Generation of cytotoxic responses in mice and human individuals against hematological malignancies using survivin-RNA-transfected dendritic cells.
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.
Zeis
Matthias
M
General Hospital St. Georg, Hamburg, Germany. mzeis47@hotmail.com
Siegel
Sandra
S
Wagner
Andreas
A
Schmitz
Marc
M
Marget
Matthias
M
Kühl-Burmeister
Rita
R
Adamzik
Ilse
I
Kabelitz
Dieter
D
Dreger
Peter
P
Schmitz
Norbert
N
Heiser
Axel
A
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
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