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Omics · study · 2026

Engineered Oncolytic Vesicular Stomatitis Virus Expressing HBsAg and IL-15 Enhances Immune Activation and Tumor Killing in Hepatitis B-Positive Hepatocellular Carcinoma （scRNA-Seq）

Listed in NCBI GEO

Hepatocellular carcinoma (HCC) is among the most prevalent and lethal cancers globally, with chronic hepatitis B virus (HBV) infection constituting a significant risk factor.

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Treating HCC is challenging due to the factors like tumor heterogeneity, limited immune infiltration, complex microenvironment. To overcome these challenges, we integrate oncolytic viral vector with therapeutic vaccine and anti-tumor cytokine.

A recombinant vesicular stomatitis virus (rVSVM51R) expressing hepatitis B surface antigen (HBsAg) and IL15 is engineered. In culture dishes, rVSVM51R specifically destructed HCC cells with minimal cytotoxicity in primary mouse hepatocytes, demonstrating tumor targeting specificity. Compared with control, VSVM51R-GFP, rVSVM51R-S showed better anti-tumor effect in syngeneic transplanted and genetically engineered HBV-positive HCC mouse models，as demonstrated by reduction of tumor and activation of HBsAg specific T cell response.

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In addition, rVSVM51R-S-mIL15-Ra, which expresses HBsAg, mouse IL15 and the IL15Rα sushi domain, showed stronger antitumor activity than rVSVM51R-mIL15-Ra or rVSVM51R-S. Tumor rechallenge experiments suggested that rVSVM51R-S-mIL15-Ra could provide durable, long-term tumor control. Single cell RNA sequencing revealed that engineered VSV increased macrophages, Th1 and memory CD4+, effector CD8+ T cells tumor infiltration, and enhanced tumor killing.

Cell depletion experiments further confirmed the critical roles of macrophages, CD4+ and CD8+ T cells in tumor inhibition. Remarkably, the effectiveness of rVSVM51R-S-hIL15-Ra, which expresses human superagonist IL15, was verified in a humanized mouse model. Overall, our data suggest that this engineered multi-functional oncolytic virus is capable of specific killing, immune activation and microenvironment modulation.

This strategy holds significant promise for the immunotherapeutic treatment of HBV-positive HCC and could be extended to other tumor types.

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Expression profiling by high throughput sequencing · Mus musculus
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Life Sciences
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Cancer 65% · RNA sequencing 75% · Sequencing 75% · Single-cell RNA sequencing 65%
Provenance · 1 source records, 11 field assertions
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NCBI GEOGSE27671615 d agoJSON v1
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