{
  "abstract": "Solid-tumor CAR T-cell programs increasingly combine biomarker selection, lymphodepletion, manufacturing-state optimization, regional or repeated administration, and engineered control modules. This growing complexity creates a distinct translational problem: the same response, non-response, or toxicity can remain compatible with several competing explanations, obscuring which component actually operated in patient tissue. Mechanism-resolving development addresses this problem by treating each consequential engineering claim as a prospectively testable proposition embedded within the product-trial system. Four questions must be resolved: which patient-relevant state was present, which control action altered it, which proximal tissue transition followed, and which unsafe or limiting state emerged next. Each claim should therefore be paired with a clinically credible lower-burden counterfactual, mechanism-proximal tissue pharmacodynamics, a prespecified falsification criterion, a rescue strategy, and an adaptive action. Boolean coincidence and veto circuits, temporal IF-THEN systems, quantitative antigen-density filters, and genotype-conditioned activator-blocker designs require distinct representations, transition-state assays, and tissue biomarkers. Clinical evidence from CLDN18.2-directed satri-cel, compartmental central nervous system programs, hypoxia-responsive CEA therapy, GPC3-armored products, PSMA programs, and early HLA-loss-gated Tmod therapy illustrates that clinical maturity and mechanistic attribution are not equivalent. Programmability becomes translationally meaningful when the operation of an added control can be distinguished from credible alternatives in patient-relevant tissue, enabling complex cellular engineering to generate falsifiable, cumulative, and clinically actionable knowledge.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Research and Development, Duy Tan University",
    "Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital",
    "Vaxcell-Bio Therapeutics",
    "Department of Hematology-Oncology, Chonnam National University Hwasun Hospital and Chonnam National University Medical School",
    "Institute of Immunology and Human Genomics of the Academy of Sciences"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Manh-Cuong Vo"
    },
    {
      "affs": [
        2
      ],
      "name": "Sang Ki Kim"
    },
    {
      "affs": [
        1,
        2,
        3
      ],
      "name": "Woo Kyun Bae"
    },
    {
      "affs": [
        4
      ],
      "name": "Nodirjon Ruzimurodov"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Sung-Hoon Jung"
    },
    {
      "affs": [
        1,
        2,
        3
      ],
      "name": "Je-Jung Lee"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6v1qr5t4jkbgy.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1983828",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13735928/",
  "id": "6v1qr5t4jkbgy",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1983828/full",
  "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",
      "Review"
    ],
    [
      "openalex",
      "2730|CAR-T cell therapy research"
    ]
  ],
  "openalex": "W7223169630",
  "pdf_url": "https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1983828/pdf",
  "pmcid": "PMC13735928",
  "pmid": "42991489",
  "published": "2026-10-22",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/6v1qr5t4jkbgy.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:17Z",
      "native_id": "10.3389/fimmu.2026.1983828",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1983828/full"
    },
    {
      "first_seen": "2026-11-09T12:21:30Z",
      "native_id": "PMC13735928",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fimmu.2026.1983828"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|CAR-T cell therapy research",
      "subfield": "oncology"
    }
  ],
  "title": "Mechanism-resolving development of solid-tumor CAR T-cell therapy: linking programmable control to tissue pharmacodynamics",
  "title_text": "Mechanism-resolving development of solid-tumor CAR T-cell therapy: linking programmable control to tissue pharmacodynamics",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:21:30Z",
  "url": "https://research.draconitic.com/paper/6v1qr5t4jkbgy",
  "venue": "Frontiers in Immunology",
  "versions": []
}