Journal Article

Oncolytic measles virus strains have significant antitumor activity against glioma stem cells

Federspiel, M J, Galanis, E, Domingo, E, Opyrchal, M, Aderca, I, Schroeder, M A, Sarkaria, J N, Allen, C

2013

Overview

Glioblastoma (GBM) is the most common primary brain tumor in adults and has a dismal prognosis despite multimodality treatment. Given the resistance of glioma stem cells (GSC) to chemotherapy and radiation therapy, their eradication could prevent tumor recurrence. We sought to evaluate the antitumor activity of measles virus (MV) derivatives against GSC. We generated neurosphere cultures from patient-derived primary tumor GBM xenografts, and we characterized them for the GSC markers CD133, SOX2, Nestin, ATF5 and OLIG2. Using the MV-strains MV-GFP, MV-CEA and MV-NIS we demonstrated infection, viral replication and significant cytopathic effect in vitro against GSC lines. In tumorigenicity experiments, GBM44 GSC were infected with MV in vitro and subsequently implanted into the right caudate nucleus of nude mice: significant prolongation of survival in mice implanted with infected GSC was observed, compared with mock-infected controls ( P =0.0483). In therapy experiments in GBM6 and GBM12 GSC xenograft models, there was significant prolongation of survival in MV-GFP-treated animals compared with inactivated virus-treated controls (GBM6 P =0.0021, GBM12 P =0.0416). Abundant syncytia and viral replication was demonstrated in tumors of MV-treated mice. Measles virus derivatives have significant antitumor activity against glioma-derived stem cells in vitro and in vivo.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/326/596/1631 / 631/378/2183 / 692/699/67/1059 / Animals / Antitumor activity / Biomarkers, Tumor - genetics / Biomarkers, Tumor - metabolism / Biomedical and Life Sciences / Biomedicine / Brain cancer / Brain Neoplasms - therapy / Brain tumors / Caudate nucleus / Cell Biology / Chemotherapy / Gene Expression / Gene Therapy / Genetic aspects / Giant Cells - pathology / Giant Cells - virology / Glioblastoma / Glioblastoma - therapy / Glioblastoma multiforme / Glioma / Glioma cells / Health aspects / Human Genetics / Humans / Measles / Measles virus / Measles virus - genetics / Measles virus - physiology / Medical prognosis / Mice / Mice, Nude / Nanotechnology / Neoplastic Stem Cells - metabolism / Neoplastic Stem Cells - pathology / Neoplastic Stem Cells - virology / Nestin / Olig2 protein / Oncology / Oncolysis / Oncolytic Virotherapy / Oncolytic Viruses - genetics / Oncolytic Viruses - physiology / original-article / Physiological aspects / Prevention / Radiation therapy / Replication / Rodents / Stem cell transplantation / Stem cells / Strains (organisms) / Syncytia / Tumor Cells, Cultured / Tumorigenicity / Virus Replication / Viruses / Xenograft Model Antitumor Assays / Xenografts