title: Identification of bladder cancer antigens recognized by IgG antibodies of a patient with metastatic bladder cancer.
abstract: To identify tumor antigens useful for the diagnosis and treatment of patients with bladder cancer, a lambda phage cDNA library constructed from a high-grade bladder cancer cell line was screened with autologous serum from a patient with metastatic bladder cancer. Forty-eight distinct antigens were isolated. By evaluating the immunogenicity and the tissue-specific expression, KU-BL-1 and KU-BL-2 were identified as immunogenic antigens with restricted tissue expression. KU-BL-1 was found to be a putative human lipoic acid synthetase with a metal-binding site, CXXXCXXC, that was expressed in bladder cancer cell lines and most bladder cancer tissues, as well as normal bladder mucosa and testis tissues. Immunoglobulin (Ig)G antibody to KU-BL-1 was detected in 2 of 28 patients with bladder cancer, but not in 30 healthy individuals. KU-BL-2 was found to be a putative human kelch-like protein that was homologous to Drosophila kelch, with a BTB/POZ domain and kelch repeats. KU-BL-2 was expressed in bladder cancer cell lines, most bladder cancer tissues, testis and heart, but not in normal bladder mucosa. IgG antibody to KU-BL-2 was detected in 8 of 28 patients with bladder cancer, but not in 16 healthy individuals. Tumor reactive T cells were induced from peripheral blood mononuclear cells (PBMC) by stimulation with one of the HLA-A24 binding KU-BL-2 peptides. Therefore, KU-BL-1 and KU-BL-2, which showed preferential expression in bladder cancer with restricted expression in normal tissues, as well as immunogenicity in multiple patients with bladder cancer, may be useful for the development of diagnostic and therapeutic methods for patients with bladder cancer.
authors.affiliation: Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University, School of Medicine, Tokyo, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ito
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Fujita
authors.forename: Masanori
authors.initials: M
authors.lastname: Akada
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kiniwa
authors.forename: Makoto
authors.initials: M
authors.lastname: Tsukamoto
authors.forename: Aiko
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Matsuzaki
authors.forename: Maiko
authors.initials: M
authors.lastname: Matsushita
authors.forename: Takako
authors.initials: T
authors.lastname: Asano
authors.forename: Jun
authors.initials: J
authors.lastname: Nakashima
authors.forename: Masaaki
authors.initials: M
authors.lastname: Tachibana
authors.forename: Masamichi
authors.initials: M
authors.lastname: Hayakawa
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ikeda
authors.forename: Masaru
authors.initials: M
authors.lastname: Murai
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kawakami
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D000912:Antibodies, Neoplasm / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000302:isolation & purification*; D001483:Base Sequence; D018076:DNA, Complementary / Q000302:isolation & purification; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008969:Molecular Sequence Data; D019042:Muscle Neoplasms / Q000276:immunology / Q000556:secondary; D009362:Neoplasm Metastasis / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000276:immunology*
chemical_list: D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D018076:DNA, Complementary; D007074:Immunoglobulin G; C481808:KU-BL-1 antigen, human; C481809:KU-BL-2 antigen, human