Abstract 1676: An agonistic antibody to EphA2 exhibits anti-tumor effect to human melanoma

EphA2 is a member of the Eph family of receptor tyrosine kinases and is highly expressed in aggressive human cancers, including melanoma. Recently, EphA2 has been found to be integral player in cancer formation and expected as a target for antibody therapy. In this study, we have investigated the therapeutic effect of various anti-EphA2 mAbs that were recently established in our laboratory. Cell surface expression of EphA2 on melanoma cell lines was analyzed by flow cytometry and therapeutic effects of anti-EphA2 mAbs were investigated using cell proliferation, cell migration, invasion and antibody-mediated drug cytotoxicity assays. We found that human melanoma cell lines expressed EphA2 on their surface, while normal dermal fibroblasts and melanocytes were negative for EphA2. Recombinant human protein of EphrinA1 (a natural ligand for EphA2) and anti-EphA2 mAbs could not suppress melanoma cell proliferation, however, one of agonistic anti-EphA2 mAb, termed SHM16, inhibited metastatic potential such as migration and invasive properties of human melanoma. In contrast, an antagonistic anti-EphA2 mAb, SHM17, had no effect on migration and invasive assay. In addition, drastic growth inhibition and cell cytotoxicity were found in targeted delivery of immunotoxin by SHM16. In conclusion, these findings indicate a promising role for EphA2 as a target for antibody treatment in melanoma and enhance the therapeutic effect as an agonistic antibody to EphA2. Citation Format: Kazunori Kato, Atsushi Sakamoto, Taro Kojima, Toshio Hasegawa, Shigaku Ikeda. An agonistic antibody to EphA2 exhibits anti-tumor effect to human melanoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1676. doi:10.1158/1538-7445.AM2015-1676