Oncolytic viruses (including measles virus) offer an alternative approach to reduce the high mortality rate of late-stage cancer. Several measles virus strains infect and lyse cancer cells efficiently, but the broad application of this therapeutic concept is hindered by the large number of infectious particles required (108-1012 TCID50 per dose). The manufacturing process must, therefore, achieve high titers of oncolytic measles virus (OMV) during upstream production and ensure that the virus product is not damaged during purification by applying appropriate downstream processing (DSP) unit operations. DSP is currently a production bottleneck because there are no specific platforms for OMV. Infectious OMV must be recovered as intact, enveloped particles, and host cell proteins and DNA must be reduced to acceptable levels to meet regulatory guidelines that were developed for virus-based vaccines and gene therapy vectors. Handling such high viral titers and process volumes is technologically challenging and expensive. This review considers the state of the art in OMV purification and looks at promising DSP technologies. We discuss here the purification of other enveloped viruses where such technologies could also be applied to OMV. The development of DSP technologies tailored for enveloped viruses is necessary to produce sufficient titers for virotherapy, which could offer hope to millions of patients suffering from incurable cancer.

中文翻译：

---

消除溶瘤性麻疹病毒下游加工机会的机会。

溶瘤病毒（包括麻疹病毒）提供了另一种方法来降低晚期癌症的高死亡率。几种麻疹病毒株可有效感染并裂解癌细胞，但由于需要大量的感染性颗粒（每剂108-1012 TCID50），阻碍了该治疗概念的广泛应用。因此，制造过程必须在上游生产过程中获得高滴度的溶瘤性麻疹病毒（OMV），并通过应用适当的下游加工（DSP）单元操作，确保病毒产物在纯化过程中不受损坏。由于没有针对OMV的特定平台，DSP目前是生产瓶颈。传染性OMV必须作为完整的包裹颗粒回收，必须将宿主细胞的蛋白质和DNA降低到可接受的水平，以符合针对基于病毒的疫苗和基因治疗载体制定的监管准则。处理如此高的病毒滴度和处理量在技术上具有挑战性且昂贵。这篇评论考虑了OMV纯化的最新技术，并探讨了有前途的DSP技术。我们在这里讨论其他包膜病毒的纯化，其中此类技术也可以应用于OMV。为包膜病毒量身定制的DSP技术的开发对于产生足够的滴度进行病毒治疗是必不可少的，这可能为数百万患有无法治愈的癌症的患者带来希望。处理如此高的病毒滴度和处理量在技术上具有挑战性且昂贵。这篇评论考虑了OMV纯化的最新技术，并探讨了有前途的DSP技术。我们在这里讨论其他包膜病毒的纯化，其中此类技术也可以应用于OMV。为包膜病毒量身定制的DSP技术的开发对于产生足够的滴度进行病毒治疗是必不可少的，这可能为数百万患有无法治愈的癌症的患者带来希望。处理如此高的病毒滴度和处理量在技术上具有挑战性且昂贵。这篇评论考虑了OMV纯化的最新技术，并探讨了有前途的DSP技术。我们在这里讨论其他包膜病毒的纯化，其中此类技术也可以应用于OMV。为包膜病毒量身定制的DSP技术的开发对于产生足够的滴度进行病毒治疗是必要的，这可能为数百万患有无法治愈的癌症的患者带来希望。