Noninvasive imaging and radiovirotherapy of prostate cancer using an oncolytic measles virus expressing the sodium iodide symporter

Pavlos Msaouel; Ianko D. Iankov; Cory Allen; Ileana Aderca; Mark J. Federspiel; Donald J. Tindall; John C. Morris; Michael Koutsilieris; Stephen J. Russell; Evanthia Galanis

doi:10.1038/mt.2009.218

Noninvasive imaging and radiovirotherapy of prostate cancer using an oncolytic measles virus expressing the sodium iodide symporter

Pavlos Msaouel, Ianko D. Iankov, Cory Allen, Ileana Aderca, Mark J. Federspiel, Donald J. Tindall, John C. Morris, Michael Koutsilieris, Stephen J. Russell, Evanthia Galanis

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66 Scopus citations

Abstract

Prostate cancer cells overexpress the measles virus (MV) receptor CD46. Herein, we evaluated the antitumor activity of an oncolytic derivative of the MV Edmonston (MV-Edm) vaccine strain engineered to express the human sodium iodide symporter (NIS; MV-NIS virus). MV-NIS showed significant cytopathic effect (CPE) against prostate cancer cell lines in vitro. Infected cells effectively concentrated radioiodide isotopes as measured in vitro by Iodide-125 ( ¹²⁵I) uptake assays. Virus localization and spread in vivo could be effectively followed by imaging of ¹²³ I uptake. In vivo administration of MV-NIS either locally or systemically (total dose of 9 × 10⁶ TCID₅₀) resulted in significant tumor regression (P<0.05) and prolongation of survival (P<0.01). Administration of ¹³¹ I further enhanced the antitumor effect of MV-NIS virotherapy (P 0.05). In conclusion, MV-NIS is an oncolytic vector with significant antitumor activity against prostate cancer, which can be further enhanced by ¹³¹ I administration. The NIS transgene allows viral localization and monitoring by noninvasive imaging which can facilitate dose optimization in a clinical setting.

Original language	English (US)
Pages (from-to)	2041-2048
Number of pages	8
Journal	Molecular Therapy
Volume	17
Issue number	12
DOIs	https://doi.org/10.1038/mt.2009.218
State	Published - Dec 2009

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Genetics
Pharmacology
Drug Discovery

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10.1038/mt.2009.218

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@article{aa0e14927a144485927421d5db4a7c6a,

title = "Noninvasive imaging and radiovirotherapy of prostate cancer using an oncolytic measles virus expressing the sodium iodide symporter",

abstract = "Prostate cancer cells overexpress the measles virus (MV) receptor CD46. Herein, we evaluated the antitumor activity of an oncolytic derivative of the MV Edmonston (MV-Edm) vaccine strain engineered to express the human sodium iodide symporter (NIS; MV-NIS virus). MV-NIS showed significant cytopathic effect (CPE) against prostate cancer cell lines in vitro. Infected cells effectively concentrated radioiodide isotopes as measured in vitro by Iodide-125 ( 125I) uptake assays. Virus localization and spread in vivo could be effectively followed by imaging of 123 I uptake. In vivo administration of MV-NIS either locally or systemically (total dose of 9 × 106 TCID50) resulted in significant tumor regression (P<0.05) and prolongation of survival (P<0.01). Administration of 131 I further enhanced the antitumor effect of MV-NIS virotherapy (P 0.05). In conclusion, MV-NIS is an oncolytic vector with significant antitumor activity against prostate cancer, which can be further enhanced by 131 I administration. The NIS transgene allows viral localization and monitoring by noninvasive imaging which can facilitate dose optimization in a clinical setting.",

author = "Pavlos Msaouel and Iankov, {Ianko D.} and Cory Allen and Ileana Aderca and Federspiel, {Mark J.} and Tindall, {Donald J.} and Morris, {John C.} and Michael Koutsilieris and Russell, {Stephen J.} and Evanthia Galanis",

