title: Identification of Novel HLA-A*24:02-Restricted Epitope Derived from a Homeobox Protein Expressed in Hematological Malignancies.
abstract: The homeobox protein, PEPP2 (RHOXF2), has been suggested as a cancer/testis (CT) antigen based on its expression pattern. However, the peptide epitope of PEPP2 that is recognized by cytotoxic T cells (CTLs) is unknown. In this study, we revealed that PEPP2 gene was highly expressed in myeloid leukemia cells and some other hematological malignancies. This gene was also expressed in leukemic stem-like cells. We next identified the first reported epitope peptide (PEPP2(271-279)). The CTLs induced by PEPP2(271-279) recognized PEPP2-positive target cells in an HLA-A*24:02-restricted manner. We also found that a demethylating agent, 5-aza-2'-deoxycytidine, could enhance PEPP2 expression in leukemia cells but not in blood mononuclear cells from healthy donors. The cytotoxic activity of anti-PEPP2 CTL against leukemic cells treated with 5-aza-2'-deoxycytidine was higher than that directed against untreated cells. These results suggest a clinical rationale that combined treatment with this novel antigen-specific immunotherapy together with demethylating agents might be effective in therapy-resistant myeloid leukemia patients.
authors.affiliation: Division of Clinical Physiology and Therapeutics, Keio University, Faculty of Pharmacy, Tokyo, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Matsushita
authors.affiliation: Division of Clinical Physiology and Therapeutics, Keio University, Faculty of Pharmacy, Tokyo, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Otsuka
authors.affiliation: Division of Clinical Physiology and Therapeutics, Keio University, Faculty of Pharmacy, Tokyo, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Tsutsumida
authors.affiliation: Division of Clinical Physiology and Therapeutics, Keio University, Faculty of Pharmacy, Tokyo, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Tanaka
authors.affiliation: Division of Clinical Physiology and Therapeutics, Keio University, Faculty of Pharmacy, Tokyo, Japan.
authors.forename: Akane
authors.initials: A
authors.lastname: Uchiumi
authors.affiliation: Division of Clinical Physiology and Therapeutics, Keio University, Faculty of Pharmacy, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ozawa
authors.affiliation: Division of Pharmacy, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Division of Clinical Physiology and Therapeutics, Keio University, Faculty of Pharmacy, Tokyo, Japan.
authors.forename: Daiju
authors.initials: D
authors.lastname: Ichikawa
authors.affiliation: Genome Science Laboratory Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.affiliation: Division of Hematology, Keio University, School of Medicine, Tokyo, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Okamoto
authors.affiliation: Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University, School of Medicine, Tokyo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kawakami
authors.affiliation: Division of Clinical Physiology and Therapeutics, Keio University, Faculty of Pharmacy, Tokyo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hattori
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D000077209:Decitabine; D000939:Epitopes / Q000276:immunology*; D059871:HLA-A24 Antigen / Q000276:immunology*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000378:metabolism
chemical_list: D000939:Epitopes; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen; D018398:Homeodomain Proteins; C471968:RHOXF2 protein, human; D000077209:Decitabine; D001374:Azacitidine