{
  "abstract": "BackgroundRegulatory T cells (Tregs) are essential for maintaining immune tolerance, and their dysfunction contributes to autoimmune diseases. Interleukin-2 (IL-2)-based therapies aiming to expand Tregs are limited by a short half-life and broad immune activation. This study aims to develop a long-acting IL-2 variant with enhanced Treg selectivity for the treatment of autoimmune diseases.MethodsUsing a computation-driven protein engineering strategy, we designed an optimized IL-2 mutein to attenuate binding to IL-2 receptor (IL-2R) βγ while preserving high-affinity engagement with IL-2Rαβγ. The mutein was fused to a human Fc fragment to generate SIM0278. Its receptor binding profile, downstream signaling, and cellular selectivity were characterized in vitro. In vivo pharmacodynamics and therapeutic efficacy were evaluated in healthy mice, multiple autoimmune disease models and cynomolgus monkeys.ResultsCompared with wild type IL-2, SIM0278 maintained comparable activity toward IL-2Rαβγ while showing reduced activity toward IL-2Rβγ. This receptor response profile translated into preferential STAT5 activation in Tregs, with substantially reduced activation of conventional T cells and CD8+ T cells. In healthy mice, SIM0278 potently expanded Tregs. In models of delayed-type hypersensitivity, atopic dermatitis, graft-versus-host disease, and systemic lupus erythematosus, SIM0278 demonstrated robust, dose-dependent therapeutic effects, reducing inflammation, autoantibody production, and mortality. In cynomolgus monkeys, SIM0278 showed prolonged half-life with sustained and selective Treg expansion.ConclusionSIM0278 is a selective and long-acting Treg-biased IL-2 mutein fusion protein with promising therapeutic potential for various autoimmune diseases.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "name": "Yuxi Yan"
    },
    {
      "name": "Wenlu Yan"
    },
    {
      "name": "Zhenna Gao"
    },
    {
      "name": "Yiming Kou"
    },
    {
      "name": "Yulu Wang"
    },
    {
      "name": "Yingying Hu"
    },
    {
      "name": "Zhuoxiao Cao"
    },
    {
      "name": "Renhong Tang"
    },
    {
      "name": "Aik Han Goh"
    },
    {
      "name": "Xiaofeng Zhao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d53z6p9bjmkm5.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.2004590",
  "fulltext_url": null,
  "id": "d53z6p9bjmkm5",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.2004590",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "feed-journal",
      "biology/immunology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-04",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/d53z6p9bjmkm5.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T06:20:39Z",
      "native_id": "10.3389/fimmu.2026.2004590",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.2004590"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "feed-journal:biology/immunology",
      "subfield": "immunology"
    }
  ],
  "title": "SIM0278, an IL-2 mutein that selectively expands regulatory T cells for the treatment of autoimmune disorders",
  "title_text": "SIM0278, an IL-2 mutein that selectively expands regulatory T cells for the treatment of autoimmune disorders",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T06:20:39Z",
  "url": "https://research.draconitic.com/paper/d53z6p9bjmkm5",
  "venue": "Frontiers in Immunology",
  "versions": []
}