Abstract
Abstract We have developed an RNAi based anticancer drug, DFP-10825 [a cationic liposome and short-hairpin RNAi molecule for thymidylate synthase (TS shRNA)] and here established an industrial method of manufacturing the formulation. The therapeutic efficacy of the DFP-10825 was examined in a MKN45 human gastric carcinoma xenograft mouse model (peritoneal disseminated gastric cancer model). The mice were received intraperitoneal injection with 5 doses of DFP-10825 or control formulation (short-hairpin RNA for luciferase) (1 mg shRNA/kg/day) once every 3 days. The treatment with DFP-10825 obviously prolonged survival time of the mice compared to control formulation and significantly suppressed the target mRNA level in the peritoneal disseminated tumors. We recently reported that DFP-10825 showed a significant therapeutic efficiency in the human malignant pleural mesothelioma orthotopic xenograft model. Accordingly, DFP-10825 may lead a clinical benefit to patients with pulmonary malignant mesothelioma or disseminated peritoneal tumor. In addition, we established an industrial method of manufacturing DFP-10825, which provides a large scale preparation. Water solution of TS shRNA was gently mixed at an optimal ratio with ethanol solution of cationic lipids, composed of DC-6-14 (a cationic lipid), DOPE and DOPC. Then, the mixture was lyophilized under optimal condition. The freeze-dried cake provided a ready for injection formulation by a one-step hydration with saline. Physicochemical properties of the obtained DFP-10825 such as particle size, zeta-potential, and size distribution were almost comparable with those of conventionally prepared DFP-10825, which prepared with conventional preparation method, mixing TS shRNA solution and cationic liposomes. Our findings in this study demonstrate that intraperitoneal chemotherapy with a simple freeze-dried RNAi medicine, DFP-10825, showing an equivalent pharmaceutical and therapeutic potency with conventionally prepared DFP-10825, meets a criteria to use for clinical settings and will have a clinical benefit to treat patients with disseminated peritoneal and pulmonary cancers. Citation Format: Tatsuhiro Ishida, Hidenori Ando, Masakazu Fukushima, Cheng-Long Huang, Hiromi Wada. An industrial method of manufacturing a novel RNAi anticancer drug, DFP-10825, for the treatment of peritoneal disseminated gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5097. doi:10.1158/1538-7445.AM2017-5097
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
