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: Matthias Zeis, Sandra Siegel, Andreas Wagner, Marc Schmitz, Matthias Marget, Rita Kühl-Burmeister, Ilse Adamzik, Dieter Kabelitz, Peter Dreger, Norbert Schmitz, Axel Heiser
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 170 Issue 11 Pg. 5391-7 (Jun 01 2003) ISSN: 0022-1767 [Print] United States
• PMID: 12759413 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BIRC5 protein, human
• Cancer Vaccines
• Epitopes, T-Lymphocyte
• Inhibitor of Apoptosis Proteins
• Microtubule-Associated Proteins
• Neoplasm Proteins
• Peptide Fragments
• RNA, Neoplasm
• Survivin

Topics

• Animals
• Blast Crisis (immunology, metabolism, pathology, therapy)
• Cancer Vaccines (biosynthesis, genetics, therapeutic use)
• Cell Death (genetics, immunology)
• Cell Line
• Clone Cells
• Cytotoxicity, Immunologic (genetics)
• Dendritic Cells (immunology, metabolism, transplantation)
• Epitopes, T-Lymphocyte (immunology)
• Humans
• Inhibitor of Apoptosis Proteins
• K562 Cells
• Leukemia, Lymphocytic, Chronic, B-Cell (immunology, metabolism, pathology, therapy)
• Leukemia, Myeloid, Acute (immunology, metabolism, pathology, therapy)
• Lymphocyte Activation (genetics)
• Mice
• Mice, Inbred BALB C
• Microtubule-Associated Proteins (biosynthesis, genetics, therapeutic use)
• Neoplasm Proteins
• Peptide Fragments (genetics, metabolism, therapeutic use)
• RNA, Neoplasm (genetics, therapeutic use)
• Survivin
• T-Lymphocytes, Cytotoxic (immunology, metabolism, transplantation)
• Transfection (methods)
• Tumor Cells, Cultured