Spontaneous cytotoxic T-cell responses against survivin-derived MHC class I-restricted T-cell epitopes in situ as well as ex vivo in cancer patients

Recent advances in therapeutic tumor vaccinations necessitate the identific ation of broadly expressed, immunogenic tumor antigens that are not prone t o immune selection. To this end, the human inhibitor of apoptosis, survivin , is a prime candidate because it is expressed in most human neoplasms but not in normal, differentiated tissues. Here, we demonstrate spontaneous cyt otoxic T-cell responses against survivin-derived MHC class I-restricted T-c ell epitopes in breast cancer, leukemia, and melanoma patients both in situ as well as ex vivo. Moreover, survivin-reactive T cells isolated by magnet ic beads coated with MHC/peptide complexes were cytotoxic against HLA-match ed tumors of different tissue types. Being a universal tumor antigen, survi vin may serve as a widely applicable target for anticancer immunotherapy.