{
  "abstract": "Chimeric antigen receptor (CAR) T cell therapy has achieved durable and complete responses in a substantial proportion of patients with B cell malignancies. However, during CAR-T cell therapy, the occurrence of adverse events—including on-target/off-tumor toxicity against healthy tissues, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and the risk of T cell malignancies arising from random genomic integration of viral vectors—significantly threatens patient safety. In this study, we developed a novel truncated HER2 (tHER2)-herpes simplex virus thymidine kinase (HSVTK) dual-switch safety system and site-specifically integrated it into the PDCD1 locus using a Cas12a/adeno-associated virus (AAV)-mediated delivery platform. Importantly, this dual-switch system enables efficient magnetic bead-based enrichment of tHER2-HSVTK (tHER2-TK)-positive T cells, allows tunable modulation of engineered T cell persistence through Herceptin or the small-molecule drug ganciclovir (GCV), and also provides a highly effective purification method before infusion. Collectively, these features enhance safety without compromising therapeutic efficacy, facilitating the development of safer and more controllable engineered T cell immunotherapies.",
  "abstract_shown": true,
  "affiliations": [
    "Changping Laboratory, Yard 28, Science Park Road, Changping District, Beijing 102206, China",
    "School of Basic Medical Sciences, Tsinghua University, Beijing 100084, China",
    "Department of Chemical Engineering, Tsinghua University, Beijing 100084, China",
    "Yifei (Hangzhou) Bio-tech Co., Ltd, Hangzhou 311305, China",
    "Tsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 10084, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Hongtao Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Huimin Wang"
    },
    {
      "affs": [
        2
      ],
      "name": "Bo Hou"
    },
    {
      "affs": [
        0
      ],
      "name": "Wenxin Zhou"
    },
    {
      "affs": [
        3
      ],
      "name": "Hanfei Zhu"
    },
    {
      "affs": [
        0,
        1,
        4
      ],
      "name": "Xin Lin"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiasheng Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3q5zvhw5ggbt7.bib",
  "cited_by": 0,
  "doi": "10.1016/j.omta.2026.201865",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13742281/",
  "id": "3q5zvhw5ggbt7",
  "issns": [
    "3117-387X"
  ],
  "landing_url": "https://doi.org/10.1016/j.omta.2026.201865",
  "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 Article"
    ],
    [
      "openalex",
      "2730|CAR-T cell therapy research"
    ]
  ],
  "openalex": "W7221806571",
  "pdf_url": null,
  "pmcid": "PMC13742281",
  "pmid": "42997744",
  "published": "2026-10-14",
  "publisher": "American Society of Gene & Cell Therapy",
  "ris": "https://research.draconitic.com/paper/3q5zvhw5ggbt7.ris",
  "sources": [
    {
      "first_seen": "2026-11-10T12:23:09Z",
      "native_id": "PMC13742281",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.omta.2026.201865"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|CAR-T cell therapy research",
      "subfield": "oncology"
    }
  ],
  "title": "A dual-switch safety system enables safety controllability and high-efficiency enrichment for T cell immunotherapy",
  "title_text": "A dual-switch safety system enables safety controllability and high-efficiency enrichment for T cell immunotherapy",
  "type": "peer-reviewed",
  "updated_at": "2026-11-10T12:23:09Z",
  "url": "https://research.draconitic.com/paper/3q5zvhw5ggbt7",
  "venue": "Molecular Therapy Advances",
  "versions": []
}