HER2-SPECIFIC MONOCLONAL ANTIBODIES AND CONJUGATES THEREOF

摘要

Disclosed herein is the identification of Her2-specific monoclonal antibody m860. The m860 antibody was identified from a human naive phage display Fab library by panning against the extracellular domain of human Her2. M860 binds to cell surface-associated Her2 with an affinity comparable to that of trastuzumab (Herceptin®), but binds to a different epitope. Using site-specific glycan engineering, m860 was conjugated to the small molecule drug auristatin F. The antibody-drug conjugate was stable, bound cell-surface expressed Her2 and exhibited potent cell killing of Her2-positive cancer cells, including trastuzumab-resistant breast cancer cells.