{
  "abstract": "Chimeric antigen receptor (CAR)-engineered natural killer (NK) cells represent a promising platform for cancer immunotherapy; however, optimization of CAR architecture and additional engineering strategies remain necessary to improve their functional activity. In this study, we generated CD19/BCMA dual-target CAR constructs based on tandem and bicistronic configurations with or without membrane-bound interleukin-15 (mbIL-15), and further evaluated engineered virus-like particle (eVLP)-mediated CREM editing as an additional strategy for CAR-NK cell engineering. Four CAR configurations were evaluated in primary human T and NK cells for CAR expression, cytotoxicity, cytokine production, and proliferative activity. Bicistronic CD19/BCMA CAR-mbIL-15 cells exhibited enhanced functional activity compared with corresponding tandem CAR-mbIL-15 cells, including increased tumor-cell killing and activation-associated functional responses in vitro . In a CD19/BCMA-positive leukemia xenograft model, bicistronic CD19/BCMA CAR-mbIL-15 T and NK cells reduced tumor burden, delayed disease progression, and prolonged survival. Furthermore, eVLP-mediated CREM editing achieved efficient genome modification in primary NK cells and remained compatible with subsequent CAR engineering. CREM-edited CAR-NK cells exhibited increased cytotoxic activity compared with unedited CAR-NK cells in vitro . Collectively, these findings support the development of modular CAR-NK engineering strategies integrating CAR architecture optimization, membrane-bound cytokine armoring, and transient genome engineering.",
  "abstract_shown": true,
  "affiliations": [
    "Shenzhen Cell Valley Biopharmaceuticals Group Co., Ltd. , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Fengqin Shang"
    },
    {
      "affs": [
        0
      ],
      "name": "Guanlie Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Shiting Gong"
    },
    {
      "affs": [
        0
      ],
      "name": "Lijiao Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Bingyu Niu"
    },
    {
      "affs": [
        0
      ],
      "name": "Hanyi Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuchen Fu"
    },
    {
      "affs": [
        0
      ],
      "name": "Lijun Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Jianxun Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yuanyuan Shi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dvxp3q61bs0dz.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1976202",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668854/?tool=EBI",
  "id": "dvxp3q61bs0dz",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13668854",
  "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": [
    [
      "openalex",
      "2730|CAR-T cell therapy research"
    ]
  ],
  "openalex": "W7215055002",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668854/pdf/?tool=EBI",
  "pmcid": "PMC13668854",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/dvxp3q61bs0dz.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:18Z",
      "native_id": "PMC:PMC13668854",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13668854"
    },
    {
      "first_seen": "2026-10-30T12:19:15Z",
      "native_id": "10.3389/fimmu.2026.1976202",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1976202/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|CAR-T cell therapy research",
      "subfield": "oncology"
    }
  ],
  "title": "eVLP-mediated CREM editing enhances cytotoxicity of bicistronic IL-15-armored CD19/BCMA dual-target CAR-NK cells",
  "title_text": "eVLP-mediated CREM editing enhances cytotoxicity of bicistronic IL-15-armored CD19/BCMA dual-target CAR-NK cells",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:15Z",
  "url": "https://research.draconitic.com/paper/dvxp3q61bs0dz",
  "venue": "Frontiers in immunology",
  "versions": []
}