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

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.

• Authors: Maria Libera Ascierto, Andrea Worschech, Zhiya Yu, Sharon Adams, Jennifer Reinboth, Nanhai G Chen, Zoltan Pos, Rahul Roychoudhuri, Giovanni Di Pasquale, Davide Bedognetti, Lorenzo Uccellini, Fabio Rossano, Paolo A Ascierto, David F Stroncek, Nicholas P Restifo, Ena Wang, Aladar A Szalay, Francesco M Marincola
• Journal: BMC cancer (BMC Cancer) Vol. 11 Pg. 451 (Oct 19 2011) ISSN: 1471-2407 [Electronic] England
• PMID: 22011439 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Culture Media

Topics

• Cell Line, Tumor
• Cluster Analysis
• Culture Media
• Gene Expression Profiling
• Gene Expression Regulation, Viral
• Genes, Reporter
• Genetic Vectors (physiology)
• HT29 Cells
• Humans
• Oncolytic Viruses (physiology)
• Transcription, Genetic
• Vaccinia virus (physiology)
• Vesiculovirus (physiology)
• Viral Tropism
• Virus Replication