Abstract

Design and Generation of Site-Specific ADCs

Dimiter Dimitrov, Senior Investigator, National Institutes of Health

Currently antibody-drug conjugates (ADCs) enjoy unprecedented success and two of them (Kadcyla and Adcetris) have been approved for clinical use. I will overview the current state of the ADC field and will discuss in more details site-specific conjugation which has certain advantages compared to random conjugation. During the last several years a number of methods have been developed for site-specific conjugation. These methods will be reviewed including engineering sites for conjugations, using naturally occurring sites for conjugation and enzymatic vs chemical methods for generation of site-specific ADCs. Conjugation of antibodies with small molecules through carbohydrates will be discussed in more details and latest results presented including generation of ADCs against cancer-related targets. Advantages of using antibody glycans for conjugation include: naturally occurring site-specific, no effect on antigen binding and thermal stability, and possibility for conjugation of multiple small molecules at one site.