{
  "abstract": "The eradication of solid tumors by chimeric antigen receptor (CAR) T cells requires dynamic therapies capable of outlasting an immune suppressive tumor microenvironment (TME). However, biological barriers--including rapid exhaustion, poor expansion, and loss of stem-like memory--quickly neutralize these therapies. Because single-technology interventions often introduce unacceptable tradeoffs between efficacy and safety, durable remission demands a paradigm where multiple engineered solutions work in concert. To holistically address these mechanisms, we rationally designed a single-vector transgene that intrinsically drives CAR T functional persistence. The platform integrates four synergistic technologies: a high-avidity mesothelin (MSLN)-targeting CAR optimized to resist shed decoy antigens, a T-cell activation-responsive promoter (OUTLAST OP1) resisting exhaustion, a CD8-targeted designed IL-2 cytokine (OUTSMART dIL-2) driving intratumoral CAR-T expansion, and an EGFRopt safety switch. In lung and ovarian cancer models, this rational integration was required to drive antigen-dependent T cell expansion and eradicate established tumors at extremely low CAR T doses. Furthermore, engineered cells established a self-renewing pool of stem-like memory T cells capable of rejecting tumor rechallenge months later. Ultimately, this work demonstrates that intrinsic T cell dysfunction and extrinsic tumor-derived barriers can be simultaneously overcome by integrating synergistic technologies.",
  "abstract_shown": true,
  "affiliations": [
    "Outpace Bio"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 27,
  "authors": [
    {
      "name": "R. H. Amin"
    },
    {
      "name": "K. G. Haworth"
    },
    {
      "name": "H. F. Moffett"
    },
    {
      "name": "J. C. Chen"
    },
    {
      "name": "L. Park"
    },
    {
      "name": "J. K. Yokoyama"
    },
    {
      "name": "A. L. Wang"
    },
    {
      "name": "L. J. Tait"
    },
    {
      "name": "M. M. Steele"
    },
    {
      "name": "J. T. Crowl"
    },
    {
      "name": "T. M. Davenport"
    },
    {
      "name": "J. DeSautelle"
    },
    {
      "name": "J. L. Hammer"
    },
    {
      "name": "W. M. Obenza"
    },
    {
      "name": "V. R. Montoya"
    },
    {
      "name": "R. L. Kirkpatrick"
    },
    {
      "name": "T. Tan"
    },
    {
      "name": "K. M. Shirley"
    },
    {
      "name": "B. Hammerson"
    },
    {
      "name": "R. A. Langan"
    },
    {
      "name": "D. S. Clausen"
    },
    {
      "name": "P. J. Sample"
    },
    {
      "name": "B. D. Weitzner"
    },
    {
      "name": "S. Yuan"
    },
    {
      "name": "M. J. Lajoie"
    },
    {
      "name": "S. E. Boyken"
    },
    {
      "affs": [
        0
      ],
      "name": "A. E. Foster"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1j7qytx0rx2v2.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.18.752754",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.18.752754v1.full",
  "id": "1j7qytx0rx2v2",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.18.752754v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "synthetic biology"
    ],
    [
      "openalex",
      "2730|CAR-T cell therapy research"
    ]
  ],
  "openalex": "W7213978773",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.18.752754v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-18",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/1j7qytx0rx2v2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:23:43Z",
      "native_id": "10.64898/2026.09.18.752754",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.18.752754v2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:synthetic biology",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "A Rationally Designed Transgene Drives CAR T Functional Persistence and Durable Regression of Solid Tumors",
  "title_text": "A Rationally Designed Transgene Drives CAR T Functional Persistence and Durable Regression of Solid Tumors",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:14Z",
  "url": "https://research.draconitic.com/paper/1j7qytx0rx2v2",
  "venue": "bioRxiv",
  "versions": []
}