Abstract B205: EphA10 targeted antibody therapy is a potential as a novel option for management of breast cancers including triple negative breast cancer

Abstract

Abstract Introduction: Triple negative breast cancer (TNBC) is defined by the absence of receptors for Her2, estrogen and progesterone and is often referred to as a refractory disease, because it is resistant to treatment with anti-Her2 antibody and anti-hormone drugs. Thus, new targets for therapeutic agents are urgently required. Using a proteomic approach, we have identified EphA10, which is more highly expressed in breast cancer, including TNBC, than in normal breast tissues. Moreover, we previously revealed that EphA10 is expressed in testis, but not in other normal tissues. This suggests that EphA10 could become a promising therapeutic target in breast cancer patients. Here, we describe a novel monoclonal antibody (mAb) against the extracellular region of EphA10 showing tumor accumulation and anti-tumor effects against EphA10-positive breast cancer. Materials and Methods: Tumor accumulation analysis of anti-EphA10 mAb; Alexa647-conjugated anti-EphA10 mAb or control mAb were administrated intravenously and observed daily using an in vivo imaging system. Tumor accumulation was quantified as the fluorescence intensity ratio of the tumor compared to that of the contralateral side. Anti-EphA10 mAb treatment in a mouse xenograft model; A mouse model was constructed by orthotopic transplantation of EphA10 stably expressing MDA-MB435 cells. When the tumor size reached approximately 100 mm3, anti-EphA10 mAb and control mAb were administrated intraperitoneally twice a week. Results and Discussion: Anti-EphA10 mAb we have developed by hybridoma methods displayed an affinity against EphA10 in the nanomolar range and specificity for EphA family proteins. Administration of the fluorescein-labeled mAb to EphA10-positive breast tumor-bearing mice showed that the mAb specifically accumulated in tumors, but not in normal organs. Furthermore, tumor growth was significantly suppressed in the mAb-treated mice in a dose-dependent manner. These data indicate that EphA10 targeted antibody therapy have a potential as a novel option for management of EphA10-positive breast cancer. We are currently generating human anti-EphA10 mAb by phage human antibody library method toward the clinical application. Conclusion: EphA10 targeted antibody therapy is effective for a mouse xenograft model. We hope that these findings will contribute to the development of a novel drug for refractory breast cancer patients. Citation Format: Mori Takahide, Nagano Kazuya, Shin-ichi Tsunoda, Yasuo Tsutsumi. EphA10 targeted antibody therapy is a potential as a novel option for management of breast cancers including triple negative breast cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B205.