Radford Georgette A, Vrbanac Laura, de Nys Rebekah T, Worthley Daniel L, Wright Josephine A, Hasty Jeff, Woods Susan L
Adelaide Medical School, University of Adelaide, Adelaide, SA 5000, Australia.
Precision Cancer Medicine, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA 5000, Australia.
Cancers (Basel). 2024 Aug 26;16(17):2971. doi: 10.3390/cancers16172971.
The last decade has seen a rapid increase in studies utilising a genetically modified probiotic, Nissle 1917 (EcN), as a chassis for cancer treatment and detection. This approach relies on the ability of EcN to home to and selectively colonise tumours over normal tissue, a characteristic common to some bacteria that is thought to result from the low-oxygen, nutrient-rich and immune-privileged niche the tumour provides. Pre-clinical studies have used genetically modified EcN to deliver therapeutic payloads that show efficacy in reducing tumour burden as a result of high-tumour and low off-target colonisation. Most recently, the EcN chassis has been expanded into an effective tumour-detection tool. These advances provide strong justification for the movement of genetically modified EcN into clinical oncology trials. What is currently unknown in the field is a deep mechanistic understanding of how EcN distributes to and localises within tumours. This review summarises the existing EcN literature, with the inclusion of research undertaken with other tumour-homing and pathogenic bacteria, to provide insights into possible mechanisms of EcN tumour homing for future validation. Understanding exactly how and why EcN colonises neoplastic tissue will inform the design and testing of the next generation of EcN chassis strains to address biosafety and containment concerns and optimise the detection and treatment of cancer.
在过去十年中，利用基因工程改造的益生菌——Nissle 1917（大肠杆菌Nissle 1917，EcN）作为癌症治疗和检测载体的研究迅速增加。这种方法依赖于EcN归巢至肿瘤并在肿瘤中选择性定殖而非在正常组织中定殖的能力，这是一些细菌共有的特性，被认为是由肿瘤提供的低氧、营养丰富和免疫豁免的微环境导致的。临床前研究使用基因工程改造的EcN来递送治疗性物质，这些物质由于在肿瘤中高定殖和在非靶标部位低定殖而显示出减轻肿瘤负担的功效。最近，EcN载体已扩展成为一种有效的肿瘤检测工具。这些进展为将基因工程改造的EcN推进到临床肿瘤学试验提供了有力的依据。该领域目前尚不清楚的是对EcN如何在肿瘤中分布和定位的深入机制理解。这篇综述总结了现有的关于EcN的文献，并纳入了对其他肿瘤归巢细菌和病原菌的研究，以深入了解EcN肿瘤归巢的可能机制，供未来验证。准确了解EcN如何以及为何在肿瘤组织中定殖，将为下一代EcN载体菌株的设计和测试提供信息，以解决生物安全和控制问题，并优化癌症的检测和治疗。
