title: EphA2 as a glioma-associated antigen: a novel target for glioma vaccines.
abstract: EphA2 is a receptor tyrosine kinase and is frequently overexpressed in a wide array of advanced cancers. We demonstrate in the current study that the EphA2 protein is restrictedly expressed in primary glioblastoma multiforme and anaplastic astrocytoma tissues in comparison to normal brain tissues. To evaluate the possibility of targeting EphA2 in glioma vaccine strategies, we stimulated human leukocyte antigen (HLA) A2+ peripheral blood mononuclear cells (PBMCs) obtained from healthy donors and glioma patients with autologous dendritic cells (DCs) loaded with synthetic EphA2883-891 peptide (TLADFDPRV), which has previously been reported to induce interferon-gamma in HLA-A2+ PBMCs. Stimulated PBMCs demonstrated antigen-specific cytotoxic T lymphocyte (CTL) responses as detected by specific lysis of T2 cells loaded with the EphA2883 peptide as well as HLA-A2+ glioma cells, SNB19 and U251, that express EphA2. Furthermore, in vivo immunization of HLA-A2 transgenic HHD mice with the EphA2883-891 peptide resulted in the development of an epitope-specific CTL response in splenocytes, despite the fact that EphA2883-891 is an autoantigen in these mice. Taken together, these data suggest that EphA2883-891 may be an attractive antigen epitope for molecularly targeted glioma vaccines.
authors.affiliation: Department of Neurological Surgery, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.
authors.forename: Manabu
authors.initials: M
authors.lastname: Hatano
authors.forename: Junichi
authors.initials: J
authors.lastname: Eguchi
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tatsumi
authors.forename: Naruo
authors.initials: N
authors.lastname: Kuwashima
authors.forename: Jill E
authors.initials: JE
authors.lastname: Dusak
authors.forename: Michel S
authors.initials: MS
authors.lastname: Kinch
authors.forename: Ian F
authors.initials: IF
authors.lastname: Pollack
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Hamilton
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Storkus
authors.forename: Hideho
authors.initials: H
authors.lastname: Okada
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000276:immunology; D001932:Brain Neoplasms / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines / Q000494:pharmacology*; D045744:Cell Line, Tumor; D005909:Glioblastoma / Q000276:immunology* / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D036104:Receptor, EphA2 / Q000008:administration & dosage / Q000096:biosynthesis* / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015789:HLA-A2 Antigen; D036104:Receptor, EphA2