Immunotherapy, and in particular immune checkpoint blockade, has revolutionised clinical practice and improved outcomes in many cancer types. Immune checkpoint blockade essentially takes the brakes off the immune system allowing the full complement of immune effector cells to enter and attack the tumour. This begs the question – what is targeted by the infiltrating immune cells? And if there is a specific target can this response be augmented or even targeted by therapeutic or prophylactic vaccination strategies.
Key to the destruction of tumours is the activity of the killer T cells which recognise peptide antigens bound to the cell surface HLA class I molecules of the tumour cell. Here I present our efforts to develop a clinically relevant workflow for the identification of different classes of peptide antigens available for precision cancer immunotherapy and the validation of these targets from tumour biopsy material using a novel approach that is amenable even to just a few hundred cancer cells. These approaches will enable to next generation of T cell receptor-based and T cell receptor like therapies.