Abstract 2958: A cancer-specific monoclonal antibody against podocalyxin developed by CasMab technology inhibited the tumor growth by antibody-dependent cellular cytotoxicity

Abstract

Abstract Background: Podocalyxin (PODXL) is a CD34-related sialomucin and a well-known marker of embryonic stem cells. PODXL is expressed in many cancers including brain tumors, breast cancers, and colorectal cancers. Overexpression of PODXL is an independent predictor of progression, metastasis, and poor outcome. In contrast, PODXL is highly expressed in normal cells such as vascular endothelial cells (VECs) or renal podocytes. Although many monoclonal antibodies (mAbs) against PODXL have been established, they bind to both cancer and normal cells. We recently established CasMab technology for developing cancer-specific mAbs, which could target only cancer cells, although those membranous proteins are highly expressed in both cancer and normal cells. Methods: We immunized mice with human PODXL, which was overexpressed in a glioblastoma cell line. Cancer-specific mAbs were screened using flow cytometry against PODXL-expressing cancer and normal cells. The cancer specificity was confirmed using immunohistochemistry against breast cancer tissues. A mouse-human chimeric anti-PODXL mAb was produced and antibody-dependent cellular cytotoxicity (ADCC) was investigated in vitro. The in vivo efficacy of anti-PODXL mAbs was evaluated using xenograft models of PODXL-expressing cell lines. Results: One clone of anti-PODXL mAbs, which was established by CasMab technology, reacted with PODXL-expressing many cancer cell lines including breast cancers, brain tumors, and malignant mesotheliomas, whereas it did not bind to VECs in flow cytometry. The anti-PODXL mAb reacted only with PODXL-expressing cancer cells, not with VECs in breast cancer tissues in immunohistochemistry. Furthermore, the anti-PODXL mAb possesses ADCC activity in vitro and anti-tumor effect in vivo. Conclusion: The anti-PODXL mAb established by CasMab technology could be useful for targeting PODXL in cancer, although PODXL is highly expressed in many normal cells. Citation Format: Yukinari Kato, Satoshi Ogasawara, Akiko Kunita, Yuki Fujii, Mika K. Kaneko. A cancer-specific monoclonal antibody against podocalyxin developed by CasMab technology inhibited the tumor growth by antibody-dependent cellular cytotoxicity. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2958.