GEOTranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE310378GEOGSEfalseEngineered Vesicular Stomatitis Virus for Cancer-Specific Delivery of Potent Immunotherapy PayloadsThe 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.2026/05/30GSE310378GSM9294937GSM9294935GSM9294936GSM9294933GSM929493434290310378Mus musculus