{
  "abstract": "While the immune reset induced by CD19 CAR T therapies has shown striking promise in systemic lupus erythematosus (SLE), the nature and duration of benefit mediated by B cell depletion remains unclear. Loss of tolerance in SLE is driven by extrafollicular and germinal center interactions between dendritic cells and self-reactive T and B cells. We hypothesized that CD19 CAR-engineered regulatory T cells (CAR19 EngTreg), capable of suppressing multiple autoimmune effector cell types, might promote long-term tolerance without producing high-levels of inflammatory mediators. To generate CAR19 EngTreg, we combined CD19 CAR delivery with homology directed repair at the FOXP3 locus to drive constitutive, stable FOXP3 expression in CD4 T cells. CAR19 EngTreg expressed canonical Treg markers; exhibited minimal inflammatory cytokine production; and blocked human B cell differentiation into antibody secreting plasma cells. In humanized mouse models, transfer of CAR19 EngTreg led to a reduction in B cell numbers with low inflammatory cytokine production relative to CD19 CAR Teff, and reduced tissue inflammation. In a short-term, in vivo imiquimod-induced inflammatory model, murine CAR19 EngTreg reduced skin pathology, spleen size, and inflammatory cytokines. Finally, in two distinct mouse models of lupus, CAR19 EngTreg persisted for >4 months leading to reduced autoimmune T and B effector populations, sustained reduction in multiple autoantibodies and improved renal function and histopathology. Thus, CAR19 EngTreg may offer a promising and durable therapeutic avenue for B cell-mediated autoimmune disorders capable of long-term regulation of both autoreactive B and T cells.",
  "abstract_shown": true,
  "affiliations": [
    "University of Washington"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 30,
  "authors": [
    {
      "name": "T. Drow"
    },
    {
      "name": "M. Doglio"
    },
    {
      "name": "A. Grimm"
    },
    {
      "name": "V. DeVault-Nelson"
    },
    {
      "name": "M. Hoover"
    },
    {
      "name": "B. McKinney"
    },
    {
      "name": "S. K. Tripathi"
    },
    {
      "name": "J. Mellen"
    },
    {
      "name": "M. Milazewski"
    },
    {
      "name": "P. Zarin"
    },
    {
      "name": "A. Burgess"
    },
    {
      "name": "C. L. Moore"
    },
    {
      "name": "P. Carulli"
    },
    {
      "name": "A. Ugolini"
    },
    {
      "name": "C. Bercher"
    },
    {
      "name": "A. Vakil"
    },
    {
      "name": "N. P. Dahl"
    },
    {
      "name": "S. M. Ponnan"
    },
    {
      "name": "N. Mungra"
    },
    {
      "name": "S. Akilesh"
    },
    {
      "name": "Y. Chen"
    },
    {
      "name": "P. Knebusch"
    },
    {
      "name": "S. W. Jackson"
    },
    {
      "name": "C. Patel"
    },
    {
      "name": "T. Chen"
    },
    {
      "name": "A. Del Rio-Espinola"
    },
    {
      "name": "C. Bonini"
    },
    {
      "name": "T. Wickham"
    },
    {
      "name": "P. J. Cook"
    },
    {
      "affs": [
        0
      ],
      "name": "D. J. Rawlings"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/71ws4j11newpb.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.05.756761",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.05.756761v1.full",
  "id": "71ws4j11newpb",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.05.756761v1",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "2403|T-cell and B-cell Immunology"
    ]
  ],
  "openalex": "W7221467717",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.05.756761v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-05",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/71ws4j11newpb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:10Z",
      "native_id": "10.64898/2026.10.05.756761",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.05.756761v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "CD19 CAR Engineered T Regulatory Cells Promote Durable Immune Tolerance in Experimental Systemic Lupus Erythematosus",
  "title_text": "CD19 CAR Engineered T Regulatory Cells Promote Durable Immune Tolerance in Experimental Systemic Lupus Erythematosus",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:10Z",
  "url": "https://research.draconitic.com/paper/71ws4j11newpb",
  "venue": "bioRxiv",
  "versions": []
}