Abstract 5613: Human interleukin 15 (IL15) humanized NCG mice support the human natural killer cells reconstitution and development

Abstract

Abstract The potential of NK cells in cancer therapy has aroused increasing attention. While highly immune deficient mice, NCG,with null mutation on Prkdc and IL2Rγ,is ideal for human immune reconstitution, the reconstitution of human NK cells is still challenging. This is mostly because species barrier on cytokines which are necessary for the proliferation and maturation of NK cells. To this end, we established a human IL-15 (hIL-15) knock-in NCG (NCG-hIL-15), which produces hIL-15 under physiological level and pattern.NCG-hIL-15 implanted with either purified human NK cells or hematopoietic stem cells (HSCs) could give rise to a longer-term maintenance of human NK cell when compared to NCG. These long-lived NK cells retained the ability of migration, as evidenced by their wide distribution in various organs (e.g. spleen, liver, and lung). We also tested the expression profiles of killer cell immunoglobulin-like receptor (KIR) molecules, as well as the secretion of granzyme and perforin, results suggested normal activity and function of these reconstituted NK cells. Moreover, after human NK cell reconstitution, efficient tumor growth inhibition of human NK-specific agonist was shown in tumor engrafted NCG-hIL15. Taken together, NCG-hIL-15 mice is a novel mouse model for studying human NK cell biology and human NK-mediated cancer immunotherapy in vivo. Citation Format: Cunxiang Ju, Mingkun Zhang, Dan Wu, Dingyu Wang, Hongyan Sun, Jin Tang, Shuai Li, Jing Zhao, Xiang Gao. Human interleukin 15 (IL15) humanized NCG mice support the human natural killer cells reconstitution and development [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5613.