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Engineered Vesicular Stomatitis Virus for Cancer-Specific Delivery of Potent Immunotherapy Payloads

GSE310378 Mus musculus Expression profiling by high throughput sequencing 5 samples Submitted 2026/05/30 Platform GPL34290
Summary
The lack of tumor-specific targeting by oncolytic viruses (OVs) restricts their therapeutic potential. Here, we report a “cap-linker” strategy to modify the vesicular stomatitis virus (VSV) glycoprotein (G protein, VSV-GIN). The modified VSV (Pro-VSVIN) loses its ability to infect cells until present in the tumor microenvironment, where the linker is cleaved by tumor-enriched matrix metalloproteases (MMPs). When Pro-VSVIN is armed with a single-chain IL-12 (Pro-VSVIN-IL-12) and systemically injected into MC38 tumor-bearing mice, Pro-VSVIN-IL-12 shows a markedly improved safety profile and eradicates tumors. The efficacy of Pro-VSVIN-IL-12 was further improved when combined with PD-1 checkpoint blockade. Compared to WT VSVIN that carries IL-12, intravenously injected Pro-VSVIN-IL-12 leads to strong Th1 immunity, near abolishment of regulatory T cells, and CD8+ T cell activation in tumors. This preclinical work demonstrates a new tumor-specific targeting strategy of VSV for enhanced immunotherapy safety with superior efficacy.
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Direct links to NCBI, no account and no request form: the whole study as GSE310378_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 5 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1365850 and SRA study SRP646661. Searching any of these in the dataset finder brings you back here.

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