title: Aberrant expression and potency as a cancer immunotherapy target of alpha-methylacyl-coenzyme A racemase in prostate cancer.
abstract: Alpha-methylacyl-CoA racemase (AMACR) is an enzyme playing an important role in the beta-oxidation of branched-chain fatty acids and fatty acid derivatives. High expression levels of AMACR have been described in various cancers, including prostate cancer, colorectal cancer and kidney cancer. Because of its cancer-specific and frequent expression, AMACR could be an attractive target for cytotoxic T-lymphocyte (CTL)-based immunotherapy for cancer. In the present study, we examined the induction of AMACR-specific CTLs from prostate cancer patients' peripheral blood mononuclear cells (PBMCs) and determined HLA-A24-restricted CTL epitopes.RT-PCR and immunohistochemical analysis revealed that AMACR was strongly expressed in prostate cancer cell lines and tissues as compared with benign or normal prostate tissues. Four AMACR-derived peptides carrying the HLA-A24-binding motif were synthesized from the amino acid sequence of this protein and analyzed to determine their binding affinities to HLA-A24. By stimulating patient's PBMCs with the peptides, specific CTLs were successfully induced in 6 of 11 patients. The peptide-specific CTLs exerted significant cytotoxic activity against AMACR-expressing prostate cancer cells in the context of HLA-A24. Our study demonstrates that AMACR could become a target antigen for prostate cancer immunotherapy, and that the AMACR-derived peptides might be good peptide vaccine candidates for HLA-A24-positive AMACR-expressing cancer patients.
authors.affiliation: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan. ichiya@sapmed.ac.jp
authors.forename: Ichiya
authors.initials: I
authors.lastname: Honma
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Torigoe
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirohashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitamura
authors.forename: Eiji
authors.initials: E
authors.lastname: Sato
authors.forename: Naoya
authors.initials: N
authors.lastname: Masumori
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Tamura
authors.forename: Taiji
authors.initials: T
authors.lastname: Tsukamoto
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D015234:HLA-A Antigens / Q000235:genetics / Q000378:metabolism; D059871:HLA-A24 Antigen; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000276:immunology / Q000628:therapy; D011485:Protein Binding; D019998:Racemases and Epimerases / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D000939:Epitopes; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D010455:Peptides; D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase