title: EBV-transformed lymphoblastoid cell lines as vaccines against cancer testis antigen-positive tumors.
abstract: EBV-transformed lymphoblastoid cell lines (LCL) are potent antigen-presenting cells. To investigate their potential use as cancer testis antigen (CTA) vaccines, we studied the expression of 12 cancer testis (CT) genes in 20 LCL by RT-PCR. The most frequently expressed CT genes were SSX4 (50 %), followed by GAGE (45 %), SSX1 (40 %), MAGE-A3 and SSX2 (25 %), SCP1, HOM-TES-85, MAGE-C1, and MAGE-C2 (15 %). NY-ESO-1 and MAGE-A4 were found in 1/20 LCL and BORIS was not detected at all. Fifteen of 20 LCL expressed at least one antigen, 9 LCL expressed ≥2 CT genes, and 7 of the 20 LCL expressed ≥4 CT genes. The expression of CT genes did not correlate with the length of in vitro culture, telomerase activity, aneuploidy, or proliferation state. While spontaneous expression of CT genes determined by real-time PCR and Western blot was rather weak in most LCL, treatment with DNA methyltransferase 1 inhibitor alone or in combination with histone deacetylase inhibitors increased CTA expression considerably thus enabling LCL to induce CTA-specific T cell responses. The stability of the CT gene expression over prolonged culture periods makes LCL attractive candidates for CT vaccines both in hematological neoplasias and solid tumors.
authors.affiliation: Department of Internal Medicine I, José Carreras-Center for Immuno- and Gene Therapy, University of Saarland Medical School, 66421, Homburg, Saar, Germany, frank.neumann@uks.eu.
authors.forename: Frank
authors.initials: F
authors.lastname: Neumann
authors.forename: Dominic
authors.initials: D
authors.lastname: Kaddu-Mulindwa
authors.forename: Thomas
authors.initials: T
authors.lastname: Widmann
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Preuss
authors.forename: Gerhard
authors.initials: G
authors.lastname: Held
authors.forename: Carsten
authors.initials: C
authors.lastname: Zwick
authors.forename: Klaus
authors.initials: K
authors.lastname: Roemer
authors.forename: Michael
authors.initials: M
authors.lastname: Pfreundschuh
authors.forename: Boris
authors.initials: B
authors.lastname: Kubuschok
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology; D000951:Antigens, Neoplasm / Q000032:analysis*; D001374:Azacitidine / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology; D008545:Melanoma; D009369:Neoplasms / Q000628:therapy*; D012333:RNA, Messenger / Q000096:biosynthesis; D019098:Telomerase / Q000378:metabolism; D016615:Telomere; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014635:Valproic Acid / Q000494:pharmacology; D000077337:Vorinostat
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C012589:trichostatin A; D000077337:Vorinostat; D014635:Valproic Acid; D007371:Interferon-gamma; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D019098:Telomerase; D001374:Azacitidine