{
  "abstract": "Background: In adoptive cell therapy with tumor-infiltrating lymphocytes (TILs), TILs are isolated and expanded ex vivo from an autologous tumor lesion. TIL therapy, comprising preparative lymphodepleting chemotherapy, TIL infusion, and post-infusion supportive interleukin-2 (IL-2) administration, has demonstrated efficacy in patients with metastatic melanoma. Interest in extending TIL therapy to other solid tumors is growing, and a tumor-agnostic manufacturing platform would allow first-in-human trials to be launched rapidly in these indications.\n\nObjective: This study investigated whether a manufacturing process and control strategy developed for metastatic melanoma-derived TILs could be adapted into a tumor-agnostic platform for the generation of TILs from different solid tumor types, referred to as NTU101.\n\nMethods: The feasibility of generating TILs from endometrial carcinoma (ENDC, n=9), non-small cell lung cancer (NSCLC, n=9), and penile cancer (PENC, n=10) lesions was assessed during process development (PD) runs using predefined quality criteria. Throughout PD runs, flow cytometry was used to characterize cells. When available, autologous tumor digest was used to assess the tumor-reactive potential of TILs. Based on PD experience, adjusted quality criteria were applied to manufacture one full-scale GMP NTU101-drug product (DP) per tumor type.\n\nResults: Overall, 89% (n=25/28) of PD NTU101-DPs manufactured met the predefined quality criteria, containing at least 0.5×10^9 and 90% viable CD45+CD3+ cells, less than 1.0% of cellular impurities (viable CD45- and CD19+ cells), and a potency of more than 1.0×10^3 pg/mL IFN-γ secretion upon CD3/CD28-polymer stimulation. Across the tumor types, PD NTU101-DPs had comparable T-cell subset and differentiation state compositions. In vitro tumor-reactive potential was detected in 82% of tested NTU101-DPs (ENDC: 71%, n=5/7; NSCLC: 80%, n= 4/5; and PENC: 100%, n=5/5), although the level of reactivity will need to be confirmed with a more in-depth assay. One GMP NTU101-DP was then manufactured from each tumor type, and all three met NTU101’s quality criteria.\n\nConclusion: The NTU101 platform produced comparable NTU101-DPs from three solid tumor types beyond melanoma, with in vitro tumor-reactive potential for some batches. This platform can be applied in TIL therapy clinical trials to generate ENDC-, NSCLC-, and PENC-derived TILs, and possibly other solid tumor types.",
  "abstract_shown": true,
  "affiliations": [
    "BioTherapeutics Unit, The Netherlands Cancer Institute-Antoni van Leeuwenhoek",
    "Division of Molecular Oncology and Immunology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek",
    "Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek",
    "Department of Research Laboratory for Cell Therapy, Sanquin Blood Supply Foundation",
    "Department of Research T-cell differentiation lab, Sanquin Blood Supply Foundation",
    "Division of Medical Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek",
    "Department of Surgery, The Netherlands Cancer Institute-Antoni van Leeuwenhoek",
    "Department of Pulmonary Disease, Leiden University Medical Center",
    "Department of Gynaecologic Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek",
    "Julius Centre for Health Science and Primary Care, University Medical Center Utrecht",
    "Department of Urology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek",
    "Oncode Institute",
    "Landsteiner Laboratory, Amsterdam Medical Center",
    "Department of Medical Oncology, Leiden University Medical Center",
    "The Melanoma Clinic, Centre Hospitalier Universitaire Vaudois",
    "Department of Pharmaceutical Sciences, Utrecht University"
  ],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 25,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Justin Lievense"
    },
    {
      "affs": [
        1
      ],
      "name": "Liselotte Tas"
    },
    {
      "affs": [
        0
      ],
      "name": "Maaike van Zon"
    },
    {
      "affs": [
        0
      ],
      "name": "Kari-Anne Legué-van Duinen"
    },
    {
      "affs": [
        2
      ],
      "name": "Rosa van Amerongen"
    },
    {
      "affs": [
        0
      ],
      "name": "Sander Kouwen"
    },
    {
      "affs": [
        0
      ],
      "name": "Rosalie van Riessen"
    },
    {
      "affs": [
        0
      ],
      "name": "Femke Sluiter"
    },
    {
      "affs": [
        0
      ],
      "name": "Jeltsje Hagg"
    },
    {
      "affs": [
        0
      ],
      "name": "Madelon Badoux"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Iris Manders"
    },
    {
      "affs": [
        1
      ],
      "name": "Eva Vedder"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Erica Sellink"
    },
    {
      "affs": [
        5
      ],
      "name": "Tom Seijkens"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Koen Hartemink"
    },
    {
      "affs": [
        8,
        9
      ],
      "name": "Marcus Rijken"
    },
    {
      "affs": [
        10
      ],
      "name": "Oscar Brouwer"
    },
    {
      "affs": [
        3,
        4,
        11,
        12
      ],
      "name": "Suzanne Castenmiller"
    },
    {
      "affs": [
        3,
        12
      ],
      "name": "Marten Hansen"
    },
    {
      "affs": [
        4,
        11,
        12
      ],
      "name": "Monika Wolkers"
    },
    {
      "affs": [
        1,
        5,
        13,
        14
      ],
      "name": "John Haanen"
    },
    {
      "affs": [
        2,
        15
      ],
      "name": "Jos Beijnen"
    },
    {
      "affs": [
        0
      ],
      "name": "Cynthia Nijenhuis"
    },
    {
      "affs": [
        1
      ],
      "name": "Inge Jedema"
    },
    {
      "affs": [
        2
      ],
      "name": "Bastiaan Nuijen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cz3yqpbg9t36m.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1854761",
  "fulltext_url": "https://europepmc.org/articles/PMC13677931",
  "id": "cz3yqpbg9t36m",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1854761/full",
  "language": "eng",
  "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": "W7220395015",
  "pdf_url": "https://europepmc.org/articles/PMC13677931?pdf=render",
  "pmcid": "PMC13677931",
  "pmid": "42898410",
  "published": "2026-10-05",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/cz3yqpbg9t36m.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:15Z",
      "native_id": "10.3389/fimmu.2026.1854761",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1854761/full"
    },
    {
      "first_seen": "2026-10-30T12:19:37Z",
      "native_id": "MED:42898410",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42898410"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|CAR-T cell therapy research",
      "subfield": "oncology"
    }
  ],
  "title": "Platform-based manufacturing of tumor-infiltrating lymphocytes derived from different solid tumor types",
  "title_text": "Platform-based manufacturing of tumor-infiltrating lymphocytes derived from different solid tumor types",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:37Z",
  "url": "https://research.draconitic.com/paper/cz3yqpbg9t36m",
  "venue": "Frontiers in Immunology",
  "versions": []
}