Yu Yong A, Shabahang Shahrokh, Timiryasova Tatyana M, Zhang Qian, Beltz Richard, Gentschev Ivaylo, Goebel Werner, Szalay Aladar A
Department of Biochemistry, School of Medicine, Loma Linda University, Loma Linda, California 92350, USA.
Nat Biotechnol. 2004 Mar;22(3):313-20. doi: 10.1038/nbt937. Epub 2004 Feb 8.
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.
我们已经证明，静脉注射到活体动物体内的细菌会进入实体瘤和转移瘤并在其中复制。利用荧光素酶催化的发光和绿色荧光蛋白荧光实时观察肿瘤特异性扩增过程，从而揭示肿瘤和转移瘤的位置。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）均进入肿瘤并进行复制。同样，胞质痘苗病毒也表现出肿瘤特异性复制，通过实时成像可见。这些发现表明，肿瘤特异性和瘤内复制既不需要营养缺陷型突变，也不需要胸苷激酶基因缺陷的痘苗病毒，也不需要厌氧生长条件。我们在具有同基因和异基因肿瘤的免疫健全和免疫受损啮齿动物中观察到发光微生物对肿瘤的定位。基于它们的“肿瘤发现”特性，细菌和病毒可被设计用于携带多个用于癌症检测和治疗的基因。
