Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human testis, primary myeloma cell and normal tissue samples to identify novel cancer-testis genes

ABSTRACT: Cancer-testis (CT) antigens are attractive targets for immunotherapeutic strategies since they are aberrantly expressed in malignant cells and not, or in limited number, in somatic tissues, except germ cells. To identify novel CT genes in multiple myeloma, we used Affymetrix HG-U133 gene expression profiles of 5 testis, 64 primary myeloma cell (MMC) and 24 normal tissue (NT) samples. A 5-filter method was developed to keep known CT genes while deleting non-CT-restricted genes. Starting from 44928 probe sets, including probe sets for 18 known CT genes, we have obtained 82 genes expressed in MMC and testis and not detected in more than 6 NT. This list includes 14 of the 18 known CT genes and 68 novel putative CT genes. Real-time RT-PCR was performed for 34 genes in 12 NT, 3 testis and 5 MMC samples and has validated the CT status of 23/34 genes (67%). We found one novel testis-restricted gene (expression in testis and tumor only) TEX14 , 8 tissue-restricted (mRNA detected in 1 or 2 non-gametogenic tissues), and 7 differentially expressed (mRNA detected in three to six non-gametogenic tissues) CT genes. Further studies are warranted to determine the immunogenicity of these novel CT antigen candidates.

ORGANISM(S): Homo sapiens

SUBMITTER: Matthieu Schoenhals

PROVIDER: E-MTAB-81 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Inhibition of aurora kinases for tailored risk-adapted treatment of multiple myeloma.

Hose Dirk D Rème Thierry T Meissner Tobias T Moreaux Jérôme J Seckinger Anja A Lewis Joe J Benes Vladimir V Benner Axel A Hundemer Michael M Hielscher Thomas T Shaughnessy John D JD Barlogie Bart B Neben Kai K Krämer Alwin A Hillengass Jens J Bertsch Uta U Jauch Anna A De Vos John J Rossi Jean-François JF Möhler Thomas T Blake Jonathon J Zimmermann Jürgen J Klein Bernard B Goldschmidt Hartmut H

Blood 20090126 18

Genetic instability and cellular proliferation have been associated with aurora kinase expression in several cancer entities, including multiple myeloma. Therefore, the expression of aurora-A, -B, and -C was determined by Affymetrix DNA microarrays in 784 samples including 2 independent sets of 233 and 345 CD138-purified myeloma cells from previously untreated patients. Chromosomal aberrations were assessed by comprehensive interphase fluorescence in situ hybridization and proliferation of prima ...[more]

PMID: 19171872

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Project description:Background Clinical success of T cell receptor (TCR) gene therapy has previously been demonstrated for NY-ESO-1 TCR gene therapy. To increase numbers of cancer patients that can be treated with TCR gene therapy we aimed to identify a novel set of high-affinity cancer specific TCRs targeting different cancer testis (CT) antigens in prevalent HLA class I alleles. Methods In this study, we selected based on publicly available gene expression databases the most promising CT genes to target. From these selected genes we identified by HLA peptidomics the naturally processed and presented HLA class I peptides. With these peptide-HLA tetramers were generated, and by single cell sorting CT specific CD8+ T cells were selected, and expanded from the allo-HLA repertoire of healthy donors. By several functional assays high avidity CT-specific T cell clones with safe recognition pattern were selected. To evaluate the potential for clinical application in TCR gene therapy, TCRs were sequenced and transferred into peripheral blood derived CD8+ T cells. Results In total we identified, 7 novel CT-specific TCRs that effectively target MAGE-A1, MAGE-A3, MAGE-A6 and MAGE-A9 in the context of human leukocyte antigen(HLA) -A1, -A2, -A3, -B7, -B35 and -C7. TCR gene transfer into CD8⁺ T cells resulted in efficient cytokine production and cytotoxicity of variety of different tumor types without detectable cross-reactivity. In addition, major in vivo antitumor effects of MAGE-A1 specific TCR engineered CD8⁺ T cells was observed in an orthotopic xenograft model for established multiple myeloma, in which bone marrow located tumor cells were completely eradicated after T cell injection. Conclusion The identification of 7 novel CT-specific TCRs, reactive against CT antigens presented in a variety of different HLA class I alleles, allows selection of therapeutic TCRs for an increased number of cancer patients, and will improve development of personalized TCR gene therapy.

Project description:Uhlén2015 - Human tissue-based proteome metabolic network - testis Human testis specific proteome metabolic network This model is described in the article: Tissue-based map of the human proteome Uhlén M, Fagerberg L, Hallström BM, Lindskog C, Oksvold P, Mardinoglu A, Sivertsson Å, Kampf C, Sjöstedt E, Asplund A, Olsson I, Edllund K, Lundberg E, Navani S, Szigyarto AC, Odeberg J, Djureinovic D, Takanen JO, Hober S, Alm T, Edqvist P, Berlin H, Tegel H, Mulder J, Rockberg J, Nilsson P, Schwenk JM, Hamsten M, von Feilitzen K, Forsberg M, Persson L, Johansson F, Zwahlen M, von Heijne G, Nielsen J, Pontén F. Science 2015 January; 347(6220) Abstract: Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray–based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body. This model is hosted on BioModels Database and identified by: MODEL1411240018. To cite BioModels Database, please use: BioModels: ten-year anniversary . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

Transcription profiling of human testis, primary myeloma cell and normal tissue samples to identify novel cancer-testis genes

Publications

Inhibition of aurora kinases for tailored risk-adapted treatment of multiple myeloma.

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