Long-term maintenance of peripheral blood derived human NK cells in a novel human IL-15- transgenic NOG mouse

Ikumi Katano, Chiyoko Nishime, Ryoji Ito, Tsutomu Kamisako, Takuma Mizusawa, Yuyo Ka, Tomoyuki Ogura, Hiroshi Suemizu, Yutaka Kawakami, Mamoru Ito, Takeshi Takahashi

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

We generated a novel mouse strain expressing transgenic human interleukin-15 (IL-15) using the severe immunodeficient NOD/Shi-scid-IL-2Rγ null (NOG) mouse genetic background (NOG-IL-15 Tg). Human natural killer (NK) cells, purified from the peripheral blood (hu-PB-NK) of normal healthy donors, proliferated when transferred into NOG-IL-15 Tg mice. In addition, the cell number increased, and the hu-PB-NK cells persisted for 3 months without signs of xenogeneic graft versus host diseases (xGVHD). These in vivo-expanded hu-PB-NK cells maintained the original expression patterns of various surface antigens, including NK receptors and killer cell immunoglobulin-like receptor (KIR) molecules. They also contained significant amounts of granzyme A and perforin. Inoculation of K562 leukemia cells into hu-PB-NK-transplanted NOG-IL-15 Tg mice resulted in significant suppression of tumor growth compared with non-transplanted mice. Furthermore, NOG-IL-15 Tg mice allowed for engraftment of in vitro-expanded NK cells prepared for clinical cell therapy. These cells exerted antibody-dependent cell-mediated cytotoxicity (ADCC) on Her2-positive gastric cancer cells in the presence of therapeutic anti-Her2 antibody, and subsequently suppressed tumor growth. Our results collectively suggest that the NOG-IL-15 Tg mice are a useful model for studying human NK biology and evaluating human NK cell-mediated in vivo cytotoxicity.

Original languageEnglish
Article number17230
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1

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Natural Killer Cells
Transgenic Mice
Interleukin-15
KIR Receptors
Antibody-Dependent Cell Cytotoxicity
Granzymes
Perforin
K562 Cells
Graft vs Host Disease
Surface Antigens
Growth
Cell- and Tissue-Based Therapy
human IL15 protein
Stomach Neoplasms
Anti-Idiotypic Antibodies
Neoplasms
Leukemia
Cell Count

ASJC Scopus subject areas

  • General

Cite this

Katano, I., Nishime, C., Ito, R., Kamisako, T., Mizusawa, T., Ka, Y., ... Takahashi, T. (2017). Long-term maintenance of peripheral blood derived human NK cells in a novel human IL-15- transgenic NOG mouse. Scientific Reports, 7(1), [17230]. https://doi.org/10.1038/s41598-017-17442-7

Long-term maintenance of peripheral blood derived human NK cells in a novel human IL-15- transgenic NOG mouse. / Katano, Ikumi; Nishime, Chiyoko; Ito, Ryoji; Kamisako, Tsutomu; Mizusawa, Takuma; Ka, Yuyo; Ogura, Tomoyuki; Suemizu, Hiroshi; Kawakami, Yutaka; Ito, Mamoru; Takahashi, Takeshi.

In: Scientific Reports, Vol. 7, No. 1, 17230, 01.12.2017.

Research output: Contribution to journalArticle

Katano, I, Nishime, C, Ito, R, Kamisako, T, Mizusawa, T, Ka, Y, Ogura, T, Suemizu, H, Kawakami, Y, Ito, M & Takahashi, T 2017, 'Long-term maintenance of peripheral blood derived human NK cells in a novel human IL-15- transgenic NOG mouse', Scientific Reports, vol. 7, no. 1, 17230. https://doi.org/10.1038/s41598-017-17442-7
Katano, Ikumi ; Nishime, Chiyoko ; Ito, Ryoji ; Kamisako, Tsutomu ; Mizusawa, Takuma ; Ka, Yuyo ; Ogura, Tomoyuki ; Suemizu, Hiroshi ; Kawakami, Yutaka ; Ito, Mamoru ; Takahashi, Takeshi. / Long-term maintenance of peripheral blood derived human NK cells in a novel human IL-15- transgenic NOG mouse. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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