Surface levels of CD20 determine anti-CD20 antibodies mediated cell death in vitro.
Surface levels of CD20 determine anti-CD20 antibodies mediated cell death in vitro.
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CD20的表面水平确定抗CD20抗体在体外介导细胞死亡。
DOI：
10.1371/journal.pone.0111113
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Macklis RM
中科院分区：
文献类型：
--
作者：
Singh V;Gupta D;Arora R;Tripathi RP;Almasan A;Macklis RM
在表面表达不同水平 CD20 的细胞上评估人伯基特淋巴瘤细胞对利妥昔单抗 (Rtx) 和托西莫单抗 (Tst) 的敏感性。 CD20 水平低的细胞可能会抵抗 CD20 特异性抗体的治疗反应。我们推测，辐射诱导的 CD20 表面水平调节可能在确定利妥昔单抗和托西莫单抗治疗伯基特淋巴瘤疾病的相对疗效中发挥关键和核心作用。在这里，我们检查了 Burkitt 淋巴瘤细胞系“Daudi”中 γ 辐射诱导的 CD20 表达以及 CD20 差异水平与抗 CD20 mAb 介导的细胞死亡的关系。在本研究中，我们检查了对 Daudi 细胞进行亚致死剂量的 γ 辐射后 CD20 表达的动力学，然后将抗 CD20 mAb（利妥昔单抗和托西莫单抗）添加到细胞悬浮液中。还检查了CD20表达与用抗CD20 mAb/或相应同种型抗体处理的细胞的动力学的相关性，特别是线粒体膜电位和活性氧生成的变化。此外，我们还研究了抗 CD20 mAb 的功效以及与 CD20 细胞表面表达水平相关的可能的细胞死亡诱导。该报告提供了证据表明，细胞暴露于 γ 辐射可以诱导 CD20 表达。此外，这些发现表明，抗 CD20 mAb 的功效取决于 CD20 的表面水平。基于这些发现，我们假设 (i) 在免疫治疗之前进行放射治疗，即使对于侵袭性 B 细胞肿瘤也可能提供新的治疗选择，因为这些肿瘤对体内现有疗法具有抗性 (ii) 体外诱导细胞凋亡的功效因单克隆抗体的类型而异。
The sensitivity of human Burkitt's lymphoma cells to rituximab (Rtx) and tositumomab (Tst) was assessed on cells expressing different levels of CD20 on surface. Cells that harbor low CD20 levels may resists against therapeutics response to CD20-specific antibodies. We postulated that, radiation-induced modulation of CD20 surface levels may play a crucial and central role in determining the relative efficacy of rituximab and tositumomab in treating Burkitt's lymphoma disease. Here, we examined the γ-radiation-induced CD20 expression in the Burkitt lymphoma cell line ‘Daudi’ and the relation of differential levels of CD20 with anti-CD20 mAbs mediated cell death. In this study we examined kinetics of CD20 expression following sub lethal doses ofγ-radiation to Daudi cells and thereafter anti-CD20 mAbs (rituximab and tositumomab) were added in cell suspensions. The correlation of kinetics of CD20 expression and cells treated with anti-CD20 mAbs/or corresponding isotype Abs with special reference to changes in mitochondrial membrane potential and reactive oxygen species generation was also examined. Further, we also investigated the efficacy of anti-CD20 mAbs and possible induction of cell death in relation to levels of CD20 cell surface expression. This report provides evidence that CD20 expression can be induced by exposure of cells to γ-radiation. In addition, these findings demonstrated that the efficacy of anti-CD20 mAbs is dependent on the surface levels of CD20. Based on these findings, we hypothesized (i) irradiation just prior to immunotherapy may provide new treatment options even in aggressive B cell tumors, which are resistant to current therapies in vivo (ii) The efficacy of induction of apoptosis varies with type of monoclonal antibodies in vitro.
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