College of Education and Human Ecology Undergraduate Research ScholarshipNeuroblastoma is the most common extra-cranial solid tumor in childhood and the leading cause of childhood cancer mortality. MIBG (meta-iodobenzylguanidine), an analogue of noradrenaline, is a form of targeted radiation therapy for high-risk neuroblastoma when bound to 131Iodine. MIBG enters cells through the norepinephrine transporter (NET), a protein expressed on the surface of neuroendocrine cells, including most neuroblastoma cells. 131I-MIBG then radiates the cells it enters and induces cytotoxicity in surrounding cells. However, 131I-MIBG is not always effective, likely in part due to low NET expression in high-risk neuroblastomas. Oncolytic virotherapy is a promising therapeutic approach currently in clinical trials. Previously, our lab has shown that preclinical models of neuroblastoma are sensitive to oncolytic herpes simplex virus (oHSV) therapy. oHSV can also be used to deliver the NET transgene to tumor cells to increase susceptibility to 131I-MIBG. In the present study, we are investigating the efficacy of HSV1716/NET in increasing NET expression and thereby increasing the efficacy of 131I-MIBG. We will also evaluate if 131I-MIBG enhances viral replication. The results to date indicate that neuroblastoma cell lines are susceptible to HSV1716/NET, and upon viral infection, there is effective transfer of the NET gene resulting in an increase in 131I-MIBG uptake.No embargoAcademic Major: Human Development and Family Scienc
