In vitro comparison of fibre-modified and replication-selective adenoviruses and role for CD40L-armed adenoviruses in the therapy of liver cancer

Karakonstantis, Stamatis (2014). In vitro comparison of fibre-modified and replication-selective adenoviruses and role for CD40L-armed adenoviruses in the therapy of liver cancer. University of Birmingham. M.Res.

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Abstract

Liver cancer is associated with a very bad prognosis. Oncolytic virotherapy seems a promising alternative to standard treatments. Here, I compared; (1) the transduction specificity and efficacy of four fibre-modified adenoviruses and the wild type fibre virus, (2) the selectivity and oncolytic potency of three conditionally-replicating viruses, and (3) the cytotoxicity of two CD40-ligand expressing adenoviruses. The comparisons were done in vitro in liver cancer cell lines and primary hepatocytes. The long term goal is to insert the best fibre, and potentially CD40L, into the best replication-competent vector. Immunohistochemistry was also performed in liver cancer sections and surrounding non-cancer tissues to compare the levels of the viral receptors and CD40 between the tumour and the surrounding liver. The Ad5/3 fibre-chimeric virus was found to have the best overall transduction efficacy although none of the fibre-modified viruses is expected to be tumour-specific according to the results from immunohistochemistry and testing in primary hepatocytes. The conditionally replicating viruses were not found to be selective, although these results will need to be replicated. The expression of CD40L didn’t have any effect on the viability of the hepatocellular carcinoma cell lines in vitro.

Type of Work:

Thesis (Masters by Research > M.Res.)

Award Type:

Masters by Research > M.Res.

Supervisor(s):