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.
- HEPATITIS C
- HEPATOCELLULAR CARCINOMA
- ANTIVIRAL THERAPY
- CANCER IMMUNOBIOLOGY
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AM and SG contributed equally.
Contributors Conceived and planned experiments: SG, AM, FE-M and AS; performed experiments: AS, MJB, KS, GN, AB, EA, RAA, RD and AP-C; provided key reagents: GT, SN and MC; reviewed manuscript: RV, KH, PS and FE-M; wrote manuscript: SG, AM and AS.
Funding AS was the recipient of a Cancer Research UK Clinical Fellowship awarded by the Cancer Research UK Leeds Centre to SG/AM.
Competing interests MC is an employee of Oncolytics Biotech, Calgary, Canada. SG and AM have received research grants from Oncolytics.
Ethics approval North East Leeds ethics committee, St. James’ University Hospital, Leeds, UK. In vivo animal models were approved by the University of Leeds local ethics review committee.
Provenance and peer review Not commissioned; externally peer reviewed.