Identification of novel MAGE-A6- and MAGE-A12-derived HLA-A24-restricted cytotoxic T lymphocyte epitopes using an in silico peptide-docking assay.
Many cancer-testis antigen genes have been identified; however, few human leukocyte antigen (HLA)-A24-restricted cytotoxic T cell (CTL) epitope peptides are available for clinical immunotherapy. To solve this problem, novel tools increasing the efficacy and accuracy of CTL epitope detection are needed. In the present study, we utilized a highly active dendritic cell (DC)-culture method and an in silico HLA-A24 peptide-docking simulation assay to identify novel CTL epitopes from MAGE-A6 and MAGE-A12 antigens. The highly active DCs, called α-type-1 DCs, were prepared using a combination of maturation reagents to produce a large amount of interleukin-12. Meanwhile, our HLA-A24 peptide-docking simulation assay was previously demonstrated to have an obvious advantage of accuracy over the conventional prediction tool, bioinformatics and molecular analysis section. For CTL induction assays, peripheral blood mononuclear cells derived from six cases of HLA-A24(+) melanoma were used. Through CTL induction against melanoma cell lines and peptide-docking simulation assays, two peptides (IFGDPKKLL from MAGE-A6 and IFSKASEYL from MAGE-A12) were identified as novel CTL epitope candidates. Finally, we verified that the combination of the highly active DC-culture method and HLA-A24 peptide-docking simulation assay might be tools for predicting CTL epitopes against cancer antigens.
Immunotherapy Division, Shizuoka Cancer Center Research Institute, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan. y.akiyama@scchr.jp
Yasuto
Y
Akiyama
Masaru
M
Komiyama
Yoji
Y
Nakamura
Akira
A
Iizuka
Chie
C
Oshita
Akiko
A
Kume
Masahiro
M
Nogami
Haruo
H
Miyata
Tadashi
T
Ashizawa
Shusuke
S
Yoshikawa
Yoshio
Y
Kiyohara
Ken
K
Yamaguchi
D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D005260:Female; D059871:HLA-A24 Antigen / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D008544:Melanocytes / Q000276:immunology / Q000378:metabolism; D008545:Melanoma / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology* / Q000378:metabolism; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D059871:HLA-A24 Antigen; C409589:MAGEA12 protein, human; C095203:MAGEA6 protein, human; D009363:Neoplasm Proteins; D010455:Peptides; D018664:Interleukin-12