{
  "abstract": "Background: Glioblastoma, the most common and aggressive primary brain malignancy, remains a lethal disease with limited therapeutic progress despite multimodal treatment. Although chimeric antigen receptor (CAR) T-cell therapy has shown promise in several solid tumors, its broader application in glioblastoma is limited by manufacturing hurdles of autologous T cells and the lack of validated tumor-specific antigens. As an alternative, gamma-delta (γδ) T cells have emerged as an attractive cellular platform, offering MHC-independent tumor recognition, robust ex vivo expansion, and suitability for allogeneic use. However, studies applying CAR engineering to γδ T cells in glioblastoma are extremely limited, and an optimal target antigen has not been clearly defined. In this context, our study identified B7-H3 as a clinically relevant target and demonstrated that B7-H3 CAR γδ T cells exhibited superior antitumor efficacy compared to unmodified γδ T cells across patient-derived and orthotopic glioblastoma models.\n\nMethods: To identify an optimal antigen for γδ CAR-T therapy in glioblastoma, we compared the expression and clinical relevance of HER2, GD2, and B7-H3 through analyses of transcriptomic datasets and patient tumor samples. Based on this, human γδ T cells from healthy donors were expanded ex vivo, engineered with a B7-H3–specific CAR, and evaluated for antitumor activity across patient-derived glioblastoma cell lines, organoids, and orthotopic xenograft models.\n\nResults: B7-H3 was identified as the most clinically relevant antigen, showing high expression in glioblastoma and correlated with poor prognosis and immunosuppressive gene signatures. B7-H3 CAR γδ T cells demonstrated potent cytotoxicity and enhanced cytokine production in B7-H3–high patient-derived glioblastoma models. In patient-derived organoids, CAR γδ T cells significantly reduced tumor viability and invasion. In orthotopic xenografts, a single intracranial administration induced tumor control and prolonged survival, with long-term survivors observed only in the CAR γδ T cell treated group. Across all preclinical models, B7-H3 CAR γδ T cells exerted superior antitumor efficacy compared with parental γδ T cells.\n\nConclusions: These findings suggest B7-H3 as a clinically meaningful and therapeutically targetable antigen in glioblastoma and demonstrate the potent preclinical efficacy of allogeneic B7-H3 CAR γδ T cells, supporting their development as a novel immunotherapeutic strategy for glioblastoma.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12916-026-05121-2.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medical Sciences, Graduate School of The Catholic, University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591 Republic of Korea",
    "Department of Microbiology, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591 Republic of Korea",
    "Department of Neurosurgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591 Republic of Korea",
    "Precision Medicine Research Center, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591 Republic of Korea",
    "Catholic Hematopoietic Stem Cell Bank, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591 Republic of Korea",
    "Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218 USA",
    "Institute for NanoBioTechnology, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218 USA",
    "Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, MD 21205 Baltimore, United States of America",
    "Laboratory of Host Defenses, Department of Biological Sciences, Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon, 34141 Republic of Korea",
    "Department of Neurosurgery, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpodae-ro, Seocho-gu Seoul, 06591, Republic of Korea"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Soohyeon Lee"
    },
    {
      "affs": [
        2
      ],
      "name": "Soon-A Park"
    },
    {
      "affs": [
        2
      ],
      "name": "Hantae Jo"
    },
    {
      "affs": [
        0,
        1,
        3
      ],
      "name": "Dokyeong Kim"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Junseong Park"
    },
    {
      "affs": [
        0,
        1,
        3,
        4
      ],
      "name": "Yeun-Jun Chung"
    },
    {
      "affs": [
        5,
        6,
        7
      ],
      "name": "Sangmoo Jeong"
    },
    {
      "affs": [
        1,
        4
      ],
      "name": "Yeong Hui Cho"
    },
    {
      "affs": [
        8
      ],
      "name": "Heung Kyu Lee"
    },
    {
      "affs": [
        9
      ],
      "name": "Stephen Ahn"
    },
    {
      "affs": [
        0,
        1,
        4
      ],
      "name": "Haeyoun Choi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/09qydzf7de9ca.bib",
  "cited_by": 0,
  "doi": "10.1186/s12916-026-05121-2",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13746759/",
  "id": "09qydzf7de9ca",
  "issns": [
    "1741-7015"
  ],
  "landing_url": "https://doi.org/10.1186/s12916-026-05121-2",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2730|CAR-T cell therapy research"
    ]
  ],
  "openalex": "W7172347955",
  "pdf_url": null,
  "pmcid": "PMC13746759",
  "pmid": "43004422",
  "published": "2026-08-03",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/09qydzf7de9ca.ris",
  "sources": [
    {
      "first_seen": "2026-11-11T12:24:05Z",
      "native_id": "PMC13746759",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s12916-026-05121-2"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|CAR-T cell therapy research",
      "subfield": "oncology"
    }
  ],
  "title": "Efficacy of allogeneic B7-H3 CAR γδ T cells with comparative target assessment across preclinical models in glioblastoma",
  "title_text": "Efficacy of allogeneic B7-H3 CAR γδ T cells with comparative target assessment across preclinical models in glioblastoma",
  "type": "peer-reviewed",
  "updated_at": "2026-11-13T12:23:24Z",
  "url": "https://research.draconitic.com/paper/09qydzf7de9ca",
  "venue": "BMC Medicine",
  "versions": []
}