EFFECTIVE RADIOVIROTHERAPY FOR MALIGNANT GLIOMAS BY USING ONCOLYTIC MEASLES VIRUS STRAINS ENCODING THE SODIUM IODIDE SYMPORTER (MV-NIS)

Tuesday, 2nd of July 2013

[source]Human Gene Therapy[|source]

In this study, genetically engineered measles virus strains that express the human sodium iodide symporter (NIS) are shown to have significant antitumor activity against glioma lines and orthotopic xenografts. The anti-tumour effects are also reported to compare favorably with the measles virus strain expressing the human carcinoembryonic antigen, which is currently in clinical testing. Full text description of the experiment is available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3327604/?report=reader

 

Abstract

Engineered measles virus (MV) strains deriving from the vaccine lineage represent a promising oncolytic platform and are currently being tested in phase I trials. In this study, we have demonstrated that MV strains genetically engineered to express the human sodium iodide symporter (NIS) have significant antitumor activity against glioma lines and orthotopic xenografts; this compares favorably with the MV strain expressing the human carcinoembryonic antigen, which is currently in clinical testing. Expression of NIS protein in infected cells results in effective concentration of radioactive iodine, which allows for in vivo monitoring of localization of MV-NIS infection by measuring uptake of ¹²³I or^99mTc. In addition, radiovirotherapy with MV-NIS followed by ¹³¹I administration resulted in significant increase of MV-NIS antitumor activity as compared with virus alone in both subcutaneous (p=0.0003) and orthotopic (p=0.004) glioblastoma models. In conclusion, MV-NIS-based radiovirotherapy has significant antitumor activity against glioblastoma multiforme and represents a promising candidate for clinical translation.