{
  "abstract": "Chimeric antigen receptor (CAR) T cell therapy is considered a therapeutic breakthrough in hematological malignancies. However, its translation to metastasized solid tumors remains limited by the paucity of “druggable” targets and the limited therapeutic potency of the cell therapeutics in solid cancers. Human epidermal growth factor receptor 2 (HER2), a promising target for treatment of metastasized solid cancers, is amplified in around 3% (HER2+ cancer) and overexpressed without amplification in ∼40% (HER2low cancer) of all carcinomas, yet the physiological expression of HER2 on healthy tissues poses the risk of on-target off-tumor effects. To address this, we utilized low-affinity (LA) Anti-HER2-CAR T cells. These CAR T cells exhibited efficient lysis of HER2+ SKOV3 ovarian cancer cells even at low effector-to-target ratios. Following stimulation through cancer cells, LA Anti-HER2-CAR T cells showed rapid proliferation and elevation of pro-inflammatory cytokines markers. Low numbers of CAR T cells were sufficient to induce durable complete remissions of systemically seeded ovarian cancer in NOD-Prkdc\n\nscid\n\n-IL2rg\n\nTm1 /Rj mice. LA Anti-HER2 CAR T cells also exhibited tumor regression and lasting tumor control in a subcutaneous in vivo model of HER2low LS174T cells. Additionally, the LA and high-affinity (HA) CAR T cells could effectively combat HER2low human colorectal cancer (CRC) cell lines and primary CRC organoids, while LA Anti-HER2-CAR T cells showed a trend-wise reduced lysis of healthy colon organoids. Our results suggest that LA Anti-HER2-CAR T cells provide a novel treatment option for HER2-overexpressing advanced systemic tumors. Importantly, they effectively distinguished between healthy colon tissue and HER2low cancer, broadening the scope of HER2-directed CAR T cells to this frequent cancer subset.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Internal Medicine III, Hematology & Internal Oncology, University Hospital Regensburg, Regensburg, Germany",
    "Division of Plastic and Reconstructive Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, United States",
    "Department of Oral and Maxillofacial Surgery, Charité–Universitätsmedizin Berlin, Berlin, Germany",
    "Leibniz Institute for Immunotherapy (LIT), Regensburg, Germany",
    "Division of Hematology and Oncology, Department of Medicine, Freiburg University Medical Center, Albert-Ludwigs-University, Freiburg, Germany",
    "Institute of Pathology, University Hospital Regensburg, Regensburg, Germany",
    "Institute of Pathology, Phillips University Marburg, Marburg, Germany",
    "School of Medicine, Center for Translational Cancer Research (TranslaTUM), Technical University of Munich, Munich, Germany",
    "German Cancer Consortium (DKTK), Partner-site Munich and German Cancer Research Center (DKFZ), Heidelberg, Germany",
    "Chair of Translational Cancer Research and Institute of Experimental Cancer Therapy, Klinikum Rechts der Isar, TUM School of Medicine and Health, Technical University of Munich, Munich, Germany",
    "Bavarian Cancer Research Center (BZKF), Regensburg, Germany"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 23,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Leonard Knoedler"
    },
    {
      "affs": [
        0
      ],
      "name": "Konstantin Herfeld"
    },
    {
      "affs": [
        0
      ],
      "name": "Julian N. Scherer"
    },
    {
      "affs": [
        0
      ],
      "name": "Kaiji Fan"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Dhyani Shah"
    },
    {
      "affs": [
        0
      ],
      "name": "Sascha Goettert"
    },
    {
      "affs": [
        0
      ],
      "name": "Luisa Becker"
    },
    {
      "affs": [
        0
      ],
      "name": "Iria Lloshi"
    },
    {
      "affs": [
        0
      ],
      "name": "Suqi Li"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Dennis C. Harrer"
    },
    {
      "affs": [
        0
      ],
      "name": "Matthias A. Fante"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Tobias Wertheimer"
    },
    {
      "affs": [
        0
      ],
      "name": "Roland Schelker"
    },
    {
      "affs": [
        0
      ],
      "name": "Severin Guetter"
    },
    {
      "affs": [
        0
      ],
      "name": "Misbah Tariq"
    },
    {
      "affs": [
        0
      ],
      "name": "Omer Khalid"
    },
    {
      "affs": [
        5
      ],
      "name": "Alexander Scheiter"
    },
    {
      "affs": [
        0
      ],
      "name": "Wolfgang Herr"
    },
    {
      "affs": [
        3
      ],
      "name": "Christian Schmidl"
    },
    {
      "affs": [
        6
      ],
      "name": "Moritz Jesinghaus"
    },
    {
      "affs": [
        7,
        8,
        9
      ],
      "name": "Markus Tschurtschenthaler"
    },
    {
      "affs": [
        0,
        3,
        10
      ],
      "name": "Hendrik Poeck"
    },
    {
      "affs": [
        0,
        10
      ],
      "name": "Markus Perl"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b9eqa517h93q7.bib",
  "cited_by": 0,
  "doi": "10.3389/fbioe.2026.1895507",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696918/",
  "id": "b9eqa517h93q7",
  "issns": [
    "2296-4185"
  ],
  "landing_url": "https://doi.org/10.3389/fbioe.2026.1895507",
  "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"
    ],
    [
      "openalex",
      "2730|CAR-T cell therapy research"
    ]
  ],
  "openalex": "W7221541069",
  "pdf_url": "https://europepmc.org/articles/PMC13696918?pdf=render",
  "pmcid": "PMC13696918",
  "pmid": "42936178",
  "published": "2026-10-12",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/b9eqa517h93q7.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:11Z",
      "native_id": "PMC13696918",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fbioe.2026.1895507"
    },
    {
      "first_seen": "2026-10-30T12:22:12Z",
      "native_id": "MED:42936178",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42936178"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|CAR-T cell therapy research",
      "subfield": "oncology"
    }
  ],
  "title": "Low-affinity anti-HER2-CAR T cells efficiently eradicate HER2+ and HER2low cancer cells with reduced toxicity on healthy tissue",
  "title_text": "Low-affinity anti-HER2-CAR T cells efficiently eradicate HER2+ and HER2low cancer cells with reduced toxicity on healthy tissue",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:34:10Z",
  "url": "https://research.draconitic.com/paper/b9eqa517h93q7",
  "venue": "Frontiers in Bioengineering and Biotechnology",
  "versions": []
}