Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Vaccine. 2013 Sep 6;31(39):4252-8. doi: 10.1016/j.vaccine.2013.05.056. Epub 2013 May 29.
Many common neoplasms are still noncurative with current standards of cancer therapy. More therapeutic modalities need to be developed to significantly prolong the lives of patients and eventually cure a wider spectrum of cancers. Oncolytic virotherapy is one of the promising new additions to clinical cancer therapeutics. Successful oncolytic virotherapy in the clinic will be those strategies that best combine tumor cell oncolysis with enhanced immune responses against tumor antigens. The current candidate oncolytic viruses all share the common property that they are relatively nonpathogenic to humans, yet they have the ability to replicate selectively in human cancer cells and induce cancer regression by direct oncolysis and/or induction of improved anti-tumor immune responses. Many candidate oncolytic viruses are in various stages of clinical and preclinical development. One such preclinical candidate is myxoma virus (MYXV), a member of the Poxviridae family that, in its natural setting, exhibits a very restricted host range and is only pathogenic to European rabbits. Despite its narrow host range in nature, MYXV has been shown to productively infect various classes of human cancer cells. Several preclinical in vivo modeling studies have demonstrated that MYXV is an attractive and safe candidate oncolytic virus, and hence, MYXV is currently being developed as a potential therapeutic for several cancers, such as pancreatic cancer, glioblastoma, ovarian cancer, melanoma, and hematologic malignancies. This review highlights the preclinical cancer models that have shown the most promise for translation of MYXV into human clinical trials.
许多常见的肿瘤仍然无法通过当前的癌症治疗标准治愈。需要开发更多的治疗方法，以显著延长患者的生命，并最终治愈更广泛的癌症谱。溶瘤病毒治疗是临床癌症治疗中一种很有前途的新方法。在临床上成功的溶瘤病毒治疗将是那些能够将肿瘤细胞溶瘤作用与增强针对肿瘤抗原的免疫反应最好地结合起来的策略。目前的候选溶瘤病毒都具有共同的特性，即它们对人类相对无毒，但它们具有选择性地在人类癌细胞中复制的能力，并通过直接溶瘤和/或诱导改善的抗肿瘤免疫反应来诱导癌症消退。许多候选溶瘤病毒处于不同的临床和临床前开发阶段。一种这样的临床前候选者是兔粘液瘤病毒（MYXV），它是痘病毒科的一员，在其自然环境中，它的宿主范围非常有限，只能感染欧洲兔。尽管它在自然界中的宿主范围很窄，但已经证明 MYXV 可以有效地感染各种人类癌细胞。几项临床前体内建模研究表明，MYXV 是一种有吸引力和安全的溶瘤候选病毒，因此，MYXV 目前正在被开发为几种癌症的潜在治疗方法，如胰腺癌、胶质母细胞瘤、卵巢癌、黑色素瘤和血液恶性肿瘤。这篇综述强调了最有希望将 MYXV 转化为人类临床试验的临床前癌症模型。
