Therapeutics: Epidermal growth factor receptor 2 (HER2; EGFR2; ErbB2; neu)

Cell culture and mouse studies suggest a bivalent antibody targeting two HER2 epitopes could help treat metastatic and HER2 inhibitor-resistant breast cancers. The bivalent antibody consisted of two single-chain variable fragments (scFv) from Herceptin trastuzumab fused to the heavy chains of a human anti-HER2 mAb, and targeted both the ligand-dependent and -independent binding domains of HER2. In multiple human breast cancer cell lines, the bivalent antibody decreased growth compared with control antibody or vehicle. In multiple xenograft mouse models of metastatic breast cancer, the bivalent antibody decreased tumor growth compared with Kadcyla trastuzumab emtansine. In a xenograft mouse model of Kadcyla-resistant breast cancer, the bivalent antibody decreased tumor growth compared with a control antibody. Next steps could include testing the bivalent antibody in other HER2 inhibitor-resistant cancers.

Roche, its Genentech Inc. unit and Chugai Pharmaceutical Co. Ltd. market Herceptin to treat breast and gastric cancers. ...