Permissivity of the NCI-60 cancer cell lines to oncolytic Vaccinia Virus GLV-1h68
1 Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center and trans-NIH Center of Human Immunology (CHI), National Institutes of Health, Bethesda, MD, USA
2 Department of Internal Medicine and Center of Excellence for Biomedical Research (CEBR), University of Genoa, Italy
3 Genelux Corporation, San Diego Science Center, San Diego, CA, USA
4 Surgery Branch, National Cancer Institute, Bethesda, MD, USA
5 Warren G. Magnuson Clinical Center, HLA Laboratory, National Institutes of Health, Bethesda, MD, USA
6 Department of Internal Medicine II Julius-Maximilian University of Würzburg, Würzburg, Germany
7 Department of Biochemistry, Biocenter, University of Würzburg, D-97074 Würzburg, Germany
8 NIDCR/Molecular Physiology and Therapeutics Branch, National Institutes of Health, Bethesda, MD, USA
9 Department of Molecular Pathology, University Federico II, Via G. Pansini, Naples, Italy
10 National Cancer Institute, "Fondazione G Pascale", via G. Semmola, Naples, Italy
11 Cell Therapy Section, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, USA
12 Department of Oncology, Biology and Genetics and Department of Internal Medicine, University of Genoa, Italy
13 Department of Medical Oncology, National Cancer Research Institute, Genoa, Italy
14 Institute of Infectious and Tropical Diseases, University of Milan, L. Sacco Hospital, Milan, Italy
15 Department of Radiation Oncology, Rebecca & John Moores Comprehensive Cancer Center, University of California, San Diego, CA, USA
BMC Cancer 2011, 11:451 doi:10.1186/1471-2407-11-451Published: 19 October 2011
Oncolytic viral therapy represents an alternative therapeutic strategy for the treatment of cancer. We previously described GLV-1h68, a modified Vaccinia Virus with exclusive tropism for tumor cells, and we observed a cell line-specific relationship between the ability of GLV-1h68 to replicate in vitro and its ability to colonize and eliminate tumor in vivo.
In the current study we surveyed the in vitro permissivity to GLV-1h68 replication of the NCI-60 panel of cell lines. Selected cell lines were also tested for permissivity to another Vaccinia Virus and a vesicular stomatitis virus (VSV) strain. In order to identify correlates of permissity to viral infection, we measured transcriptional profiles of the cell lines prior infection.
We observed highly heterogeneous permissivity to VACV infection amongst the cell lines. The heterogeneity of permissivity was independent of tissue with the exception of B cell derivation. Cell lines were also tested for permissivity to another Vaccinia Virus and a vesicular stomatitis virus (VSV) strain and a significant correlation was found suggesting a common permissive phenotype. While no clear transcriptional pattern could be identified as predictor of permissivity to infection, some associations were observed suggesting multifactorial basis permissivity to viral infection.
Our findings have implications for the design of oncolytic therapies for cancer and offer insights into the nature of permissivity of tumor cells to viral infection.