{
  "abstract": "Inflammatory bowel disease (IBD) remains a substantial therapeutic challenge, largely due to the limitations of single-target monotherapies. Here, we engineered two bispecific antibodies, KA-4316 and its half-life-extended derivative KA-5817, which co-target TL1A and IL-12/23p40 utilizing a common light chain design and knobs-into-holes Fc engineering. To improve clinical translatability, KA-5817 was modified with YTE Fc mutations to enhance FcRn binding. KA-4316 exhibited high binding affinity for both targets, high monomer purity, and favorable thermal stability. In vitro functional assays demonstrated that KA-4316 potently blocked TL1A-DR3 and IL-12/23p40-IL-12Rβ1 interactions, suppressing downstream signaling and pro-inflammatory cytokine release. In vivo, KA-5817 alleviated pathological severity in dextran sulfate sodium (DSS)-induced colitis in TL1A/IL23A/IL12B triple-humanized mice and showed a prolonged serum half-life in FcRn-humanized mice. KA-4316 and KA-5817 exhibit beneficial manufacturability and favorable biological activity. Our results support dual inhibition of TL1A and IL-12/23p40 as a potential therapeutic strategy for IBD.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "Xia Li"
    },
    {
      "name": "Hao Peng"
    },
    {
      "name": "Feng Hao",
      "orcid": "0000-0002-6057-1097"
    },
    {
      "name": "Yi Gu"
    },
    {
      "name": "Jinying Ning"
    },
    {
      "name": "Changyuan Yu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4a6z100vccezb.bib",
  "cited_by": 0,
  "doi": "10.1016/j.isci.2026.117795",
  "fulltext_url": "https://europepmc.org/articles/PMC13677191",
  "id": "4a6z100vccezb",
  "issns": [
    "2589-0042"
  ],
  "landing_url": "https://www.cell.com/iscience/fulltext/S2589-0042(26)03176-7",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "http://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Biological sciences"
    ],
    [
      "heading",
      "Gastroenterology"
    ],
    [
      "heading",
      "Health sciences"
    ],
    [
      "heading",
      "Immunology"
    ],
    [
      "heading",
      "Immunology specialty"
    ],
    [
      "heading",
      "Internal medicine"
    ],
    [
      "heading",
      "Medical manufactured object"
    ],
    [
      "heading",
      "Medicine"
    ],
    [
      "heading",
      "Natural sciences"
    ],
    [
      "openalex",
      "1311|Inflammatory Bowel Disease"
    ]
  ],
  "openalex": "W7221162324",
  "pdf_url": "https://europepmc.org/articles/PMC13677191?pdf=render",
  "pmcid": "PMC13677191",
  "pmid": "42894862",
  "published": "2026-10-09",
  "publisher": "Elsevier BV",
  "ris": "https://research.draconitic.com/paper/4a6z100vccezb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:16Z",
      "native_id": "10.1016/j.isci.2026.117795",
      "source": "feed-cell",
      "url": "https://www.cell.com/iscience/fulltext/S2589-0042(26)03176-7"
    },
    {
      "first_seen": "2026-10-30T12:17:49Z",
      "native_id": "10.1016/j.isci.2026.117795",
      "source": "crossref",
      "url": "https://linkinghub.elsevier.com/retrieve/pii/S2589004226031767"
    },
    {
      "first_seen": "2026-10-30T12:19:33Z",
      "native_id": "MED:42894862",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42894862"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "heading:Immunology",
      "subfield": "immunology"
    },
    {
      "field": "medicine",
      "origin": "heading:Medicine",
      "subfield": "general"
    }
  ],
  "title": "Bispecific antibodies targeting TL1A and IL-12/23p40 suppress pathogenic Th1/Th17 responses and ameliorate colitis in mice",
  "title_text": "Bispecific antibodies targeting TL1A and IL-12/23p40 suppress pathogenic Th1/Th17 responses and ameliorate colitis in mice",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:33Z",
  "url": "https://research.draconitic.com/paper/4a6z100vccezb",
  "venue": "iScience",
  "versions": []
}