Dataset Information

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.

SUBMITTER: Ascierto ML

PROVIDER: S-EPMC3213037 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Publications

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

Ascierto Maria Libera ML Worschech Andrea A Yu Zhiya Z Adams Sharon S Reinboth Jennifer J Chen Nanhai G NG Pos Zoltan Z Roychoudhuri Rahul R Di Pasquale Giovanni G Bedognetti Davide D Uccellini Lorenzo L Rossano Fabio F Ascierto Paolo A PA Stroncek David F DF Restifo Nicholas P NP Wang Ena E Szalay Aladar A AA Marincola Francesco M FM

BMC cancer 20111019

<h4>Background</h4>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.<h4>Methods</h4>In the current study we surveyed the in vitro permissivity to GLV-1h68 replication of the NCI-60 panel of ...[more]

PMID: 22011439

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Project description:Oncolytic viral therapy represents an alternative therapeutic strategy for the treatment of cancer. This therapy relies on efficient replication of virus in tumor cells in vivo with minimal or no replication in normal tissues. We recently described GLV-1h68 as a modified Vaccinia Virus (VACV) construct with exclusive in vivo tropism for tumor cells in experimental animal models. Moreover, we had previously observed a cell line-specific relationship between the ability of GLV-1h68 to replicate in vitro during the first 20 hours following infection and the in vivo ability to colonize and eliminate the corresponding tumor implant. Thus, we surveyed the in vitro permissivity to GLV-1h68 replication of the NCI-60 panel of cell lines, extensively characterized and used for the assessment of novel therapeutic modalities. All cell lines were cultured and infected in identical conditions. Pre-infection transcriptional profiling was obtained to search for correlates of permissivity to viral infection. Selected cell lines were also tested for permissivity to another VACV and a vesicular stomatitis virus (VSV) strain. We observed that permissivity to VACV infection during the first 20 hours is quite heterogeneous among cell lines but highly reproducible within each cell line. The tissue of origin of each cell line does not influence permissivity to infection with the exception of B cell derivation. Permissivity correlates between two VACV constructs and between them and VSV suggesting a common permissive phenotype. No clear transcriptional pattern predictive of permissivity to infection could be identified though weak associations were observed that suggest a multifactorial control of viral replication. This study adds to the current characterization of the NCI-60 panel to guide the design and interpretation of experimental models testing oncolytic therapies. Seventy-four microarray samples were obtained from 8 renal cancer cell lines (786-0, A498, ACHN, CAKI-I, RXF-393, SN12C, TK-10, UO-31); 12 melanoma cell lines (888-MEL, 1858-MEL, 1936-MEL, 397, A375-MEL, LOX IMVI, M14, SK-MEL-2, SK-MEL-5, SK-MEL-28, UACC 62, UACC 257 ); 11 lung cancer cell lines (A549 p7, A549 p107, EKVX, HOP-62, HOP-92, NCI-H23, NCI-H226, NCI-H322M, NCI-H460, NCI-H522, NCI-H1299); 13 colon cancer cell lines (HCT-15, HCT-116, HT-29 p155, HT-29 p9, KM-12, SW-620, Colo 205, HCC 2998, NCI-ADR-RES, OVCAR 3 p7, OVCAR 3 p42, OVCAR 5, SK-OV-3); 3 ovarian cancer cell lines (OVCAR 4, OVCAR 8, IGROV); 1 cervical cancer cell line (Siha); 6 brain cancer cell lines (SNB 19, SF 295, SF 298, SNB 75, U251, SF 539); 7 breast cancer cell lines (BT-549, GI101A, HS-578T, MCF 7, MDA-MB-231 p41, MDA-MB-435, MDA-MB-231 p6); 7 hematopoietic cancer cell lines (CCFR-CEM, HL-60, K-562, MOLT-4, RPMI 8226, SR, T-47D); 3 prostatic cancer cell lines (Du-145, PC 3 p7, PC 3 p35); 1 hepatic cancer cell lines (Huh 7.5.1); and 2 pancreatic cancer cell lines (MIA PACA 2, Panc 1). Two technical repeats were performed (cell lines Siha and SNB-19). Reference T-RNA was obtained from 6 normal donor PBMCs.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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