Authors: Xiuling Li, Christopher G. Nelson, Rajesh R. Nair, Lori Hazlehurst, Tina Moroni, Pablo Martinez-Acedo, Alex R. Nanna, David Hymel, Terrence R. Burke, Christoph Rader
Summary:
Selenomabs are engineered monoclonal antibodies with one or more translationally incorporated selenocysteine residues. The unique reactivity of the selenol group of selenocysteine permits site-specific conjugation of drugs. Compared with other natural and unnatural amino acid and carbohydrate residues that have been used for the generation of site-specific antibody-drug conjugates, selenocysteine is particularly reactive, permitting fast, single-step, and efficient reactions under near physiological conditions. Using a tailored conjugation chemistry, we generated highly stable selenomab-drug conjugates and demonstrated their potency and selectivity in vitro and in vivo. These site-specific antibody-drug conjugates built on a selenocysteine interface revealed broad therapeutic utility in liquid and solid malignancy models.
Source:
Cell Chemical Biology; 2017