AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025440462
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ORIGINAL RESEARCH ARTICLE

Evaluation of the efficiency of double recombinant vaccinia virus VV-GMCSF-Lact against glioblastoma using 3D spheroid and cerebral organoid models

Maya Dymova1†* ,  Gleb Petrov1† ,  Danil Drokov1 ,  Tatiana Shnaider2 ,  Sophia Yakovleva2 ,  Elena Kuligina1 ,  Vladimir Richter1
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1 Laboratory of Biotechnology, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Novosibirsk Region, Russia
2 Department of Molecular Mechanisms of Ontogenesis, Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Novosibirsk Region, Russia
†These authors contributed equally to this work.
EJMO, 025440462 https://doi.org/10.36922/EJMO025440462
Received: 1 November 2025 | Revised: 11 December 2025 | Accepted: 14 January 2026 | Published online: 20 February 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: Human cerebral organoids (COs) are sophisticated three-dimensional (3D) models that successfully replicate the 3D cytoarchitecture of human brain development in its early stages. Co-cultivation of COs obtained from human-induced pluripotent stem cells with 3D U-87 MG glioblastoma cell spheroids (glioblastoma–CO assembloid [GCOA]) represents a robust strategy for modeling brain cancer behavior.

Objectives: This study aims to evaluate the feasibility of using GCOAs and 3D U-87 MG glioblastoma cell spheroids as in vitro cell models to evaluate the cytotoxic effect of the oncolytic recombinant vaccinia virus-granulocyte–macrophage colony-stimulating factor (VV-GM-CSF)-Lact compared to the VV-GMCSF-del virus.

Methods: To assess the cytotoxicity of two virus strains, we used fluorescent and confocal microscopy, spectrophotometry, the MTT assay, and real-time polymerase chain reaction

Results: Glioblastoma cells died faster in the presence of VV-GMCSF-Lact virus, and 3D spheroids infected with this virus contained more caspase-3-positive cells. On the 10th day in GCOA, glioblastoma cells began to invade the interior of the CO. Under conditions of 3D spheroid and GCOA infection with recombinant viruses, three differentially expressed genes – FSCN1, SCUBE2, and TNFRSF9 – associated with invasion were analyzed.

Conclusion: These 3D models of glioblastoma can be used in the development of antitumor drugs to study their cytotoxic effects.

Keywords
Glioblastoma
Cerebral organoids
Three-dimensional spheroids
Glioblastoma–cerebral organoid assembloid
VV-GMCSF-Lact
Oncolytic virus
Funding
This study, including cell viability assays, polymerase chain reaction, immunohistochemistry, and quantitative polymerase chain reaction, was supported by the Russian Science Foundation (Grant No. 22-64-00041; available at https://rscf.ru/project/22-64-00041/, accessed on November 1, 2025). Cell culture maintenance was supported by the Russian state-funded project of the Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences (Grant No.: 125012900932-4).
Conflict of interest
The authors declare they have no competing interests.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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