{
  "abstract": "Immune aplastic anemia (AA) is a rare and life-threatening acquired bone marrow failure syndrome characterized by the immune-mediated destruction of hematopoietic stem and progenitor cells, leading to hypocellular bone marrow and consequent pancytopenia. Autoreactive cytotoxic lymphocytes and sustained inflammatory signaling play central roles in disease pathogenesis. Although immunosuppressive therapy and allogeneic hematopoietic stem cell transplantation have significantly improved clinical outcomes, treatment-related toxicity, relapse, refractoriness, clonal evolution, and donor availability remain important challenges. Novel strategies capable of controlling disease driving immune cells more selectively than systemic immunosuppression are therefore needed. Here, we developed an engineered CAR-NK-92 platform directed against a disease-relevant immune antigen associated with the pathogenic immune response in AA. NK-92 cells constitute a clinically evaluated platform with a favorable safety profile and offer reproducible, donor-independent manufacturing, efficient genetic engineering, scalable expansion, and rapid off-the-shelf availability. Importantly, pre-infusion irradiation restricts their proliferation and persistence in vivo, providing a controllable therapeutic window that may reduce the risk of prolonged on-target, off-tissue toxicity, an especially relevant safety feature when targeting immune cells in a nonmalignant disorder. Based on this rationale, we developed a novel CAR-NK-92 platform directed against an immune target involved in the pathogenic activation of autoreactive T cells in AA and engineered to minimize fratricide. A lentiviral vector encoding the CAR construct was successfully generated and used to establish stable CAR-NK-92 cells following transduction and selection. Functional characterization demonstrated that engineered CAR-NK-92 cells maintained robust proliferative capacity compared with parental NK-92 cells under both IL-2-supplemented and IL-2-deprived culture conditions, confirming the functional activity of the construct. Furthermore, CAR-NK-92 cells exhibited significantly enhanced cytotoxicity against target cells compared with unmodified NK-92 cells, demonstrating the functional efficacy of the engineered platform. Collectively, these findings demonstrate the feasibility of this CAR-NK-92 platform and provide encouraging proof-of-concept for further investigation of its therapeutic potential, supporting its future application as a targeted cellular immunotherapy for immune aplastic anemia.",
  "abstract_shown": true,
  "affiliations": [
    "Faculdade de Medicina de Ribeirão Preto (FMRP), Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Maria Cláudia Magalhães Tristão CAVALLINI"
    },
    {
      "affs": [
        0
      ],
      "name": "Rodrigo Tocantis CALADO"
    },
    {
      "affs": [
        0
      ],
      "name": "Virginia PICANçO-CASTRO"
    },
    {
      "affs": [
        0
      ],
      "name": "Luis Roberto Fonseca LIMA"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/400x8h4bwj67n.bib",
  "cited_by": 0,
  "doi": "10.1016/j.htct.2026.106906",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S253113792600653X",
  "id": "400x8h4bwj67n",
  "issns": [
    "2531-1379",
    "2531-1387"
  ],
  "landing_url": "https://doi.org/10.1016/j.htct.2026.106906",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC633-647.5"
    ],
    [
      "openalex",
      "2730|CAR-T cell therapy research"
    ]
  ],
  "openalex": "W7223556665",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/400x8h4bwj67n.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:43:25Z",
      "native_id": "439ec4ef33cc4287be005d135a1ef241",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.htct.2026.106906"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|CAR-T cell therapy research",
      "subfield": "oncology"
    }
  ],
  "title": "TARGETING PATHOGENIC IMMUNITY IN ACQUIRED APLASTIC ANEMIA WITH AN OFF-THE-SHELF CAR-NK-92 PLATFORM",
  "title_text": "TARGETING PATHOGENIC IMMUNITY IN ACQUIRED APLASTIC ANEMIA WITH AN OFF-THE-SHELF CAR-NK-92 PLATFORM",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:25Z",
  "url": "https://research.draconitic.com/paper/400x8h4bwj67n",
  "venue": "Hematology, Transfusion and Cell Therapy",
  "versions": []
}