Prostate-related antigen-derived new peptides having the capacity of inducing prostate cancer-reactive CTLs in HLA-A2+ prostate cancer patients.
Prostate-related antigens, including prostate-specific membrane antigen (PSMA) and prostatic acid phosphatase (PAP), can be targets in specific immunotherapy for prostate cancer. In this study, we attempted to newly identify epitope peptides from these 2 antigens, which are immunogenic in human histocompatibility leukocyte antigen (HLA)-A2+ prostate cancer patients. Twenty-nine peptides (PSMA with 15 and PAP with 14) were prepared based on the HLA-A2 binding motif. Based on our previous finding that antigenic peptides recognized by both cellular and humoral immune systems are useful for peptide-based immunotherapy, peptide candidates were screened first by their ability to be recognized by immunoglobulin G (IgG), and then by their ability to induce peptide-specific cytotoxic T lymphocytes (CTLs). As a result, PSMA441-450 and PAP112-120 peptides were found to be frequently recognized by IgG in plasma from prostate cancer patients. These 2 candidates effectively induced HLA-A2-restricted and prostate cancer-reactive CTLs in HLA-A2+ prostate cancer patients with several HLA-A2 subtypes. In addition, their cytotoxicity was mainly dependent on peptide-specific and CD8+ T cells. These results indicate that these PSMA441-450 and PAP112-120 peptides could be promising candidates for peptide-based immunotherapy for HLA-A2(+) prostate cancer.
Harada
Mamoru
M
Department of Immunology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan. haramamo@med.kurume-u.ac.jp
Matsueda
Satoko
S
Yao
Akihisa
A
Ogata
Rika
R
Noguchi
Masanori
M
Itoh
Kyogo
K
D000483:Alleles; D000954:Antigens, Surface / Q000737:chemistry*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry; D043425:Glutamate Carboxypeptidase II / Q000737:chemistry*; D015789:HLA-A2 Antigen / Q000096:biosynthesis*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D007167:Immunotherapy / Q000379:methods*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*; D013997:Time Factors
D000954:Antigens, Surface; D000939:Epitopes; D015789:HLA-A2 Antigen; D007074:Immunoglobulin G; D010455:Peptides; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II