Woo Yanghee, Kelly Kaitlyn J, Stanford Marianne M, Galanis Charles, Chun Yun Shin, Fong Yuman, McFadden Grant
Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Ann Surg Oncol. 2008 Aug;15(8):2329-35. doi: 10.1245/s10434-008-9924-z. Epub 2008 May 3.
Viral oncolytic therapy, which seeks to exploit the use of live viruses to treat cancer, has shown promise in the treatment of cancers resistant to conventional anticancer therapies. Among the most difficult to treat cancers is advanced pancreatic adenocarcinoma. Our study investigates the ability of a novel oncolytic agent, myxoma virus, to infect, productively replicate in, and kill human pancreatic cancer cells in vitro.
The myxoma virus vMyxgfp was tested against a panel of human pancreatic adenocarcinoma cell lines. Infectivity, viral proliferation, and tumor cell kill were assessed.
Infection of tumor cells was assessed by expression of the marker gene enhanced green fluorescent protein (e-GFP). vMyxgfp had the ability to infect all pancreatic cancer cell lines tested. Killing of tumor cells varied among the 6 cell lines tested, ranging from >90% cell kill at 7 days for the most sensitive Panc-1 cells, to 39% in the most resistant cell line Capan-2. Sensitivity correlated to replication of virus, and was found to maximally exhibit a four-log increase in foci-forming units for the most sensitive Panc-1 cells within 72 h.
Our study demonstrates for the first time the ability of the myxoma virus to productively infect, replicate in, and lyse human pancreatic adenocarcinoma cells in vitro. These data encourage further investigation of this virus, which is pathogenic only in rabbits, for treatment of this nearly uniformly fatal cancer.
病毒溶瘤疗法旨在利用活病毒治疗癌症，在治疗对传统抗癌疗法耐药的癌症方面已显示出前景。最难治疗的癌症之一是晚期胰腺腺癌。我们的研究调查了一种新型溶瘤剂黏液瘤病毒在体外感染、有效复制并杀死人胰腺癌细胞的能力。
黏液瘤病毒vMyxgfp针对一组人胰腺腺癌细胞系进行了测试。评估了其感染性、病毒增殖和肿瘤细胞杀伤情况。
通过标记基因增强绿色荧光蛋白（e-GFP）的表达评估肿瘤细胞的感染情况。vMyxgfp能够感染所有测试的胰腺癌细胞系。在所测试的6种细胞系中，肿瘤细胞的杀伤情况各不相同，最敏感的Panc-1细胞在7天时细胞杀伤率>90%，而最耐药的细胞系Capan-2为39%。敏感性与病毒复制相关，在最敏感的Panc-1细胞中，在72小时内病灶形成单位最多可呈现四对数级的增加。
我们的研究首次证明了黏液瘤病毒在体外能够有效感染、在人胰腺腺癌细胞中复制并裂解这些细胞。这些数据鼓励对这种仅对兔子致病的病毒进行进一步研究，以治疗这种几乎一致致命的癌症。
