Scripps researchers design new ADCs

Researchers from The Scripps Research Institute have designed antibodies based on engineered selenocysteine residues that they say can be used to produce highly stable, potent, and selective antibody-drug conjugates. In a paper published in Cell Chemical Biology, the researchers showed ADCs made with the engineered antibodies were effective in mouse models of breast cancer and multiple myeloma.

The paper's authors sought to avoid an extra step required when conjugating drugs to antibodies with engineered reactive cysteine residues. These antibodies, known as thiomabs, can be used to create homogeneous ADCs with higher therapeutic indexes than heterogeneous ADCs, but thiomabs require the reformation of disulfide bridges to link to small molecules. Becasue selenocysteine is more nucleophilic than cysteine, the authors were able to simplify the process of conjugation by using antibodies with selenocysteine residues...