Identification of a cytotoxic T lymphocyte response to the apoptosis inhibitor protein survivin in cancer patients

During the last decade, a large number of human tumor-associated antigens h ave been identified that are recognized by CTLs in a MHC-restricted fashion . The apoptosis inhibitor protein survivin is overexpressed in most human c ancers, and inhibition of its function results in increased apoptosis. Ther efore, this protein may serve as a target for therapeutic CTL responses. He re, using CTL epitopes deduced from survivin, we describe specific T-cell r eactivity against this antigen in peripheral blood from chronic lymphatic l eukemia patients and in tumor-infiltrated lymph nodes from melanoma patient s by ELISPOT analysis. CTL responses against two survivin-deduced peptide e pitopes were detected in three of six melanoma patients and three of four c hronic lymphatic leukemia patients. No T-cell reactivity was detected in pe ripheral blood lymphocytes from six healthy controls. Thus, survivin may se rve as an important and widely applicable target for anticancer immunothera peutic strategies.