note = "Funding Information: We acknowledge Teresa D. Decklever for excellent technical assistance with the radioiodide imaging and Alan R. Penheiter for helpful discussions. We also thank the members of the Mayo Clinic Viral Vector Production Laboratory: Linda Gregory, Guy Griesmann, Kirsten Langfield, Julie Sauer, Sharon Stephan, Henry Walker, Troy Wegman, and Cindy Whitcomb. Finally, we thank Raquel Ostby for help with manuscript preparation. This study was supported by the Mayo Clinic Prostate SPORE grant P50 CA 091956 (E.G., P.M., J.C.M.).",

year = "2009",

month = dec,

doi = "10.1038/mt.2009.218",

language = "English (US)",

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T1 - Noninvasive imaging and radiovirotherapy of prostate cancer using an oncolytic measles virus expressing the sodium iodide symporter

AU - Msaouel, Pavlos

AU - Iankov, Ianko D.

AU - Allen, Cory

AU - Aderca, Ileana

AU - Federspiel, Mark J.

AU - Tindall, Donald J.

AU - Morris, John C.

AU - Koutsilieris, Michael

AU - Russell, Stephen J.

AU - Galanis, Evanthia

N1 - Funding Information: We acknowledge Teresa D. Decklever for excellent technical assistance with the radioiodide imaging and Alan R. Penheiter for helpful discussions. We also thank the members of the Mayo Clinic Viral Vector Production Laboratory: Linda Gregory, Guy Griesmann, Kirsten Langfield, Julie Sauer, Sharon Stephan, Henry Walker, Troy Wegman, and Cindy Whitcomb. Finally, we thank Raquel Ostby for help with manuscript preparation. This study was supported by the Mayo Clinic Prostate SPORE grant P50 CA 091956 (E.G., P.M., J.C.M.).

PY - 2009/12

Y1 - 2009/12

N2 - Prostate cancer cells overexpress the measles virus (MV) receptor CD46. Herein, we evaluated the antitumor activity of an oncolytic derivative of the MV Edmonston (MV-Edm) vaccine strain engineered to express the human sodium iodide symporter (NIS; MV-NIS virus). MV-NIS showed significant cytopathic effect (CPE) against prostate cancer cell lines in vitro. Infected cells effectively concentrated radioiodide isotopes as measured in vitro by Iodide-125 ( 125I) uptake assays. Virus localization and spread in vivo could be effectively followed by imaging of 123 I uptake. In vivo administration of MV-NIS either locally or systemically (total dose of 9 × 106 TCID50) resulted in significant tumor regression (P<0.05) and prolongation of survival (P<0.01). Administration of 131 I further enhanced the antitumor effect of MV-NIS virotherapy (P 0.05). In conclusion, MV-NIS is an oncolytic vector with significant antitumor activity against prostate cancer, which can be further enhanced by 131 I administration. The NIS transgene allows viral localization and monitoring by noninvasive imaging which can facilitate dose optimization in a clinical setting.

AB - Prostate cancer cells overexpress the measles virus (MV) receptor CD46. Herein, we evaluated the antitumor activity of an oncolytic derivative of the MV Edmonston (MV-Edm) vaccine strain engineered to express the human sodium iodide symporter (NIS; MV-NIS virus). MV-NIS showed significant cytopathic effect (CPE) against prostate cancer cell lines in vitro. Infected cells effectively concentrated radioiodide isotopes as measured in vitro by Iodide-125 ( 125I) uptake assays. Virus localization and spread in vivo could be effectively followed by imaging of 123 I uptake. In vivo administration of MV-NIS either locally or systemically (total dose of 9 × 106 TCID50) resulted in significant tumor regression (P<0.05) and prolongation of survival (P<0.01). Administration of 131 I further enhanced the antitumor effect of MV-NIS virotherapy (P 0.05). In conclusion, MV-NIS is an oncolytic vector with significant antitumor activity against prostate cancer, which can be further enhanced by 131 I administration. The NIS transgene allows viral localization and monitoring by noninvasive imaging which can facilitate dose optimization in a clinical setting.

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Noninvasive imaging and radiovirotherapy of prostate cancer using an oncolytic measles virus expressing the sodium iodide symporter

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