Although immune checkpoint inhibitors (ICIs) have demonstrated clinical efficacy in cancer treatment, their success is often limited by low tumour mutation burden and poor immunogenicity in many patients. T cell therapies targeting tumour-associated antigens offer a synergic strategy to enhance immune recognition and tumour clearance. CEP55, a mitotic regulator overexpressed across a wide range of malignancies but largely absent from healthy adult tissues, represents an attractive pan-cancer immunotherapy target.
In this study, we investigate the therapeutic potential of CEP55-directed T cell-based approaches to selectively recognise and eliminate tumour cells across multiple cancer types. Through a combination of immunopeptidomics and a robust in vitro and in vivo validation pipeline, we identified immunogenic epitopes derived from CEP55 and presented by the most common HLA class I molecules. These epitopes were then exploited for the development of T cell-based immunotherapies, including cancer vaccines.
We demonstrated the in vivo efficacy of CEP55-targeting therapies using advanced humanized tumour models recently developed in our lab. Furthermore, the same epitopes elicited robust spontaneous immune responses in peripheral blood mononuclear cells from cancer patients, underscoring both their in vivo immunogenicity and shared nature across patients. These findings highlight the clinical relevance of CEP55 as a pan-cancer immunotherapeutic target.
Finally, the availability of validated CEP55-derived epitopes presented by frequent HLA molecules supports not only the development of broadly applicable immunotherapies but also enables the implementation of immune monitoring assays. These assays can be used to detect and track cancer-specific T cell responses in patients receiving immunotherapy, providing valuable tools for both therapeutic intervention and clinical monitoring.