Tumor antigens

The concept of specific immunotherapy depends on the notion that tumors may be specifically targeted by immune effectors such as T cells and antibodies that distinguish distinct differences between normal tissues and tumors. This is in contrast to the concept of non-specific immunotherapy which is mediated by effectors such as NK cells that kill tumor in a non-antigen dependent fashion. Tumor antigens are protein, peptide, or carbohydrate molecules that the immune system uses to distinguish tumor cells from normal cells. While target antigens in the form of surface proteins or carbohydrates that may be recognized by antibodies had been well accepted for quite some time, it was not until observations on the MHC-restricted killing of tumor cells by cytolytic T cells, that attempts were made to clone the genes that encoded the antigens recognized by the T cells. In 1991, the first human tumor antigen recognized by T cells, called MAGE-1, was first discovered [1]. The ensuing years saw an explosion in the number of tumor antigens described and an even greater growth in the number of immunogenic peptide epitopes present within these antigenic molecules. These have now been catalogued in recent, excellent reviews [2] or published on websites (http://www.cancerimmunity.org/peptidedatabase/differentiation.htm). To create some order to the long list of varied antigens, it is helpful to group them according to their expression patterns (for example, cancer-testis antigens found predominantly in tumors or germ cells or differentiation antigens, found predominantly during fetal development in normal tissues) and we will discuss them in this order. Nonetheless, the purpose of this chapter is not to recapitulate the information collected in these publications, but to briefly describe the categories of tumor antigens, explain their relevance to cancer immunotherapy strategies, and to discuss how tumor antigens are discovered. Also, while some tumor antigens may be recognized by T cells or antibodies, we will focus on the antigens recognized by T cells, the primary immune effector for destroying tumor cells.

Duke Scholars

Author Michael Aaron Morse Medicine, Medical Oncology

Author Herbert Kim Lyerly Surgery, Surgical Sciences