Department of Pediatric Surgery, Major Laboratory of Chinese Health Ministry for Congenital Malformations, Shengjing Hospital of China Medical University, 36 Sanhao Street Heping District, Shenyang 110004, P.R. China.
BMC Cancer. 2012 Sep 25;12:427. doi: 10.1186/1471-2407-12-427.
Hepatoblastoma (HB) is the most common primary, malignant pediatric liver tumor in children. The treatment results for affected children have markedly improved in recent decades. However, the prognosis for high-risk patients who have extrahepatic extensions, invasion of the large hepatic veins, distant metastases and very high alpha-fetoprotein (AFP) serum levels remains poor. There is an urgent need for the development of novel therapeutic approaches.
An attenuated strain of measles virus, derived from the Edmonston vaccine lineage, was genetically engineered to produce carcinoembryonic antigen (CEA). We investigated the antitumor potential of this novel viral agent against human HB both in vitro and in vivo.
Infection of the Hep2G and HUH6 HB cell lines, at multiplicities of infection (MOIs) ranging from 0.01 to 1, resulted in a significant cytopathic effect consisting of extensive syncytia formation and massive cell death at 72-96 h after infection. Both of the HB lines overexpressed the measles virus receptor CD46 and supported robust viral replication, which correlated with CEA production. The efficacy of this approach in vivo was examined in murine Hep2G xenograft models. Flow cytometry assays indicated an apoptotic mechanism of cell death. Intratumoral administration of MV-CEA resulted in statistically significant delay of tumor growth and prolongation of survival.
The engineered measles virus Edmonston strain MV-CEA has potent therapeutic efficacy against HB cell lines and xenografts. Trackable measles virus derivatives merit further exploration in HB treatment.
肝细胞瘤（HB）是儿童中最常见的原发性恶性小儿肝脏肿瘤。近几十年来，受影响儿童的治疗效果有了显著改善。然而，对于具有肝外扩展、大肝静脉浸润、远处转移和非常高的甲胎蛋白（AFP）血清水平的高危患者，预后仍然很差。迫切需要开发新的治疗方法。
从 Edmonston 疫苗系中遗传工程改造出一种减毒麻疹病毒，以产生癌胚抗原（CEA）。我们研究了这种新型病毒制剂对体外和体内人 HB 的抗肿瘤潜力。
在感染复数（MOI）为 0.01 至 1 范围内感染 Hep2G 和 HUH6 HB 细胞系时，在感染后 72-96 小时会导致广泛的合胞体形成和大量细胞死亡，从而产生显著的细胞病变效应。两种 HB 细胞系均过表达麻疹病毒受体 CD46，并支持强大的病毒复制，这与 CEA 产生相关。在 Hep2G 异种移植模型中检查了这种方法在体内的效果。流式细胞术检测表明细胞死亡的凋亡机制。肿瘤内给予 MV-CEA 可显著延迟肿瘤生长并延长存活时间。
工程化的麻疹病毒 Edmonston 株 MV-CEA 对 HB 细胞系和异种移植物具有强大的治疗功效。可追踪的麻疹病毒衍生物值得进一步探索用于 HB 治疗。
