{
  "abstract": "Intracellular immune checkpoints regulate activation thresholds in cytotoxic immune cells. Casitas B-lineage lymphoma proto-oncogene B (CBL-B) is an E3 ubiquitin ligase that negatively regulates antigen receptor signaling and T cell activation. APN401 is an autologous peripheral blood mononuclear cell (PBMC) therapy incorporating transient small interfering RNA (siRNA)-mediated CBL-B silencing. Two phase 1 studies evaluated escalating doses of APN401 in patients with advanced treatment-refractory solid tumors. APN401 was manufactured from leukapheresis-derived PBMCs using the EPiC point-of-care platform. Seventeen patients received APN401 across three dose levels. APN401 demonstrated a favorable safety profile, with no dose-limiting toxicities, cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or grade ≥3 treatment-related adverse events. Manufacturing was reproducible across sites. Although no objective responses were observed, disease stabilization occurred in 5 of 10 Response Evaluation Criteria in Solid Tumors (RECIST)-evaluable patients (50.0%), corresponding to 29.4% of all 17 treated patients. Exploratory analyses identified treatment-associated systemic immune changes, including enrichment of circulating CD8⁺ T cells, induction of cytotoxic mediators, and expansion of dominant T cell receptor β (TCRβ) clonotypes. These changes were most pronounced in patients with stable disease but remain exploratory and hypothesis-generating. These findings support further evaluation of APN401 in larger, controlled studies.",
  "abstract_shown": true,
  "affiliations": [
    "InvIOs GmbH, Campus Vienna Biocenter 5, 1030 Vienna, Austria",
    "Medical University of Vienna, Department of Transfusion Medicine and Cell Therapy, Waehringer Guertel 18-20, 1090 Vienna, Austria",
    "Medical University of Vienna, Department of Medicine I, Division of Oncology, Waehringer Guertel 18-20, 1090 Vienna, Austria",
    "Ordensklinikum Linz GmbH, Barmherzige Schwestern, Seilerstaette 4, 4020 Linz, Austria",
    "Medical University Innsbruck, Department of Internal Medicine V, Hematology and Oncology, Anichstrasse 35, 6020 Innsbruck, Austria",
    "Salzburg Cancer Research Institute, Center for Clinical Cancer and Immunology Trials, Paracelsus Medical University Salzburg, Muellner Hauptstrasse 48, 5020 Salzburg, Austria",
    "Austrian Red Cross, Blood Transfusion Service for Upper Austria, Krankenhaustrasse 7, 4010 Linz, Austria"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 25,
  "authors": [
    {
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        0
      ],
      "name": "Alexander Dohnal"
    },
    {
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        1
      ],
      "name": "Nina Worel"
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    {
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        0
      ],
      "name": "Thomas Bogenrieder"
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    {
      "affs": [
        2
      ],
      "name": "Thorsten Fuereder"
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    {
      "affs": [
        3
      ],
      "name": "Martin Burian"
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    {
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        4
      ],
      "name": "Dominik Wolf"
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    {
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        2
      ],
      "name": "Gerald Prager"
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    {
      "affs": [
        5
      ],
      "name": "Richard Greil"
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    {
      "affs": [
        6
      ],
      "name": "Anja Peterbauer-Scherb"
    },
    {
      "affs": [
        1
      ],
      "name": "Beate Schrenk"
    },
    {
      "affs": [
        0
      ],
      "name": "Stefan Bunka"
    },
    {
      "affs": [
        0
      ],
      "name": "Ernesto Abila"
    },
    {
      "affs": [
        1
      ],
      "name": "Felix Batrina"
    },
    {
      "affs": [
        0
      ],
      "name": "Maria Urban"
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    {
      "affs": [
        0
      ],
      "name": "Julia Buchberger"
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    {
      "affs": [
        0
      ],
      "name": "Alice Schwarzboeck"
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    {
      "affs": [
        0
      ],
      "name": "Bernhard Peball"
    },
    {
      "affs": [
        0
      ],
      "name": "Sandra Seidl"
    },
    {
      "affs": [
        0
      ],
      "name": "Hannes Muehleisen"
    },
    {
      "affs": [
        0
      ],
      "name": "Stefan Stranner"
    },
    {
      "affs": [
        0
      ],
      "name": "Mario Kuttke"
    },
    {
      "affs": [
        0
      ],
      "name": "Angela Halfmann"
    },
    {
      "affs": [
        0
      ],
      "name": "Sarah Bischof"
    },
    {
      "affs": [
        0
      ],
      "name": "Andreas Birbach"
    },
    {
      "affs": [
        0
      ],
      "name": "Romana Gugenberger"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0bvxjjk54dq0q.bib",
  "cited_by": 0,
  "doi": "10.1016/j.omton.2026.201357",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13717735/?tool=EBI",
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  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13717735/pdf/?tool=EBI",
  "pmcid": "PMC13717735",
  "pmid": "42959597",
  "published": "2026-10-05",
  "publisher": "American Society of Gene & Cell Therapy",
  "ris": "https://research.draconitic.com/paper/0bvxjjk54dq0q.ris",
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  "subjects": [
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      "field": "medicine",
      "origin": "openalex:2730|CAR-T cell therapy research",
      "subfield": "oncology"
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  ],
  "title": "Phase 1 evaluation of APN401, an autologous CBL-B-silenced PBMC therapy, in advanced solid tumors",
  "title_text": "Phase 1 evaluation of APN401, an autologous CBL-B-silenced PBMC therapy, in advanced solid tumors",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:22:00Z",
  "url": "https://research.draconitic.com/paper/0bvxjjk54dq0q",
  "venue": "Molecular Therapy Oncology",
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