{
  "abstract": "Patient T cells modified with chimeric antigen receptors (CARs) have shown remarkable therapeutic success in previously incurable cancers. However, despite its success in hematological malignancies, CAR-T therapy has shown only modest efficacy in solid tumors. The medical field has focused on developing new molecular designs that enhance CAR-T persistence, prevent exhaustion in the tumor microenvironment (TME), and increase the specificity of the CAR-T cell to various tumor antigens. However, much less effort has been placed on enhancing CAR-T cells' invasion into and migration through the stromal matrix of the TME, where they can elicit tumor-directed cytotoxicity. Here, we engineered CAR-T cells with synthetic cytokine receptors targeting inflammatory cytokines produced by the cells themselves, which increase their speed through collagen I matrices. We show that this enhanced motility is driven by increased CAR-T cell translocation through confined microchannels via cellular deformation, together with elevated migratory speeds in proximity to neighboring cells, suggesting improved responsiveness to local cues. These migration-enhanced CAR-T cells significantly reduce both primary tumor size and distant organ metastasis in triple-negative breast cancer (TNBC) mouse models compared to standard CAR-T cells. These results support molecular design strategies that exploit mechanisms to improve cellular therapies for metastatic solid tumors.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "name": "Eban A. Hanna",
      "orcid": "0000-0001-7277-4038"
    },
    {
      "name": "Alice Amitrano",
      "orcid": "0000-0001-7919-2225"
    },
    {
      "name": "Andre Forjaz",
      "orcid": "0009-0002-5115-2293"
    },
    {
      "name": "Zhiliang Bai",
      "orcid": "0000-0002-3977-3057"
    },
    {
      "name": "Chanhong Min",
      "orcid": "0000-0003-1018-9057"
    },
    {
      "name": "Yoseph Dance",
      "orcid": "0009-0003-0843-898X"
    },
    {
      "name": "Immanuel Etoh"
    },
    {
      "name": "Bryce Lloyd"
    },
    {
      "name": "Xinyun Jiang",
      "orcid": "0009-0008-7388-8369"
    },
    {
      "name": "Vasco Queiroga",
      "orcid": "0009-0004-7812-0472"
    },
    {
      "name": "Praful Nair",
      "orcid": "0000-0001-5875-4743"
    },
    {
      "name": "Victoria Duarte",
      "orcid": "0009-0004-4397-4259"
    },
    {
      "name": "Saurabh Joshi"
    },
    {
      "name": "Konstantinos Konstantopoulos",
      "orcid": "0000-0003-2623-1459"
    },
    {
      "name": "Jude Phillip",
      "orcid": "0000-0002-2999-5254"
    },
    {
      "name": "Rong Fan",
      "orcid": "0000-0001-7805-8059"
    },
    {
      "name": "Pei-Hsun Wu",
      "orcid": "0000-0002-7371-2960"
    },
    {
      "name": "Denis Wirtz",
      "orcid": "0000-0001-6147-3045"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b6c17tttq7vnw.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.22.760671",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.22.760671v1.full",
  "id": "b6c17tttq7vnw",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.22.760671v1",
  "language": "en",
  "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",
      "bioengineering"
    ],
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2730|CAR-T cell therapy research"
    ]
  ],
  "openalex": "W7223565483",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.22.760671v1.full.pdf",
  "pmcid": "PMC13738764",
  "pmid": "42996147",
  "published": "2026-10-22",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/b6c17tttq7vnw.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:29:37Z",
      "native_id": "10.64898/2026.10.22.760671",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.22.760671v1"
    },
    {
      "first_seen": "2026-11-09T12:23:42Z",
      "native_id": "PMC13738764",
      "source": "pmc",
      "url": "https://doi.org/10.64898/2026.10.22.760671"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioengineering",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "Reprogramming CAR-T cell function through synthetic cytokine receptors suppresses metastatic progression of TNBC",
  "title_text": "Reprogramming CAR-T cell function through synthetic cytokine receptors suppresses metastatic progression of TNBC",
  "type": "preprint",
  "updated_at": "2026-11-09T12:23:42Z",
  "url": "https://research.draconitic.com/paper/b6c17tttq7vnw",
  "venue": "bioRxiv",
  "versions": []
}