Combined IL-2DT and anti–PD-L1 mAb had superior antitumor effect to either treatment alone and, when coupled with anti-AML CTLs, more rapidly and uniformly reduced AML tumor burden. B6 mice (10 mice/group) were injected with 106 C1498FFDsR cells followed by IL-2DT, anti–PD-L1 mAb, and/or anti-AML CTL treatment as described. Whole body imaging was performed to determine tumor burden 19, 26, and 33 days after AML injection. (A) Tumor burden was decreased by combination therapy. IL-2DT, but not anti–PD-L1 mAb alone, significantly reduced tumor burden at an early time point (day 19). Combined IL-2DT and anti–PD-L1 had superior effect compared with either treatment alone. Although CTL therapy alone did not significantly decrease AML tumor burden at any time point, adding CTL therapy to IL-2DT and anti–PD-L1 mAb treatment resulted in the greatest and most consistent decrease in AML tumor burden throughout the 33-day post-AML challenge observation period. *P < .05 compared with nontreated AML controls. Error bars represent SEM. (B) BLI studies of 5 mice per group receiving AML with or without IL-2DT, anti–PD-L1 mAb, and CTL therapy are shown. On day 19, 2 of 5 mice receiving IL-2DT and anti–PD-L1 mAb had detectable tumor versus 0 of 5 mice also receiving CTLs. (C) IL-2DT or anti–PD-L1 mAb treatment alone significantly prolonged the survival mice compared with either control mice or mice treated with CTLs alone (♦ and ▴ vs ■ or ▾, P < .05). Combined IL-2DT with CTLs or anti–PD-L1 mAb with CTLs had superior effect compared with either control mice (■, P < .05) or mice receiving IL-2DT (♦, P < .05), anti–PD-L1 mAb (▴, P < .05), or CTL single treatment (▾, P < .05). Combined IL-2DT and anti–PD-L1 mAb with (●) or without CTLs (▿) had the best survival outcome compared with single treatment or in combination with CTLs.