{
  "abstract": "Living cell therapies lack robust, reversible mechanisms for externally controlling therapeutic activity after administration, limiting their safety and clinical adaptability. Here we engineer a drug‐gated cellular immunotherapy platform in which T cells function as programmable factories that secrete two inactive antibody modules whose extracellular assembly into a functional bispecific T cell engager (TCE) is controlled by a small‐molecule input. Using a rapalog‐inducible FKBP‐FRB* heterodimerization switch, we design a split CD19 × CD3 engager architecture that remains inactive in the absence of drug and assembles on demand upon rapalog exposure. A 2A‐peptide bicistronic construct enables coordinated expression and secretion of both modules, allowing precise drug‐dependent control of TCE formation in situ. Drug administration quantitatively regulates T cell activation and cytotoxicity against CD19+ targets in vitro, with stringent OFF‐state behavior in the absence of rapalog. In xenograft models, systemic rapalog administration induces on‐demand anti‐tumor activity without evidence of treatment‐related toxicity, demonstrating reversible pharmacological control of a locally secreted therapeutic interface. We further extend this strategy to an EGFR‐targeting TCE, demonstrating the modularity and broad adaptability of the platform across distinct antigen specificities. This work introduces a generalizable engineering framework for externally programmable cell therapies, enabling tunable, safety‐by‐design control of T cell‐based immunotherapies.",
  "abstract_shown": true,
  "affiliations": [
    "Cancer Immunotherapy Unit (UNICA) Department of Immunology Hospital Universitario 12 de Octubre Madrid Spain",
    "Immuno‐Oncology and Immunotherapy Group Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12) Madrid Spain",
    "CNIO‐HMRIB Cancer Immunotherapy Clinical Research Unit Spanish National Cancer Research Centre (CNIO) Madrid Spain",
    "Centro de Biología Molecular (CBM) Severo Ochoa CSIC‐UAM Madrid Spain",
    "Department of Immunology Ophthalmology and ENT School of Medicine Universidad Complutense Madrid Spain",
    "Lymphocyte Immunobiology Group Instituto De Investigación Sanitaria 12 De Octubre (imas12) Madrid Spain",
    "Experimental Therapeutics Programme Spanish National Cancer Research Centre (CNIO) Madrid Spain",
    "Protein Production Unit Spanish National Cancer Research Center (CNIO) Madrid Spain",
    "Department of Advanced Therapy Drug Development Instituto De Salud Carlos III Madrid Spain",
    "Cancer Immunotherapy Hospital Del Mar Research Institute Barcelona (HMRIB) Barcelona Spain",
    "Advanced Therapies Program Hospital Del Mar Research Institute Barcelona (HMRIB) Barcelona Spain",
    "Banc de Sang i Teixits Barcelona Spain"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 24,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Susana Luengo‐Arias",
      "orcid": "0009-0002-1674-228X"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Carmen Domínguez‐Alonso"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Ivana Zagorac",
      "orcid": "0000-0002-7135-8283"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Antonio Tapia‐Galisteo",
      "orcid": "0000-0002-0507-8435"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Eva García‐Veros",
      "orcid": "0000-0003-0479-1113"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Laura Rubio‐Pérez",
      "orcid": "0000-0002-2877-6092"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Marina Gómez‐Rosel",
      "orcid": "0000-0001-8816-9844"
    },
    {
      "affs": [
        3
      ],
      "name": "Patricia Fuentes",
      "orcid": "0000-0003-4597-1022"
    },
    {
      "affs": [
        2
      ],
      "name": "Patricia Hernández‐López",
      "orcid": "0000-0002-3741-3613"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Óscar Aguilar‐Sopeña",
      "orcid": "0000-0002-2435-8598"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Laura Almagro‐Puente",
      "orcid": "0000-0002-2418-2772"
    },
    {
      "affs": [
        6
      ],
      "name": "Sonia Martínez‐González",
      "orcid": "0000-0003-2230-7794"
    },
    {
      "affs": [
        6
      ],
      "name": "Lucía Cañizares‐Moscato",
      "orcid": "0000-0003-4060-5365"
    },
    {
      "affs": [
        7
      ],
      "name": "María Rivas‐Sánchez",
      "orcid": "0009-0002-6470-3111"
    },
    {
      "affs": [
        0,
        1,
        8
      ],
      "name": "Belén Blanco",
      "orcid": "0000-0001-5085-7756"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ángel Ramírez‐Fernández",
      "orcid": "0000-0002-3265-6878"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Laura Díez‐Alonso",
      "orcid": "0000-0002-9545-6910"
    },
    {
      "affs": [
        6
      ],
      "name": "Carmen Blanco‐Aparicio",
      "orcid": "0000-0002-3249-6595"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Javier Arroyo‐Ródenas",
      "orcid": "0000-0003-1099-2018"
    },
    {
      "affs": [
        7
      ],
      "name": "Jorge Martínez‐Torrecuadrada",
      "orcid": "0000-0002-8240-6623"
    },
    {
      "affs": [
        3
      ],
      "name": "María L. Toribio",
      "orcid": "0000-0002-8637-0373"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Pedro Roda‐Navarro"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Anaïs Jiménez‐Reinoso",
      "orcid": "0000-0001-8229-1881"
    },
    {
      "affs": [
        2,
        9,
        10,
        11
      ],
      "name": "Luis Álvarez‐Vallina",
      "orcid": "0000-0003-3053-6757"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1z68bnae89ajf.bib",
  "cited_by": 0,
  "doi": "10.1002/advs.77236",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13502364/",
  "id": "1z68bnae89ajf",
  "issns": [
    "2198-3844"
  ],
  "landing_url": "https://doi.org/10.1002/advs.77236",
  "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",
      "Research Article"
    ],
    [
      "openalex",
      "2730|CAR-T cell therapy research"
    ]
  ],
  "openalex": "W7204070661",
  "pdf_url": null,
  "pmcid": "PMC13502364",
  "pmid": "42635975",
  "published": "2026-08-24",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/1z68bnae89ajf.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T12:23:14Z",
      "native_id": "PMC13502364",
      "source": "pmc",
      "url": "https://doi.org/10.1002/advs.77236"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|CAR-T cell therapy research",
      "subfield": "oncology"
    }
  ],
  "title": "A Drug‐Gated, Modular STAb‐T Immunotherapy With External Control",
  "title_text": "A Drug‐Gated, Modular STAb‐T Immunotherapy With External Control",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:20:33Z",
  "url": "https://research.draconitic.com/paper/1z68bnae89ajf",
  "venue": "Advanced Science",
  "versions": []
}