Open Access Highly Accessed Research article

Permissivity of the NCI-60 cancer cell lines to oncolytic Vaccinia Virus GLV-1h68

Maria Libera Ascierto1102*, Andrea Worschech1367, Zhiya Yu4, Sharon Adams5, Jennifer Reinboth137, Nanhai G Chen153, Zoltan Pos1, Rahul Roychoudhuri4, Giovanni Di Pasquale8, Davide Bedognetti11213, Lorenzo Uccellini114, Fabio Rossano9, Paolo A Ascierto10, David F Stroncek11, Nicholas P Restifo4, Ena Wang1, Aladar A Szalay1537 and Francesco M Marincola1*

Author Affiliations

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

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BMC Cancer 2011, 11:451  doi:10.1186/1471-2407-11-451

Published: 19 October 2011

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.