Development of Humanized Mouse Models for Studying Human NK Cells in Health and Disease

doi:10.1007/978-1-0716-2160-8_5

. 2022:2463:53-66.

doi: 10.1007/978-1-0716-2160-8_5.

Development of Humanized Mouse Models for Studying Human NK Cells in Health and Disease

Liang Shan^{1

2}, Richard A Flavell^{3

4}, Dietmar Herndler-Brandstetter^{5

6}

Affiliations

¹ Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, Saint Louis, MO, USA. liang.shan@wustl.edu.
² Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA. liang.shan@wustl.edu.
³ Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA. richard.flavell@yale.edu.
⁴ Howard Hughes Medical Institute, Yale University, New Haven, CT, USA. richard.flavell@yale.edu.
⁵ Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria. dietmar.herndler-brandstetter@meduniwien.ac.at.
⁶ Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria. dietmar.herndler-brandstetter@meduniwien.ac.at.

PMID: 35344167
PMCID: PMC9116980
DOI: 10.1007/978-1-0716-2160-8_5

Development of Humanized Mouse Models for Studying Human NK Cells in Health and Disease

Liang Shan et al. Methods Mol Biol. 2022.

. 2022:2463:53-66.

doi: 10.1007/978-1-0716-2160-8_5.

Authors

Liang Shan^{1

2}, Richard A Flavell^{3

4}, Dietmar Herndler-Brandstetter^{5

6}

Affiliations

¹ Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, Saint Louis, MO, USA. liang.shan@wustl.edu.
² Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA. liang.shan@wustl.edu.
³ Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA. richard.flavell@yale.edu.
⁴ Howard Hughes Medical Institute, Yale University, New Haven, CT, USA. richard.flavell@yale.edu.
⁵ Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria. dietmar.herndler-brandstetter@meduniwien.ac.at.
⁶ Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria. dietmar.herndler-brandstetter@meduniwien.ac.at.

PMID: 35344167
PMCID: PMC9116980
DOI: 10.1007/978-1-0716-2160-8_5

Abstract

Humanized mice, which we define as immunodeficient mice that have been reconstituted with a human immune system, represent promising preclinical models for translational research and precision medicine as they allow modeling and therapy of human diseases in vivo. The first generation of humanized mice showed insufficient development, diversity and function of human immune cells, in particular human natural killer (NK) cells and type 1 innate lymphoid cells (ILC1). This limited the applicability of humanized mice for studying ILC1 and NK cells in the context of human cancers and immunotherapeutic manipulation. However, since 2014, several next-generation humanized mouse models have been developed that express human IL-15 either as a transgene or knock-in (NOG-IL15, NSG-IL15, NSG-IL7-IL15, SRG-15) or show improved development of human myeloid cells, which express human IL-15 and thereby promote human NK cell development (NSG-SGM3, MISTRG, BRGSF). Here we compare the various next-generation humanized mouse models and describe the methodological procedures for creating mice with a functioning human immune system and how they can be used to study and manipulate human NK cells in health and disease.

Keywords: Cancer immunotherapy; Hematopoietic stem cells; Humanized mice; Immuno-oncology; Innate lymphoid cells; NK cells; Precision medicine; Preclinical model; Translational research.

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References

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1. Gao Y, Souza-Fonseca-Guimaraes F, Bald T, Ng SS, Young A et al. Tumor immunoevasion by the conversion of effector NK cells into type 1 innate lymphoid cells. Nat Immunol 18, 1004–1015, doi:10.1038/ni.3800 (2017). - DOI - PubMed
1. Kennedy MK, Glaccum M, Brown SN, Butz EA, Viney JL, Embers M, Matsuki N, Charrier K, Sedger L, Willis CR, Brasel K, Morrissey PJ, Stocking K, Schuh JC, Joyce S & Peschon JJ Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice. J Exp Med 191, 771–780 (2000). - PMC - PubMed

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[1] Spits H, Artis D, Colonna M, Diefenbach A, Di Santo JP, Eberl G, Koyasu S, Locksley RM, McKenzie AN, Mebius RE, Powrie F & Vivier E Innate lymphoid cells--a proposal for uniform nomenclature. Nat Rev Immunol 13, 145–149, doi:10.1038/nri3365 (2013). - DOI - PubMed

[2] Spits H, Artis D, Colonna M, Diefenbach A, Di Santo JP, Eberl G, Koyasu S, Locksley RM, McKenzie AN, Mebius RE, Powrie F & Vivier E Innate lymphoid cells--a proposal for uniform nomenclature. Nat Rev Immunol 13, 145–149, doi:10.1038/nri3365 (2013). - DOI - PubMed

[3] Bjorkstrom NK, Ljunggren HG & Michaelsson J Emerging insights into natural killer cells in human peripheral tissues. Nat Rev Immunol 16, 310–320, doi:10.1038/nri.2016.34 (2016). - DOI - PubMed

[4] Bjorkstrom NK, Ljunggren HG & Michaelsson J Emerging insights into natural killer cells in human peripheral tissues. Nat Rev Immunol 16, 310–320, doi:10.1038/nri.2016.34 (2016). - DOI - PubMed

[5] Chiossone L, Dumas PY, Vienne M & Vivier E Natural killer cells and other innate lymphoid cells in cancer. Nat Rev Immunol 18, 671–688, doi:10.1038/s41577-018-0061-z (2018). - DOI - PubMed

[6] Chiossone L, Dumas PY, Vienne M & Vivier E Natural killer cells and other innate lymphoid cells in cancer. Nat Rev Immunol 18, 671–688, doi:10.1038/s41577-018-0061-z (2018). - DOI - PubMed

[7] Gao Y, Souza-Fonseca-Guimaraes F, Bald T, Ng SS, Young A et al. Tumor immunoevasion by the conversion of effector NK cells into type 1 innate lymphoid cells. Nat Immunol 18, 1004–1015, doi:10.1038/ni.3800 (2017). - DOI - PubMed

[8] Gao Y, Souza-Fonseca-Guimaraes F, Bald T, Ng SS, Young A et al. Tumor immunoevasion by the conversion of effector NK cells into type 1 innate lymphoid cells. Nat Immunol 18, 1004–1015, doi:10.1038/ni.3800 (2017). - DOI - PubMed

[9] Kennedy MK, Glaccum M, Brown SN, Butz EA, Viney JL, Embers M, Matsuki N, Charrier K, Sedger L, Willis CR, Brasel K, Morrissey PJ, Stocking K, Schuh JC, Joyce S & Peschon JJ Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice. J Exp Med 191, 771–780 (2000). - PMC - PubMed

[10] Kennedy MK, Glaccum M, Brown SN, Butz EA, Viney JL, Embers M, Matsuki N, Charrier K, Sedger L, Willis CR, Brasel K, Morrissey PJ, Stocking K, Schuh JC, Joyce S & Peschon JJ Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice. J Exp Med 191, 771–780 (2000). - PMC - PubMed

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Development of Humanized Mouse Models for Studying Human NK Cells in Health and Disease

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Development of Humanized Mouse Models for Studying Human NK Cells in Health and Disease

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