{
  "abstract": "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 metalloproteinases (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 eradicates established tumors while avoiding systemic toxicity, and elicits long-term anti-tumor immune memory. Systemic administration of Pro-VSVIN-IL-12 also markedly inhibits the growth of metastatic cancers in the lung. 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 potent CD8⁺ T cell activation and clonal expansion in tumors. This preclinical work demonstrates a new tumor-specific targeting strategy of VSV for enhanced immunotherapy safety with superior efficacy.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Immunology, University of Connecticut School of Medicine, UConn Health, Farmington, CT, USA.",
    "Department of Molecular Medicine, Mayo Clinic, Rochester, MN, USA.",
    "Department of Surgery, University of Connecticut School of Medicine, UConn Health, Farmington, CT, USA.",
    "Johns Hopkins University, Baltimore, MD, USA.",
    "University of Connecticut, Storrs, CT, USA.",
    "Department of Immunology, Mayo Clinic, Rochester, MN, USA.",
    "Comprehensive Cancer Centre, School of Cancer & Pharmaceutical Sciences, School of Immunology and Microbial Sciences, King's College London, London, UK.",
    "Department of Immunology, University of Connecticut School of Medicine, UConn Health, Farmington, CT, USA. kewang@uchc.edu."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Eileen Victoria Theune"
    },
    {
      "affs": [
        0
      ],
      "name": "William C Theune"
    },
    {
      "affs": [
        0
      ],
      "name": "Elham Ahmadi"
    },
    {
      "affs": [
        0
      ],
      "name": "Conner C Chiari"
    },
    {
      "affs": [
        0
      ],
      "name": "Neha Singh",
      "orcid": "0000-0001-9137-1103"
    },
    {
      "affs": [
        0
      ],
      "name": "Rory Geyer"
    },
    {
      "affs": [
        1
      ],
      "name": "Jason Tonne"
    },
    {
      "affs": [
        1
      ],
      "name": "Muriel Metko"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Olamide T Olaoba"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Isabella China Wang"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Dylan Dai"
    },
    {
      "affs": [
        0
      ],
      "name": "Jianbin Ruan",
      "orcid": "0000-0001-5843-8273"
    },
    {
      "affs": [
        0
      ],
      "name": "Robert Clark"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Guangfu Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Penghua Wang",
      "orcid": "0000-0002-7332-1871"
    },
    {
      "affs": [
        0
      ],
      "name": "Evan R Jellison"
    },
    {
      "affs": [
        0
      ],
      "name": "Anthony T Vella"
    },
    {
      "affs": [
        1,
        5,
        6
      ],
      "name": "Richard Vile"
    },
    {
      "affs": [
        7
      ],
      "name": "Kepeng Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8twvvbw5sxrzx.bib",
  "cited_by": 0,
  "doi": "10.1038/s41392-026-02888-x",
  "fulltext_url": "https://europepmc.org/articles/PMC13680497",
  "id": "8twvvbw5sxrzx",
  "issns": [
    "2095-9907",
    "2059-3635"
  ],
  "landing_url": "https://europepmc.org/article/MED/42897128",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "QH301-705.5"
    ],
    [
      "lcc",
      "R"
    ],
    [
      "openalex",
      "1311|Virus-based gene therapy research"
    ]
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  "openalex": "W7222967400",
  "pdf_url": "https://europepmc.org/articles/PMC13680497?pdf=render",
  "pmcid": "PMC13680497",
  "pmid": "42897128",
  "published": "2026-10-20",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/8twvvbw5sxrzx.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:32Z",
      "native_id": "MED:42897128",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42897128"
    },
    {
      "first_seen": "2026-10-30T13:46:33Z",
      "native_id": "6ca2347f16964013a189fdb7d1e111fe",
      "source": "doaj",
      "url": "https://doi.org/10.1038/s41392-026-02888-x"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Virus-based gene therapy research",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Matrix metalloproteinase-guided targeting of vesicular stomatitis virus to tumors following systemic administration.",
  "title_text": "Matrix metalloproteinase-guided targeting of vesicular stomatitis virus to tumors following systemic administration.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:46:33Z",
  "url": "https://research.draconitic.com/paper/8twvvbw5sxrzx",
  "venue": "Signal transduction and targeted therapy",
  "versions": []
}