TY - JOUR
T1 - Long-term maintenance of peripheral blood derived human NK cells in a novel human IL-15- transgenic NOG mouse
AU - Katano, Ikumi
AU - Nishime, Chiyoko
AU - Ito, Ryoji
AU - Kamisako, Tsutomu
AU - Mizusawa, Takuma
AU - Ka, Yuyo
AU - Ogura, Tomoyuki
AU - Suemizu, Hiroshi
AU - Kawakami, Yutaka
AU - Ito, Mamoru
AU - Takahashi, Takeshi
N1 - Funding Information:
The authors would like to thank Dr. Yaguchi from Keio University for helpful discussion. We thank Keiko Endo, Takahiro Kagawa, Ryutaro Aizawa, and Yasuhiko Ando for animal production and care, and Dr. Masafumi Yamamoto for genotyping. This project was supported by a Grant in Aid (S) (2222007 to M.I.) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan. A Grant in Aid (B) (26290034 to T.T.), and Grant in Aid for Young Researchers (B) (25871074, 16K18405 to I.K.) were provided by the Japanese Society for the Promotion of Science (JSPS). This project was also commissioned by the New Energy and Industrial Technology Development Organization (NEDO) (No. 0527001 to M.I.) and partly supported by a Grant-in-Aid for Research on Hepatitis from the Japan Agency for Medical Research and Development.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-017-17442-7
DO - 10.1038/s41598-017-17442-7
M3 - Article
AN - SCOPUS:85037614366
SN - 2045-2322
VL - 7
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 17230
ER -
