Treatment of allo-HCT recipients with the ADCC-defective anti-Fn14 mAb variant 18D1-dead delays the onset of acute GVHD while maintaining GVL effects. The effect of 18D1-dead on GVL activity was investigated in IM380 and A20 B-cell lymphoma models. Balb/c (H-2^d) mice were either injected with 10⁵ syngenic, luciferase-transgenic IM380 B-cell lymphoma cells iv 6 days before allo-HCT or with 10⁵ syngenic, luciferase-transgenic A20 cells along with allogeneic 5 × 10⁶ B6 (H-2^b) BM cells alone or together with 1 × 10⁶ enriched B6 (H-2^b) T cells. Starting on day 1 post–allo-HCT, mice were treated daily for a week with 100 µg of 18D1-dead or with 100 µg of an irrelevant hIgG1 mAb (n = 5 for each group). (A) In vivo bioluminescence imaging of luciferase⁺ lymphoma cells of a representative mouse of the indicated groups. Upper panels represent data at 8 days after transplantation; lower panels show images of a representative mouse of each group throughout the first 8 days of the experiment. (B) Survival analysis of allo-HCT recipients (right panel). Data from both GVL models are displayed, along with data from mice of the myeloablative conditioning control (irradiation only) and the BM engraftment control (BM control). Weight change after allo-HCT in percent of the initial weight (left panel). Statistics of hIgG1 vs 18D1-dead are indicated: mean ± SEM. *P ≤ .05; **P ≤ .01.