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Chase Burton,1,* Arabinda Das,2,* Daniel McDonald,3 William A Vandergrift III,2 Sunil J Patel,2 David Cachia,2 Eric Bartee1 1Department of Microbiology and Immunology, Medical University of South Carolina, SC, USA; 2Department of Neurosurgery, Medical University of South Carolina, SC, USA; 3Department of Radiation Oncology, Medical University of South Carolina, SC, USA *These authors contributed equally to this work Background: Glioblastoma multiforme (GBM) is an aggressive form of brain cancer which is associated with poor prognosis. A variety of oncolytic viruses have previously shown positive efficacy against GBM, potentially offering new treatment options for patients. One such oncolytic virus is Myxoma virus (MYXV), a rabbit-specific poxvirus that has been shown to be efficacious against a variety of tumor models including GBM. Purpose: The purpose of this study was to test the efficacy of MYXV combined with current treatment regimens for GBM in both established cell lines as well as patient biopsy samples. Materials and methods: U118 gliobastoma cell lines were treated under various standard of care combinations (untreated, radiation and chemotherapeutic) prior to infection with MYXV. Infection was then monitored for differences in rate of infection, titer and rate of spread. Cellular death was measured by MTT assay and Caspase-3 colorimetric assay. Patient biopsies were harvested and treated under similar treatment conditions. Results: The addition of GBM standard of care to MYXV infection resulted in an increased rate of spread compared to single treatment with either radiation or chemotherapeutic alone. SOC did not alter viral replication or infection rates. Similar effects were seen in ex vivo patient biopsies. Cellular viability was significantly decreased with the combination therapy of SOC and MYXV infection compared to any other treatment outcome. Caspase-3 activity was also significantly increased in samples treated with combination therapy when compared to any other treatment combination. Conclusion: Our results show that the combination of MYXV with current SOC results in both increased killing of GBM cells compared to either treatment regime alone as well as increased spread of MYXV infection. These findings lay the foundation for future in vivo studies on combining MYXV with GBM SOC. Keywords: myxoma virus, glioblastoma multiforme, standard of care, oncolytic virotherapy |
