Expanded g-NK cells have markedly enhanced ADCC activity when combined with daratumumab in vivo. (A) Effect of treatment with g-NK cells and daratumumab (n = 7) on MM.1S tumor burden (BLI) in NSG mice relative to a cNK cell control plus daratumumab (n = 7) and mice treated with vehicle (n = 8). The cell and antibody combination therapies were given once per week for 5 weeks with IL-15 support (2 µg per mouse IP every 3 days). One mouse (labeled as &) in the g-NK plus daratumumab group missed the first week of treatment and received the treatment from weeks 2 to 6. (B) All remaining mice from the g-NK plus daratumumab group were euthanized on day 57 after tumor inoculation (day 43 after initial therapy). The quantitative BLI (photons per second [p/s]) values for vehicle control and mice treated with cNK plus daratumumab or g-NK plus daratumumab. (C) Effect of treatment with g-NK plus daratumumab on survival relative to treatment with cNK plus daratumumab or vehicle. (D) Comparison of body weight (g) in mice treated with vehicle, cNK plus daratumumab, or g-NK plus daratumumab. (E) Comparison of MM.1S tumor burden (number of CD45^–/CD138⁺ cells) in bone marrow of NSG mice treated with cNK plus daratumumab or g-NK plus daratumumab. (F) Representative flow cytometry dot plots depicting tumor burden and persistence of NK cells in bone marrow for mice treated with vehicle, cNK plus daratumumab, or g-NK plus daratumumab. One-way ANOVA tests were used to determine the differences in BLI and body weight between different groups at each measurement day. For tumor burden and body weight comparisons when only 2 groups remained, independent samples Student t tests were used. Log-rank tests were used to determine differences between survival curves (P < .0001). Independent samples Student t tests were used to determine the differences in bone marrow tumor burden between mice treated with g-NK plus daratumumab or cNK plus daratumumab when the mice were euthanized. Values are mean ± SD for the BLI (B) and body weight (D) graphs and mean ± SEM for the tumor burden graph (E). *P < .05 (one-way ANOVA); #P < .001 (Student t test).