Vaccinia Virus Converts Microglia into Potent Oncolytic Agent for Glioblastoma and Neuroblastoma

Abstract

Highlights: What are the main findings? Microglia infected with vaccinia virus (VV) efficiently deliver viruses to neuroblastoma and glioblastoma cells. Infected microglia promote oncolysis and viral spread in both 2D and 3D tumor models. What are the implications of the main findings? Microglia act as effective carriers for VV. This platform can enhance oncolytic virotherapy and potentially integrate with immuno- or radiotherapy. Background: Glioblastoma and neuroblastoma are aggressive brain and pediatric tumors with limited treatment options. Vaccinia virus (VV) has demonstrated potent oncolytic and immunomodulatory properties but faces challenges in tumor targeting. Methods: We developed an in vitro co-culture model using mouse microglia (BV2) infected with VV (LIVP strain) to deliver the virus to glioblastoma (U87) and neuroblastoma (SH-SY5Y) cells in both 2D and 3D systems. Our results demonstrated that VV-infected Microglia can efficiently deliver the virus to tumor cells, inducing substantial cytotoxic effects in both 2D and 3D models. Notably, the 3D cultures, which more closely mimic the native tumor microenvironment, exhibited the most pronounced enhancement in oncolysis. Conclusions: This microglia-based delivery strategy enables potent oncolytic activity against brain tumor cells and warrants further exploration in in vivo and combinational therapies.