Anti-cancer vaccine candidates in specific immunotherapy for bladder carcinoma.
We have previously identified numerous tumor-rejection antigens and their epitope peptides having the potential to induce cancer-reactive cytotoxic T lymphocytes (CTLs) in patients with various types of cancer. In the present study, we attempted to determine which antigens and their peptides are useful in specific immunotherapy for bladder carcinoma (BC) patients, especially those with human leukocyte antigen (HLA)-A24+ alleles. The mRNA expression of a panel of cancer-associated antigens was examined regarding four BC cell lines. As a result, three candidate antigens, including SART3, multidrug resistance-associated protein 3 (MRP3), and polycomb group protein enhancer of zeste homolog 2 (EZH2), were expressed in three of four BC cell lines. Thereafter, antigen-derived peptides which we reported to induce cancer-reactive CTLs from HLA-A24+ patients with various types of cancer were examined for their potential to induce CTLs from peripheral-blood mononuclear cells of HLA-A24+ BC patients. Among these antigen-derived six peptides, SART3109-118, MRP31293-1301, and EZH2735-742 peptides efficiently induced peptide-specific and BC cell-reactive CTLs from HLA-A24+ BC patients. The cytotoxicity against BC cells was dependent on peptide-specific CD8+ T cells. IgG reactive to the SART3109-118 peptide was frequently detected in the plasma of BC patients. This information could facilitate the development of effective peptide-based immunotherapy for HLA-A24+ BC patients.
Komohara
Yoshihiro
Y
Cancer Vaccine Development Division, Kurume University Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan. ycomo@med.kurume-u.ac.jp
Harada
Mamoru
M
Arima
Yoshimi
Y
Suekane
Shigetaka
S
Noguchi
Masanori
M
Yamada
Akira
A
Itoh
Kyogo
K
Matsuoka
Kei
K
D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000276:immunology; D000071221:Enhancer of Zeste Homolog 2 Protein; D015234:HLA-A Antigens / Q000276:immunology*; D059871:HLA-A24 Antigen; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D016233:Immunotherapy, Active / Q000379:methods*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000276:immunology; D063151:Polycomb Repressive Complex 2; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D016601:RNA-Binding Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014157:Transcription Factors / Q000276:immunology; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000628:therapy*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D004268:DNA-Binding Proteins; D000071221:Enhancer of Zeste Homolog 2 Protein; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D007074:Immunoglobulin G; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D063151:Polycomb Repressive Complex 2; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C416530:SART3 protein, human; C114462:multidrug resistance-associated protein 3; C498409:EZH2 protein, human