Induction of protective and therapeutic antitumor immunity by a DNA vaccine with a glioma antigen, SOX6

Int J Cancer. 2008 May 15;122(10):2274-9. doi: 10.1002/ijc.23366.

Abstract

We previously reported identifying SOX6 as a glioma antigen by serological screening using a testis cDNA library. Its preferential expression and frequent IgG responses in glioma patients indicate that SOX6 may be a useful target for immunotherapy. To examine whether cytotoxic T-lymphocyte (CTL) responses specific for SOX6 to destroy glioma can be generated in vivo, we treated glioma-bearing mice by vaccination with a plasmid DNA encoding murine full-length SOX6 protein. Following SOX6-DNA vaccination, CTLs specific for SOX6-expressing glioma cells were induced, while normal autologous-cells that had restrictedly expressed SOX6 during embryogenesis were not destroyed. Furthermore, DNA vaccination with SOX6 exerted protective and therapeutic antitumor responses in the glioma-bearing mice. This antitumor activity was abrogated by the depletion of CD4 positive T cells and/or CD8 positive T cells. These results suggest that the SOX6 protein has multiple CTL and helper epitopes to induce antitumor activity and the effectiveness of SOX6-DNA vaccine for the prevention and treatment of glioma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • DNA-Binding Proteins / immunology*
  • DNA-Binding Proteins / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glioma / immunology*
  • Glioma / metabolism
  • Glioma / therapy*
  • High Mobility Group Proteins / immunology*
  • High Mobility Group Proteins / metabolism
  • Immunotherapy*
  • Japan
  • Lymphocyte Depletion
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Plasmids / administration & dosage
  • SOXD Transcription Factors
  • Survival Rate
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transcription Factors / immunology*
  • Transcription Factors / metabolism
  • Vaccination
  • Vaccines, DNA / therapeutic use*

Substances

  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • SOXD Transcription Factors
  • Sox6 protein, mouse
  • Transcription Factors
  • Vaccines, DNA