{
  "abstract": "Glioblastoma is a lethal brain tumour for which current multimodal treatment rarely prevents recurrence 1 . Therapeutic failure is driven by extensive intratumoural cellular heterogeneity 2 with a microenvironment dominated by tumour-associated macrophages that sustain tumour growth and immunosuppression 3 . Although chimeric antigen receptor (CAR)-T cell therapies are being developed for glioblastoma, sustained response has been undermined by non-uniform antigen expression, antigen loss and microenvironmental barriers that are not directly engaged by tumour-targeting designs 4 . These limitations motivate new strategies that address the disease as a coupled tumour–immune system rather than a single malignant compartment. Here we use a multi-omic target discovery platform to identify GPNMB as a dual-compartment antigen in glioblastoma. Anti-GPNMB CAR-T cells showed potent anti-tumour activity, with long-term disease control in orthotopic patient-derived xenografts and syngeneic glioma models through concomitant depletion of GPNMB + tumour and immunosuppressive myeloid populations. By collapsing tumour control and microenvironmental reprogramming, these findings provide a new strategy for antigen selection and targeting in heterogenous, myeloid-rich solid cancers.",
  "abstract_shown": true,
  "affiliations": [
    "Centre for Discovery in Cancer Research, McMaster University, Hamilton, Ontario, Canada",
    "Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada",
    "Department of Surgery, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada",
    "Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada",
    "Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada",
    "Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada",
    "Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada",
    "Feinberg School of Medicine, Northwestern University, Chicago, IL, USA",
    "McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada",
    "Division of Neurosurgery, Department of Surgery, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada",
    "Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada",
    "Department of Microbiology, Immunology and Infectious Disease, University of Calgary, Calgary, Alberta, Canada",
    "Centre for Discovery in Cancer Research, McMaster University, Hamilton, Ontario, Canada. sheila.singh@kcl.ac.uk",
    "Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada. sheila.singh@kcl.ac.uk",
    "Department of Surgery, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada. sheila.singh@kcl.ac.uk",
    "School of Cancer and Pharmaceutical Sciences, Comprehensive Cancer Centre, King's College London, London, UK. sheila.singh@kcl.ac.uk"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 35,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Neil J. Savage",
      "orcid": "0009-0004-5940-0567"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Shan Grewal"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Muhammad Vaseem Shaikh",
      "orcid": "0009-0009-6929-1209"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Franz J. Zemp",
      "orcid": "0000-0002-8845-3535"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Dillon McKenna",
      "orcid": "0009-0000-6803-9786"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Nicholas Mikolajewicz",
      "orcid": "0000-0002-7525-0384"
    },
    {
      "affs": [
        7
      ],
      "name": "Hinda Najem",
      "orcid": "0000-0003-4432-9708"
    },
    {
      "affs": [
        3
      ],
      "name": "Joanna Pyczek",
      "orcid": "0000-0002-0157-2049"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Jiuran Wei"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Mohamed Taleb",
      "orcid": "0000-0002-6153-8782"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Lucas C. Asselstine"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Alisha Anand",
      "orcid": "0000-0002-7111-1256"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Shawn C. Chafe",
      "orcid": "0000-0001-8802-651X"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Kui Zhai",
      "orcid": "0000-0003-4725-190X"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "William T. Maich",
      "orcid": "0009-0000-5491-3452"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Chirayu Chokshi",
      "orcid": "0000-0003-0831-0217"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Hardikkumar Patel"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Tiegan Korman",
      "orcid": "0009-0005-9805-8669"
    },
    {
      "affs": [
        8
      ],
      "name": "Minomi Subapanditha",
      "orcid": "0009-0000-5619-5976"
    },
    {
      "affs": [
        8
      ],
      "name": "Zoya Tabunshchyk"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Nazanin Tatari",
      "orcid": "0000-0002-0003-6121"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Petar Miletic",
      "orcid": "0009-0008-6248-588X"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Di Chen",
      "orcid": "0000-0001-9509-2814"
    },
    {
      "affs": [
        7
      ],
      "name": "Sebastián Pacheco",
      "orcid": "0000-0002-3235-6226"
    },
    {
      "affs": [
        9
      ],
      "name": "Abdelsimar Tan Omar",
      "orcid": "0000-0002-2965-8506"
    },
    {
      "affs": [
        9
      ],
      "name": "Bo Wang",
      "orcid": "0000-0001-5132-7685"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "韩红"
    },
    {
      "affs": [
        3
      ],
      "name": "Jennifer Ai-wen Chan",
      "orcid": "0000-0001-9798-1551"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Kevin R. Brown",
      "orcid": "0000-0002-5514-2538"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Chitra Venugopal",
      "orcid": "0009-0000-2968-2971"
    },
    {
      "affs": [
        10
      ],
      "name": "Thomas Kislinger",
      "orcid": "0000-0003-3525-5540"
    },
    {
      "affs": [
        7
      ],
      "name": "Amy B. Heimberger",
      "orcid": "0000-0002-9970-8695"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Jason Moffat",
      "orcid": "0000-0002-5663-8586"
    },
    {
      "affs": [
        3,
        11
      ],
      "name": "Douglas J. Mahoney",
      "orcid": "0000-0002-0642-992X"
    },
    {
      "affs": [
        12,
        13,
        14,
        15
      ],
      "name": "Sheila Kumari Singh",
      "orcid": "0000-0003-1272-5300"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bc0xfgc10cjhf.bib",
  "cited_by": 14,
  "doi": "10.1038/s41586-026-10641-1",
  "fulltext_url": null,
  "id": "bc0xfgc10cjhf",
  "issns": [
    "0028-0836",
    "1476-4687"
  ],
  "landing_url": "https://doi.org/10.1038/s41586-026-10641-1",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2730|CAR-T cell therapy research"
    ]
  ],
  "openalex": "W7166813464",
  "pdf_url": null,
  "pmcid": "PMC13518245",
  "pmid": "42386964",
  "published": "2026-07-01",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/bc0xfgc10cjhf.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:54Z",
      "native_id": "W7166813464",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41586-026-10641-1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|CAR-T cell therapy research",
      "subfield": "oncology"
    }
  ],
  "title": "Dual tumour–myeloid targeting of glioblastoma with GPNMB CAR-T cells",
  "title_text": "Dual tumour–myeloid targeting of glioblastoma with GPNMB CAR-T cells",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T13:20:51Z",
  "url": "https://research.draconitic.com/paper/bc0xfgc10cjhf",
  "venue": "Nature",
  "versions": []
}