ArticlePloS one2017
Creation of an immunodeficient HLA-transgenic mouse (HUMAMICE) and functional validation of human immunity after transfer of HLA-matched human cells.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Development of humanized mouse with patient-derived xenografts for cancer immunotherapy studies: A comprehensive review.Cancer science · 2021Pooled it
- Beyond the blood-brain barrier: humanised mice, the missing link in glioblastoma research.Oncogene · 2026Review
- Patient-Derived Models of Liver Cancer to Inform Clinical Treatment Paradigms: Recent Updates.Seminars in liver disease · 2026Review
- Harnessing PDX and PDX 2.0: the next-generation paradigm for precision oncology and translational breakthroughs.Molecular cancer · 2026Review
- Preclinical ex vivo and in vivo models to study immunotherapy agents and their combinations as predictive tools toward the clinic.Journal for immunotherapy of cancer · 2025Review
- CAR-NK cells: harnessing the power of natural killers for advanced cancer therapy.Frontiers in immunology · 2025Review
- Pathophysiology and preclinical relevance of experimental graft-versus-host disease in humanized mice.Biomarker research · 2024Review
- MHC class I and II-deficient humanized mice are suitable tools to test the long-term antitumor efficacy of immune checkpoint inhibitors and T-cell engagers.Journal for immunotherapy of cancer · 2024Article
- Orthotopic and metastatic tumour models in preclinical cancer research.Pharmacology & therapeutics · 2024Review
- Advances in cell-based delivery of oncolytic viruses as therapy for lung cancer.Molecular therapy. Oncology · 2024Review
- Progress in building clinically relevant patient-derived tumor xenograft models for cancer research.Animal models and experimental medicine · 2023Review
- Modeling the Tumor Microenvironment and Cancer Immunotherapy in Next-Generation Humanized Mice.Cancers · 2023Review
- Humanized mouse models for immuno-oncology research.Nature reviews. Clinical oncology · 2023Review
- Critical evaluation of an autologous peripheral blood mononuclear cell-based humanized cancer model.PloS one · 2022Article
- Advances in Transgenic Mouse Models to Study Infections by Human Pathogenic Viruses.International journal of molecular sciences · 2020Review
- The Development of Next-generation PBMC Humanized Mice for Preclinical Investigation of Cancer Immunotherapeutic Agents.Anticancer research · 2020Review
- Leveraging Patient-Derived Models for Immunotherapy Research.American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting · 2020Article
- Review
- Patient-derived xenograft models to optimize kidney cancer therapies.Translational andrology and urology · 2019Review
- Humanizing the mouse immune system to study splanchnic organ inflammation.The Journal of physiology · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Research on human immunology has been hindered by the lack of optimal small animal models, given that the protective immune responses of human and non-human species show significant differences. However, due to ethical constraints[1] and the high cost of clinical trials, it is urgent to improve the current animal models that can mimic faithfully human physiology, particularly the human immune system (HIS). HIS mice had been generated recently by engrafting human hematopoietic stem cells (hHSCs) or human peripheral mononuclear cells (hPBMCs) into highly immuno-deficient mice such as NSG, NOG or NRG mice. However, a major experimental drawback for studies using these models is the rapid onset of Graft-versus-Host Disease (GvHD). In the present study, we overcome this limitation by generating new immuno-deficient mice named "HUMAMICE" (HLA-A2+/+/DR1+/+/H-2-β2m-/-/IAβ-/-/Rag2-/-/IL2rγ-/-/Perf-/- mice), which expressed human HLA molecules instead of mouse MHC molecules (H-2), and whose immuno-deficient status was reversed by transferring functional HLA-matched PBMCs thus producing mice with an immuno-competent status with a functional human immune system. We showed that in this HLA-matched context, the hPBMC-transfer led to high lymphocytes engraftment rates without GvHD over three months in this novel mouse model. Furthermore, to evaluate the utility of the hPBMC-HUMAMICE, we immunized them with commercial vaccine of Hepatitis B virus (HBsAg, Hepvac@) which resulted in robust and reproducible production of high levels of HBsAg-specific antibodies, implying that both transferred T and B lymphocytes were functional in HUMAMICE. These responses are comparable to those observed in human clinical trials with this identical vaccine. In conclusion, these findings indicated that the HLA-matched-hPBMC-HUMAMICE represents a promising model for dissecting human immune responses in various human diseases, including infectious diseases, cancers and tumors, and to facilitate the development of novel vaccines and cellular therapies.
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