Induction of protective and therapeutic antitumor immunity by a DNA vaccine with a glioma antigen, SOX6.
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.
Ueda
Ryo
R
Neuroimmunology Research Group, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan.
Kinoshita
Eiko
E
Ito
Rena
R
Kawase
Takeshi
T
Kawakami
Yutaka
Y
Toda
Masahiro
M
D000818:Animals; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005910:Glioma / Q000276:immunology* / Q000378:metabolism / Q000628:therapy*; D006609:High Mobility Group Proteins / Q000276:immunology* / Q000378:metabolism; D007167:Immunotherapy; D007564:Japan; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D010957:Plasmids / Q000008:administration & dosage; D055755:SOXD Transcription Factors; D015996:Survival Rate; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014157:Transcription Factors / Q000276:immunology* / Q000378:metabolism; D014611:Vaccination; D019444:Vaccines, DNA / Q000627:therapeutic use*
D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D055755:SOXD Transcription Factors; C095939:Sox6 protein, mouse; D014157:Transcription Factors; D019444:Vaccines, DNA