{
  "abstract": "Cancer-testis antigens (CTAs) are attractive targets for tumour immunotherapy due to their restricted expression in human malignancies and broad population-level prevalence. However, naturally occurring CTA-reactive T cells are often exhausted or functionally compromised, limiting their direct therapeutic utility. Here, using a non-viral orthotopic TCR replacement system, we systematically evaluated two patient-derived HLA-A*02:01-restricted TCRs specific for the synovial sarcoma X breakpoint 2 (SSX2) epitope SSX2 ₄₁₋₄₉ (KASEKIFYV). Although both TCRs conferred SSX2 specificity, one displayed markedly higher functional avidity and superior antigen responsiveness. Primary CD8 ⁺ T cells redirected with this high-avidity TCR showed CD8-independent recognition, enhanced tetramer binding, and stronger functional responses against SSX2-expressing tumour cells. Notably, the same TCR also redirected CD4 ⁺ T cells toward the MHC-I-restricted SSX2 epitope, inducing polyfunctional cytokine release and direct tumour cytotoxicity. Moreover, it remained highly functional when introduced into unconventional T cell subsets, including NKT and γδ T cells, thereby expanding the range of potential cellular platforms for TCR-based therapeutics. Together, these findings identify a naturally derived, high functional avidity SSX2-reactive TCR with broad activity across conventional and unconventional T cell subsets, supporting its further development for future TCR-T cell-based immunotherapies.",
  "abstract_shown": true,
  "affiliations": [
    "CAMS Oxford Institute, Chinese Academy of Medical Sciences & Peking Union Medical College, University of Oxford",
    "MRC Translational Immune Discovery Unit (TIDU), MRC Weatherall Institute of Molecular Medicine (WIMM), Radcliffe Department of Medicine (RDM), University of Oxford",
    "Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford University Hospitals NHS Foundation Trust",
    "Oxford National Institute of Health Research (NIHR) Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust",
    "Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Fei Gao"
    },
    {
      "affs": [
        0
      ],
      "name": "Yanchun Peng"
    },
    {
      "affs": [
        1
      ],
      "name": "Ji-Li Chen"
    },
    {
      "affs": [
        1
      ],
      "name": "Mariana Pereira Pinho"
    },
    {
      "affs": [
        0
      ],
      "name": "Xuan Yao"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yi-Ling Chen"
    },
    {
      "affs": [
        1
      ],
      "name": "Uzi Gileadi"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Adam Bates"
    },
    {
      "affs": [
        1
      ],
      "name": "Craig Waugh"
    },
    {
      "affs": [
        1
      ],
      "name": "Paul Sopp"
    },
    {
      "affs": [
        0,
        2,
        3,
        4
      ],
      "name": "Nikolaos I. Kanellakis"
    },
    {
      "affs": [
        0,
        2,
        3,
        4
      ],
      "name": "Najib M. Rahman"
    },
    {
      "affs": [
        0
      ],
      "name": "Ricardo A. Fernandes"
    },
    {
      "affs": [
        0,
        1,
        3
      ],
      "name": "Graham S. Ogg"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Tao Dong"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5h0rgrn07hrrq.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1964649",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13724408/?tool=EBI",
  "id": "5h0rgrn07hrrq",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1964649/full",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2403|Immunotherapy and Immune Responses"
    ]
  ],
  "openalex": "W7222968682",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1964649/pdf",
  "pmcid": "PMC13724408",
  "pmid": "42973514",
  "published": "2026-10-19",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/5h0rgrn07hrrq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
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      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1964649/full"
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      "url": "https://europepmc.org/article/PMC/PMC13724408"
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      "url": "https://doi.org/10.3389/fimmu.2026.1964649"
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immunotherapy and Immune Responses",
      "subfield": "immunology"
    }
  ],
  "title": "Patient-derived high functional avidity TCR empowers diverse T cell subsets for tumour immunotherapy",
  "title_text": "Patient-derived high functional avidity TCR empowers diverse T cell subsets for tumour immunotherapy",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:20:54Z",
  "url": "https://research.draconitic.com/paper/5h0rgrn07hrrq",
  "venue": "Frontiers in Immunology",
  "versions": []
}