Visualization of tumors and metastases in live animals with bacteria and vaccinia virus encoding light-emitting proteins.
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.
Department of Biochemistry, School of Medicine, Loma Linda University, Loma Linda, California 92350, USA.
Yong A
YA
Yu
Shahrokh
S
Shabahang
Tatyana M
TM
Timiryasova
Qian
Q
Zhang
Richard
R
Beltz
Ivaylo
I
Gentschev
Werner
W
Goebel
Aladar A
AA
Szalay
D000818:Animals; D001419:Bacteria / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure*; D001681:Biological Assay / Q000379:methods*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008856:Microscopy, Fluorescence / Q000379:methods*; D009362:Neoplasm Metastasis / Q000473:pathology; D009367:Neoplasm Staging / Q000379:methods; D009369:Neoplasms / Q000382:microbiology* / Q000473:pathology* / Q000821:virology; D051381:Rats; D014616:Vaccinia virus / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure*
D008164:Luminescent Proteins