ArticleProceedings of the National Academy of Sciences of the United States of America2022
A novel mouse strain optimized for chronic human antibody administration.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Dissecting NMOSD pathogenesis through animal models: a mechanism-oriented systems perspective.Frontiers in immunology · 2026Review
- Asymmetrically glycosylated IgG1 antibodies are universal and drive human disease.Nature communications · 2025Article
- Application of humanized mice in the safety experiments of antibody drugs.Animal models and experimental medicine · 2025Review
- Plant-derived recombinant macromolecular PAP-IgG Fc as a novel prostate cancer vaccine candidate eliciting robust immune responses.Transgenic research · 2025Article
- Linker minimization and characterization of Fc-fused interleukin-17A for increased in vivo half-life.Protein engineering, design & selection : PEDS · 2025Article
- Article
- Fcγ receptors and immunomodulatory antibodies in cancer.Nature reviews. Cancer · 2024Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Therapeutic human IgG antibodies are routinely tested in mouse models of oncologic, infectious, and autoimmune diseases. However, assessing the efficacy and safety of long-term administration of these agents has been limited by endogenous anti-human IgG immune responses that act to clear human IgG from serum and relevant tissues, thereby reducing their efficacy and contributing to immune complex–mediated pathologies, confounding evaluation of potential toxicity. For this reason, human antibody treatment in mice is generally limited in duration and dosing, thus failing to recapitulate the potential clinical applications of these therapeutics. Here, we report the development of a mouse model that is tolerant of chronic human antibody administration. This model combines both a human IgG1 heavy chain knock-in and a full recapitulation of human Fc receptor (FcγR) expression, providing a unique platform for in vivo testing of human monoclonal antibodies with relevant receptors beyond the short term. Compared to controls, hIgG1 knock-in mice mount minimal anti-human IgG responses, allowing for the persistence of therapeutically active circulating human IgG even in the late stages of treatment in chronic models of immune thrombocytopenic purpura and metastatic melanoma.
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Registered trials
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