What question did this study set out to answer?

The research aims to evaluate the antitumor effects of VV-GMCSF-Lact vs. recombinant human GM-CSF in a glioma model.

March 8, 2026Pharmaceuticals0 citationsOpen Access

Oncolytic Virus VV-GMCSF-Lact and Human GM-CSF Against GL261 Glioma in Immunocompetent Mice

AAAlisa AgeenkoInstitute of Chemical Biology and Fundamental Medicine NVNatalia VasilevaInstitute of Chemical Biology and Fundamental Medicine ACA. Yu. ChesnokovaRussian Cancer Research Center NN Blokhin

Key Points

The research aims to evaluate the antitumor effects of VV-GMCSF-Lact vs. recombinant human GM-CSF in a glioma model.
Used subcutaneous GL261 glioma model in immunocompetent C57BL/6 mice
Compared intratumoral treatments of VV-GMCSF-Lact and rhGM-CSF
Evaluated immune cell populations using flow cytometry
Analyzed tumor morphology with H&E staining
Performed RNA sequencing for tumor transcriptome profiling
VV-GMCSF-Lact reduced immunosuppressive cells in the tumor microenvironment
Histological analysis showed fewer mitotic figures in tumors from female mice post-treatment
Transcriptome profiling indicated distinct gene expression patterns between treatment groups
VV-GMCSF-Lact led to reduced malignant GL261 cell proportions while rhGM-CSF increased MDSCs and macrophages

Abstract

Background/Objectives: Oncolytic viruses are an immunotherapeutic approach that can modulate the tumor microenvironment (TME), transforming immunologically ‘cold’ tumors into ‘hot’ ones. Insertion of genes encoding immunomodulatory proteins can further enhance antitumor immune responses. In this study, we compared the antitumor and immunomodulatory effects of the double recombinant vaccinia virus VV-GMCSF-Lact, which carries the human GM-CSF gene, with those of recombinant human GM-CSF (rhGM-CSF) in an immunocompetent murine GL261 glioma model. Methods: The study was conducted using a subcutaneous GL261 glioma model in immunocompetent C57BL/6 mice, comparing intratumoral VV-GMCSF-Lact and rhGM-CSF treatments with evaluation of immune cell populations by flow cytometry, tumor morphology by H&E staining, and tumor transcriptome profiles by RNA sequencing. Results: Flow cytometry showed that VV-GMCSF-Lact reduced the number of immunosuppressive cells in the TME of subcutaneously transplanted gliomas, targeting different components of the TME depending on animal sex. The immunotherapeutic effects of rhGM-CSF were less pronounced and primarily affected peripheral immune cells. Histological analysis revealed a decrease in mitotic figures in tumors from female mice after viral therapy. Transcriptome profiling of GL261 tumors demonstrated divergent gene expression patterns and cellular compositions between treatment groups. VV-GMCSF-Lact treatment was associated with a decreased proportion of malignant GL261 cells and CD8+ T lymphocytes, while rhGM-CSF treatment increased proportions of MDSCs, macrophages, NK cells, and tumor-associated neutrophils. Conclusions: Taken together, our data demonstrate that VV-GMCSF-Lact induces antitumor immune responses in murine GL261 glioma in vivo and modulates the tumor microenvironment more effectively than rhGM-CSF alone, supporting its potential for developing new strategies for glioma treatment.

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