{
  "abstract": "Background: Most tumor-infiltrating lymphocyte (TIL) studies and therapies have focused on tumors with high T-cell infiltration and mutational burden. Glioblastoma (GBM) represents a challenging indication for TIL therapy because of its limited T-cell infiltration and low mutational burden. We investigated whether targeted enrichment of tumor-reactive T cells using CD137-based selection could enable robust, clinical-scale production of TIL products from GBM.\n\nMethods: Ultrasonic aspirates (UAs), routinely collected during GBM resections, were evaluated as a source of TILs for clinical manufacturing. TILs were generated from GBM UAs under GMP-like conditions at clinical scale using the closed, automated TRT Process on the CliniMACS Prodigy. Matched TRT products that were enriched for CD137+ cells, depleted of CD137+ cells, or left unselected were generated in parallel at full manufacturing scale. Products were characterized by cellular and transcriptomic analyses and evaluated in functional assays for cytotoxicity against autologous and non-autologous patient-derived GBM cell lines.\n\nResults: Cellular and transcriptomic analyses revealed that UA-derived CD137+ (4-1BB/TNFRSF9) T cells were clonally expanded, exhibited activated and memory phenotypes, and displayed transcriptional profiles associated with tumor reactivity. The closed manufacturing process preserved phenotypic features previously associated with clinical benefit in other TIL indications. Functional assays demonstrated potent, tumor-reactive cytotoxicity of CD137-enriched TRT products against autologous GBM cell lines compared with TILs generated in parallel without selection.\n\nDiscussion/Conclusions: These findings establish the feasibility of a clinical-scale TIL manufacturing approach using the CliniMACS Prodigy that enables production of clinically relevant quantities of TILs from GBM while enriching for cells with tumor-reactive characteristics. This approach may broaden the application of TIL therapy to immunologically cold tumors with limited T-cell infiltration or low mutational burden that have historically been challenging to manufacture using conventional TIL production methods.",
  "abstract_shown": true,
  "affiliations": [
    "Miltenyi Biotec GmbH, Bergisch Gladbach, Germany",
    "Division of Clinical Neurooncology, University Hospital of Essen, Essen, Germany",
    "Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Hospital of Essen, Essen, Germany",
    "Department of Neurosurgery and Spine Surgery, Center for Translational Neuro- and Behavioural Sciences (C-TNBS), University Hospital of Essen, Essen, Germany",
    "Department of Neurology and Neurooncology, St. Marien Hospital, Lünen, Germany",
    "Department of Neurooncology, Center for Neurology, University Hospital Bonn, Bonn, Germany",
    "Department of Neurosurgery, University Hospital Bonn, Bonn, Germany",
    "Department of Neurosurgery, University Hospital Frankfurt, Frankfurt, Germany",
    "Department of Surgery, Institute of Clinical Sciences, University of, Gothenburg, Sweden"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 27,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Arina Riabinska"
    },
    {
      "affs": [
        0
      ],
      "name": "Elvira Criado-Moronati"
    },
    {
      "affs": [
        0
      ],
      "name": "Emre Balta"
    },
    {
      "affs": [
        0
      ],
      "name": "Denis Frison"
    },
    {
      "affs": [
        0
      ],
      "name": "Cristina Berganza-Irusqueta"
    },
    {
      "affs": [
        0
      ],
      "name": "Tümay Telatar"
    },
    {
      "affs": [
        0
      ],
      "name": "Donata Maciaczyk"
    },
    {
      "affs": [
        0
      ],
      "name": "Johanna Engeln"
    },
    {
      "affs": [
        0
      ],
      "name": "Laura Fischer"
    },
    {
      "affs": [
        0
      ],
      "name": "Marieke Domdey"
    },
    {
      "affs": [
        0
      ],
      "name": "Imran Siddiqui"
    },
    {
      "affs": [
        0
      ],
      "name": "Velita Miranda"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Teresa Schmidt"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Sied Kebir"
    },
    {
      "affs": [
        3
      ],
      "name": "Yahya Ahmadipour"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Martin Glas"
    },
    {
      "affs": [
        5
      ],
      "name": "Ulrich Herrlinger"
    },
    {
      "affs": [
        6
      ],
      "name": "Matthias Schneider"
    },
    {
      "affs": [
        6
      ],
      "name": "Anna-Laura Potthoff"
    },
    {
      "affs": [
        7
      ],
      "name": "Marcus Czabanka"
    },
    {
      "affs": [
        7
      ],
      "name": "Thomas Broggini"
    },
    {
      "affs": [
        8
      ],
      "name": "Sofia Stenqvist"
    },
    {
      "affs": [
        8
      ],
      "name": "Lisa M. Nilsson"
    },
    {
      "affs": [
        8
      ],
      "name": "Jonas A. Nilsson"
    },
    {
      "affs": [
        0
      ],
      "name": "Martina Ott"
    },
    {
      "affs": [
        0
      ],
      "name": "Andrzej Dzionek"
    },
    {
      "affs": [
        0
      ],
      "name": "Ian R. Hardy"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6f0fs3bnv8hcj.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1866645",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13697625/",
  "id": "6f0fs3bnv8hcj",
  "issns": [
    "1664-3224"
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  "landing_url": "https://doi.org/10.3389/fimmu.2026.1866645",
  "language": "en",
  "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"
    ],
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      "openalex",
      "2730|CAR-T cell therapy research"
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  "openalex": "W7221556373",
  "pdf_url": "https://europepmc.org/articles/PMC13697625?pdf=render",
  "pmcid": "PMC13697625",
  "pmid": "42935925",
  "published": "2026-10-12",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/6f0fs3bnv8hcj.ris",
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|CAR-T cell therapy research",
      "subfield": "oncology"
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  ],
  "title": "Clinical-scale manufacturing of CD137+ enriched tumor-reactive T cells for glioblastoma in the CliniMACS Prodigy",
  "title_text": "Clinical-scale manufacturing of CD137+ enriched tumor-reactive T cells for glioblastoma in the CliniMACS Prodigy",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:34:38Z",
  "url": "https://research.draconitic.com/paper/6f0fs3bnv8hcj",
  "venue": "Frontiers in Immunology",
  "versions": []
}