Abstract

Background: Glioblastoma (GBM) is characterised by therapeutic resistance and high invasiveness, so the development of new treatments is essential. Oncolytic virotherapy using the vesicular stomatitis virus (VSV) is a promising approach as it is inherently tumour-selective and immunostimulatory. This study evaluated the antitumour efficacy of a recombinant VSV engineered to co-express mouse interleukin-12 and granulocyte-macrophage colony-stimulating factor (rVSV-dM51-mIL12-mGMCSF) using in vitro and in vivo U-87 MG models. Methods: The oncolytic activity of rVSV-dM51-mIL12-mGMCSF was evaluated in vitro against human U-87 MG and mouse GL-261 glioblastoma cells using flow cytometry (MOI 0.1) and MTT assays (MOIs 0.1 and 0.001). In vivo, tumour progression was monitored in U-87 MG xenograft mice for 30 days after inoculation. At the study endpoint, tumour tissues from treated and control animals were subjected to immunohistochemical (IHC) analysis; the H-score method was used to quantify expression of the Ki-67 proliferation marker, VSV glycoprotein (VSV-G), and mIL-12. Results: rVSV-dM51-mIL12-mGMCSF demonstrated oncolytic activity against both cell lines in vitro; however, its cytotoxicity was lower compared to the parental control virus (rVSV-dM51-GFP). In contrast, treatment in vivo resulted in greater tumour growth inhibition. IHC analysis revealed a significant reduction in the Ki-67 H-score alongside high levels of VSV glycoprotein and mIL-12 expression. These results confirm that, although the payloads do not enhance direct viral oncolysis in vitro, they significantly improve antitumour efficacy in vivo. Conclusions: rVSV-dM51-mIL12-mGMCSF effectively inhibited tumour growth in the U-87 MG xenograft model, supporting further evaluation of glioblastoma-directed oncolytic virotherapy.

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