{
  "abstract": "Background: Poorly differentiated thyroid carcinoma (PDTC) has no effective systemic treatment option once radioactive iodine and tyrosine kinase inhibitors fail. The thyroid-stimulating hormone receptor (TSHR) is highly tissue-restricted and the anti-TSHR autoantibody repertoire of thyroid autoimmunity offers sequence-defined, fully human binders. We asked whether this repertoire can be converted into an off-the-shelf T cell-redirecting therapy for PDTC. Methods: TSHR expression was profiled on a 151-case thyroid cancer tissue microarray (TMA), 50 healthy controls and on fresh tumor material. Eight anti-TSHR clones, four of human autoimmune origin (M22, K1-18, K1-70, 5C9) and four murine (IRI-SAb2, IRI-SAb3, 9D33, 1H7), were reformatted as CD3-engaging bispecific antibodies (bsAbs; anti-TSHR Fab x anti-CD3 scFv) and, for leading clones, as chimeric antigen receptor (CAR) T cells. Activity was compared in vitro, across graded and mixed antigen densities and in a CAL-62-Luc-TSHR xenograft model, using healthy-donor (HD) or thyroid cancer-patient T cells. Results: TSHR was retained on a substantial fraction of PDTC, including metastatic lesions. Both formats mediated potent, antigen-selective killing and the leading bsAbs suppressed xenograft growth in vivo. For CAR T cells, scFv heavy/light-chain orientation was decisive. Anti-TSHR bsAbs cleared mixed cultures far beyond the antigen-positive fraction matching mosunetuzumab and indicating a modality-intrinsic bystander effect. Patient-derived T cells obtained on or after oncological treatment retained full effector function. Conclusions: The anti-TSHR autoantibody repertoire provides a promising source of binders for off-the-shelf bispecific antibodies targeting TSHR-positive thyroid cancer, while CAR T cells offer an autologous alternative.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory of Translational Immuno-Oncology, Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 21,
  "authors": [
    {
      "name": "C. Fischer"
    },
    {
      "name": "A. Eugster"
    },
    {
      "name": "B. Besemer"
    },
    {
      "name": "M. Buchi"
    },
    {
      "name": "M. Bauer"
    },
    {
      "name": "C. Schultheiss"
    },
    {
      "name": "E. D'Arcangelo"
    },
    {
      "name": "F. Filipsky"
    },
    {
      "name": "C. Wickenhauser"
    },
    {
      "name": "A. Wilfer"
    },
    {
      "name": "K. Lorenz"
    },
    {
      "name": "J. Jakscha"
    },
    {
      "name": "L. Muller"
    },
    {
      "name": "R. Köberle-Wührer"
    },
    {
      "name": "B. Kasenda"
    },
    {
      "name": "C. Rottenburger"
    },
    {
      "name": "R. Latif"
    },
    {
      "name": "T. F. Davies"
    },
    {
      "name": "H. Läubli"
    },
    {
      "name": "M. Peipp"
    },
    {
      "affs": [
        0
      ],
      "name": "M. Binder"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3rkywbz66cxm0.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.19.760040",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.19.760040v1.full",
  "id": "3rkywbz66cxm0",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.19.760040v1",
  "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",
      "cancer biology"
    ],
    [
      "openalex",
      "2712|Thyroid Cancer Diagnosis and Treatment"
    ]
  ],
  "openalex": "W7223024586",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.19.760040v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-19",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/3rkywbz66cxm0.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:45Z",
      "native_id": "10.64898/2026.10.19.760040",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.19.760040v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Targeting poorly differentiated thyroid cancer with bispecific antibodies and CAR T cells from the human anti-TSHR autoantibody repertoire",
  "title_text": "Targeting poorly differentiated thyroid cancer with bispecific antibodies and CAR T cells from the human anti-TSHR autoantibody repertoire",
  "type": "preprint",
  "updated_at": "2026-10-30T12:28:45Z",
  "url": "https://research.draconitic.com/paper/3rkywbz66cxm0",
  "venue": "bioRxiv",
  "versions": []
}