Treating Drug-Resistant Ovarian Cancer With Oncolytic Measles Virus
Ovarian cancer is the second most common malignancy of the female genital tract in the United States, causing an estimated 14,000 deaths in 2013. Although ovarian cancer is often initially sensitive to platinum-based chemotherapy, patients ultimately develop resistance. While agents are used to try and prevent resistance, most clinical trials in patients with platinum-resistant ovarian cancer report median overall survival in 12 months or less. There is a pressing need for more effective treatments to improve the outcome of these patients.
Edmonston vaccine strains of measles virus (MV) have significant antitumor activity in mouse xenograft models of ovarian cancer. MV engineered to express the sodium iodide symporter gene (MV-NIS) facilitates localization of viral gene expression and offers a tool for tumor radiovirotherapy.
Given the favorable performance features with MV-NIS, Mayo Clinic researchers, first author Evanthia Galanis, M.D., launched a phase I/II trial in women with treatment-resistant ovarian cancer. As reported in the Cancer Research journal, the goal of the study was to determine the effect of MV-NIS in patients with treatment-resistant ovarian cancer.
MV-NIS was given intraperitoneally every four weeks for up to six cycles. Treatment was well tolerated and associated with promising median overall survival in these patients with heavily pretreated ovarian cancer. No dose-limiting toxicity was observed in 16 patients treated at high-dose levels, and their median overall survival of 26.5 months compared favorably with other contemporary series.
MV receptor CD46 and nectin-4 expression was confirmed by immunohistochemistry in patient tumors. Sodium iodide symporter expression in patient tumors after treatment was confirmed in three patients and was associated with long progression-free survival. Immune monitoring posttreatment showed an increase in effector T cells recognizing the tumor antigens IGFBP2 and FRα, indicating that MV-NIS treatment triggered cellular immunity against the patients' tumor and suggesting that an immune mechanism mediating the observed antitumor effect.
In summary, intraperitoneal administration of MV-NIS in patients with recurrent ovarian cancer was associated with compelling survival outcomes and merits further prospective testing. The findings support further clinical evaluation of MV-NIS as an effective immunovirotherapy.