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首页> 外文期刊>Experimental Hematology Oncology >Daratumumab binds to mobilized CD34+ cells of myeloma patients in vitro without cytotoxicity or impaired progenitor cell growth
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Daratumumab binds to mobilized CD34+ cells of myeloma patients in vitro without cytotoxicity or impaired progenitor cell growth

机译:达拉穆曼在没有细胞毒性或祖细胞生长受损的情况下,在体外动员骨髓瘤患者的CD34 +细胞。祖细胞生长受损

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The monoclonal antibody daratumumab, approved for treating myeloma, targets CD38, a protein on myeloma and also on CD34+?hematopoietic progenitor cells. Because mobilized CD34+ cells are critical for stem cell transplant, we investigated the in vitro activity of daratumumab on mobilized CD34+?cells from myeloma patients with no prior exposure to daratumumab. We determined the number of CD38 molecules per CD34+?cell, and whether daratumumab bound to CD34+?cells, whether C1q bound to daratumumab-coated CD34+?cells and whether daratumumab-related complement-dependent cytotoxicity (CDC) occurred. We also examined CD34+?cell progenitor cell colony capacity in assays with pre-plating incubation of CD34+?cells with daratumumab alone or with daratumumab and the CD59 inhibitory antibody BRIC229, and also assessed CD34+?cell responses to increasing doses of daratumumab in caspase 3/7 activity assays. Although 75% of mobilized CD34+?cells co-express CD38, CD38 was minimally present on CD34+?cells compared to Daudi and KG-1 controls, C1q did not bind to daratumumab-coated CD34+?cells, and CDC did not occur. CD34+?cells incubated in complement-rich human serum with daratumumab alone or with daratumumab and BRIC229, and then plated in progenitor cell assays, produced similar numbers of colonies as controls. In progenitor cell assays with cryopreserved or fresh unselected or CD34-selected cells, daratumumab did not affect progenitor cell capacity, and in caspase 3/7 activity assays CD34+?cells were not affected by increasing doses of daratumumab. In vitro, daratumumab is not toxic to mobilized CD34+?progenitor cells from myeloma patients.
机译:单克隆抗体达拉姆姆人们批准用于治疗骨髓瘤,靶向CD38,骨髓瘤蛋白质和CD34 +?造血祖细胞。因为动员的CD34 +细胞对于干细胞移植至关重要,我们研究了达拉姆宫对动员的CD34 +?来自骨髓瘤患者的细胞的体外活性,没有以前暴露在达拉穆曼。我们确定了每CD34 +α细胞的CD38分子的数量,以及达拉姆巴的细胞是否与CD34 +?细胞结合,是否与达拉坦覆盖的CD34 +?细胞的C1Q是否与达拉穆巴布相关的补体依赖性细胞毒性(CDC)结合。我们还研究了CD34 +?细胞祖细胞群能力,在测定的测定中,单独使用Daratumumab和Daratumumab和CD59抑制抗体BRIC229,并评估CD34 +的细胞对Caspase 3中的达拉穆曼剂量增加的细胞反应/ 7活性测定。尽管75%的动员CD34 +?细胞共同表达CD38,与Daudi和KG-1对照相比,CD38的CD38,CD34 +细胞上最小存在,C1Q没有结合达拉努姆涂覆的CD34 +?细胞,并且没有发生CDC。 CD34 +的细胞单独用侏儒或用达拉穆曼和Bric229孵育的细胞,用达拉穆曼和Bric229,然后在祖细胞测定中接种,产生类似的菌落数量作为对照。在用冷冻保存或新鲜未选择或CD34所选细胞的祖细胞测定中,达拉穆曼不影响祖细胞容量,并且在Caspase 3/7活性测定中,CD34 +细胞不受增加的达拉姆布剂量的影响。体外,达拉姆宫不会毒性从骨髓瘤患者动员的CD34 +?祖细胞。

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