Edmonston vaccine strains of measles virus (MV) have significant antitumor activity in mouse xenograft models of ovarian cancer (OvCa). MV engineered to express the sodium iodide symporter gene (MV-NIS) facilitates localization of viral gene expression and offers a tool for tumor radiovirotherapy. Here we report results from a clinical evaluation of MV-NIS delivery in patients with taxol and platinum resistant OvCa. MV-NIS was given intraperitoneally every 4 wk for up to 6 cycles. Treatment was well tolerated and associated with promising median overall survival in these heavily pretreated OvCa patients: no dose limiting toxicity was observed in 16 patients treated at high dose levels (108 -109 TCID50). Median overall survival of 26.5 months compared favorably with other contemporary series. MV receptor CD46 and nectin-4 expression was confirmed by IHC in patient tumors. Sodium iodide symporter expression in patient tumors after treatment was confirmed in 3 patients by 123I uptake on SPECT/CTs and was associated with long progression-free survival. Immune monitoring post-treatment showed increased levels of T cells recognizing the tumor antigens IGFBP2 and FRα, suggesting that MV-NIS treatment triggered cellular immunity against the patients' tumor and supporting an immune mechanism in mediating antitumor effects. Our findings support further clinical evaluation of MV-NIS as an effective viral immunotherapy.