In vivo administration of tmTNF-α antibody inhibits AML cell growth in NOD-SCID mice but does not impair the repopulation capacity of normal hematopoietic cells. (A) An overview of the experimental design: each NOD-SCID recipient mouse was transplanted with 1 × 105 leukemia cells. Treatment with C1 or IgG1 control antibody (n = 5) was initiated at day 1 posttransplantation. Antibodies were administered intraperitoneally at 10 μg per 1 g body weight twice per week for 6 weeks; mice were euthanized at the end of the 6-week period. (B) The percentage of human AML cells in PB of mice. Values represent means ± SEM; *P < .05; **P < .01 between IgG1 control and C1-treated groups. (C) Kaplan-Meier survival curves of NOD-SCID mice treated with C1 or IgG1 control antibody. For the survival curve analysis, twice weekly antibody treatment was continued until a mouse died. Survival curves were compared using the log-rank test. Error bars represent means ± SEM; *P < .05 between control and C1-treated groups. (D-F) Percentage of human AML cells in murine BM (D), spleen (E), or liver (F) at the end of the experiment, as assessed by FCM. Error bars represent means ± SEM for the percentage of leukemia cells in each group. (G-I) Each NOD-SCID recipient mouse was transplanted with 1 × 105 CD34+ cells harvested from the BM of healthy human donors. Treatment with C1 or IgG1 control antibody (n = 4 each group) was administered following the same protocol described previously. The effects of C1 on normal hematopoietic cells were assessed at the experimental end point. (G) The proportion of various types of human blood cells in PB of mice from the C1 or IgG1 control group. Human engraftment in mouse BM (H) and the percentage of CD34+ cells in human grafts within mouse BM (I) are shown. Error bars represent means ± SEM in the C1 vs IgG1 groups; no significant difference was detected between the groups.
