Oncolytic virus immunotherapy to sensitise liver cancers to immune checkpoint blockade

Summary

Hepatocellular carcinoma (HCC) is acknowledged as a cancer of unmet need, with overall survival frequently less than 7 months in patients with advanced disease. Immune checkpoint inhibitors targeting T-cell signalling pathways are producing unprecedented results in solid malignancies, including recent advances in liver cancer. However, the majority of patients derive no benefit from these drugs. We and others have reported that oncolytic viruses, therapeutic viruses that preferentially replicate in malignant cells, can be employed to prime the tumour microenvironment, rendering previously resistant tumours susceptible to immune checkpoint blockade (1,2). We have also shown that oncolytic viruses can suppress both Hepatitis B and C virus infections (3).

The trainee will investigate the use of oncolytic virus therapy to increase T-cell priming against HCC tumour specific antigens, and prime tumours for subsequent immune checkpoint blockade, thus enhancing therapy. Other areas of research include the effects of oncolytic viruses and checkpoint blockade on Natural Killer cell activity and HCV/HBV infections.

HCC research at Leeds Teaching Hospitals Trust and Leeds Institute of Cancer and Pathology (LICAP) is delivered through stakeholders including patient groups, charities, clinicians across a range of specialities and the scientific community to develop and deliver high quality translational research using new agents and technologies to improve outcomes for patients. The group has active collaborations in the UK (ICR, London, Birmingham) and elsewhere (notably the Mayo Clinic, USA and the University of Madrid, Spain). HCC research at LICAP is supported by colleagues in virology, medical oncology, surgical oncology and hepatology, with collaborative translational clinical trials spanning all the aforememntioned specialities.

The trainee will be supervised by a translational oncologist, Dr Adel Samson and a professional scientist-virologist, Dr Stephen Griffin. This mixed clinical and scientific team will provide the trainee with an excellent background in basic science research, as well as clinically relevant models of cancer immunotherapy, leading to translational clinical trials in patients with cancer.

References:

1. Samson A, Scott KJ, Taggart D, West EJ, Wilson E, Nuovo GJ, et al. Intravenous delivery of oncolytic reovirus to brain tumor patients immunologically primes for subsequent checkpoint blockade. Sci Transl Med [Internet]. 2018 Jan 3 [cited 2018 Jan 4];10(422):eaam7577. Available from: http://stm.sciencemag.org/lookup/doi/10.1126/scitranslmed.aam7577
2. Bourgeois-Daigneault M-C, Roy DG, Aitken AS, El Sayes N, Martin NT, Varette O, et al. Neoadjuvant oncolytic virotherapy before surgery sensitizes triple-negative breast cancer to immune checkpoint therapy. Sci Transl Med [Internet]. 2018 Jan 3 [cited 2018 Jan 17];10(422):eaao1641. Available from: http://www.ncbi.nlm.nih.gov/pubmed/29298865
3. Samson A, Bentham MJ, Scott K, Nuovo G, Bloy A, Appleton E, et al. Oncolytic reovirus as a combined antiviral and anti-tumour agent for the treatment of liver cancer. Gut [Internet]. 2016 Nov 15 [cited 2017 Apr 1];gutjnl-2016-312009. Available from: http://gut.bmj.com/lookup/doi/10.1136/gutjnl-2016-312009

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