Identification of Relevant Antigenic Targets for Successful Liver Cancer Immunotherapy

HCC is a major cause of cancer-related death in the world and the current available treatments are effective only at an early stage. For advanced HCC the only approved therapy is Sorafenib (a multi kinase inhibitor) which has low response rate (about 3%). New immunotherapies for HCC, like anti- PD-1 treatment, can achieve a higher response rate, but still in only a minority of patients (20%). To boost this rate, it is critical to guide the immune response towards relevant antigens expressed by all tumor cells. Genome-wide sequencing of HCC showed presence of mutations that theoretically could give rise to neoantigen-specific T cell responses. However, the presence of these immune responses has not been investigated yet. Our approach is to focus on mutations that are expressed on all cancer cells, like mutations in driver oncogenes. The central goal is to identify neoantigens in HCC and evaluate the presence of an immunological response to HCC- specific neoantigens with particular attention to hot-spot mutations in driver oncogenes.