title: Identification of an epitope derived from CML66, a novel tumor-associated antigen expressed broadly in human leukemia, recognized by human leukocyte antigen-A*2402-restricted cytotoxic T lymphocytes.
abstract: CML66 is a newly identified differentiation antigen that is expressed broadly in human leukemia and solid tumors, but its physiological function remains unknown. In the present study, to clarify the feasibility of CML66-targeted cancer immunotherapy, we attempted to identify cytotoxic T lymphocyte (CTL) epitopes derived from CML66. An immunogenic CML66-derived epitope (amino acid residues 76-84; YYIDTLGRI) capable of inducing human leukocyte antigen (HLA)-A*2402-restricted CTL specific for this peptide was identified. CML66-derived peptide-specific CTL efficiently lysed human leukemia cells, but not normal cells, in a HLA-A*2402-restricted fashion. Quantitative real-time polymerase chain reaction revealed that CML66 mRNA is expressed abundantly in primary acute myeloid leukemia cells, acute lymphoid leukemia cells, and chronic myelogenous leukemia cells in advanced phase, and that the expression level of CML66 mRNA in normal cells is low compared with that in leukemia cells. CML66-specific CTL precursors were detected in the peripheral blood of patients with acute leukemia. These data indicate that the CML66-derived epitope identified in the present study is a new target antigen for cellular immunotherapy of human leukemia.
authors.affiliation: Department of Bioregulatory Medicine, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Suemori
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Toshiki
authors.initials: T
authors.lastname: Ochi
authors.forename: Taichi
authors.initials: T
authors.lastname: Azuma
authors.forename: Jun
authors.initials: J
authors.lastname: Yamanouchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Narumi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yakushijin
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hato
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Masaki
authors.initials: M
authors.lastname: Yasukawa
mesh_terms: D018952:Antigens, CD34 / Q000032:analysis; D000951:Antigens, Neoplasm / Q000276:immunology*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D015234:HLA-A Antigens / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D007938:Leukemia / Q000276:immunology* / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D018952:Antigens, CD34; D000951:Antigens, Neoplasm; D000939:Epitopes; D015234:HLA-A Antigens; C431278:NUDCD1 protein, human