{
  "abstract": "Introduction: Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment of B-cell malignancies. However, strategies that improve the modularity and controllability of CAR signaling could broaden its applicability and safety across additional clinical contexts. Here, we describe a regulable CAR T-cell platform based on split intein-mediated protein trans-splicing (PTS) to conditionally reconstitute functional receptors in primary T-cells.\n\nMethods: As a proof of concept, we engineered a split CAR targeting CD1a (NCT05679895), a surface antigen expressed in T-cell acute lymphoblastic leukemia (T-ALL). The system consists of a membrane-anchored C-terminal scaffold containing the IMPDH.1 C split intein fused to 4-1BB and CD3ζ signaling domains, and a soluble N-terminal adaptor composed of an anti-CD1a single-chain variable fragment (scFv) fused to the complementary IMPDH.1 N split intein.\n\nResults: Upon delivery of the adaptor module, the intein fragments undergo PTS, generating a functional membrane-bound CD1a CAR with splicing efficiencies of 85%. Reconstituted CAR T-cells exhibited antigen-specific cytotoxicity against CD1a ⁺ T-ALL cells coupled to high levels of interferon-γ secretion.\n\nDiscussion: These findings demonstrate that split intein-mediated CAR reconstitution enables a modular platform for conditional CAR reconstitution and transient control of receptor availability.",
  "abstract_shown": true,
  "affiliations": [
    "Josep Carreras Leukemia Research Institute (IJC) , ,",
    "ZIP Solutions SL. , ,",
    "Department of Clinical Sciences and Translational Medicine, Universityof Rome “Tor Vergata” , ,",
    "OneChain Immunotherapeutics SL. , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Vladimir Mulens-Arias"
    },
    {
      "affs": [
        1
      ],
      "name": "Marco Archinti"
    },
    {
      "affs": [
        1
      ],
      "name": "Miriam Bastida"
    },
    {
      "affs": [
        1
      ],
      "name": "Nuria Martínez"
    },
    {
      "affs": [
        2
      ],
      "name": "Eleonora Pinto"
    },
    {
      "affs": [
        3
      ],
      "name": "Víctor M. Díaz"
    },
    {
      "affs": [
        0
      ],
      "name": "Pablo Menéndez"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9f1v7270n3bdb.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1844972",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672617/?tool=EBI",
  "id": "9f1v7270n3bdb",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13672617",
  "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": "W7216346331",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13672617/pdf/?tool=EBI",
  "pmcid": "PMC13672617",
  "pmid": null,
  "published": "2026-10-02",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/9f1v7270n3bdb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:18Z",
      "native_id": "PMC:PMC13672617",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13672617"
    },
    {
      "first_seen": "2026-10-30T12:19:15Z",
      "native_id": "10.3389/fimmu.2026.1844972",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1844972/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|CAR-T cell therapy research",
      "subfield": "oncology"
    }
  ],
  "title": "Split intein-mediated reconstitution of regulatable CAR T-cells",
  "title_text": "Split intein-mediated reconstitution of regulatable CAR T-cells",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:15Z",
  "url": "https://research.draconitic.com/paper/9f1v7270n3bdb",
  "venue": "Frontiers in immunology",
  "versions": []
}