NK cells expand and proliferate after ALT-803 administration. (A) NK cell percentages increase following ALT-803 administration as shown in a representative patient treated at the 10 μg/kg SQ dose level (UMN019). Bivariate flow cytometry plots show CD56 vs CD3 expression, resolving NK cells and T cells. Percentage of NK cells at the indicated time point after the first ALT-803 administration is annotated. (B) Summary data of NK cell percentages during ALT-803 therapy, comparing IV to SQ administration, combining 6 and 10 μg/kg dose levels. Both the IV (P = .04) and SQ (P < .01) cohorts show curves significant increases in NK cell percentage over time compared with time 0 (ANOVA). Comparisons of the curves revealed a significant increase in SQ over IV (P < .01, 2-way ANOVA). (C) NK cell number increases during ALT-803 therapy, comparing IV to SQ administration, combining the 6 and 10 μg/kg dose levels. The IV (P = .03) and SQ (P < .01) curves both significantly increase over time (ANOVA), and comparison of the curves reveals a significant increase in SQ (P = .029, 2-way ANOVA). Fold change comparing IV and SQ demonstrates a significant increase in the peak fold change (Mann-Whitney test) determined as the peak absolute NK cell count during ALT-803 therapy divided by the absolute NK cell count pretherapy. (D) Representative flow cytometry plots demonstrating changes in Ki67 (surrogate for proliferation) over time with IV vs SQ ALT-803. (E) Summary data from panel D. Both the IV (P < .01) and SQ (P < .01) curves significantly increase in Ki67⁺ NK cell percentage over time compared with time 0 (2-way ANOVA). Comparisons of the curves revealed a significant increase in SQ Ki67⁺ NK cells that is most apparent at day 7 (2-way ANOVA).