肿瘤细菌疗法作为一种新型治疗模式正逐渐引起医学界的关注。基于肿瘤微环境低氧、免疫缺失等特点，细菌可在肿瘤靶向聚集并增殖。而某些经遗传改造的细菌则可将所表达免疫治疗分子递送至肿瘤，实现靶向治疗，这一模式也已进入临床试验阶段。然而，缺乏理想的实时监测手段及药物控释方法阻碍了肿瘤细菌疗法的进一步推广。因此，项目组拟通过对大肠杆菌MG1655进行遗传改造，构建可自合成生物气泡及PD-L1单链抗体的“超声可视化治疗型细菌”，将其注入卵巢癌荷瘤小鼠后，在超声示踪细菌的基础上，采用聚焦超声辐照介导细菌控释PD-L1单链抗体，实现细菌的超声可视化监测及控释治疗。项目组前期已构建“超声可视化治疗型细菌”，并证实其肿瘤靶向性、超声成像效果及超声控释能力，在本研究中拟进一步探讨超声示踪细菌及介导PD-L1抗体控释治疗卵巢癌的效果，以期为卵巢癌免疫治疗提供一种靶向性好、可控性强的可视化治疗模式。

As a novel cancer treatment, bacteria-mediated tumor therapy is arousing concern. Based on the characteristics of hypoxia and immune deficiency of tumor microenviroment, Bacteria could accumulate and proliferate in tumor specifically. It was demonstrated that genetic engineering bacteria could express and delivery immunotherapy drugs locally and achieve ideal therapeutic effect, which was also applied in clinical. However, the lack of real-time monitoring and controlled release methods for tumor-mediated bacteria therapy has become increasingly prominent. Therefore, this research intends to propose a new mode of tumor immunotherapy: to construct a " visual therapeutic bacteria" through genetic engineering technology, which can express biogenic gas vesicles and Programmed death-ligand 1 (PD-L1) single chain variable fragment. After systematic administration of “visual therapeutic bacteria” into ovarian cancer xenograft model, ultrasound was used to trace the real-time distribution of " visual therapeutic bacteria" in vivo as well as the process of colonization in tumor sites. Focused ultrasound was used to mediate the controlled-release of PD-L1 single chain variable fragment locally. Our group has made a preliminary exploration on the targeting effect of bacteria and construction of “visual therapeutic bacteria”, which showed ideal ultrasound imaging effect and responsiveness to focused ultrasound. Then we will explore its further application in the ovarian cancer immunotherapy. In summary, the aim of this project is to provide a new strategy for ovarian cancer immunotherapy with noninvasive, targeted and visualized methods by ultrasound combined “visual therapeutic bacteria”.