Poster Presentation Advances in Neuroblastoma Research Congress 2016

Enhancing 131I-mIBG radiation therapy with oncolytic HSV1716 and NAT gene therapy in high-risk neuroblastoma (#294)

Keri A Streby 1 , Pin-Yi Wang 2 , Anne Kunkler 2 , Hayley Swain 2 , Joe Conner 3 , Timothy Cripe 1 2
  1. Division of Hematology, Oncology and BMT, Nationwide Children's Hospital, Columbus, Ohio, United States
  2. Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Children's Hospital, The Ohio State University, Columbus, Ohio, United States
  3. Virttu Biologics, Ltd., Glasgow, United Kingdom

Increasing NAT (noradrenaline transporter) expression to enhance 131I-mIBG therapy is a targeted approach to improving survival and outcomes in children with high-risk neuroblastoma. Seprehvir (HSV1716) is a Δγ134.5 attenuated HSV currently in a pediatric phase 1 clinical trial (NCT00931931). HSV1716/NAT is a derivative of Seprehvir constructed to deliver NAT cDNA to cancer cells. Previous studies show increased antitumor effects in glioma and melanoma xenografts exposed to 131I-mIBG and HSV1716/NAT.1 We sought to determine the antitumor efficacy of the oncolytic virus HSV1716/NAT in combination with 131I-mIBG in preclinical models of neuroblastoma. We determined endogenous NAT expression in 12 neuroblastoma cell lines and in xenograft tumors grown in athymic nude mice by qRT-PCR. Gene transfer, viral production, and cytotoxicity assays demonstrated each cell lines’ response to HSV1716/NAT. We exposed neuroblastoma cells and xenografts in mice to HSV1716NAT and/or 131I-mIBG to determine differences in cytotoxicity and 131I-mIBG uptake. We found variation in endogenous NAT mRNA expression, in HSV1716/NAT susceptibility and permissivity, in effective NAT production, and in radiation sensitivity among the neuroblastoma cell lines. Neuroblastoma cells and xenograft tumors infected with HSV1716/NAT showed increased NAT mRNA expression, increased specific uptake of 131I-mIBG via NAT (see Fig 1), and increased cytotoxicity with 131I-mIBG. We are currently evaluating animal survival in mice with neuroblastoma xenografts exposed to HSV1716/NAT, 131I-mIBG, and the combination of HSV1716/NAT and 131I-mIBG. We aim to translate this project into a clinical trial with potential to expand to other pediatric tumor types.


  1. 1. Sorensen A, Mairs RJ, Braidwood L, et al., J Nucl Med, 2012 Apr; 53 (4):647-54.