ArticlePloS one2016
TGN1412 Induces Lymphopenia and Human Cytokine Release in a Humanized Mouse Model.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Development of humanized mouse with patient-derived xenografts for cancer immunotherapy studies: A comprehensive review.Cancer science · 2021Pooled it
- Wnt Signaling Downregulation Mediates T Cell Apoptosis Following OKT3-Induced T Cell Activation in Preclinical Models.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- A novel mRNA-based therapeutic vaccine elicits robust anti-tumor immunity against HPV-associated malignancies.Frontiers in immunology · 2026Article
- Evaluation of a reference antibody panel for prediction of cytokine release in humanised mouse modelsFrontiers in immunology · 2026Article
- Application of humanized mice in the safety experiments of antibody drugs.Animal models and experimental medicine · 2025Review
- Neoadjuvant radiotherapy in ERFrontiers in immunology · 2024Article
- Cytokine release syndrome and cancer immunotherapies - historical challenges and promising futures.Frontiers in immunology · 2023Review
- Identification of Novel Modalities Through Bibliometric Analysis for Timely Development of Regulatory Guidance: A Case Study of T Cell Immunity.Frontiers in medicine · 2021Article
- A rapid, sensitive, and reproducible in vivo PBMC humanized murine model for determining therapeutic-related cytokine release syndrome.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Innovations, challenges, and minimal information for standardization of humanized mice.EMBO molecular medicine · 2020Review
- Humanized Mouse as a Tool to Predict Immunotoxicity of Human Biologics.Frontiers in immunology · 2020Article
- Use of human splenocytes in an innovative humanised mouse model for prediction of immunotherapy-induced cytokine release syndrome.Clinical & translational immunology · 2020Article
- Humanized mouse models of immunological diseases and precision medicine.Mammalian genome : official journal of the International Mammalian Genome Society · 2019Review
- Humanized Mice as Unique Tools for Human-Specific Studies.Archivum immunologiae et therapiae experimentalis · 2018Review
- A non-conserved amino acid variant regulates differential signalling between human and mouse CD28.Nature communications · 2018Article
- CD28 between tolerance and autoimmunity: the side effects of animal models.F1000Research · 2018Review
- Immunosuppression for in vivo research: state-of-the-art protocols and experimental approaches.Cellular & molecular immunology · 2017Review
- Humanized Mouse Models of Clinical Disease.Annual review of pathology · 2017Review
- Translational Rodent Models for Research on Parasitic Protozoa-A Review of Confounders and Possibilities.Frontiers in cellular and infection microbiology · 2017Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Therapeutic monoclonal antibodies (mAbs) such as the superagonistic, CD28-specific antibody TGN1412, or OKT3, an anti-CD3 mAb, can cause severe adverse events including cytokine release syndrome. A predictive model for mAb-mediated adverse effects, for which no previous knowledge on severe adverse events to be expected or on molecular mechanisms underlying is prerequisite, is not available yet. We used a humanized mouse model of human peripheral blood mononuclear cell-reconstituted NOD-RAG1-/-Aβ-/-HLADQ(tg+ or tg-)IL-2Rγc-/- mice to evaluate its predictive value for preclinical testing of mAbs. 2-6 hours after TGN1412 treatment, mice showed a loss of human CD45+ cells from the peripheral blood and loss of only human T cells after OKT3 injection, reminiscent of effects observed in mAb-treated humans. Moreover, upon OKT3 injection we detected selective CD3 downmodulation on T cells, a typical effect of OKT3. Importantly, we detected release of human cytokines in humanized mice upon both OKT3 and TGN1412 application. Finally, humanized mice showed severe signs of illness, a rapid drop of body temperature, and succumbed to antibody application 2-6 hours after administration. Hence, the humanized mouse model used here reproduces several effects and adverse events induced in humans upon application of the therapeutic mAbs OKT3 and TGN1412.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.