ERBB2 and cancer: Trastuzumab is a well-established therapeutic specific to human epidermal growth factor receptor 2 (HER2), overexpressed in ~15% of breast cancers, and is the first-line treatment to these cancers.45 Considering the limitations of existing protein language models trained solely on antibody repertoire data (hereafter antibody language models, or AbLMs) for FW mutagenesis, we opted instead for a structure-based approach to predict stabilizing FW mutations, and verified the stability, antigen binding and downstream functional effects of these mutants using in vitro assays.