Human NK-Cells Engraft in hIL-15 NOG Mice

Distribution of long-term engrafting human NK cells in hIL-15 transgenic NOG mice

Figure 1: (a) Expansion of transferred human NK cells in NOG mice expressing human IL-15. X-irradiated NOG and hIL-15 NOG mice received human NK cells from peripheral blood magnetic cell sorting. Blood was collected and analyzed by FACS every week for 24 weeks after transfer. The absolute numbers of human NK cells in mouse peripheral blood are shown. (n = 6 for NOG and hIL-15 NOG mice). (b) Means +/- SD of the human NK-cell frequencies in each tissue are shown (n = 6). (c) Frequencies of CD56^dimCD16⁺ and CD56^hiCD16⁻ subpopulations in total CD56⁺ NK cells are shown (n = 6 for bone marrow (BM), spleen, and PB; n = 3 for liver and lung). Adapted from Katano, et al. 2018 under Creative Commons Attribution License.

Human NK cells expand in hIL-15 NOG engrafted with human PBMCs

Figure 2: Human immune cell engraftment in hIL-15 NOG vs NOG mice. Data from peripheral blood analysis of human T cells (a), B cells (b), NK cells (c), and monocytes (d), performed at 18, 25, and 32 days post PBMC engraftment. Single donor's cells were engrafted into both models at the indicated cell dose. Adapted from Volden, et al. 2018.

Anti-tumor ADCC with NK-cell Humanized hIL-15 NOG Mice

In vivo antibody-dependent cell-mediated cytotoxicity (ADCC) activity human NK-cell engrafted hIL-15 transgenic NOG

Figure 3: (a) Tumor suppression by in vitro-expanded human peripheral blood NK cells and anti-Her2 treatment. Her2-positive NCI-N87 cells, a gastric-cancer cell line, were inoculated into X-irradiated hIL-15 NOG mice. Human peripheral blood NK cells, expanded in vitro, were transplanted with or without anti-Her2 antibody. (b) Tumor suppression by in vitro-expanded human NK cells and anti-CCR4 treatment. X-irradiated hIL-15 NOG mice were subsequently inoculated with L428 Hodgkin lymphoma cells. In vitro-expanded human peripheral blood NK cells were transplanted 1 week after tumor inoculation and administration of anti-CCR4 antibody or control antibody was started. Adapted from Katano, et al. 2018 under Creative Commons Attribution License.

Human NK-cell engrafted hIL-15 NOG as a model for antibody-mediated NK cell depletion and ADCC

Figure 4: (a) Experimental timeline and (b) study groups. (c) Dynamics of absolute NK cell numbers per microliter of blood over the course of the study. (d) NK cell staining with viability dye Zombie Violet. (e) Raji tumor growth kinetics and CD69 activation marker on peripheral blood (f) and tumor infiltrating (g) human NK cells. Adapted from Bunin, et al. 2019.

hIL-15 expression levels: A cohort of 12 female and 10 male hIL-15 NOG mice were assayed for hIL-15 levels in serum via Luminex assay. hIL-15 levels in serum were in the range of ~150-250 pg/mL.