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- W4308382402 abstract "<h3>Background</h3> IL-15 is a four α-helix bundle cytokine produced by dendritic cells, monocytes, and epithelial cells. IL-15 is necessary for the development, survival, and activation of natural killer (NK) cells. <h3>Methods</h3> Human <i>IL-15</i> (<i>hIL-15</i>) was knocked into NCG mice to create a model (NCG-hIL15) that can assist the reconstitution of human NK cells. <h3>Results</h3> Compared with NCG, hIL-15 expression was significantly increased in NCG-hIL15het and NCG-hIL15homo. The development and function of human NK cells were evaluated in the NCG-hIL15 mouse reconstituted with three different types of human cell sources: (1) purified NK from human PBMC, (2) human PBMC, and (3) human CD34+ hematopoietic stem cells (HSC). In PBMC and CD34+ HSC-reconstituted mice, NK cell development was evident, with approximately 20% of hCD45+hCD56+ NK cells detected in the peripheral blood within weeks of engraftment. The level of hCD45+hCD3+ T cells reached 10 to 30% within 12 weeks of HSC reconstitution, while it reached greater than 80% within 2 weeks of PBMC reconstitution. In the purified NK engrafted cohort, the hCD45+hCD56+ NK cell numbers increased by at least two-fold within the first 3 weeks. Human NK cells were detected in multiple tissues and organs of all reconstituted NCG-hIL15 mice regardless of source of engraftment, except the colon, in the hPBMC-reconstituted NCG-IL15 mice. It was also noted that the level of NK cells post-engraftment varied depending on the donor of the PBMC. To determine whether the reconstituted NK cells remain functional, purified NK cells from CD34+ HSC engrafted NCG-IL15 were isolated. Data showed that the NK cells could exert cell cytotoxicity when tested in vitro with leukemia cells, Raji, and Rituximab. Similarly, in vivo tumor growth inhibition (TGI= 49%) was observed with Raji. <h3>Conclusions</h3> Overall, the addition of human IL-15, via genetic engineering in immunodeficient NCG mice provides excellent support for NK cell development. The NCG-hIL15 is a valuable tool for NK cell research and preclinical agent evaluation that requires NK and T cell activity." @default.
- W4308382402 created "2022-11-11" @default.
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- W4308382402 date "2022-11-01" @default.
- W4308382402 modified "2023-10-18" @default.
- W4308382402 title "1226 NCG-hIL15 humanized mice – an excellent model for human immune reconstitution of NK cells" @default.
- W4308382402 doi "https://doi.org/10.1136/jitc-2022-sitc2022.1226" @default.
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