[vc_row][vc_column][vc_column_text]Background and rationale: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Identification and immunological validation of specific mutated neo-antigens may help at improving therapeutic outcome in HCC patients.
Hypothesis: The hypothesis is that identification and immunological validation of HCC-specific mutated neo-antigens will be critical for developing immunotherapy strategies for better clinical outcome in HCC patients.
Aims: The primary aim is the identification and immunological validation of mutated neo-antigens specific to HCC. Specific aims will be: 1) evaluate the mutational rate in HCC and predict the presentation of neo-epitopes by HLA-A2*01 allele; 2) assess the frequency of specific T cells to such mutant epitopes in HCC patients, before and after treatment with checkpoint inhibitors (CI); 3) validate the immunogenicity of neo-epitopes in an HLA-transgenic mice and their therapeutic effect in a PDX animal model; 4) identify mutated full-length proteins on the surface of HCC cancer cells; 5) develop MAbs to such mutated proteins and validate their specificity in a PDX animal model.
Potential impact: HCC specific mutated neo-antigens will provide a source of immunogens for immunotherapies to be used alone or in combination with HCC specific shared wild-type antigens identified within the ongoing FP7-funded HEPAVAC project (Coordinator L. Buonaguro).
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