Abstract 1211: Anti-LSR mAb with carboplatin shows the synergistic effect in epithelial ovarian cancer

Abstract

Abstract Objectives : Previously, we demonstrated anti-cancer effect of our newly developed monoclonal antibody (mAb) targeting lipolysis-stimulated lipoprotein receptor (LSR) in LSR-positive epithelial ovarian cancer (EOC) in vitro and in vivo. In EOC treatment, platinum agents which induce apoptosis are the key drugs over the decades, therefore, we aimed to demonstrate the synergistic effect of anti-LSR mAb and platinum agent against LSR-positive EOC cells. Methods : We administrated anti-LSR mAb and carboplatin to RMG-I cells (platinum resistant and LSR-positive EOC cell line) and evaluated cell proliferation in vitro and in vivo. We also investigated whether anti-LSR mAb reverse platinum resistance of RMG-I in vitro. In addition, we analyzed changes in protein expression related to MAPK/ERK and apoptosis using western blotting after treatment. Results : In RMG-I, anti-LSR mAb inhibited phosphorylation of MAPK pathway-related proteins including MEK and ERK, and activated apoptosis-related proteins. Although RMG-I showed the refractory for carboplatin, anti-LSR mAb reversed its platinum resistance and decreased IC50 value of carboplatin. As a result, anti-LSR mAb induced the apoptotic effect of carboplatin in RMG-I. Finally, the combination therapy of anti-LSR mAb and carboplatin significantly inhibited the tumor growth of RMG-I in a synergistic manner in vitro and in vivo (p<0.05). The combination therapy caused strong apoptotic changes in tumor. Conclusions : We confirmed the synergistic effect of the combination therapy of anti-LSR mAb and platinum agent against LSR-positive EOC cells via apoptotic pathway. Our findings demonstrated that this combination therapy might be a new treatment option of EOC. Citation Format: Masashi Funauchi, Kosuke Hiramatsu, Satoshi Serada, Minoru Fujimoto, Tetsuji Naka. Anti-LSR mAb with carboplatin shows the synergistic effect in epithelial ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1211.