Survivin - a universal tumor antigen

Abstract

Tu m o r-associated antigens recognized by cellular effectors of the immune system are potential t a rgets for antigen-specific cancer immunotherapy. These antigens are classified as tissue (melanocy t e ) - s p e c i fic proteins, cancer-testis antigens (proteins expressed in normal testis and various cancers), tumorspecific peptides derived from mutations in tumor cells, and others. Clinical studies with peptides and proteins derived from these antigens have been initiated to study the effi c a cy of inducing specific cytotoxic T lymphocytes (CTL) responses in vivo. However, most of the peptide epitopes used in these vaccination trials are m e l a n o cy t e - s p e c i fic, and these peptides cannot be applied for tumors of non-melanocyte origin. Furthermore, the expression of most tumor antigens is heterogeneous among tumors from different patients and can even vary among metastases obtained from one patient. Immune selection of antigen loss variants may p r ove to be an additional obstacle for the clinical applicability of most of the known CTL epitopes. R e c e n t l y, a new tumor antigen, survivin, has been identified on the basis of spontaneous CTL responses in d i fferent cancer patients. Survivin is expressed in most human neoplasms, but not in normal, diff e r e n t i a t e d tissues. Importantly, dow n r egulation or loss of surviv i n would severely inflict the growth potential of the tumor cell. Since survivin is expressed by a variety of different tumors MHC-restricted survivin epitopes may serve as important and widely applicable targets for anti-cancer immunotherapeutic strategies.