Figure 7
Figure 7. GVHD induction is impaired, whereas GVL effects are preserved in R524-treated recipients in an MiHA-mismatch BMT model. C57BL/6 recipients received total-body irradiation (1200 cGy) and were transplanted with donor C3SW.H TCD-BM alone (n = 6) or in combination with 3 × 106 T cells (CD4+, CD8+, CD25–, and CD44–) and treated with vehicle (n = 6) or 40 mg/kg R524 (n = 6) twice daily for 6 weeks beginning on day 0. Additional recipients were intravenously injected with 5 × 104 C1498 luciferase-transduced leukemia cells at the time as BMT (n = 10 vehicle treated and n = 10 R524 treated). Recipients without tumor (A-B) and with tumor (C-E) were monitored throughout the experimental period for survival (A,C) and weight change (B,D). In leukemia recipients, tumor expansion was tracked by luciferin intraperitoneal injection and whole body BLI (E). Leukemia growth was confirmed in recipients at necropsy. Average survival and weight changes across 3 separate repeat experiments and recipient BLI images from 1 of 2 repeating experiments are shown. *P < .05; **P < .01; ***P < .001 (compared with vehicle-treated recipients).

GVHD induction is impaired, whereas GVL effects are preserved in R524-treated recipients in an MiHA-mismatch BMT model. C57BL/6 recipients received total-body irradiation (1200 cGy) and were transplanted with donor C3SW.H TCD-BM alone (n = 6) or in combination with 3 × 106 T cells (CD4+, CD8+, CD25, and CD44) and treated with vehicle (n = 6) or 40 mg/kg R524 (n = 6) twice daily for 6 weeks beginning on day 0. Additional recipients were intravenously injected with 5 × 104 C1498 luciferase-transduced leukemia cells at the time as BMT (n = 10 vehicle treated and n = 10 R524 treated). Recipients without tumor (A-B) and with tumor (C-E) were monitored throughout the experimental period for survival (A,C) and weight change (B,D). In leukemia recipients, tumor expansion was tracked by luciferin intraperitoneal injection and whole body BLI (E). Leukemia growth was confirmed in recipients at necropsy. Average survival and weight changes across 3 separate repeat experiments and recipient BLI images from 1 of 2 repeating experiments are shown. *P < .05; **P < .01; ***P < .001 (compared with vehicle-treated recipients).

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