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.
|
|