Personalised anti-viral immunotherapies for hepatitis B and C virus-associated hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a cancer of hepatocytes commonly caused by hepatitis B and C virus (HBV/HCV) infections. Only 12% of HCC patients survive for five-years, due to late diagnosis and inadequate non-personalised therapies. Promising results are being obtained with immune checkpoint blockade (ICB), which stimulates T-cell anti-cancer immunity. However, only a minority of HCC patients currently benefit from ICB, primarily due to the presence of powerful immunosuppressive mechanisms. Two important immunosuppressive factors are active HBV and HCV infections, which suppress and evade innate and adaptive immunity, thereby enabling cancerous hepatocytes to survive immune attack.

Our research indicates that active HBV and HCV infections can limit the efficacy of ICB against HCC. Personalised therapies for HBV and HCV therefore hold the potential to improve the efficacy of immunotherapies against HCC. 

Objectives 
To define the extent and mechanisms of HBV/HCV-mediated suppression of immunotherapy activity against HCC.
To design and test the potential of personalised anti-HBV/HCV therapies to improve cancer immunotherapy.

Experimental Approach
The successful student will be trained in a variety of virology, immunology and molecular biology techniques:

Category 2 and 3 biosafety tissue culture of subgenomic and infectious HBV and HCV.
In vitro T-cell priming assay to determine the interaction of HBV and HCV on the efficacy of cancer immunotherapy.
Designing and testing personalised anti-viral therapies for the eradication of HBV and HCV, including small molecule inhibitors, CRISPR-Cas9 and anti-viral cytokines.
Characterisation and functional assessment of immune cell anti-cancer effects, including flow cytometry immunophenotyping, cytotoxicity assays and T-cell ELISpot.
Xenograft models of HBV/HCV-associated HCC

Clinical Impact 
Current anti-cancer therapies for HCC do not take into account the presence of HBV and HCV infections. This project will highlight the need for a personalised approach to HCC immunotherapies, which includes individualised anti-viral therapies as a standard component of anti-cancer therapy. We anticipate that successful completion of this project will directly inform early phase clinical trials. 

Eligibility:

You should hold a first degree equivalent to at least a UK upper second class honours degree in a relevant subject.

The Faculty minimum requirements for candidates whose first language is not English are:
• British Council IELTS – score of 6.5 overall, with no element less than 6.0
• TOEFL iBT – overall score of 92 with the listening and reading element no less than 21, writing element no less than 22 and the speaking element no less than 23.


How to apply:

To apply for this project applicants should complete a Faculty Scholarship Application form using the link below https://medicinehealth.leeds.ac.uk/downloads/download/78/fmh_scholarship_application_form_2018_2019 and send this alongside a full academic CV, degree certificates and transcripts (or marks so far if still studying) to the Faculty Graduate School at [Email Address Removed]

We also require 2 academic references to support your application. Please ask your referees to send these references on your behalf, directly to [Email Address Removed] by no later than 28 February 2020.

Any queries regarding the application process should be directed to [Email Address Removed]

If you would like to know more about this scholarship or the project please contact: Dr Adel Samson ([Email Address Removed])