{
  "abstract": "Local tumor therapies rarely induce systemic immunity capable of controlling metastatic disease. Here, we engineer an mRNA lipid nanoparticle (LNP) platform to coordinate innate immune sensing and T cell activation in situ through co-delivery of an autoactivated cyclic GMP-AMP synthase mutant (cGASR241E) and membrane-tethered IL-12 (IL-12TM). cGASR241E mRNA LNPs autonomously generated cyclic GMP-AMP in vivo, activating host STING signaling and initiating antitumor responses. Co-administration with IL-12TM mRNA LNPs promoted localized cytokine production, reduced regulatory T cells, and restored effector function in tumor-infiltrating T cells. This combination elicited systemic antitumor immunity and suppressed distal tumors across multiple mouse models. The therapeutic efficacy required CD8+ T cells and IFNg; signaling in host, supporting a model in which innate DNA sensing is coupled to IL-12-mediated T cell functional reinforcement. In addition, the combination enhanced responsiveness to PD-L1 blockade. Together, these findings establish a clinically translatable strategy to integrate cGAS-STING activation with cytokine-driven T cell programming to drive systemic tumor control.",
  "abstract_shown": true,
  "affiliations": [
    "UT Southwestern Medical Center"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "A. Zhang"
    },
    {
      "name": "Y. Fang"
    },
    {
      "name": "R. Peng"
    },
    {
      "name": "M. Yan"
    },
    {
      "affs": [
        0
      ],
      "name": "Z. Chen"
    },
    {
      "name": "T. Li"
    },
    {
      "name": "J. Tan"
    },
    {
      "name": "L. Sun"
    },
    {
      "affs": [
        0
      ],
      "name": "Z. Chen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5t43qpfnswe65.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.15.759215",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.15.759215v1.full",
  "id": "5t43qpfnswe65",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.15.759215v1",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "2403|Immunotherapy and Immune Responses"
    ]
  ],
  "openalex": "W7222484514",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.15.759215v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-15",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5t43qpfnswe65.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:07Z",
      "native_id": "10.64898/2026.10.15.759215",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.15.759215v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Combining an autoactivated cGAS mutant with membrane-tethered IL-12 via mRNA lipid nanoparticles promotes systemic tumor control",
  "title_text": "Combining an autoactivated cGAS mutant with membrane-tethered IL-12 via mRNA lipid nanoparticles promotes systemic tumor control",
  "type": "preprint",
  "updated_at": "2026-10-30T12:28:07Z",
  "url": "https://research.draconitic.com/paper/5t43qpfnswe65",
  "venue": "bioRxiv",
  "versions": []
}