Individualised heteroclitic peptide immunotherapies for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a cancer of unmet need. Immune checkpoint blockade (ICB) therapies show promising results for just a minority of patients, justifying this project which aims to predict ICB-resistant tumours and sensitise them. Evidence indicates that tumours with a low neoepitope load have a poor response to ICB, so defining the T cell response to ICB in HCC accounting for the neoepitope load will provide support for this theory. Tumours identified with low neoepitope loads will be used to build upon the concept of using heteroclitic peptides, modified peptides capable of initiating a T cell response to wild-type tumour epitopes, in combination with ICB to re-sensitise these tumours. The Samson lab has access to paired peripheral blood and HCC tumour samples, long-standing expertise in immunological assays, including human in vitro T-cell priming, and experience of running clinical trials; Prof Reuben Tooze is an expert in pathology and data analytics which provides complementary support, together this expertise enables the project to have a translational nature with the potential to directly inform early phase clinical trials.