Abstract 5062: Modeling NK cells activities in full human immune system mouse models

Abstract

Abstract The cytotoxic potential of NK-cells for the elimination of cancer cells represents the basis for many important ongoing clinical efforts. These efforts can now be supported by the humanized immune system mouse models (Hu-Mice), which offer an improved in vivo system for translating therapies to the clinic. Using hydrodynamic injection of human IL-15, TransCure bioServices has developed a NK boosted hu-Mice (CD34+ engrafted NCG) providing sufficient and functional human NK cells. The transient and physiological expression of IL-15 allow the expansion of human NK cells in the context of a full and stable human immune system bringing numerous advantages compared to the NK infused mouse model in IL15 transgenic mouse models. One week after boost, three times more NK cells are present in peripheral blood of IL15-boosted hu-Mice and this level is stable up to five weeks, providing sufficient time to engraft tumor cells and test drug efficacy. A better infiltration of the tumor by human NK cells is also visible in IL-15 boosted mice. Furthermore, the efficacy of ADCC dependent drugs (administered prophylactically or therapeutically) have been highlighted in IL-15 boosted hu-Mice engrafted with melanoma and multiple myeloma cells. In conclusion, the IL-15 boosted hu-Mice provide a reliable and validated in vivo model to better assess the efficacy and MOA of drug depending on NK cell activity. Citation Format: Kiave Yune Ho Wang Yin. Modeling NK cells activities in full human immune system mouse models [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 5062.