An Oncolytic Myxoma Virus Construct (M011L Knock-out) Induces Apoptosis and is a Potent Pro-Apoptotic Therapy in both Human and Immunocompetent Murine Glioblastoma Cancer Stem Cells Models (P4.247)

TL;DRAbstract

OBJECTIVE: Develop effective GBM therapeutics via targeting anti-apoptotic gene in oncolytic Myxoma Virus. BACKGROUND: GBM is a deadly brain cancer with 12 month average survival. In the past, a treatment-resistant Brain Tumor Initiating Cell (BTIC) compartment was identified and thought to drive GBM recurrence. One experimental strategy to target BTICs is the use of oncolytic viruses (OVs). Various studies found OVs may be used to target BTICs in vivo; some require the innate immunity for their efficacy. Myxoma Virus (MyxV-WT) is a promising oncolytic virus that is highly effective against glioma cell lines but less effective for BTICs. We hypothesized that MyxV encoded anti-apoptotic proteins is a limiting factor for oncolytic efficacy. By manipulating MyxV-WT and genetic deletion of the anti-apoptotic gene M11L we will have better therapeutic efficacy in BTICs that might be synergistic with conventional Temozolomide therapy. DESIGN/METHODS: We utilized a panel of patient-derived BTI

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