Cancer Immunology, Immunotherapy

, Volume 57, Issue 12, pp 1827–1835

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

  • Michael J. Ciesielski
  • Danuta Kozbor
  • Carla A. Castanaro
  • Tara A. Barone
  • Robert A. Fenstermaker
Original Article

Abstract

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-Kb and human HLA-A*0201 antigens in peptide-loaded dendritic cell (DC) vaccines. H2-Kb-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-Kb:Ig to peptide-specific CD8+ T cells. Two survivin peptides (SVN57–64 and SVN82–89) generated specific CD8+ T cells. We chose to focus on the SVN57–64 peptide because that region of the molecule is 100% homologous to human survivin. A larger peptide (SVN53–67), 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 SVN53–67 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 SVN53–67 vaccine was significantly more effective than the SVN57–64 core epitope as a cancer vaccine, emphasizing the potential benefit of incorporating multiple class I epitopes and associated cytokine support within a single peptide.

Keywords

Dendritic cell Glioma Peptide Survivin Tumor antigen Vaccine 

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Michael J. Ciesielski
    • 1
    • 2
  • Danuta Kozbor
    • 2
  • Carla A. Castanaro
    • 1
  • Tara A. Barone
    • 1
  • Robert A. Fenstermaker
    • 1
  1. 1.Department of NeurosurgeryRoswell Park Cancer InstituteBuffaloUSA
  2. 2.Department of ImmunologyRoswell Park Cancer InstituteBuffaloUSA

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