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EBV-transformed lymphoblastoid cell lines as vaccines against cancer testis antigen-positive tumors. 2013

Frank Neumann, and Dominic Kaddu-Mulindwa, and Thomas Widmann, and Klaus-Dieter Preuss, and Gerhard Held, and Carsten Zwick, and Klaus Roemer, and Michael Pfreundschuh, and Boris Kubuschok
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.

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.

UI MeSH Term Description Entries
D007371 Interferon-gamma The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES. Interferon Type II,Interferon, Immune,gamma-Interferon,Interferon, gamma,Type II Interferon,Immune Interferon,Interferon, Type II
D008545 Melanoma A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445) Malignant Melanoma,Malignant Melanomas,Melanoma, Malignant,Melanomas,Melanomas, Malignant
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D002461 Cell Line, Transformed Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals. Transformed Cell Line,Cell Lines, Transformed,Transformed Cell Lines
D004248 DNA (Cytosine-5-)-Methyltransferases Enzymes that catalyzes the transfer of a methyl group from S-ADENOSYLMETHIONINE to the 5-position of CYTOSINE residues in DNA. DNA (Cytosine-5-)-Methyltransferase,DNA Cytosine-5-Methylase,DNA (Cytosine 5) Methyltransferase,Cytosine-5-Methylase, DNA,DNA Cytosine 5 Methylase
D004854 Herpesvirus 4, Human The type species of LYMPHOCRYPTOVIRUS, subfamily GAMMAHERPESVIRINAE, infecting B-cells in humans. It is thought to be the causative agent of INFECTIOUS MONONUCLEOSIS and is strongly associated with oral hairy leukoplakia (LEUKOPLAKIA, HAIRY;), BURKITT LYMPHOMA; and other malignancies. Burkitt Herpesvirus,Burkitt Lymphoma Virus,E-B Virus,EBV,Epstein-Barr Virus,Human Herpesvirus 4,Infectious Mononucleosis Virus,Burkitt's Lymphoma Virus,HHV-4,Herpesvirus 4 (gamma), Human,Burkitts Lymphoma Virus,E B Virus,E-B Viruses,Epstein Barr Virus,Herpesvirus, Burkitt,Infectious Mononucleosis Viruses,Lymphoma Virus, Burkitt,Mononucleosis Virus, Infectious,Mononucleosis Viruses, Infectious
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006877 Hydroxamic Acids A class of weak acids with the general formula R-CONHOH. Hydroxamic Acid,Acid, Hydroxamic,Acids, Hydroxamic
D000076123 DNA (Cytosine-5-)-Methyltransferase 1 A DNA (cytosine-5-)-methyltransferase that contains a central CxxC type zinc finger motif. It binds poly(ADP)-ribose and its expression is regulated by POLY (ADP-RIBOSE) POLYMERASE-1. DNMT1 methylates CpG residues, with a preference for hemimethylated DNA, and associates with DNA replication sites in S PHASE to maintain the methylation pattern in the newly synthesized strand, which is essential for EPIGENETIC PROCESSES. It also associates with CHROMATIN during G2 PHASE and MITOSIS to maintain DNA methylation independently of replication. It is responsible for maintaining methylation patterns established in development; mutations in the DNMT1 gene are associated with HEREDITARY SENSORY NEUROPATHY TYPE 1 class E. DNMT1 Enzyme,Enzyme, DNMT1
D000077337 Vorinostat A hydroxamic acid and anilide derivative that acts as a HISTONE DEACETYLASE inhibitor. It is used in the treatment of CUTANEOUS T-CELL LYMPHOMA and SEZARY SYNDROME. 18F-SAHA,18F-Suberoylanilide Hydroxamic Acid,M344,MK-0683,MK0683,N-Hydroxy-N'-phenyloctanediamide,N1-Hydroxy-N8-phenyloctanediamide,NHNPODA,Suberanilohydroxamic Acid,Suberoyl Anilide Hydroxamic Acid,Suberoylanilide Hydroxamic Acid,Zolinza,18F Suberoylanilide Hydroxamic Acid,MK 0683,N Hydroxy N' phenyloctanediamide,N1 Hydroxy N8 phenyloctanediamide

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