Abstract 949: An ER-α36 monoclonal antibody exhibits anticancer activity in triple-negative breast cancer cells

Abstract

Abstract ER-α36 is a novel variant of ER-α, plays an important role in mitogenic estrogen signaling and tamoxifen resistance in both ER-positive and -negative breast cancer. ER-α36 is highly expressed on the plasma membrane of both ER-positive and -negative breast cancer stem/progenitor cells and critical for maintenance of the breast cancer stem/progenitor cells, which make it a promising target for antibody-based breast cancer treatment. In this study, we have screened and identified a candidate of therapeutic antibody named 3C11 that specifically recognizes ER-α36 at its unique C-terminal residues. The antibody 3C11 showed pM affinity to ER-α36 in the BiaCore assay and potent growth inhibitory activity in multiple breast cancer cell lines in vitro. In addition, 3C11 also showed dose-dependent inhibition of tumor growth in a xenograft model formed by a triple-negative breast cancer cell line SUM159 that was generated from a refractory breast cancer. Furthermore, we found that 3C11 was quickly and efficiently internalized into cells, which makes it a potential candidate for development of the antibody-drug conjugate approaches. These results demonstrated that ER-α36 is promising cancer target for development of antibody-based therapeutic approaches. Citation Format: Qingcong Lin, Junma Zhou, Jing Wang, Zonghui Wang, Jun Wang, Feng Chen, Xueming Qian, Xiao Shang, Jun Bao, Zhaoyi Wang, Kun Meng. An ER-α36 monoclonal antibody exhibits anticancer activity in triple-negative breast cancer cells. [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 949. doi:10.1158/1538-7445.AM2015-949