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

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 dono...

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Autores principales:	Ikumi Katano, Chiyoko Nishime, Ryoji Ito, Tsutomu Kamisako, Takuma Mizusawa, Yuyo Ka, Tomoyuki Ogura, Hiroshi Suemizu, Yutaka Kawakami, Mamoru Ito, Takeshi Takahashi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1b2e88d48ff34234a3d4354ee0c12aff
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spelling	oai:doaj.org-article:1b2e88d48ff34234a3d4354ee0c12aff2021-12-02T15:05:40ZLong-term maintenance of peripheral blood derived human NK cells in a novel human IL-15- transgenic NOG mouse10.1038/s41598-017-17442-72045-2322https://doaj.org/article/1b2e88d48ff34234a3d4354ee0c12aff2017-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-17442-7https://doaj.org/toc/2045-2322Abstract 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.Ikumi KatanoChiyoko NishimeRyoji ItoTsutomu KamisakoTakuma MizusawaYuyo KaTomoyuki OguraHiroshi SuemizuYutaka KawakamiMamoru ItoTakeshi TakahashiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ikumi Katano Chiyoko Nishime Ryoji Ito Tsutomu Kamisako Takuma Mizusawa Yuyo Ka Tomoyuki Ogura Hiroshi Suemizu Yutaka Kawakami Mamoru Ito Takeshi Takahashi Long-term maintenance of peripheral blood derived human NK cells in a novel human IL-15- transgenic NOG mouse
description	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.
format	article
author	Ikumi Katano Chiyoko Nishime Ryoji Ito Tsutomu Kamisako Takuma Mizusawa Yuyo Ka Tomoyuki Ogura Hiroshi Suemizu Yutaka Kawakami Mamoru Ito Takeshi Takahashi
author_facet	Ikumi Katano Chiyoko Nishime Ryoji Ito Tsutomu Kamisako Takuma Mizusawa Yuyo Ka Tomoyuki Ogura Hiroshi Suemizu Yutaka Kawakami Mamoru Ito Takeshi Takahashi
author_sort	Ikumi Katano
title	Long-term maintenance of peripheral blood derived human NK cells in a novel human IL-15- transgenic NOG mouse
title_short	Long-term maintenance of peripheral blood derived human NK cells in a novel human IL-15- transgenic NOG mouse
title_full	Long-term maintenance of peripheral blood derived human NK cells in a novel human IL-15- transgenic NOG mouse
title_fullStr	Long-term maintenance of peripheral blood derived human NK cells in a novel human IL-15- transgenic NOG mouse
title_full_unstemmed	Long-term maintenance of peripheral blood derived human NK cells in a novel human IL-15- transgenic NOG mouse
title_sort	long-term maintenance of peripheral blood derived human nk cells in a novel human il-15- transgenic nog mouse
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/1b2e88d48ff34234a3d4354ee0c12aff
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Long-term maintenance of peripheral blood derived human NK cells in a novel human IL-15- transgenic NOG mouse

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