Visualization of tumors and metastases in live animals with bacteria and vaccinia virus encoding light-emitting proteins
Visualization of tumors and metastases in live animals with bacteria and vaccinia virus encoding light-emitting proteins
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DOI：
10.1038/nbt937
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发表时间：
2004-03-01
影响因子：
46.9
通讯作者：
Szalay, AA
中科院分区：
文献类型：
--
作者：
Yu, YA;Shabahang, S;Szalay, AA
我们已经证明，静脉注射到活体动物体内的细菌进入实体瘤和转移瘤并在其中复制。肿瘤特异性扩增过程是在真实的时间可视化使用酶催化的发光和绿色荧光蛋白荧光，这揭示了肿瘤和转移的位置。大肠杆菌和三种减毒病原体（霍乱弧菌、鼠伤寒沙门氏菌和单核细胞增生李斯特菌）都进入肿瘤并复制。类似地，胞质牛痘病毒也显示出肿瘤特异性复制，如通过实时成像所可视化的。这些发现表明，无论是营养缺陷型突变，也不是缺乏胸苷激酶基因的牛痘病毒，也不是厌氧生长条件所需的肿瘤特异性和瘤内复制。我们观察了发光微生物在免疫功能正常和免疫功能低下的同基因和同种异体肿瘤啮齿动物中的肿瘤定位。基于其“发现肿瘤”的性质，细菌和病毒可能被设计为携带多个基因来检测和治疗癌症。
We have shown that bacteria injected intravenously into live animals entered and replicated in solid tumors and metastases. The tumor-specific amplification process was visualized in real time using luciferase-catalyzed luminescence and green fluorescent protein fluorescence, which revealed the locations of the tumors and metastases. Escherichia coli and three attenuated pathogens (Vibrio cholerae, Salmonella typhimurium, and Listeria monocytogenes) all entered tumors and replicated. Similarly, the cytosolic vaccinia virus also showed tumor-specific replication, as visualized by real-time imaging. These findings indicate that neither auxotrophic mutations, nor vaccinia virus deficient for the thymidine kinase gene, nor anaerobic growth conditions were required for tumor specificity and intratumoral replication. We observed localization of tumors by light-emitting microorganisms in immunocompetent and in immunocompromised rodents with syngeneic and allogeneic tumors. Based on their 'tumor-finding' nature, bacteria and viruses may be designed to carry multiple genes for detection and treatment of cancer.