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Oncolytic measles virus expressing the sodium iodide symporter to treat drug-resistant ovarian cancer.

Cancer research (2014-11-16)
Evanthia Galanis, Pamela J Atherton, Matthew J Maurer, Keith L Knutson, Sean C Dowdy, William A Cliby, Paul Haluska, Harry J Long, Ann Oberg, Ileana Aderca, Matthew S Block, Jamie Bakkum-Gamez, Mark J Federspiel, Stephen J Russell, Kimberly R Kalli, Gary Keeney, Kah Whye Peng, Lynn C Hartmann
ABSTRACT

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. Here, we report results from a clinical evaluation of MV-NIS in patients with taxol- and platinum-resistant ovarian cancer. MV-NIS was given intraperitoneally every 4 weeks for up to 6 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 (10(8)-10(9) TCID50), 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 by (123)I uptake on SPECT/CTs 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. Our findings support further clinical evaluation of MV-NIS as an effective immunovirotherapy.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Ethyl alcohol, Pure, 190 proof, ACS spectrophotometric grade, 95.0%
Sigma-Aldrich
Ethyl alcohol, Pure, 200 proof, meets USP testing specifications
Supelco
Ethanol solution, certified reference material, 2000 μg/mL in methanol
Sigma-Aldrich
Ethanol, absolute, denaturated with 0.5-1.5 Vol.% 2-butanone and approx. 0.001% Bitrex (GC), ≥98% (GC)