Lirilumab therapy enhances the antilymphoma activity of rituximab in vivo and is NK-cell–dependent. (A) Schema of lirilumab and rituximab administration. (B) To determine the therapeutic efficacy of drug combination vs monotherapy, 221 HLA-Cw3 tumor cells (107 cells) were injected intravenously into Rag1KO-Tg KIR mice. Starting 5 days after tumor challenge, groups (n = 8 mice per group) received (♢) IC, (●) lirilumab intravenously at 0.5 mg/kg on day 5, or (▼) rituximab (RTX) intraperitoneally at 0.12 mg/kg on days 5, 8, and 12. Mice were then monitored for overall survival. (C) To determine the role of NK cells, 221 HLA-Cw3 tumor cells (107 cells) were injected intravenously into Rag1KO-Tg KIR mice and, starting 5 days after tumor challenge, groups (n = 8 mice per group) received (♢) IC, (♦) lirilumab at 0.5 mg/kg on day 5 and RTX at 0.12 mg/kg on days 5, 8, and 12, or (▪) lirilumab at 0.5 mg/kg on day 5 and RTX at 0.12 mg/kg on days 5, 8, and 12 and 100 µg of anti-NK1.1 mAb on day 4 to deplete NK cells. Mice were then monitored for overall survival. *P < .001. (B) and (C) show several groups of the same experiments. One experiment representative of 2 experiments is shown.
