The last decade has seen a rapid increase in studies utilising a genetically modified probiotic,Escherichia coliNissle 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.
过去十年间,利用基因工程益生菌——大肠杆菌Nissle 1917(EcN)作为癌症治疗与检测载体的研究呈现快速增长态势。该方法基于EcN能够特异性归巢并选择性定植于肿瘤组织而非正常组织的特性,这种某些细菌共有的特性被认为源于肿瘤提供的低氧、营养富集及免疫豁免的微环境。临床前研究通过基因改造EcN递送治疗性载荷,凭借其在肿瘤组织的高定植率与低脱靶效应,展现出减轻肿瘤负荷的显著疗效。最新进展更将EcN载体拓展为有效的肿瘤检测工具。这些突破为基因工程EcN进入临床肿瘤学试验提供了充分依据。目前该领域尚未明确的是EcN在肿瘤内分布与定位的深层机制。本综述系统梳理现有EcN相关文献,并结合其他肿瘤归巢菌及致病菌的研究成果,为未来验证EcN肿瘤归巢的可能机制提供理论视角。精确解析EcN定植肿瘤组织的机制原理,将指导新一代EcN载体菌株的设计与测试,以应对生物安全与防控挑战,并优化癌症检测与治疗策略。
Towards Understanding Tumour Colonisation by Probiotic BacteriumE. coliNissle 1917