IL1RAP antibodies kill primary BP CML cells in vivo by effector cell–mediated mechanisms. (A-F) NOD/SCID mice engrafted with CML-BP1 cells were treated biweekly with 100 μg IL1RAP antibody mAb81.2 or a mIgG2a control antibody (n = 6 per group). Treatment was initiated 3 days after transplantation, and the mice were euthanized 33 days after transplantation. Contour plot showing a distinct human cell population of CD45⁺CD19⁺ cells in both mAb81.2-treated (red) and isotype control–treated (black) mice (A). Platelet counts (B) and levels of leukemic cells in PB, BM, and spleen (C). Spleen weight (D). Morphology of cells from representative mAb81.2-treated and isotype control–treated mice (E). Levels of BCR/ABL1 transcripts in the spleens from mAb81.2 and isotype control–treated mice (F). (G-H) Spleen cells from mAb81.2-treated and mIgG2a control antibody–treated mice were harvested and transplanted into NSG mice (n = 7 per group). White blood cell (WBC) counts in secondary recipients 6 weeks after transplantation (G). Survival of mice transplanted with cells from mAb81.2 or mIgG2a control antibody–treated mice (median 81 days vs 68 days; H). (I-L) NOD/SCID mice engrafted with CML-BP1 cells were treated biweekly with the IL1RAP antibody mAb81.2, the Fab fragment of mAb81.2 (Fab81.2), or a mIgG2a control antibody (n = 6-8 per group) until euthanized 29 days after transplantation. Treatment was initiated 3 days after transplantation. Levels of leukemic cells in PB (I), BM (J), and spleen (K). Spleen weight (L). n.s., not significant.