The repertoire of human tumor-associated epitopes--identification and selection of antigens and their application in clinical trials

Abstract

In cancer patients, active immunotherapy has gained significant importance in recent years by implementation of novel substances into standard clinical care. These new drugs represent strategies which either use defined cancer associated antigens as vaccines or induce tumor-directed immune responses through generation of a general inflammatory state which has extensive autoinflammatory side effects by induction of autoreactive immune cells. Hence, the definition of suitable target antigens for immunotherapy remains a major challenge. These antigens should ideally be specific markers for individual tumors or should be at least structures overexpressed on the tumor as compared to normal cells. Recent approaches have defined algorithms and refined analytical methods for antigen identification and immunological validation that have already been evaluated in clinical studies. This article summarizes recent developments in tissue analysis on genome, transcriptome and HLA-ligandome levels and of antigen application in recent clinical vaccination trials.