Hepatocellular carcinoma (HCC) is the fourth most frequent cause of cancer-related death. The disease is considered an immune-reactive tumor type, as 25% of patients respond to immune checkpoint inhibition. However, the impact of these treatments is often limited due to primary and acquired resistance in most patients. We recently identified the T-cell phenotypes responsible for immunotherapy response in HCC. Here, we will use the TCR sequences of these tumor-reactive T-cells as input for an in vitro antigen screen developed. By identifying up to 240 tumor antigens, we will uniquely characterize the tumor antigen landscape of HCC and develop methods to identify tumor-reactive T-cells in individual patients. In a second part, this knowledge will be applied within a small feasibility clinical trial, in which HCC patients treated with checkpoint inhibitors will receive a custom-made mRNA vaccine, based on tumor antigens identified in their corresponding tumor biopsies.