Permissivity of the NCI-60 cancer cell lines to oncolytic Vaccinia Virus GLV-1h68.
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.
Infectious Disease and Immunogenetics Section, Department of Transfusion Medicine, Clinical Center and trans-NIH Center of Human Immunology, National Institutes of Health, Bethesda, MD, USA. asciertoml@cc.nih.gov
Maria Libera
ML
Ascierto
Andrea
A
Worschech
Zhiya
Z
Yu
Sharon
S
Adams
Jennifer
J
Reinboth
Nanhai G
NG
Chen
Zoltan
Z
Pos
Rahul
R
Roychoudhuri
Giovanni
G
Di Pasquale
Davide
D
Bedognetti
Lorenzo
L
Uccellini
Fabio
F
Rossano
Paolo A
PA
Ascierto
David F
DF
Stroncek
Nicholas P
NP
Restifo
Ena
E
Wang
Aladar A
AA
Szalay
Francesco M
FM
Marincola
D045744:Cell Line, Tumor; D016000:Cluster Analysis; D003470:Culture Media; D020869:Gene Expression Profiling; D015967:Gene Expression Regulation, Viral; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000502:physiology*; D019073:HT29 Cells; D006801:Humans; D050504:Oncolytic Viruses / Q000502:physiology*; D014158:Transcription, Genetic; D014616:Vaccinia virus / Q000502:physiology*; D018116:Vesiculovirus / Q000502:physiology; D056189:Viral Tropism; D014779:Virus Replication
D003470:Culture Media