On the development of neoantigen vaccine for HCC cure: from genomics of Hepatitis B Virus (HBV) integration in liver cells to immunological host response toward neoepitopes as novel immunotherapeutic approaches

Details

ERC sector: LS6 - Immunity, Infection and Immunotherapy
ERC subsector: LS6_11 - Innovative immunological tools and approaches, including therapies
Project start date: 28/09/2023
CUP: D53D23001690001
Financial support received: €82.458,00

Description and purpose

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, frequently associated with chronic HBV infection, with poor prognosis and limited therapeutic options. The project aims to develop a patient-specific vaccino-therapy based on the identification of neo-epitopes derived from HBV integrations and on the ex vivo/in vitro characterization of CD4/CD8 T-cell responses, with the goal of restoring antitumor immunity and opening new perspectives for personalized medicine in HCC.

Purpose

The project aims to develop new vaccino-therapy strategies for HBV-related HCC through the characterization of HBV genomic integrations and chimeric transcripts, with the identification of neo-epitopes recognized by CD4/CD8 T lymphocytes. Ex vivo/in vitro validation of immune responses will enable the design of personalized and innovative immunotherapeutic approaches to improve patient prognosis.

Expected results

The project will generate new insights into the role of HBV integrations during different stages of infection and in progression toward HCC, characterize peripheral and intrahepatic immune responses against HBV integration–derived neo-epitopes, and exploit neo-transcripts as innovative diagnostic biomarkers. It will also assess the impact of therapies on the integration pool and lay the foundation for personalized immunotherapies based on neo-epitopes.

Achieved results

HBV-specific genomic and transcriptomic analyses have enabled the identification of integrations in enrolled patients, for which in silico analyses are ongoing to predict CD4/CD8 neo-epitopes. Current activities include HLA typing, selection of the most promising neo-epitopes, peptide design and synthesis, as well as the set-up of ex vivo/in vitro assays on PBMCs and TILs to validate their immunogenicity and define functional profiles.