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Oncolytic reovirus as a combined antiviral and anti-tumour agent for the treatment of liver cancer
- Source :
- Gut
- Publication Year :
- 2016
-
Abstract
- Objective Oncolytic viruses (OVs) represent promising, proinflammatory cancer treatments. Here, we explored whether OV-induced innate immune responses could simultaneously inhibit HCV while suppressing hepatocellular carcinoma (HCC). Furthermore, we extended this exemplar to other models of virus-associated cancer. Design and results Clinical grade oncolytic orthoreovirus (Reo) elicited innate immune activation within primary human liver tissue in the absence of cytotoxicity and independently of viral genome replication. As well as achieving therapy in preclinical models of HCC through the activation of innate degranulating immune cells, Reo-induced cytokine responses efficiently suppressed HCV replication both in vitro and in vivo. Furthermore, Reo-induced innate responses were also effective against models of HBV-associated HCC, as well as an alternative endogenous model of Epstein–Barr virus-associated lymphoma. Interestingly, Reo appeared superior to the majority of OVs in its ability to elicit innate inflammatory responses from primary liver tissue. Conclusions We propose that Reo and other select proinflammatory OV may be used in the treatment of multiple cancers associated with oncogenic virus infections, simultaneously reducing both virus-associated oncogenic drive and tumour burden. In the case of HCV-associated HCC (HCV-HCC), Reo should be considered as an alternative agent to supplement and support current HCV-HCC therapies, particularly in those countries where access to new HCV antiviral treatments may be limited.
- Subjects :
- Herpesvirus 4, Human
Carcinoma, Hepatocellular
Hepacivirus
Mice, SCID
Reoviridae
Virus Replication
Mice
Cell Line, Tumor
Animals
Humans
HEPATOCELLULAR CARCINOMA
IMMUNOTHERAPY
Oncolytic Virotherapy
Hepatology
Interleukins
Liver Neoplasms
Interferon-alpha
Interferon-beta
ANTIVIRAL THERAPY
Burkitt Lymphoma
Xenograft Model Antitumor Assays
digestive system diseases
Immunity, Innate
Oncolytic Viruses
Liver
Culture Media, Conditioned
CANCER IMMUNOBIOLOGY
Hepatocytes
Leukocytes, Mononuclear
HEPATITIS C
Natural Killer T-Cells
Interferons
Subjects
Details
- ISSN :
- 14683288
- Volume :
- 67
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Gut
- Accession number :
- edsair.pmid..........788e5c678837efa263828ddb03b9c74d