Oncolytic measles viruses encoding interferon Β and the thyroidal sodium iodide symporter gene for mesothelioma virotherapy

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Abstract

Mesothelioma usually leads to death within 8-14 months of diagnosis. To increase the potency of oncolytic measles viruses (MVs) for mesothelioma therapy, we inserted the interferon Β (IFNΒ) gene alone or with the human thyroidal sodium iodide symporter (NIS) gene into attenuated MV of the Edmonston lineage. The corresponding mouse IFNΒ (mIFNΒ) viruses, MV-mIFNΒ and MV-mIFNΒ-NIS, successfully propagated in human mesothelioma cells, leading to intercellular fusion and cell death. High levels of mIFNΒ were detected in the supernatants of the infected cells, and radioiodine uptake was substantial in the cells infected with MV-mIFNΒ-NIS. MV with mIFNΒ expression triggered CD68-positive immune cell infiltration 2-4 times higher than MV-GFP injected into the tumor site. The numbers of CD31-positive vascular endothelial cells within the tumor were decreased at day 7 after intratumoral injection of MV-mIFNΒ or MV-mIFNΒ-NIS, but not after MV-GFP and PBS administration. Immunohistochemical analysis showed that MV-mIFNΒ changed the microenvironment of the mesothelioma by increasing innate immune cell infiltration and inhibiting tumor angiogenesis. Oncolytic MVs coding for IFNΒ effectively retarded growth of human mesotheliomas and prolonged survival time in several mesothelioma tumor models. The results suggest that oncolytic MVs that code for IFNΒ and NIS will be potent and versatile agents for the treatment of human mesothelioma.

Original languageEnglish (US)
Pages (from-to)550-558
Number of pages9
JournalCancer Gene Therapy
Volume17
Issue number8
DOIs
StatePublished - Aug 2010

Fingerprint

Oncolytic Viruses
Measles virus
Mesothelioma
Interferons
Genes
sodium-iodide symporter
Neoplasms

Keywords

  • Interferon
  • Mesothelioma
  • Oncolytic measles virus
  • Thyroidal sodium iodide symporter

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Molecular Biology
  • Medicine(all)

Cite this

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title = "Oncolytic measles viruses encoding interferon Β and the thyroidal sodium iodide symporter gene for mesothelioma virotherapy",
abstract = "Mesothelioma usually leads to death within 8-14 months of diagnosis. To increase the potency of oncolytic measles viruses (MVs) for mesothelioma therapy, we inserted the interferon Β (IFNΒ) gene alone or with the human thyroidal sodium iodide symporter (NIS) gene into attenuated MV of the Edmonston lineage. The corresponding mouse IFNΒ (mIFNΒ) viruses, MV-mIFNΒ and MV-mIFNΒ-NIS, successfully propagated in human mesothelioma cells, leading to intercellular fusion and cell death. High levels of mIFNΒ were detected in the supernatants of the infected cells, and radioiodine uptake was substantial in the cells infected with MV-mIFNΒ-NIS. MV with mIFNΒ expression triggered CD68-positive immune cell infiltration 2-4 times higher than MV-GFP injected into the tumor site. The numbers of CD31-positive vascular endothelial cells within the tumor were decreased at day 7 after intratumoral injection of MV-mIFNΒ or MV-mIFNΒ-NIS, but not after MV-GFP and PBS administration. Immunohistochemical analysis showed that MV-mIFNΒ changed the microenvironment of the mesothelioma by increasing innate immune cell infiltration and inhibiting tumor angiogenesis. Oncolytic MVs coding for IFNΒ effectively retarded growth of human mesotheliomas and prolonged survival time in several mesothelioma tumor models. The results suggest that oncolytic MVs that code for IFNΒ and NIS will be potent and versatile agents for the treatment of human mesothelioma.",
keywords = "Interferon, Mesothelioma, Oncolytic measles virus, Thyroidal sodium iodide symporter",
author = "H. Li and Kah-Whye Peng and Dingli, {David M} and Kratzke, {R. A.} and Russell, {Stephen J}",
year = "2010",
month = "8",
doi = "10.1038/cgt.2010.10",
language = "English (US)",
volume = "17",
pages = "550--558",
journal = "Cancer Gene Therapy",
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T1 - Oncolytic measles viruses encoding interferon Β and the thyroidal sodium iodide symporter gene for mesothelioma virotherapy

AU - Li, H.

AU - Peng, Kah-Whye

AU - Dingli, David M

AU - Kratzke, R. A.

AU - Russell, Stephen J

PY - 2010/8

Y1 - 2010/8

N2 - Mesothelioma usually leads to death within 8-14 months of diagnosis. To increase the potency of oncolytic measles viruses (MVs) for mesothelioma therapy, we inserted the interferon Β (IFNΒ) gene alone or with the human thyroidal sodium iodide symporter (NIS) gene into attenuated MV of the Edmonston lineage. The corresponding mouse IFNΒ (mIFNΒ) viruses, MV-mIFNΒ and MV-mIFNΒ-NIS, successfully propagated in human mesothelioma cells, leading to intercellular fusion and cell death. High levels of mIFNΒ were detected in the supernatants of the infected cells, and radioiodine uptake was substantial in the cells infected with MV-mIFNΒ-NIS. MV with mIFNΒ expression triggered CD68-positive immune cell infiltration 2-4 times higher than MV-GFP injected into the tumor site. The numbers of CD31-positive vascular endothelial cells within the tumor were decreased at day 7 after intratumoral injection of MV-mIFNΒ or MV-mIFNΒ-NIS, but not after MV-GFP and PBS administration. Immunohistochemical analysis showed that MV-mIFNΒ changed the microenvironment of the mesothelioma by increasing innate immune cell infiltration and inhibiting tumor angiogenesis. Oncolytic MVs coding for IFNΒ effectively retarded growth of human mesotheliomas and prolonged survival time in several mesothelioma tumor models. The results suggest that oncolytic MVs that code for IFNΒ and NIS will be potent and versatile agents for the treatment of human mesothelioma.

AB - Mesothelioma usually leads to death within 8-14 months of diagnosis. To increase the potency of oncolytic measles viruses (MVs) for mesothelioma therapy, we inserted the interferon Β (IFNΒ) gene alone or with the human thyroidal sodium iodide symporter (NIS) gene into attenuated MV of the Edmonston lineage. The corresponding mouse IFNΒ (mIFNΒ) viruses, MV-mIFNΒ and MV-mIFNΒ-NIS, successfully propagated in human mesothelioma cells, leading to intercellular fusion and cell death. High levels of mIFNΒ were detected in the supernatants of the infected cells, and radioiodine uptake was substantial in the cells infected with MV-mIFNΒ-NIS. MV with mIFNΒ expression triggered CD68-positive immune cell infiltration 2-4 times higher than MV-GFP injected into the tumor site. The numbers of CD31-positive vascular endothelial cells within the tumor were decreased at day 7 after intratumoral injection of MV-mIFNΒ or MV-mIFNΒ-NIS, but not after MV-GFP and PBS administration. Immunohistochemical analysis showed that MV-mIFNΒ changed the microenvironment of the mesothelioma by increasing innate immune cell infiltration and inhibiting tumor angiogenesis. Oncolytic MVs coding for IFNΒ effectively retarded growth of human mesotheliomas and prolonged survival time in several mesothelioma tumor models. The results suggest that oncolytic MVs that code for IFNΒ and NIS will be potent and versatile agents for the treatment of human mesothelioma.

KW - Interferon

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