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

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

doi:10.1158/0008-5472.CAN-14-2533

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

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

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Abstract

Edmonstonvaccinestrains ofmeasles virus (MV) have significant antitumor activity in mouse xenograft models of ovarian cancer. MV engineered to express the sodium iodide symporter gene (MVNIS) facilitates localization of viral gene expression and offers a tool for tumor radiovirotherapy. Here, we report results from a clinical evaluation of MV-NIS inpatients 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 toxicitywas observed in 16 patients treated at high-dose levels (10⁸-10⁹ 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 ¹²³I 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.

Original language	English (US)
Pages (from-to)	22-30
Number of pages	9
Journal	Cancer research
Volume	75
Issue number	1
DOIs	https://doi.org/10.1158/0008-5472.CAN-14-2533
State	Published - Jan 1 2015

ASJC Scopus subject areas

Oncology
Cancer Research

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Galanis, E., Atherton, P. J., Maurer, M. J., Knutson, K. L., Dowdy, S. C., Cliby, W. A., Haluska, P., Long, H. J., Oberg, A., Aderca, I., Block, M. S., Bakkum-Gamez, J., Federspiel, M. J., Russell, S. J., Kalli, K. R., Keeney, G., Peng, K. W., & Hartmann, L. C. (2015). Oncolytic measles virus expressing the sodium iodide symporter to treat drug-resistant ovarian cancer. Cancer research, 75(1), 22-30. https://doi.org/10.1158/0008-5472.CAN-14-2533

Galanis, E, Atherton, PJ, Maurer, MJ , Knutson, KL , Dowdy, SC , Cliby, WA, Haluska, P, Long, HJ, Oberg, A, Aderca, I, Block, MS , Bakkum-Gamez, J, Federspiel, MJ, Russell, SJ, Kalli, KR, Keeney, G , Peng, KW & Hartmann, LC 2015, 'Oncolytic measles virus expressing the sodium iodide symporter to treat drug-resistant ovarian cancer', Cancer research, vol. 75, no. 1, pp. 22-30. https://doi.org/10.1158/0008-5472.CAN-14-2533

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title = "Oncolytic measles virus expressing the sodium iodide symporter to treat drug-resistant ovarian cancer",

abstract = "Edmonstonvaccinestrains ofmeasles virus (MV) have significant antitumor activity in mouse xenograft models of ovarian cancer. MV engineered to express the sodium iodide symporter gene (MVNIS) facilitates localization of viral gene expression and offers a tool for tumor radiovirotherapy. Here, we report results from a clinical evaluation of MV-NIS inpatients 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 toxicitywas observed in 16 patients treated at high-dose levels (108-109 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 123I 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.",

author = "Evanthia Galanis and Atherton, {Pamela J.} and Maurer, {Matthew J.} and Knutson, {Keith L.} and Dowdy, {Sean C.} and Cliby, {William A.} and Paul Haluska and Long, {Harry J.} and Ann Oberg and Ileana Aderca and Block, {Matthew S.} and Jamie Bakkum-Gamez and Federspiel, {Mark J.} and Russell, {Stephen J.} and Kalli, {Kimberly R.} and Gary Keeney and Peng, {Kah Whye} and Hartmann, {Lynn C.}",

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doi = "10.1158/0008-5472.CAN-14-2533",

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T1 - Oncolytic measles virus expressing the sodium iodide symporter to treat drug-resistant ovarian cancer

AU - Galanis, Evanthia

AU - Atherton, Pamela J.

AU - Maurer, Matthew J.

AU - Knutson, Keith L.

AU - Dowdy, Sean C.

AU - Cliby, William A.

AU - Haluska, Paul

AU - Long, Harry J.

AU - Oberg, Ann

AU - Aderca, Ileana

AU - Block, Matthew S.

AU - Bakkum-Gamez, Jamie

AU - Federspiel, Mark J.

AU - Russell, Stephen J.

AU - Kalli, Kimberly R.

AU - Keeney, Gary

AU - Peng, Kah Whye

AU - Hartmann, Lynn C.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Edmonstonvaccinestrains ofmeasles virus (MV) have significant antitumor activity in mouse xenograft models of ovarian cancer. MV engineered to express the sodium iodide symporter gene (MVNIS) facilitates localization of viral gene expression and offers a tool for tumor radiovirotherapy. Here, we report results from a clinical evaluation of MV-NIS inpatients 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 toxicitywas observed in 16 patients treated at high-dose levels (108-109 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 123I 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.

AB - Edmonstonvaccinestrains ofmeasles virus (MV) have significant antitumor activity in mouse xenograft models of ovarian cancer. MV engineered to express the sodium iodide symporter gene (MVNIS) facilitates localization of viral gene expression and offers a tool for tumor radiovirotherapy. Here, we report results from a clinical evaluation of MV-NIS inpatients 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 toxicitywas observed in 16 patients treated at high-dose levels (108-109 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 123I 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.

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

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