Abstract
Tumor-specific replication-competent viruses represent a novel approach for the treatment of neoplastic disease. These vectors can be used to directly label tumor cells in vivo, as they are designed to selectively replicate within such cells. To target cancer cells, there is a need for tissue- or cell-specific promoters that are expressed in diverse tumor types and are silent in normal cells. Telomerase activation is considered to be a critical step in carcinogenesis through the maintenance of telomeres, and its activity is closely correlated with human telomerase reverse transcriptase (hTERT) expression. We constructed a green fluorescent protein (GFP)-expressing attenuated adenovirus-5 vector, in which the hTERT promoter regulates viral replication (TelomeScan, OBP-401). We used TelomeScan to establish a new approach for visualizing metastatic or disseminated human tumors in vivo. Visualization is achieved via illumination with an excitation lamp under a three-chip color-cooled charged-coupled device camera following injection of TelomeScan into primary tumors or tumor-disseminated cavities. TelomeScan infection increases the signal-to-background ratio as a tumor-specific probe, because the fluorescent signals are only amplified in tumor cells by viral replication. This technology is adaptable to detect tumor metastasis and/or dissemination in vivo as a preclinical model of surgical navigation.
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Acknowledgments
The authors would like to thank Dr. Robert M. Hoffman for his helpful discussion and encouragement. The authors also thank Tomoko Sueishi and MitsukoYokota for the excellent technical support. This work was supported in part by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (to T.F.) and by grants from the Ministry of Health, Labour, and Welfare of Japan (to T.F.).
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Fujiwara, T. (2012). In Vivo Imaging of Human Cancer with Telomerase-Specific Replication-Selective Adenovirus. In: Hoffman, R. (eds) In Vivo Cellular Imaging Using Fluorescent Proteins. Methods in Molecular Biology, vol 872. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-797-2_9
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DOI: https://doi.org/10.1007/978-1-61779-797-2_9
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