Zeis Matthias, Siegel Sandra, Wagner Andreas, Schmitz Marc, Marget Matthias, Kühl-Burmeister Rita, Adamzik Ilse, Kabelitz Dieter, Dreger Peter, Schmitz Norbert, Heiser Axel
General Hospital St. Georg, Hamburg, Germany.
J Immunol. 2003 Jun 1;170(11):5391-7. doi: 10.4049/jimmunol.170.11.5391.
Survivin is a member of the inhibitors of apoptosis family and is overexpressed in many types of human cancers, making it an attractive target for T cell-based immunotherapeutic strategies. Recently, HLA-A2-binding peptides derived from the survivin protein were identified as capable of inducing specific T cell responses in cancer patients. Here we demonstrate that human survivin-specific CTLs generated from PBMC by stimulation with autologous dendritic cells transfected with survivin-RNA were cytotoxic for a range of hemopoietic malignant cell lines and primary tumor cells isolated from patients with acute myeloid leukemia. We also show that vaccination of mice with survivin-RNA-transfected dendritic cells leads to long term resistance to challenge by a survivin-expressing lymphoma, demonstrating the potential of survivin as a tumor rejection Ag. Our data provide evidence for the use of survivin as a target structure for immunotherapeutic strategies against hematological neoplasms.