific antibody conjugations are likely to be applied to different therapeutic areas for preparing homogeneous immunoconjugates.
