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.
Bibliographical noteFunding Information:
The project was funded by Schulze Family Foundation, Minnesota Partnership for Biotechnology and Medical Genomics and the National Institutes of Health (CA100634). We thank Dr Steven M Albelda (University of Pennsylvania) for kindly providing the REN, M30, and MSTO-211H cells.
- Oncolytic measles virus
- Thyroidal sodium iodide symporter