Nature Biotechnology22, 313 - 320 (2004)
Published online: 8 February 2004; | doi:10.1038/nbt937
There is a Corrigendum (April 2004) associated with this document.
Visualization of tumors and metastases in live animals with bacteria and vaccinia virus encoding light-emitting proteins
Yong A Yu1, 3, Shahrokh Shabahang1, Tatyana M Timiryasova2, 3, Qian Zhang3, Richard Beltz1, Ivaylo Gentschev4, Werner Goebel4
& Aladar A Szalay1, 4, 5
1
Department of Biochemistry, School of Medicine, Loma Linda University, Loma Linda, California 92350, USA.
2
Center for Molecular Biology and Gene Therapy, School of Medicine, Loma Linda University, Loma Linda, California 92350, USA.
3
Genelux Corp., San Diego Science Center, 3030 Bunker Hill St., Ste. 310, San Diego, California 92109, USA.
4
Department of Microbiology, Biocenter, DFG-Research Center for Experimental Biomedicine, University of Wuerzburg, Wuerzburg D97074, Germany.
5
Rudolf-Virchow-Center, DFG-Research Center for Experimental Biomedicine, University of Wuerzburg, Wuerzburg D97074, Germany.
Correspondence should be addressed to Aladar A Szalay Msz1998@aol.com
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.
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