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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Matthias Zeis - , Asklepios Klinik St. Georg (Author)
  • Sandra Siegel - , Asklepios Klinik St. Georg (Author)
  • Andreas Wagner - , Kiel University (Author)
  • Marc Schmitz - , Institute for Immunology, University Medicine (Faculty of Medicine and University Hospital) (Author)
  • Matthias Marget - , Kiel University (Author)
  • Rita Kühl-Burmeister - , Kiel University (Author)
  • Ilse Adamzik - , Kiel University (Author)
  • Dieter Kabelitz - , Kiel University (Author)
  • Peter Dreger - , Asklepios Klinik St. Georg (Author)
  • Norbert Schmitz - , Asklepios Klinik St. Georg (Author)
  • Axel Heiser - , Kiel University (Author)

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.

Details

Original languageEnglish
Pages (from-to)5391-5397
Number of pages7
JournalJournal of Immunology
Volume170
Issue number11
Publication statusPublished - 1 Jun 2003
Peer-reviewedYes

External IDs

PubMed 12759413

Keywords

Sustainable Development Goals

ASJC Scopus subject areas