Generation of cytotoxic responses in mice and human individuals against hematological malignancies using survivin-RNA-transfected dendritic cells

被引:88
作者
Zeis, M
Siegel, S
Wagner, A
Schmitz, M
Marget, M
Kühl-Burmeister, R
Adamzik, I
Kabelitz, D
Dreger, P
Schmitz, N
Heiser, A
机构
[1] Gen Hosp St Georg, D-20099 Hamburg, Germany
[2] Univ Kiel, Inst Immunol, Kiel, Germany
[3] Univ Kiel, Inst Transfus Med, Kiel, Germany
[4] Carl Gustav Carus Tech Univ, Inst Immunol, Dresden, Germany
关键词
D O I
10.4049/jimmunol.170.11.5391
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
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收藏
页码:5391 / 5397
页数:7
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