Oncolytic Coxsackievirus A21 as a novel therapy for multiple myeloma
Oncolytic Coxsackievirus A21 as a novel therapy for multiple myeloma
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DOI：
10.1111/j.1365-2141.2007.06550.x
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发表时间：
2007-04-01
影响因子：
6.5
通讯作者：
Shafren, Darren R.
中科院分区：
文献类型：
--
作者：
Au, Gough G.;Lincz, Lisa F.;Shafren, Darren R.
溶瘤病毒是控制人类恶性肿瘤的极具吸引力的生物制剂。本研究利用已建立的多发性骨髓瘤(MM)细胞系和15例患者骨髓(BM)活检[10例MM和5例意义不明的单抗(MGUS)]，评价了柯萨奇病毒A21(CVA21)体外靶向和破坏多发性骨髓瘤(MM)和前体异常浆细胞的能力。细胞表面分析显示，所有肿瘤细胞株都表达高水平的细胞间黏附分子-1(ICAM-1)和衰变加速因子(DAF)，这是CVA21可以结合的受体分子，导致随后的细胞进入和感染。MM细胞对CVA21裂解感染非常敏感，在24小时内产生100-1000倍的病毒后代，而正常外周血细胞对CVA21感染是屈光的。此外，用CVA21刺激患者骨髓活检48小时后，CD138(+)浆细胞的特异性清除率高达98.7%，而祖细胞功能没有明显下降。本研究中产生的数据表明，CVA21病毒疗法可能作为MM的全身抗肿瘤药物，或在自体干细胞移植前的体外清除恶性浆细胞方面具有潜在的应用。
Oncolytic viruses are attractive biological agents for the control of human malignancy. This study assessed the capacity of Coxsackievirus A21 (CVA21) to target and destroy multiple myeloma (MM) and precursor aberrant plasma cells in vitro using established MM cell lines and 15 patient bone marrow (BM) biopsies [n = 10 MM and five monoclonal gammopathy of undetermined significance (MGUS)]. Cell surface analysis revealed that all tumour cells lines expressed high levels of intercellular adhesion molecule-1 (ICAM-1) and decay-accelerating factor (DAF), the receptor molecules to which CVA21 can bind, leading to subsequent cell-entry and infection. MM cell lines were remarkably susceptible to CVA21 lytic infection, producing 100-1000-fold increases in viral progeny within 24 h. In contrast, normal peripheral blood cells were refractile to CVA21 infection. Furthermore, challenge of patient BM biopsies with CVA21 for 48 h resulted in specific purging of up to 98.7% of CD138(+) plasma cells, with no significant decrease in progenitor cell function. Data generated in this study suggests that CVA21 virotherapy may have potential applications as a systemic anti-tumour agent for MM, or in the ex vivo purging of malignant plasma cells prior to autologous stem cell transplantation.