Mesenchymal Stem Cells Successfully Deliver Oncolytic Virotherapy to Diffuse Intrinsic Pontine Glioma
Year: 2020
Type: article
Abstract: Diffuse intrinsic pontine glioma (DIPG) is among the deadliest of pediatric brain tumors. Radiation therapy is the standard of care treatment for DIPG, but offers only transient relief of symptoms for DIPG patients without providing significant survival benefit. Oncolytic virotherapy (OV) is an anticancer treatment that has been investigated for treating various types of brain tumors. Here, we have explored the use of mesenchymal stem cells (MSC) for OV delivery and evaluated treatment efficacy using preclinical models of DIPG. Our results show that DIPG cells and tumors exhibit robust expression of cell surface proteins that are important for OV entry, and that MSCs loaded with OV disseminate within and release OV throughout the tumor in mice bearing DIPG brainstem xenografts. When combining administration of OV-loaded MSCs with radiotherapy, mice bearing brainstem DIPG xenografts experience a significant survival benefit, relative to that conferred by either therapy alone (p<0.0001). Our results support further preclinical investigation of cell-based OV therapy with radiation for potential translation in treating DIPG patients.
Source: Clinical Cancer Research
Authors: Michael I. Chastkofsky, Katarzyna C. Pituch, Hiroaki Katagi, Markella Zannikou, Liliana Ilut, Ting Xiao, Yu Han, Adam M. Sonabend, David T. Curiel, Erin R. Bonner, Javad Nazarian, Craig M. Horbinski, C. David James, Amanda M. Saratsis, Rintaro Hashizume, Maciej S. Lesniak, Irina V. Balyasnikova
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Awards: Preparation and Distribution of Adult Stem Cells, Therapeutic Targeting of Malignant Glioma Stem Cells, Neural Stem Cell Carriers for Glioblastoma Immunotherapy, Targeting histone demethylase activity for the treatment of pediatric brainstem glioma, Genetic Approaches to Optimize CAR T cells for Glioblastoma Therapy, Intranasal Stem-Cell Based Therapy for Glioblastoma, SPORE for Translational Approaches to Brain Cancer, The Robert H. Lurie Comprehensive Cancer Center, Targeting Transcriptional Elongation in Pediatric Glioma
OpenAlex ID: W3109688872
