{
  "abstract": "Background: Autologous chimeric antigen receptor (CAR)-T cell therapy exhibits remarkable clinical efficacy for hematologic malignancies; however, its efficacy against solid tumors is limited by the immunosuppressive tumor microenvironment and the lack of effective strategies to induce broader antitumor immunity. Invariant natural killer T (iNKT) cells are known to elicit antitumor effects by activating tumor antigen-specific cytotoxic T lymphocytes, promoting dendritic cells maturation, and modulating macrophage activity, thereby providing a mechanism distinct from conventional T cell-based therapies. To couple this immunomodulatory capacity of iNKT cells with CAR technology, we developed allogeneic induced pluripotent stem cell (iPSC)-derived iNKT cells bearing a human epidermal growth factor receptor 2 (HER2) reactive CAR (HER2 CAR) and evaluated their cytotoxic and immunomodulatory functions.\n\nMethod: HER2 CAR-expressing iPSC-derived iNKT (HER2 CAR-ipsNKT) cells were generated and characterized for cytotoxic and immunomodulatory functions, including T-cell recruitment, and M2 macrophage re-polarization, and were evaluated for antitumor efficacy in xenograft mouse models.\n\nResults: HER2 CAR-ipsNKT cells specifically recognized HER2-positive tumor cells and exerted potent antitumor activity through NK-like cytotoxicity. In addition to direct tumor killing, HER2 CAR-ipsNKT cells promoted the expansion of tumor-reactive T cells, and this effect was diminished following depletion of CD11c+ cells. HER2 CAR-ipsNKT cells also demonstrated immunomodulatory properties, including T-cell recruitment activity and M2 macrophage killing and re-polarization, supporting remodeling of the tumor immune microenvironment.\n\nConclusion: Our findings demonstrate that HER2 CAR-ipsNKT cells not only exert direct antitumor activity but also promote CD11c-dependent expansion of antigen-reactive CD8+ T cells, suggesting their capacity to induce broader antitumor immunity.",
  "abstract_shown": true,
  "affiliations": [
    "BrightPath Biotherapeutics Co Ltd, Tokyo, Japan",
    "Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan",
    "Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan",
    "Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Koichiro Shioya",
      "orcid": "0000-0001-7913-755X"
    },
    {
      "affs": [
        0
      ],
      "name": "Tomio Matsumura",
      "orcid": "0009-0001-4471-9151"
    },
    {
      "affs": [
        0
      ],
      "name": "Akane Urakami",
      "orcid": "0009-0009-4999-3297"
    },
    {
      "affs": [
        0
      ],
      "name": "Tomokuni Shigeura",
      "orcid": "0009-0005-6246-1587"
    },
    {
      "affs": [
        0
      ],
      "name": "Yu-Ching Lin",
      "orcid": "0009-0002-5501-682X"
    },
    {
      "affs": [
        0
      ],
      "name": "Mio Fujimaki",
      "orcid": "0009-0008-9255-7020"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuji Mishima",
      "orcid": "0000-0002-5116-0835"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Takahiro Aoki",
      "orcid": "0000-0002-9148-2871"
    },
    {
      "affs": [
        1
      ],
      "name": "Momoko Okoshi",
      "orcid": "0009-0000-2507-0433"
    },
    {
      "affs": [
        1
      ],
      "name": "Kiwamu Motoyoshi",
      "orcid": "0009-0008-1551-4043"
    },
    {
      "affs": [
        2
      ],
      "name": "Shinichiro Motohashi",
      "orcid": "0000-0002-9332-3129"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Haruhiko Koseki",
      "orcid": "0000-0001-8424-5854"
    },
    {
      "affs": [
        0
      ],
      "name": "Lilin Zhang",
      "orcid": "0009-0001-0624-0537"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1wg8bnck04sph.bib",
  "cited_by": 0,
  "doi": "10.1136/jitc-2026-016268",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13711592/",
  "id": "1wg8bnck04sph",
  "issns": [
    "2051-1426"
  ],
  "landing_url": "https://doi.org/10.1136/jitc-2026-016268",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "1506"
    ],
    [
      "heading",
      "2436"
    ],
    [
      "heading",
      "Immune Cell Therapies and Immune Cell Engineering"
    ],
    [
      "openalex",
      "2730|CAR-T cell therapy research"
    ]
  ],
  "openalex": "W7223003146",
  "pdf_url": "https://jitc.bmj.com/content/14/10/e016268.full.pdf",
  "pmcid": "PMC13711592",
  "pmid": "42901718",
  "published": "2026-10-20",
  "publisher": "BMJ Publishing Group",
  "ris": "https://research.draconitic.com/paper/1wg8bnck04sph.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:22:20Z",
      "native_id": "PMC13711592",
      "source": "pmc",
      "url": "https://doi.org/10.1136/jitc-2026-016268"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|CAR-T cell therapy research",
      "subfield": "oncology"
    }
  ],
  "title": "HER2 CAR-expressing iPSC-derived iNKT cells exhibit multifaceted immunomodulatory functions beyond direct tumor killing",
  "title_text": "HER2 CAR-expressing iPSC-derived iNKT cells exhibit multifaceted immunomodulatory functions beyond direct tumor killing",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:22:20Z",
  "url": "https://research.draconitic.com/paper/1wg8bnck04sph",
  "venue": "Journal for Immunotherapy of Cancer",
  "versions": []
}