Generation of survivin-specific CD8+ T effector cells by dendritic cells pulsed with protein or selected peptides

Cancer Res. 2000 Sep 1;60(17):4845-9.

Abstract

The identification of tumor-associated antigens recognized by CD8+ cytotoxic T cells paved the way to new concepts in adjuvant anticancer therapy. However, the number of tumor-associated proteins found to be expressed in the majority of human cancers is still rather limited. Recently, the newly identified apoptosis inhibitor protein survivin has been recognized as a widely occurring tumor-associated protein. In the present study, we demonstrate that survivin is capable of inducing specific CD8+ effector T cells in vitro. T cells from healthy donors were subjected to several cycles of stimulation by autologous dendritic cells (DCs) pulsed with soluble recombinant survivin protein. Activation of CD8+ cytotoxic T cells by survivin-derived peptides cross-presented by DCs was demonstrated by lysis of autologous survivin-expressing B cell transfectants. Using a peptide-motif scoring system, two survivin peptides (ELTLGE-FLKL and TLPPAWQPFL) were predicted and proved to bind to the HLA-A*0201 molecule. Both peptides were shown to induce CD8+ effector T cells when presented on DCs; one peptide could be verified to result from natural intracellular processing of survivin. These findings recommend survivin as a new and widely applicable target for protein- and peptide-based immunotherapy of tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigen Presentation / immunology
  • Cell Communication / immunology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Epitopes, T-Lymphocyte / immunology
  • HLA-A Antigens / immunology
  • HLA-A Antigens / metabolism
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Jurkat Cells
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Microtubule-Associated Proteins*
  • Neoplasm Proteins
  • Peptide Fragments / immunology*
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology
  • Proteins / immunology*
  • Proteins / metabolism
  • Survivin
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • BIRC5 protein, human
  • Epitopes, T-Lymphocyte
  • HLA-A Antigens
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Peptide Fragments
  • Proteins
  • Survivin