Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus

@article{Stojdl2000ExploitingTD,
  title={Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus},
  author={David F. Stojdl and Brian Dennis Lichty and Shane Knowles and Ricardo Marius and Harold L Atkins and Nahum Sonenberg and John Cameron Bell},
  journal={Nature Medicine},
  year={2000},
  volume={6},
  pages={821-825}
}
Interferons are circulating factors that bind to cell surface receptors, activating a signaling cascade, ultimately leading to both an antiviral response and an induction of growth inhibitory and/or apoptotic signals in normal and tumor cells. Attempts to exploit the ability of interferons to limit the growth of tumors in patients has met with limited results because of cancer-specific mutations of gene products in the interferon pathway. Although interferon-non-responsive cancer cells may have… 
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References

SHOWING 1-10 OF 24 REFERENCES
Interferon-alpha resistance in a cutaneous T-cell lymphoma cell line is associated with lack of STAT1 expression.
TLDR
The development of an IFN alpha-resistant CTCL cell line (HUT78R), characterized by its ability to proliferate in high concentration of recombinant IFNalpha, which can be used as a model system to study IFN resistance.
Use of carrier cells to deliver a replication-selective herpes simplex virus-1 mutant for the intraperitoneal therapy of epithelial ovarian cancer.
TLDR
Results indicate that replication-competent attenuated HSV-1 exerts a potent oncolytic effect on EOC, which may be further enhanced by the utilization of a delivery system with carrier cells, based on amplification of the viral load and possibly on preferential binding of carrier cells to tumor surfaces.
Inhibition of vesicular stomatitis viral mRNA synthesis by interferons
TLDR
It appears that IFN exerts a direct effect on the VSV transcriptional process in GM2767 and JLSV-11 cells, and the accumulation of primary viral transcripts was strongly inhibited in these cells by IFN treatment.
Interferon-resistant Human Melanoma Cells Are Deficient in ISGF3 Components, STAT1, STAT2, and p48-ISGF3γ*
TLDR
It is concluded that a defect in the level of STAT1 and possibly all three ISGF3 components in IFN-resistant human melanoma cells may be a general phenomenon responsible for reduced cellular responsiveness of melanomas to IFNs.
Cooperation of B cells and T cells is required for survival of mice infected with vesicular stomatitis virus.
TLDR
It was found that in nude mice a lethal outcome could be prevented by transfer of CD8-depleted cells from B cell-deficient mice, demonstrating that while antibodies are pivotal for survival in the early phase of VSV infection, T cells are required for long-term survival, with CD4- T cells being more effective in controlling this infection than CD8+ T cells.
Characterization of a gastric tumor cell line defective in MHC class I inducibility by both α- and γ-interferon
TLDR
In this context, overlapping factors in the signal transduction pathway of both type I and II interferons may be involved in the non-responsiveness of this gastric carcinoma tumor cell line.
Correlation between interferon (IFN) alpha resistance and deletion of the IFN alpha/beta genes in acute leukemia cell lines suggests selection against the IFN system.
TLDR
The data presented here suggest that selection against the IFN alpha/beta system could play a role or accompany the development of the malignant phenotype.
Characterization of a gastric tumor cell line defective in MHC class I inducibility by both alpha- and gamma-interferon.
TLDR
In this context, overlapping factors in the signal transduction pathway of both type I and II interferons may be involved in the non-responsiveness of this gastric carcinoma tumor cell line.
Replication of ONYX-015, a Potential Anticancer Adenovirus, Is Independent of p53 Status in Tumor Cells
TLDR
dl1520 replicates independently of the p53 status in various tumor cell lines (U87, RKO, A549, H1299, and U373) and it is shown that, depending on the multiplicity of infection, the deleted virus is able to replicate in and to kill primary human cells.
The molecular basis of viral oncolysis: usurpation of the Ras signaling pathway by reovirus
TLDR
The emerging picture is one in which early viral transcripts trigger PKR phosphorylated in untransformed cells, which in turn leads to inhibition of translation of viral genes; this phosphorylation event is blocked by an element(s) in the Ras pathway in the transformed cells, allowing viral protein synthesis to ensue.
...
...