With increasing evidence that microbes colonize tumors, synthetic biology tools are being leveraged to repurpose bacteria as tumor-specific delivery systems. These engineered systems can modulate the tumor microenvironment using a combination of their inherent immunogenicity and local payload production. Here, we review genetic circuits that enhance spatial and temporal control of therapeutic bacteria to improve their safety and efficacy. We describe the engineering of interactions among bacteria, tumor cells, and immune cells, and the progression from bacteria as single agents toward their rational combination with other modalities. Together, these efforts are building toward an emerging concept of engineering interactions between programmable medicines using synthetic biology.

中文翻译：

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将细菌改造为交互式癌症疗法

随着越来越多的证据表明微生物定植于肿瘤，合成生物学工具被用来将细菌重新用作肿瘤特异性递送系统。这些工程系统可以结合其固有的免疫原性和局部有效负载产生来调节肿瘤微环境。在这里，我们回顾了增强治疗性细菌的空间和时间控制的遗传回路，以提高其安全性和有效性。我们描述了细菌、肿瘤细胞和免疫细胞之间相互作用的工程，以及从细菌作为单一药物到与其他形式的合理组合的进展。这些努力共同致力于构建利用合成生物学的可编程药物之间的工程相互作用的新兴概念。