PMID- 22707303 OWN - NLM STAT- MEDLINE DCOM- 20130507 LR - 20240426 IS - 1432-0851 (Electronic) IS - 0340-7004 (Print) IS - 0340-7004 (Linking) VI - 61 IP - 12 DP - 2012 Dec TI - Identification of novel MAGE-A6- and MAGE-A12-derived HLA-A24-restricted cytotoxic T lymphocyte epitopes using an in silico peptide-docking assay. PG - 2311-9 LID - 10.1007/s00262-012-1298-1 [doi] AB - 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 alpha-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. FAU - Akiyama, Yasuto AU - Akiyama Y AD - Immunotherapy Division, Shizuoka Cancer Center Research Institute, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan. y.akiyama@scchr.jp FAU - Komiyama, Masaru AU - Komiyama M FAU - Nakamura, Yoji AU - Nakamura Y FAU - Iizuka, Akira AU - Iizuka A FAU - Oshita, Chie AU - Oshita C FAU - Kume, Akiko AU - Kume A FAU - Nogami, Masahiro AU - Nogami M FAU - Miyata, Haruo AU - Miyata H FAU - Ashizawa, Tadashi AU - Ashizawa T FAU - Yoshikawa, Shusuke AU - Yoshikawa S FAU - Kiyohara, Yoshio AU - Kiyohara Y FAU - Yamaguchi, Ken AU - Yamaguchi K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120616 PL - Germany TA - Cancer Immunol Immunother JT - Cancer immunology, immunotherapy : CII JID - 8605732 RN - 0 (Antigens, Neoplasm) RN - 0 (Epitopes, T-Lymphocyte) RN - 0 (HLA-A24 Antigen) RN - 0 (MAGEA12 protein, human) RN - 0 (MAGEA6 protein, human) RN - 0 (Neoplasm Proteins) RN - 0 (Peptides) RN - 187348-17-0 (Interleukin-12) SB - IM MH - Antigens, Neoplasm/*immunology/metabolism MH - Cell Line, Tumor MH - Dendritic Cells/immunology/metabolism MH - Epitopes, T-Lymphocyte/*immunology/metabolism MH - Female MH - HLA-A24 Antigen/*immunology/metabolism MH - Humans MH - Interleukin-12/immunology/metabolism MH - Leukocytes, Mononuclear/immunology/metabolism MH - Male MH - Melanocytes/immunology/metabolism MH - Melanoma/immunology/metabolism MH - Middle Aged MH - Neoplasm Proteins/*immunology/metabolism MH - Peptides/*immunology/metabolism MH - T-Lymphocytes, Cytotoxic/*immunology/metabolism PMC - PMC11029329 COIS- The authors declare that they have no conflict of interest. EDAT- 2012/06/19 06:00 MHDA- 2013/05/08 06:00 PMCR- 2012/06/16 CRDT- 2012/06/19 06:00 PHST- 2011/10/27 00:00 [received] PHST- 2012/05/29 00:00 [accepted] PHST- 2012/06/19 06:00 [entrez] PHST- 2012/06/19 06:00 [pubmed] PHST- 2013/05/08 06:00 [medline] PHST- 2012/06/16 00:00 [pmc-release] AID - 1298 [pii] AID - 10.1007/s00262-012-1298-1 [doi] PST - ppublish SO - Cancer Immunol Immunother. 2012 Dec;61(12):2311-9. doi: 10.1007/s00262-012-1298-1. Epub 2012 Jun 16.