Analysis of the HLA peptidome for development of personalized cancer immunotherapy

The MHC peptidome is the assortment of peptides presented by the Major Histocompatibility Molecules on the surface of most nucleated cells in the body, providing the immune system with information about the ‘health state’ of the cells and the organism. The MHC molecules (called the Human Leukocyte Antigens in humans, HLA) are the most polymorphic protein/genes in the human genome and each allomorph binds and presents a different HLA peptidome comprising of tens of thousands different peptides. The presentation of disease-related peptides may cause immune reactions that can bring about the elimination of the diseased cells, and therefore, while aiming to develop cancer vaccines, extensive efforts are made to identify those HLA peptides that are derived from cancer-specific proteins that are not expressed by any of the normal/essential cells in the body, so that these may be administered as immunotherapeutics for cancer, without the fear of inducing adverse effects. The most important cancer candidates are Cancer/Testis Antigens, which are proteins that are expressed only in the germline cells or in embryonal tissues, and neoantigens, which are expressed only in the cancer cells since they contain mutated sequences unique to the cancer cells. The approach we take is to combine the commonly used exome analyses of the tumor and normal cells with and transcriptome and HLA peptidome analyses of the tumor cells alone and look among the identified peptides for those that are derived from Cancer/Testis antigens and neoantigens. This approach is advantageous since it can identify from among the thousands of possible candidate peptides, those few that are really produced and presented by the cancer cells and prioritize them for further immunogenicity testing and clinical applications. This is done separately for every patient, and the results are highly personalized cancer vaccines.