A comprehensive antigen discovery study to identify immunotherapeutic targets in paediatric diffuse midline glioma

Diffuse midline glioma (DMG) is a lethal paediatric brain tumour with no effective treatment. Recent studies have demonstrated the promise of immunotherapy—strategies that harness the immune system to target cancer. A key step for successful immunotherapy is identifying tumour-specific antigens (peptides from cancer-specific proteins presented by HLA molecules). In this project, I employed a multi-omics approach combined with immunological validation using patient-derived cell lines to identify hundreds of DMG-specific antigens from both canonical and non-canonical genomic regions. A subset of these antigens was shown to be immunogenic and capable of inducing DMG cell lysis in vitro. This thesis establishes a preclinical framework for developing precision immunotherapies, including cancer vaccines and T-cell-based therapies for DMG.