title: Generation of cytotoxic responses in mice and human individuals against hematological malignancies using survivin-RNA-transfected dendritic cells.
abstract: 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.
authors.affiliation: General Hospital St. Georg, Hamburg, Germany. mzeis47@hotmail.com
authors.forename: Matthias
authors.initials: M
authors.lastname: Zeis
authors.forename: Sandra
authors.initials: S
authors.lastname: Siegel
authors.forename: Andreas
authors.initials: A
authors.lastname: Wagner
authors.forename: Marc
authors.initials: M
authors.lastname: Schmitz
authors.forename: Matthias
authors.initials: M
authors.lastname: Marget
authors.forename: Rita
authors.initials: R
authors.lastname: Kühl-Burmeister
authors.forename: Ilse
authors.initials: I
authors.lastname: Adamzik
authors.forename: Dieter
authors.initials: D
authors.lastname: Kabelitz
authors.forename: Peter
authors.initials: P
authors.lastname: Dreger
authors.forename: Norbert
authors.initials: N
authors.lastname: Schmitz
authors.forename: Axel
authors.initials: A
authors.lastname: Heiser
mesh_terms: D000818:Animals; D001752:Blast Crisis / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D019496:Cancer Vaccines / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic / Q000235:genetics*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D020014:K562 Cells; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000627:therapeutic use; D009363:Neoplasm Proteins; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D012334:RNA, Neoplasm / Q000235:genetics / Q000627:therapeutic use*; D000077022:Survivin; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D014162:Transfection / Q000379:methods*; D014407:Tumor Cells, Cultured
chemical_list: C107489:BIRC5 protein, human; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D012334:RNA, Neoplasm; D000077022:Survivin