抗cd20单克隆抗体的差异作用:诱导细胞死亡的作用

D. Gupta, V. Singh
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引用次数: 2

摘要

目的:研究和评价细胞表面CD20水平不同的伯基特淋巴瘤细胞对抗CD20单克隆抗体的敏感性。材料和方法:本研究采用伯基特淋巴瘤细胞系“Daudi”。细胞暴露于单剂量γ-辐射(0.5 Gy)后,与利妥昔单抗(Rtx)或托昔单抗(Tst)(浓度分别为0.5 μg/ ml)孵育。检测RelA、Akt和Bax/Bcl-2的表达变化,以评估细胞对细胞死亡的敏感性。结果:在本研究中,我们发现在辐射暴露后+20小时用抗cd20单抗孵育的细胞在Bax/Bcl-2比值方面显示出更高水平的细胞死亡。此外,我们还发现促生存信号蛋白如RelA和Akt通路的表达发生了显著变化。此外,我们发现tositumomab是凋亡细胞死亡的有效诱导剂。结论:抗CD20单克隆抗体的作用取决于细胞表面表达CD20分子的数量和使用的抗体类型。它可能为抗CD20单克隆抗体的选择提供新的治疗选择,甚至在侵袭性b细胞淋巴瘤中,体内CD20水平低,甚至对目前的治疗方法有抗性。
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Differential Action of Anti-CD20 Monoclonal Antibodies: Role in Induction of Cell Death
Purpose: To study and assess to the sensitivity of Burkitt’s lymphoma cells harboring differential levels of cell surface CD20 for anti-CD20 monoclonal Antibodies. Material and methods: Burkitt’s lymphoma cell line ‘Daudi’ was used during present study. Cells were exposed to single dose of γ-radiation (0.5 Gy) and thereafter incubated with rituximab (Rtx) or tositumomab (Tst) (0.5 μg/ ml concentration each). The changes in expression of RelA, Akt and Bax/Bcl-2 ratio was measured to assess sensitivity of cells in term of cell death. Results: During the present investigation, we found that cells incubated with anti-CD20 mAbs at +20 hrs post radiation exposure showed higher levels of cell death in term of Bax/Bcl-2 ratio. In addition, we also found the significant changes in expression of pro-survival signaling proteins such as RelA and Akt pathways. Moreover, we found that tositumomab is a potent inducer of apoptotic cell death. Conclusion: These findings suggested that the efficacy of anti-CD20 mAbs depends on the number of CD20 molecules expressed on cell surface and type of antibody used. It may provide new treatment options for selection of anti-CD20 mAbs even in aggressive B-cell lymphoma, which harbors low levels of CD20 or even resistant to current therapies in vivo.
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