PMID- 19728337
OWN - NLM
STAT- MEDLINE
DCOM- 20100201
LR  - 20160303
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Linking)
VI  - 126
IP  - 4
DP  - 2010 Feb 15
TI  - Identification of HLA-A2- and A24-restricted T-cell epitopes derived from SOX6 
      expressed in glioma stem cells for immunotherapy.
PG  - 919-29
LID - 10.1002/ijc.24851 [doi]
AB  - 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.
FAU - Ueda, Ryo
AU  - Ueda R
AD  - Neuroimmunology Research Group, Keio University School of Medicine, Shinjuku-ku, 
      Tokyo, Japan.
FAU - Ohkusu-Tsukada, Kozo
AU  - Ohkusu-Tsukada K
FAU - Fusaki, Noemi
AU  - Fusaki N
FAU - Soeda, Akio
AU  - Soeda A
FAU - Kawase, Takeshi
AU  - Kawase T
FAU - Kawakami, Yutaka
AU  - Kawakami Y
FAU - Toda, Masahiro
AU  - Toda M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (Epitopes)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (HLA-A24 Antigen)
RN  - 0 (HLA-B Antigens)
RN  - 0 (Peptide Fragments)
RN  - 0 (SOX6 protein, human)
RN  - 0 (SOXD Transcription Factors)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Brain/immunology/pathology
MH  - Brain Neoplasms/epidemiology/immunology/pathology
MH  - Cell Survival/immunology
MH  - Epitopes/immunology
MH  - Female
MH  - Glioma/epidemiology/*immunology/pathology
MH  - HLA-A Antigens/genetics/*immunology
MH  - HLA-A2 Antigen/*immunology
MH  - HLA-A24 Antigen
MH  - HLA-B Antigens/genetics
MH  - Humans
MH  - Immunotherapy/methods
MH  - Male
MH  - Mice
MH  - Peptide Fragments/immunology
MH  - SOXD Transcription Factors/*genetics/*immunology
MH  - Stem Cells/*immunology
MH  - T-Lymphocytes/*immunology
MH  - T-Lymphocytes, Cytotoxic/immunology/pathology
MH  - United States/epidemiology
MH  - Young Adult
EDAT- 2009/09/04 06:00
MHDA- 2010/02/02 06:00
CRDT- 2009/09/04 06:00
PHST- 2009/09/04 06:00 [entrez]
PHST- 2009/09/04 06:00 [pubmed]
PHST- 2010/02/02 06:00 [medline]
AID - 10.1002/ijc.24851 [doi]
PST - ppublish
SO  - Int J Cancer. 2010 Feb 15;126(4):919-29. doi: 10.1002/ijc.24851.