Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Pediatr Blood Cancer. 2010 Dec 15;55(7):1253-63. doi: 10.1002/pbc.22724. Epub 2010 Aug 23.
Lytic viruses kill cells as a consequence of their normal replication life cycle. The idea of harnessing viruses to kill cancer cells arose over a century ago, before viruses were even discovered, from medical case reports of infections associated with cancer remissions. Since then, there has been no shortage of hype, hope, or fear regarding the prospect of oncolytic virotherapy for cancer. Early developments in the field included encouraging antitumor efficacy both in animal studies in the 1920s-1940s and in human clinical trials in the 1950s-1970s. Despite its long-standing history, oncolytic virotherapy was an idea ahead of its time. Without needed advances in molecular biology, virology, immunology, and clinical research ethics, early clinical trials resulted in infectious complications and were fraught with controversial research conduct, so that enthusiasm in the medical community waned. Oncolytic virotherapy is now experiencing a major growth spurt, having sustained numerous laboratory advances and undergone multiple encouraging adult clinical trials, and is now witnessing the emergence of pediatric trials. Here we review the history and salient biology of the field, including preclinical and clinical data, with a special emphasis on those agents now being tested in pediatric cancer patients.
溶瘤病毒会因其正常的复制生命周期而杀死细胞。利用病毒杀死癌细胞的想法早在一个多世纪前就出现了，当时甚至还没有发现病毒，这是从与癌症缓解相关的感染的医学病例报告中得出的。从那时起，人们对溶瘤病毒疗法治疗癌症的前景一直充满了炒作、希望和恐惧。该领域的早期发展包括在 20 世纪 20 年代至 40 年代的动物研究和 50 年代至 70 年代的人类临床试验中都观察到了令人鼓舞的抗肿瘤疗效。尽管溶瘤病毒疗法历史悠久，但它的出现还是有些超前。由于缺乏分子生物学、病毒学、免疫学和临床研究伦理学方面的必要进展，早期临床试验导致了感染并发症，并充满了有争议的研究行为，因此医学界的热情逐渐消退。溶瘤病毒疗法现在正在经历一次重大的发展，经历了众多实验室的进展，并进行了多次令人鼓舞的成人临床试验，现在正在见证儿科试验的出现。在这里，我们回顾了该领域的历史和显著生物学特性，包括临床前和临床数据，特别强调了那些正在接受测试的儿科癌症患者的药物。
