Mapping the antigenic landscape of Multiple Myeloma to inform the development of precision cancer immunotherapies

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This project aims to use RNASeq, whole exome and whole genome sequencing (WES and WGS) data fromMM patients to predict neoantigens from common fusion events/sequences and test putative peptides in co-culture assays of autologous T cells to provide proof of principle to target fusion-derived neoantigensfor MM treatment.To achieve this, we will pursue the following objectives:1. Identify distribution of shared fusion events amongst patients to create a comprehensive map ofpotential personal/shared tumour neoantigens;2. Validate presence of neoantigen-reactive T cells in patients with MM and SMM, characterise themphenotypically and validate their cytotoxic capability;3. Provide proof of concept (PoC) of expansion and activity of neoantigen-reactive T cells forpotential clinical development.Importance. This project is the first comprehensive study of MM neoantigens, potentially leading to thediscovery of new targets for MM treatment. Following this project, these neoantigens could be used forthe development of off the shelf T cell therapy-based treatments and/or prophylactic vaccines for patientswith SMM. The collaboration with Achilles, a leading company developing neoantigen-based T celltherapies, guarantees a clear translational outcome.