Analysis of Monoclonal Antibodies with Carboxypeptidase B

The heavy chain of human IgG contains a C-terminal lysine residue which is typically cleaved off by carboxypeptidase in vivo. For decades, it was believed that the C-terminal clipping of lysine residues did not affect antibody structure and function, and was therefore not considered a critical quality attribute (CQA). However, the significance of C-terminal lysine clipping is just now being recognized, with a recent study demonstrating that antibodies that retain the C-terminal lysine are attenuated for complement-dependent cytotoxicity. Thus, assessing C-terminal lysine variants is required in monoclonal antibody (mAb) process development.