title: HER-2, gp100, and MAGE-1 are expressed in human glioblastoma and recognized by cytotoxic T cells.
abstract: It has recently been demonstrated that malignant glioma cells express certain known tumor-associated antigens, such as HER-2, gp100, and MAGE-1. To further determine the possible utilization of these antigens for glioma immunotherapy and as surrogate markers for specific tumor antigen cytotoxicity, we characterized the presence of mRNA and protein expression in 43 primary glioblastoma multiforme (GBM) cell lines and 7 established human GBM cell lines. HER-2, gp100, and MAGE-1 mRNA expression was detected in 81.4%, 46.5%, and 39.5% of the GBM primary cell lines, respectively. Using immunoreactive staining analysis by flow cytometry, HER-2, gp100, and MAGE-1 protein expression was detected in 76%, 45%, and 38% of the GBM primary cell lines, respectively. HLA-A1-restricted epitope specific for MAGE-1 peptide (EADPTGHSY) CTL clone B07 and HLA-A2-restricted epitope specific for HER-2 peptide (KIFGSLAFL) CTL clone A05 and gp100 peptide (ITDQVPFSV) CTL clone CK3H6 were used in this study. The specificity of CTL clone was verified by HLA/peptide tetramer staining. Three CTL clones could efficiently recognize GBM tumor cells in an antigen-specific and MHC class I-restricted manner. IFN-gamma treatment can dramatically increase MHC class I expression of GBM tumor cells and significantly increase CTL recognition of tumor cells. Treatment with the DNA hypomethylating agent 5-aza-2'-deoxycytidine induced and up-regulated the mRNA expression of MAGE-1 and epitope presentation by autologous MHC. These data indicate that HER-2, gp100, and MAGE-1 could be used as tumor antigen targets for surrogate assays for antigen-specific CTLs or to develop antigen-specific active immunotherapy strategies for glioma patients.
authors.affiliation: Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, 8631 West Third Street, Suite 800E, Los Angeles, CA 90048, USA.
authors.forename: Gentao
authors.initials: G
authors.lastname: Liu
authors.forename: Han
authors.initials: H
authors.lastname: Ying
authors.forename: Gang
authors.initials: G
authors.lastname: Zeng
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Wheeler
authors.forename: Keith L
authors.initials: KL
authors.lastname: Black
authors.forename: John S
authors.initials: JS
authors.lastname: Yu
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000951:Antigens, Neoplasm; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000276:immunology / Q000494:pharmacology; D001932:Brain Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D019175:DNA Methylation; D000077209:Decitabine; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D058950:Melanoma-Specific Antigens; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D058951:gp100 Melanoma Antigen
chemical_list: D000951:Antigens, Neoplasm; D001374:Azacitidine; D000077209:Decitabine; D018984:Epitopes, T-Lymphocyte; D007371:Interferon-gamma; D058950:Melanoma-Specific Antigens; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D058951:gp100 Melanoma Antigen; C072011:MAGEA1 protein, human; C548637:PMEL protein, human