Figure 6. ALT-803 rescue of 2DG-treated mice requires NK cells, and ALT-803 priming can eliminate susceptibility to MCMV caused by mTOR inhibition.

(A) Mice were either depleted of NK cells using α-NK1.1 or treated with IgG2a; they were given 2 doses of ALT-803 and infected with 1 × 10⁵ PFU murine cytomegalovirus (MCMV). 2-Deoxy-ᴅ-glucose (2DG) was given every 24 hours, and mice were euthanized on day 2 for assessment of (B) clearance of m157-transgenic targets from the spleen and (C) viral copy number from the spleen and liver; they were measured by quantitative PCR and log-transformed (n = 10 individuals/group, 2 separate experiments, 2-tailed t test). (D) To assess susceptibility, an additional NK depletion was given at day 3 (red, n = 30); control mice were treated with IgG2a (black, n = 23). Mice were followed for 10 days (3 separate experiments). (E) Mice were infected with MCMV, given daily i.p. injections of 1.5 mg/kg rapamycin (green) or vehicle (black), and monitored for susceptibility (n = 10/group, 1 experiment). (F) ALT-803 was given to MCMV-infected, rapamycin-treated mice on the same schedule as for 2DG-treated mice, with doses at –3, –1, and +2 days relative to infection (n = 10/group, 1 experiment). Data show mean ± SEM or survival in D–F analyzed by log-rank Mantel-Cox test. ***P < 0.001. Asterisks in A and D indicate treatment with ALT-803.