RRC ID 55032
Author Katano I, Nishime C, Ito R, Kamisako T, Mizusawa T, Ka Y, Ogura T, Suemizu H, Kawakami Y, Ito M, Takahashi T.
Title Long-term maintenance of peripheral blood derived human NK cells in a novel human IL-15- transgenic NOG mouse.
Journal Sci Rep
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.
Volume 7(1)
Pages 17230
Published 2017-12-8
DOI 10.1038/s41598-017-17442-7
PII 10.1038/s41598-017-17442-7
PMID 29222435
PMC PMC5722902
MeSH Animals Humans Interleukin-15 / blood* Interleukin-15 / genetics* Killer Cells, Natural / cytology* Mice Mice, Transgenic
IF 4.011
Times Cited 8
DNA material hIL-15 cDNA (RDB01866)