Noninvasive Imaging and Radiovirotherapy of Prostate Cancer Using an Oncolytic Measles Virus Expressing the Sodium Iodide Symporter

被引:67
作者
Msaouel, Pavlos [2 ,5 ]
Iankov, Ianko D. [5 ]
Allen, Cory [5 ]
Aderca, Ileana [5 ]
Federspiel, Mark J. [5 ]
Tindall, Donald J. [3 ]
Morris, John C. [4 ]
Koutsilieris, Michael [2 ]
Russell, Stephen J. [5 ]
Galanis, Evanthia [1 ,5 ]
机构
[1] Mayo Clin, Coll Med, Div Med Oncol, Rochester, MN 55905 USA
[2] Univ Athens, Dept Expt Physiol, Athens, Greece
[3] Mayo Clin, Dept Urol Res, Rochester, MN 55905 USA
[4] Mayo Clin, Dept Internal Med, Div Endocrinol, Rochester, MN 55905 USA
[5] Mayo Clin, Dept Mol Med, Rochester, MN 55905 USA
关键词
SUICIDE GENE-THERAPY; PHASE-I TRIAL; COMPLEMENT REGULATORY PROTEINS; REPLICATION-COMPETENT; CARCINOEMBRYONIC ANTIGEN; ADENOVIRUS; RECEPTOR; CELLS;
D O I
10.1038/mt.2009.218
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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 (I-125) uptake assays. Virus localization and spread in vivo could be effectively followed by imaging of I-123 uptake. In vivo administration of MV-NIS either locally or systemically (total dose of 9 x 10(6) TCID50) resulted in significant tumor regression (P < 0.05) and prolongation of survival (P < 0.01). Administration of I'll 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 I-131 administration. The NIS transgene allows viral localization and monitoring by noninvasive imaging which can facilitate dose optimization in a clinical setting.
引用
收藏
页码:2041 / 2048
页数:8
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