Therapeutic effect of a T helper cell supported CTL response induced by a survivin peptide vaccine against murine cerebral glioma

Cancer Immunol Immunother. 2008 Dec;57(12):1827-35. doi: 10.1007/s00262-008-0510-9. Epub 2008 Apr 26.


Survivin is a tumor-associated antigen (TAA) that has significant potential for use as a cancer vaccine target. To identify survivin epitopes that might serve as targets for CTL-mediated, anti-tumor responses, we evaluated a series of survivin peptides with predicted binding to mouse H2-K(b) and human HLA-A*0201 antigens in peptide-loaded dendritic cell (DC) vaccines. H2-K(b)-positive, C57BL/6 mice were vaccinated using syngeneic, peptide-loaded DC2.4 cells. Splenocytes from vaccinated mice were screened by flow cytometry for binding of dimeric H2-K(b):Ig to peptide-specific CD8+ T cells. Two survivin peptides (SVN(57-64) and SVN(82-89)) generated specific CD8+ T cells. We chose to focus on the SVN(57-64) peptide because that region of the molecule is 100% homologous to human survivin. A larger peptide (SVN(53-67)), containing multiple class I epitopes, and a potential class II ligand, was able to elicit both CD8+ CTL and CD4+ T cell help. We tested the SVN(53-67) 15-mer peptide in a therapeutic model using a peptide-loaded DC vaccine in C57BL/6 mice with survivin-expressing GL261 cerebral gliomas. This vaccine produced significant CTL responses and helper T cell-associated cytokine production, resulting in a significant prolongation of survival. The SVN(53-67) vaccine was significantly more effective than the SVN(57-64) core epitope as a cancer vaccine, emphasizing the potential benefit of incorporating multiple class I epitopes and associated cytokine support within a single peptide.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms / immunology
  • Brain Neoplasms / therapy*
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Dendritic Cells / immunology
  • Dendritic Cells / transplantation
  • Epitopes, T-Lymphocyte / immunology
  • Flow Cytometry
  • Glioma / immunology
  • Glioma / therapy*
  • Histocompatibility Antigens / genetics
  • Histocompatibility Antigens / immunology
  • Inhibitor of Apoptosis Proteins
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microtubule-Associated Proteins / immunology*
  • Neoplasm Proteins / immunology*
  • Survivin
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Vaccines, Subunit / immunology
  • Vaccines, Subunit / therapeutic use


  • BIRC5 protein, human
  • Cancer Vaccines
  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Survivin
  • Vaccines, Subunit