{
  "abstract": "Background Chimeric antigen receptor (CAR)-T cell therapy has achieved significant success in hematologic malignancies; however, its efficacy in solid tumors remains limited. A major limitation is the difficulty in identifying suitable target antigens that are abundantly expressed on the surface of tumor cells while sparing life-sustaining normal tissues.Methods We identified MUC17, a membrane-tethered mucin-type glycoprotein with minimal expression in normal tissues and frequent upregulation in gastric cancers, as a potential target for CAR-T therapy. We developed and validated MUC17-specific CAR-T cells incorporating a 4-1BB/CD3ζ signaling domain. In vitro assays assessed cytotoxicity, cytokine secretion, and T cell phenotypes across multiple gastric cancer cell lines, including CRISPR-mediated MUC17 knockout controls. In vivo efficacy was evaluated using NSG xenograft models.Results MUC17 CAR-T cells exhibited potent, antigen-specific cytotoxicity, robust cytokine release, and sustained effector functions characterized by enrichment of central memory phenotypes. In vivo, MUC17 CAR-T cells significantly suppressed tumor growth without signs of toxicity in GSU and ASPC-1 models.Conclusions These findings support MUC17 as a promising immunotherapeutic target for gastric cancer and demonstrate how targeting glycocalyx-associated antigens can expand the range of surface proteins amenable to CAR-T cell-based therapies in solid tumors.",
  "authors": [
    {
      "affiliations": [
        "Krantz Family Center for Cancer Research and Cellular Immunotherapy Program, Massachusetts General Hospital, Boston, Massachusetts, USA",
        "Harvard Medical School, Boston, Massachusetts, USA",
        "Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA"
      ],
      "name": "Sangwoo Park"
    },
    {
      "affiliations": [
        "Krantz Family Center for Cancer Research and Cellular Immunotherapy Program, Massachusetts General Hospital, Boston, Massachusetts, USA",
        "Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA"
      ],
      "name": "Cassidy E Ho"
    },
    {
      "affiliations": [
        "Krantz Family Center for Cancer Research and Cellular Immunotherapy Program, Massachusetts General Hospital, Boston, Massachusetts, USA",
        "Harvard Medical School, Boston, Massachusetts, USA",
        "Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA"
      ],
      "name": "Filippo Birocchi"
    },
    {
      "affiliations": [
        "Krantz Family Center for Cancer Research and Cellular Immunotherapy Program, Massachusetts General Hospital, Boston, Massachusetts, USA",
        "Harvard Medical School, Boston, Massachusetts, USA",
        "Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA"
      ],
      "name": "Alexandra N Wolff"
    },
    {
      "affiliations": [
        "Krantz Family Center for Cancer Research and Cellular Immunotherapy Program, Massachusetts General Hospital, Boston, Massachusetts, USA",
        "Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA"
      ],
      "name": "Amanda A Bouffard"
    },
    {
      "affiliations": [
        "Krantz Family Center for Cancer Research and Cellular Immunotherapy Program, Massachusetts General Hospital, Boston, Massachusetts, USA",
        "Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA"
      ],
      "name": "Christopher Kelly"
    },
    {
      "affiliations": [
        "Krantz Family Center for Cancer Research and Cellular Immunotherapy Program, Massachusetts General Hospital, Boston, Massachusetts, USA",
        "Harvard Medical School, Boston, Massachusetts, USA",
        "Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA"
      ],
      "name": "Diego Salas-Benito"
    },
    {
      "affiliations": [
        "Krantz Family Center for Cancer Research and Cellular Immunotherapy Program, Massachusetts General Hospital, Boston, Massachusetts, USA",
        "Harvard Medical School, Boston, Massachusetts, USA",
        "Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA"
      ],
      "name": "Giulia Escobar"
    },
    {
      "affiliations": [
        "Krantz Family Center for Cancer Research and Cellular Immunotherapy Program, Massachusetts General Hospital, Boston, Massachusetts, USA",
        "Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA"
      ],
      "name": "Adele Mucci"
    },
    {
      "affiliations": [
        "Krantz Family Center for Cancer Research and Cellular Immunotherapy Program, Massachusetts General Hospital, Boston, Massachusetts, USA",
        "Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA"
      ],
      "name": "Trisha Berger"
    },
    {
      "affiliations": [
        "Krantz Family Center for Cancer Research and Cellular Immunotherapy Program, Massachusetts General Hospital, Boston, Massachusetts, USA",
        "Harvard Medical School, Boston, Massachusetts, USA",
        "Cellular Immunotherapy Program, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA"
      ],
      "name": "Marcela V Maus"
    }
  ],
  "title": "CAR-T cell therapy targeting MUC17 in gastric tumors",
  "uid": "cf1537d0-37d6-51b4-91aa-96c833fe3f92"
}