Thirukkumaran C M, Russell J A, Stewart D A, Morris D G
Department of Medicine, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada.
Bone Marrow Transplant. 2007 Jul;40(1):1-12. doi: 10.1038/sj.bmt.1705668. Epub 2007 Apr 23.
High-dose cytotoxic chemotherapy followed by autologous haematopoietic stem cell transplantation (ASCT) is extensively used for the treatment of many haematopoietic, as well as several epithelial cancers. Disease relapse may be the result of tumour contamination within autograft as evidenced by gene marking studies. The multiple purging strategies that have been described to date have not proven effective in most ASCT settings. This review addresses the possibility of using oncolytic viruses as a novel purging strategy. DNA viruses such as genetically engineered adenoviral vectors have widely been used to deliver either a prodrug-activating enzyme or express wild-type p53 selectively in tumour cells in ex vivo purging protocols. In addition, conditionally replicating adenoviruses that selectively replicate in tumour cells and herpes simplex virus type 1 are other DNA viruses that have been tested as ex vivo purging agents under laboratory conditions. Vesicular stomatitis virus (VSV) and reovirus are naturally occurring RNA viruses that appear to hold promise as purging agents under ex vivo and in vivo settings. Preclinical data demonstrate reovirus's purging potential against breast, monocytic and myeloma cell lines as well as patient-derived tumours of diffuse large B-cell lymphoma, chronic lymphocytic leukaemia, Waldenstrom macroglobulinemia and small lymphocytic lymphoma. In addition, VSV has shown effective killing of leukaemic cell lines and multiple myeloma patient specimens. Given the increasing interest in the utilization of viruses as purging agents, the following review provides a timely summary of the potential and the challenges of oncolytic viruses as purging modalities during ASCT.
大剂量细胞毒性化疗后进行自体造血干细胞移植（ASCT）被广泛用于治疗多种血液系统疾病以及几种上皮癌。基因标记研究表明，疾病复发可能是自体移植物中肿瘤污染的结果。迄今为止所描述的多种清除策略在大多数ASCT情况下尚未被证明有效。本综述探讨了使用溶瘤病毒作为一种新型清除策略的可能性。DNA病毒，如基因工程腺病毒载体，已广泛用于在体外清除方案中递送前药激活酶或在肿瘤细胞中选择性表达野生型p53。此外，在肿瘤细胞中选择性复制的条件性复制腺病毒和单纯疱疹病毒1型是其他已在实验室条件下作为体外清除剂进行测试的DNA病毒。水疱性口炎病毒（VSV）和呼肠孤病毒是天然存在的RNA病毒，在体外和体内环境中似乎有望成为清除剂。临床前数据表明，呼肠孤病毒对乳腺癌、单核细胞和骨髓瘤细胞系以及弥漫性大B细胞淋巴瘤、慢性淋巴细胞白血病、华氏巨球蛋白血症和小淋巴细胞淋巴瘤患者来源的肿瘤具有清除潜力。此外，VSV已显示出对白血病细胞系和多发性骨髓瘤患者标本的有效杀伤作用。鉴于人们对利用病毒作为清除剂的兴趣日益增加，以下综述及时总结了溶瘤病毒作为ASCT期间清除方式的潜力和挑战。
