Oncolytic vaccinia virus as a vector for therapeutic sodium iodide symporter gene therapy in prostate cancer

• DOI: 10.1038/gt.2016.5
• Publication Date: 2016-01-27T15:40:46Z
• Authors: D C Mansfield; J N Kyula; N Rosenfelder; J Chao-Chu; G Kramer-Marek; A A Khan; V Roulstone; M McLaughlin; A A Melcher; R G Vile; H S Pandha; V Khoo; K J Harrington
• Keywords: Sodium-iodide symporter; Virotherapy; DU145

Oncolytic strains of vaccinia virus are currently in clinical development with clear evidence safety and promising signs efficacy. Addition therapeutic genes to the viral genome may increase efficacy vaccinia. We evaluated potential expressing sodium iodide symporter (NIS) prostate cancer models, combining oncolysis, external beam radiotherapy NIS-mediated radioiodide therapy. The NIS-expressing (VV-NIS), GLV-1h153, was tested vitro analyzes cell killing, combination radiotherapy, NIS expression, cellular uptake apoptotic death PC3, DU145, LNCaP WPMY-1 human lines. In vivo experiments were carried out PC3 xenografts CD1 nude mice assess expression tumor uptake. addition, benefit treatment oncolysis measured. killing cancers dose- time-dependent through mechanisms. Importantly, combined therapy iodizing radiation did not adversely affect oncolysis. gene infected cells functional mediated both vivo. Therapy xenograft immunocompetent Transgenic Adenocarcinoma Mouse Prostate (TRAMP) mouse models showed that addition VV-NIS-infected tumors more effective than each single-agent therapy, restricting growth increasing survival. conclusion, VV-NIS is models. This modality would be an attractive complement existing practice.