Oncolytic measles virus targets high CD46 expression on multiple myeloma cells
Oncolytic measles virus targets high CD46 expression on multiple myeloma cells
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DOI：
10.1016/j.exphem.2006.03.002
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发表时间：
2006-06-01
影响因子：
2.6
通讯作者：
Peng, Kah-Whye
中科院分区：
文献类型：
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作者：
Ong, Hooi Tin;Timm, Michael M.;Peng, Kah-Whye
目标。多发性骨髓瘤(MM)是一种无法治愈的B细胞恶性肿瘤，迫切需要新的治疗方法。减毒活麻疹病毒(MV)对多发性骨髓瘤(MM)移植瘤具有较强的溶瘤活性。该病毒对肿瘤具有选择性，并优先针对表达高水平CD46受体的细胞。然而，CD46在MM上的水平以前没有被评估过。在这项研究中，我们研究了CD46作为MM治疗靶点的潜力以及MM细胞表面CD46水平与其对MV诱导的细胞病变效应的易感性之间的关系。材料和方法。用流式细胞仪检测38例MM患者肿瘤浆细胞(PC)和非浆细胞(NP)表面CD46的表达，并用BD QuantiBRITE PE珠定量测定受体数量。结果显示，恶性PC的CD46受体表达水平显著高于NC(p<；0.0001)。细胞表面CD46受体平均数目分别为49,130个/细胞和7340个/细胞。在麻疹感染的PC中观察到了广泛的细胞间融合的强大的细胞病变效应，但在NC中没有观察到。MV诱导的细胞融合的细胞病变程度与MM细胞CD46的表达水平相关。正常浆细胞不表达CD46，集落形成实验证实MV对正常骨髓祖细胞无细胞毒作用。本研究确定CD46是一种表面抗原，与骨髓中不同谱系的正常造血细胞相比，CD46在原代MM细胞上表达更丰富，使CD46成为靶向细胞减少治疗MM的一种有前景的表面标志。(C)2006国际实验血液学学会。由爱思唯尔公司出版。
Objective. Multiple myeloma (MM) is an incurable B cell malignancy and novel therapeutics are urgently needed. Live attenuated measles virus (MV) has potent oncolytic activity against MM tumor xenografts. The virus is tumor selective and preferentially targets cells that express high levels of CD46 receptors. However, CD46 levels on MM have not previously been evaluated. In this study, we investigated the potential of CD46 as a target for MM therapy and correlated surface levels of CD46 on MM cells with their susceptibility to MV-induced cytopathic effects.Materials and Methods. CD46 expression on neoplastic plasma cells (PCs) and nonplasma cells (NPCs) from 38 MM patients was analyzed by flow cytometry and receptor numbers were quantitated using BD QuantiBRITE PE beads.Results. Results showed that malignant PCs expressed significantly higher levels of CD46 receptors compared to NPCs (p < 0.0001). The mean CD46 receptor numbers on PCs and NPCs were 49,130/cell and 7340/cell, respectively. Potent cytopathic effects of extensive intercellular fusion were observed in measles-infected PCs but not in NPCs. The extent of MV-induced cytopathic effects of cell fusion correlated with CD46 expression levels on the MM cells. Normal plasma cells do not overexpress CD46 and colony-forming assays demonstrated that MV was not cytotoxic to normal bone marrow progenitor cells.Conclusion. The present study establishes CD46 as a surface antigen that is expressed more abundantly on primary MM cells compared to normal hematopoietic cells of various lineages in the bone marrow, making CD46 a promising surface marker for targeted cytoreductive therapy of MM. (c) 2006 International Society for Experimental Hematology. Published by Elsevier Inc.