文章：

肿瘤靶向细菌被设计用来对抗癌症

Tumour-targeting bacteria engineered to fight cancer

原文发布日期：2018-11-07

DOI: 10.1038/s41568-018-0070-z

类型: Review Article

开放获取: 否

英文摘要：

Recent advances in targeted therapy and immunotherapy have once again raised the hope that a cure might be within reach for many cancer types. Yet, most late-stage cancers are either insensitive to the therapies to begin with or develop resistance later. Therapy with live tumour-targeting bacteria provides a unique option to meet these challenges. Compared with most other therapeutics, the effectiveness of tumour-targeting bacteria is not directly affected by the ‘genetic makeup’ of a tumour. Bacteria initiate their direct antitumour effects from deep within the tumour, followed by innate and adaptive antitumour immune responses. As microscopic ‘robotic factories’, bacterial vectors can be reprogrammed following simple genetic rules or sophisticated synthetic bioengineering principles to produce and deliver anticancer agents on the basis of clinical needs. Therapeutic approaches using live tumour-targeting bacteria can either be applied as a monotherapy or complement other anticancer therapies to achieve better clinical outcomes. In this Review, we summarize the potential benefits and challenges of this approach. We discuss how live bacteria selectively induce tumour regression and provide examples to illustrate different ways to engineer bacteria for improved safety and efficacy. Finally, we share our experience and insights on oncology clinical trials with tumour-targeting bacteria, including a discussion of the regulatory issues.

摘要翻译： 

靶向治疗和免疫疗法的最新进展再次燃起了人们对多种癌症类型可能迎来治愈的希望。然而，大多数晚期癌症要么从一开始就对治疗不敏感，要么随后产生耐药性。利用靶向肿瘤的活菌疗法为应对这些挑战提供了独特选择。与大多数其他治疗方法相比，靶向肿瘤细菌的疗效不受肿瘤"基因构成"的直接影响。细菌从肿瘤深部启动直接抗肿瘤效应，继而引发先天性和适应性抗肿瘤免疫反应。作为微型"机器人工厂"，细菌载体可依据简单遗传法则或复杂合成生物工程原理进行重编程，根据临床需求生产并递送抗癌制剂。这种靶向肿瘤的活菌疗法既可单独实施，也可与其他抗癌疗法联合应用以获得更佳临床效果。本综述将系统阐述该疗法的潜在优势与挑战，探讨活菌选择性诱导肿瘤消退的机制，并通过案例说明细菌工程化改造以提升安全性与有效性的多种路径。最后，我们将结合靶向菌肿瘤临床试验的经验与见解，对相关监管问题进行探讨。

原文链接：

Tumour-targeting bacteria engineered to fight cancer