Early Detection and Diagnosis
Real-time intraoperative detection of melanoma lymph node metastases using recombinant vaccinia virus GLV-1h68 in an immunocompetent animal model†
Article first published online: 30 SEP 2008
Copyright © 2008 Wiley-Liss, Inc.
International Journal of Cancer
Volume 124, Issue 4, pages 911–918, 15 February 2009
How to Cite
Kelly, K. J., Brader, P., Woo, Y., Li, S., Chen, N., Yu, Y. A., Szalay, A. A. and Fong, Y. (2009), Real-time intraoperative detection of melanoma lymph node metastases using recombinant vaccinia virus GLV-1h68 in an immunocompetent animal model. Int. J. Cancer, 124: 911–918. doi: 10.1002/ijc.24037
Conflict of Interest: A financial conflict of interest does exist for co-authors affiliated with Genelux Corporation. Specifically, Dr. Yong A. Yu and Dr. Aladar Szalay are shareholders of and are employed by Genelux Corporation. Dr. Nanhai Chen is employed by Genelux Corporation.
- Issue published online: 11 DEC 2008
- Article first published online: 30 SEP 2008
- Accepted manuscript online: 30 SEP 2008 12:00AM EST
- Manuscript Accepted: 12 SEP 2008
- Manuscript Received: 19 JUN 2008
- National Institute of Health. Grant Number: R01 CA 76416
- Flight Attendant Medical Research Institute (FAMRI)
- malignant melanoma;
- sentinel lymph node biopsy;
- oncolytic virus
There is a clinical need for improved intraoperative detection of lymph node metastases from malignant melanoma (MM). We aimed to investigate the use of recombinant vaccinia virus GLV-1h68, expressing green fluorescent protein (GFP), for real-time intraoperative detection of melanoma lymph node metastases in an immunocompetent animal model. Mice bearing foot pad tumors received intratumoral injections of GLV-1h68, and 48 hr later were evaluated for popliteal lymph node metastasis using noninvasive bioluminescence imaging and fluorescence imaging. Histologic analysis of lymph nodes was performed to determine sensitivity and specificity of virus-mediated detection. Intratumoral injection of GLV-1h68 into primary foot pad melanoma tumors resulted in viral transmission to popliteal lymph nodes, infection of lymphatic metastases, and transgene expression that was reliably and easily detected. Histologic confirmation demonstrated favorable operating characteristics of this assay (sensitivity 80%, specificity 100%, positive predictive value [PPV] 100%, negative predictive value [NPV] 91%). Detection of marker gene expression by GLV-1h68 allowed the detection of lymphatic metastases in an immunocompetent animal model of MM. This assay is rapid, sensitive, specific and easy to perform and interpret. As a candidate gene therapy virusfor killing cancer, GLV-1h68 may also have significant concomitant diagnostic utility in the staging of cancer patients. © 2008 Wiley-Liss, Inc.