Recognition of tumor-associated antigens by T-lymphocytes: perspectives for peptide-based vaccines.

Over the last 10 years, studies of T-cell-mediated responses in vitro have clearly demonstrated that some cancer patients have (mainly but not exclusively) CD8 cytolytic T-lymphocytes (CTL) that can recognize specifically autologous tumor cells [1]. Until 1991, however, no CTL-defined tumor antigen was characterized in molecular terms in humans. With the development of new approaches based on recent advances in our basic understanding of the processes involved in antigen recognition by T-cells [2, 3] the past 5 years have witnessed the molecular definition of more than a dozen human tumor antigens recognized by CD8 T-cells. While studies in murine tumor model systems suggested that peptides derived from mutated gene products would be the primary candidates for tumor antigens recognized by CTL [4-7], most of the human tumor-associated antigens defined thus far are derived from normal (non-mutated) proteins. Since these antigens have been identified by virtue of their recognition by autologous CTL clones, it is now evident that the field of tumor immunology is more closely related to autoimmunity (or immune recognition of serf proteins) than to immune responses to foreign antigens. In this review, we first discuss the strategies used to identify tumor-associated, CTL-defined peptide antigens. We then describe some of the antigens that are currently considered as potential targets for peptide-based vaccines. Finally, we briefly summarize the first attempts to elicit specific CTL responses in cancer patients with such vaccines.