Abstract 4583: A blocking antibody to HB-EGF inhibits the growth of tumor xenograft

Abstract

Abstract Heparin-binding epidermal growth factor (HB-EGF), a member of the EGF family of growth factors, is widely expressed in many human cancers compared with normal tissues. HB-EGF is initially produced as a membrane-anchored form (pro-HB-EGF) and later processed to a soluble form (s-HB-EGF), which exert its biological activity through activation of EGFR and EGFR4. A key role of HB-EGF in the acquisition of malignant phenotypes has been well documented, such as tumorigenicity, invasion, metastasis, angiogenesis, and resistance to chemotherapy. In this study, we demonstrate the potential of an anti-HB-EGF mAb for cancer therapy by generating a potent blocking monoclonal antibody, HC-15. The HC-15 mAb recognized both forms of HB-EGF, pro- and s-HB-EGF. HC-15 efficiently blocked the binding of HB-EGF to EGFR-Fc in the ELISA. Furthermore, HC-15 substantially inhibited the HB-EGF-dependent proliferation of the EGFR expressing Ba/F3 transfectant lines. To investigate the potential of HC-15 for cancer therapy, the in vivo antitumor activity of HC-15 was tested. Significant growth inhibition by treatment of HC-15 (10mg/kg once a week) was observed in established human tumor models, such as ovarian cancer (MCAS), pancreatic cancer (BXPC-3), and breast cancer (MDA-MB-231) in athymic nude mice. Thus, we conclude that the anti-HB-EGF mAb HC-15 has strong anti-tumor activity in various models, supporting the inhibition of HB-EGF functions by mAb is useful in cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4583. doi:10.1158/1538-7445.AM2011-4583