{
  "abstract": "Background\n\nMonoclonal antibody (mAb) therapies are limited by factors affecting their pharmacokinetics (PK), such as anti-idiotypic antibodies (anti-ID Abs) and the antigen sink effect. To address this, we developed six pro-anti-TNFα Abs (pro-Infliximab) incorporating unique hinge regions (\"Ab locks\") from different immunoglobulin subtypes linked via protease-sensitive peptides. The steric shielding formed by the endogenous hinge's disulfide bonds provides a modular design that can be applied to various Ab drugs with minimal structural modification. Compared to other spatial hindrance strategies, this Ab lock approach is anticipated to offer a favorable immunogenicity profile.Results\n\nAmong the variants, The IgG1 hinge exhibited the most robust masking capability among the evaluated domains, resulting in a 128-fold reduction in Infliximab's antigen binding. IgG1 pro-Infliximab demonstrated low immunogenicity after repeated dosing and maintained stable PK in both naïve and immunized mice, retaining 74.2% serum levels one hour after TNFα challenge. It also reduced anti-ID Ab binding by 87.3-fold, while showing a trend toward decreasing Ab-mediated drug clearance in these treated mice.Conclusions\n\nThis IgG1 Ab lock strategy provides binding-level proof of concept for several pro-Abs, offering the potential to mitigate immunogenicity. It blocked systemic hTNFα in an acute target challenge model and reduced clearance to preserve pro-Infliximab PK, ultimately helping to enhance patient quality of life.",
  "abstract_shown": true,
  "affiliations": [
    "Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.",
    "Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan.",
    "PrecisemAb Biotech Co., Ltd., Taipei, Taiwan.",
    "Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.",
    "Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan.",
    "Department of Medical Imaging, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.",
    "School of Post-Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.",
    "School of Medicine, I-Shou University, Kaohsiung, Taiwan. ijuchen003@isu.edu.tw.",
    "Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan. weber06272000@gmail.com.",
    "Department of Laboratory Medicine, Post Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. weber06272000@gmail.com.",
    "Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. weber06272000@gmail.com."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Bo-Cheng Huang"
    },
    {
      "affs": [
        2
      ],
      "name": "Yun-Chi Lu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Chih-Hung Chuang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Shih-Ting Hong"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Kai-Wen Ho"
    },
    {
      "affs": [
        2,
        4
      ],
      "name": "Yi-An Cheng"
    },
    {
      "affs": [
        3
      ],
      "name": "Tzu-Yi Liao"
    },
    {
      "affs": [
        3
      ],
      "name": "En-Shuo Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Jun-Min Liao"
    },
    {
      "affs": [
        0,
        5,
        6
      ],
      "name": "Chiao-Yun Chen"
    },
    {
      "affs": [
        0,
        3,
        4
      ],
      "name": "Tian-Lu Cheng"
    },
    {
      "affs": [
        7
      ],
      "name": "I-Ju Chen"
    },
    {
      "affs": [
        8,
        9,
        10
      ],
      "name": "Wen-Wei Lin",
      "orcid": "0000-0002-5144-6868"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7fn8cd52aqsz1.bib",
  "cited_by": 0,
  "doi": "10.1186/s13036-026-00741-x",
  "fulltext_url": "https://europepmc.org/articles/PMC13721414",
  "id": "7fn8cd52aqsz1",
  "issns": [
    "1754-1611"
  ],
  "landing_url": "https://europepmc.org/article/MED/42958426",
  "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": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2741|Monoclonal and Polyclonal Antibodies Research"
    ]
  ],
  "openalex": "W7172093846",
  "pdf_url": "https://europepmc.org/articles/PMC13721414?pdf=render",
  "pmcid": "PMC13721414",
  "pmid": "42958426",
  "published": "2026-08-01",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/7fn8cd52aqsz1.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T00:20:47Z",
      "native_id": "MED:42958426",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42958426"
    },
    {
      "first_seen": "2026-11-03T12:22:06Z",
      "native_id": "PMC13721414",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s13036-026-00741-x"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2741|Monoclonal and Polyclonal Antibodies Research",
      "subfield": "imaging"
    }
  ],
  "title": "Autologous hinge-masked anti-TNFα antibody to mitigate immunogenicity, antigen sink effects, and anti-idiotypic antibody interference.",
  "title_text": "Autologous hinge-masked anti-TNFα antibody to mitigate immunogenicity, antigen sink effects, and anti-idiotypic antibody interference.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:22:06Z",
  "url": "https://research.draconitic.com/paper/7fn8cd52aqsz1",
  "venue": "Journal of biological engineering",
  "versions": []
}