Malignant gliomas are the most aggressive human
primary brain tumors and are currently incurable.
Immunotherapies have the potential to target
glioma and
glioma stem cells (GSCs) that are resistant to conventional
therapies. We previously identified SOX6 as a human
glioma antigen and demonstrated that vaccination with SOX6
DNA induced cytotoxic T lymphocytes (CTLs) specific for
glioma, thereby exerting therapeutic antitumor responses in
glioma-bearing mice. In this study, we attempted to identify SOX6-derived
peptides as specific targets for effective and safe T-cell-mediated
immunotherapy targeting SOX6-positive
glioma and GSCs. In vitro stimulation with
human leukocyte antigen (
HLA)-A*2402 (A24)-restricted
peptides, RFENLGPQL (SOX6(504)) and PYYEEQARL (SOX6(628)) or the
HLA-A*0201 (A2)-restricted
peptide, ALFGDQDTV (SOX6(447)) was capable of inducing SOX6
peptide-specific CTLs in peripheral blood mononuclear cells derived from healthy donors and
glioma patients. These CTLs were able to lyse a majority of
glioma cell lines and a GSC line derived from human
glioblastoma in an HLA Class I-restricted and an
antigen-dependent manner. Furthermore,
peptide vaccines of SOX6(628), which was conserved in the murine SOX6
protein and expected to bind to major histocompatibility complex (MHC) H-2(d), induced CTLs specific for SOX6(628) in H-2(d) mice. Normal autologous cells from mice, in which SOX6-specific immune responses were generated, were not destroyed. These results suggest that these SOX6
peptides are potnetially immunogenic in
HLA-A24 or -A2 positive
glioma patients and should be considered as a promising strategy for safe and effective T-cell-based
immunotherapy of patients with
gliomas.