Abstract 2585: The development of a novel microRNA replacement therapy for ovarian cancer - a potential of patient derived-exosomes as a carrier

Abstract

Abstract Objective: microRNAs (miRNAs) affect key features of cancer cells and some are identified as tumor suppressor (TS) miRNAs. In spite of many preclinical studies with promising results, all translational clinical trials with TS miRNAs have failed due to the difficulties of miRNA systemic delivery. Therefore, the development of a novel carrier is urgently needed. Exosomes, non-sized vesicles secreted from cells, are stable in body fluid and therefore can serve as a promising candidate for miRNA carrier. In ovarian cancer treatment, omentum should be taken at surgery and normal fibroblasts can be collected from omentum. The aim of this study is to pursue the possibility of fibroblast derived-exosomes as a carrier for miRNA replacement therapy to treat ovarian cancer. Methods: At surgery, omentum was collected and fibroblasts were primary cultured. Thereafter, exosomes were collected from culture media. miR-199a-3p was selected as a TS miRNA. Synthesized miR-199a-3p was corporated into exosomes by electroporation. miR-199a-3p-loaded exosomes (M199-exosomes) were treated with ovarian cancer cells and the expression levels of miR-199a-3p and target genes were assessed. The treatment effect of M199-exosomes was analyzed focusing on peritoneal dissemination. Results: The treatment of M199-exosomes drastically increased miR-199a-3p expression in ovarian cancer cells (CaOV3; 8592-fold, SKOV3; 67188-fold, OVCAR3; 2280-fold). Treatment with M199-exosomes suppressed c-Met expression and significantly inhibited the proliferation and invasion of ovarian cancer cells in vitro (P<0.01). In a xenograft study, M199-exosomes significantly inhibited peritoneal dissemination and extended the survival of mice. Citation Format: Masaki Kobayashi, Kenjiro Sawada, Aasa Shimizu, Mayuko Miyamoto, Erika Nakatsuka, Mahiru Kawano, Yuri Matsumoto, Michiko Kodama, Kae Hashimoto, Seiji Mabuchi, Tadashi Kimura. The development of a novel microRNA replacement therapy for ovarian cancer - a potential of patient derived-exosomes as a carrier [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2585.