title: Cep55/c10orf3, a tumor antigen derived from a centrosome residing protein in breast carcinoma.
abstract: Identification of tumor-associated antigens may facilitate vaccination strategies to treat patients with malignant diseases. We have found that the centrosomal protein, Cep55/c10orf3 acts as a novel breast carcinoma-associated tumor-associated antigen. Cep55/c10orf3 mRNA was detectable in a wide variety of tumor cell lines. Expression was barely detectable in normal tissues except for testis and thymus. Moreover, Cep55/c10orf3 protein could be detected by a monoclonal anti-Cep55/c10orf3 antibody (# 11-55) in 69.8% of breast carcinoma, 25% of colorectal carcinoma, and 57.8% of lung carcinoma tissues. The expression of Cep55/c10orf3 protein did not show any relationship with the hormone receptors such as estrogen receptor and progesterone receptor or expression patterns of p185 HER2/neu. We designed 11 peptides which displayed a human leukocyte antigen-A24 binding motif. One Cep55/c10orf3-peptide, Cep55/c10orf3_193(10) (VYVKGLLAKI), induced cytotoxic T lymphocytes (CTLs) in 3 of 3 patients with Cep55/c10orf3 (# 11-55)-positive breast carcinoma. A Cep55/c10orf3_193(10)-specific CTL clone could also recognize Cep55/c10orf3 (+) displayed on human leukocyte antigen-A24 (+) cancer cell lines. These data indicate that Cep55/c10orf3 peptides were naturally presented by breast cancer cells and can cause CTL clonal expansion in vivo. Monoclonal antibody # 11-55 and the Cep55/c10orf3_193(10) peptides may be useful as part of a therapeutic strategy for hormonal therapy or anti-p185 HER2/neu monoclonal antibody therapy-resistant breast carcinoma patients.
authors.affiliation: Department of Pathology, Sapporo Medical University, School of Medicine, Chuo-Ku, Sapporo, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Inoda
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirohashi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Torigoe
authors.forename: Munehide
authors.initials: M
authors.lastname: Nakatsugawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Kiriyama
authors.forename: Emiri
authors.initials: E
authors.lastname: Nakazawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Harada
authors.forename: Hideo
authors.initials: H
authors.lastname: Takasu
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Tamura
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kamiguchi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Asanuma
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Tsuruma
authors.forename: Takeshi
authors.initials: T
authors.lastname: Terui
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Ishitani
authors.forename: Tosei
authors.initials: T
authors.lastname: Ohmura
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Mark I
authors.initials: MI
authors.lastname: Greene
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Sato
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology; D001943:Breast Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D018797:Cell Cycle Proteins / Q000276:immunology* / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism; D003001:Cloning, Molecular; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling; D045325:HCT116 Cells; D015234:HLA-A Antigens / Q000378:metabolism; D059871:HLA-A24 Antigen; D006801:Humans; D007150:Immunohistochemistry; D016233:Immunotherapy, Active; D020014:K562 Cells; D046228:Microarray Analysis; D009687:Nuclear Proteins / Q000276:immunology* / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs / Q000276:immunology; D021381:Protein Transport; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D000951:Antigens, Neoplasm; D018797:Cell Cycle Proteins; C505378:Cep55 protein, human; D015234:HLA-A Antigens; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen; D009687:Nuclear Proteins; D010446:Peptide Fragments