{
  "abstract": "Introduction: Chimeric antigen receptor (CAR)-T cell therapy requires individual production for each patient, starting with a heterogeneous apheresis product of variable cellular composition and function. This inter-patient variability presents a major challenge for standardizing manufacturing processes and may lead to delays or even production failure. The primary aim of this study was to identify pre-leukapheresis characteristics associated with subsequent manufacturing deviations.\n\nMethods: Multiple T cell-related parameters including T cell receptor (TCR) Vβ repertoire, differentiation status, proliferation capacity (e.g. fraction diluted – DIL), and exhaustion were examined in n = 27 patients before leukapheresis for Kymriah ® immunotherapy. These parameters were analyzed for associations with manufacturing specification compliance and out-of-specification (OOS) events.\n\nResults: Impaired T-cell proliferation was the parameter most strongly associated with manufacturing specification non-conformance. Six of 21 evaluable patients showed poor proliferation (DIL <80%), including all four patients with OOS manufacturing outcomes. In contrast, all remaining patients had DIL values ≥84.9%. Exploratory associations between selected TCR Vβ subsets and manufacturing specifications were also identified.\n\nConclusion: DIL was the parameter most strongly associated with manufacturing specification compliance and may represent a simple functional measure of pre-apheresis T-cell fitness.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pediatrics, Goethe-University Frankfurt",
    "Department of Hematology and Oncology, University Medical Center of the Johannes Gutenberg University",
    "Department of Pediatric Hematology/Oncology and BMT, Wroclaw Medical University",
    "Department of Pediatric Oncology, Hematology and Clinical Immunology, Division of Pediatric Stem Cell Therapy, Medical Faculty, Heinrich Heine University",
    "Pediatric Hematology and Oncology, Hannover Medical School",
    "Department of Pediatric Hematology and Oncology, University Children’s Hospital Münster"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Melanie Bremm"
    },
    {
      "affs": [
        0
      ],
      "name": "Greta Heinze"
    },
    {
      "affs": [
        0
      ],
      "name": "Lara Schneeberger"
    },
    {
      "affs": [
        0
      ],
      "name": "Emilia Salzmann-Manrique"
    },
    {
      "affs": [
        0
      ],
      "name": "Julia Banisharif Dehkordi"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Andreas Peinelt"
    },
    {
      "affs": [
        2
      ],
      "name": "Krzysztof Kalwak"
    },
    {
      "affs": [
        2
      ],
      "name": "Monika Mielcarek-Siedziuk"
    },
    {
      "affs": [
        3
      ],
      "name": "Roland Meisel"
    },
    {
      "affs": [
        4
      ],
      "name": "Rita Beier"
    },
    {
      "affs": [
        5
      ],
      "name": "Claudia Rossig"
    },
    {
      "affs": [
        0
      ],
      "name": "Andrea Jarisch"
    },
    {
      "affs": [
        0
      ],
      "name": "Juliane Schlueter"
    },
    {
      "affs": [
        0
      ],
      "name": "Eva Rettinger"
    },
    {
      "affs": [
        0
      ],
      "name": "Jan-Henning Klusmann"
    },
    {
      "affs": [
        0
      ],
      "name": "Claudia Cappel"
    },
    {
      "affs": [
        0
      ],
      "name": "Peter Bader"
    },
    {
      "affs": [
        0
      ],
      "name": "Sabine Huenecke"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/brmva46bbk9vd.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1973579",
  "fulltext_url": null,
  "id": "brmva46bbk9vd",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1973579/full",
  "language": null,
  "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": [
    [
      "openalex",
      "2730|CAR-T cell therapy research"
    ]
  ],
  "openalex": "W7223924062",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1973579/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-27",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/brmva46bbk9vd.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1973579",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1973579/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|CAR-T cell therapy research",
      "subfield": "oncology"
    }
  ],
  "title": "Impaired ex vivo T-cell expansion before leukapheresis is associated with out-of-specification tisagenlecleucel manufacturing in pediatric CD19+ALL",
  "title_text": "Impaired ex vivo T-cell expansion before leukapheresis is associated with out-of-specification tisagenlecleucel manufacturing in pediatric CD19+ALL",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:17Z",
  "url": "https://research.draconitic.com/paper/brmva46bbk9vd",
  "venue": "Frontiers in Immunology",
  "versions": []
}