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  1. Article ; Online: Miniaturized CAR knocked onto CD3ε extends TCR function with CAR specificity under control of endogenous TCR signaling cascade.

    Manske, Katrin / Dreßler, Lisa / Fräßle, Simon P / Effenberger, Manuel / Tschulik, Claudia / Cletiu, Vlad / Benke, Eileen / Wagner, Michaela / Schober, Kilian / Müller, Thomas R / Stemberger, Christian / Germeroth, Lothar / Busch, Dirk H / Poltorak, Mateusz P

    Journal of immunological methods

    2024  Volume 526, Page(s) 113617

    Abstract: Immunotherapy using TCR and especially CAR transgenic T cells is a rapidly advancing field with the potential to become standard of care for the treatment of multiple diseases. While all current FDA approved CAR T cell products are generated using ... ...

    Abstract Immunotherapy using TCR and especially CAR transgenic T cells is a rapidly advancing field with the potential to become standard of care for the treatment of multiple diseases. While all current FDA approved CAR T cell products are generated using lentiviral gene transfer, extensive work is put into CRISPR/Cas mediated gene delivery to develop the next generation of safer and more potent cell products. One limitation of all editing systems is the size restriction of the knock-in cargo. Targeted integration under control of an endogenous promotor and/or signaling cascades opens the possibility to reduce CAR gene size to absolute minimum. Here we demonstrate that a first-generation CAR payload can be reduced to its minimum component - the antigen-binding domain - by targeted integration under control of the CD3ε promoter generating a CAR-CD3ε fusion protein that exploits the endogenous TCR signaling cascade. Miniaturizing CAR payload in this way results in potent CAR activity while simultaneously retaining the primary antigen recognition function of the TCR. Introducing CAR-specificity using a CAR binder only while maintaining endogenous TCR function may be an appealing design for future autologous CAR T cell therapies.
    MeSH term(s) T-Lymphocytes ; Immunotherapy, Adoptive/methods ; Immunotherapy ; Receptors, Antigen, T-Cell
    Chemical Substances Receptors, Antigen, T-Cell
    Language English
    Publishing date 2024-01-11
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 120142-6
    ISSN 1872-7905 ; 0022-1759
    ISSN (online) 1872-7905
    ISSN 0022-1759
    DOI 10.1016/j.jim.2024.113617
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 795: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Interleukin-12/23 deficiency differentially affects pathology in male and female Alzheimer's disease-like mice.

    Eede, Pascale / Obst, Juliane / Benke, Eileen / Yvon-Durocher, Genevieve / Richard, Bernhard C / Gimber, Niclas / Schmoranzer, Jan / Böddrich, Annett / Wanker, Erich E / Prokop, Stefan / Heppner, Frank L

    EMBO reports

    2020  Volume 21, Issue 3, Page(s) e48530

    Abstract: Pathological aggregation of amyloid-β (Aβ) is a main hallmark of Alzheimer's disease (AD). Recent genetic association studies have linked innate immune system actions to AD development, and current evidence suggests profound gender differences in AD ... ...

    Abstract Pathological aggregation of amyloid-β (Aβ) is a main hallmark of Alzheimer's disease (AD). Recent genetic association studies have linked innate immune system actions to AD development, and current evidence suggests profound gender differences in AD pathogenesis. Here, we characterise gender-specific pathologies in the APP23 AD-like mouse model and find that female mice show stronger amyloidosis and astrogliosis compared with male mice. We tested the gender-specific effect of lack of IL12p40, the shared subunit of interleukin (IL)-12 and IL-23, that we previously reported to ameliorate pathology in APPPS1 mice. IL12p40 deficiency gender specifically reduces Aβ plaque burden in male APP23 mice, while in female mice, a significant reduction in soluble Aβ
    MeSH term(s) Alzheimer Disease/genetics ; Amyloid beta-Peptides/metabolism ; Amyloid beta-Protein Precursor/metabolism ; Animals ; Brain/metabolism ; Disease Models, Animal ; Female ; Interleukin-12/deficiency ; Interleukin-12/genetics ; Interleukin-12 Subunit p40/deficiency ; Interleukin-12 Subunit p40/genetics ; Interleukin-23 Subunit p19/deficiency ; Interleukin-23 Subunit p19/genetics ; Male ; Mice ; Mice, Transgenic ; Plaque, Amyloid
    Chemical Substances Amyloid beta-Peptides ; Amyloid beta-Protein Precursor ; Il12b protein, mouse ; Il23a protein, mouse ; Interleukin-12 Subunit p40 ; Interleukin-23 Subunit p19 ; Interleukin-12 (187348-17-0)
    Language English
    Publishing date 2020-01-30
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2020896-0
    ISSN 1469-3178 ; 1469-221X
    ISSN (online) 1469-3178
    ISSN 1469-221X
    DOI 10.15252/embr.201948530
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5433: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 41: Show issues

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  3. Article ; Online: Next generation automated traceless cell chromatography platform for GMP-compliant cell isolation and activation.

    Radisch, Sabine / Poltorak, Mateusz P / Wagner, Michaela / Cletiu, Vlad / Radisch, Christian / Treise, Irina / Pann, Steffi / Weigt, Alexis / Artner, Sophie / Dreher, Stefan / Fechner, Fabian / Borjan, Bojana / Fraessle, Simon P / Effenberger, Manuel / Benke, Eileen / Navratil, Gottfried / Hentschel, Norbert / Busch, Dirk H / Schmidt, Thomas /
    Stemberger, Christian / Germeroth, Lothar

    Scientific reports

    2022  Volume 12, Issue 1, Page(s) 6572

    Abstract: Large-scale target cell isolation from patient blood preparations is one of the critical operations during drug product manufacturing for personalized cell therapy in immuno-oncology. Use of high-affinity murine antibody coated magnetic nanoparticles ... ...

    Abstract Large-scale target cell isolation from patient blood preparations is one of the critical operations during drug product manufacturing for personalized cell therapy in immuno-oncology. Use of high-affinity murine antibody coated magnetic nanoparticles that remain on isolated cells is the current standard applied for this purpose. Here, we present the transformation of previously described technology - non-magnetic immunoaffinity column chromatography-based cell selection with reversible reagents into a new clinical-grade cell isolation platform called Automated Traceless Cell affinity chromatography (ATC). ATC is a fully closed and GMP-compliant cell selection and manufacturing system. Reversibility of reagents enables (sequential) positive cell selection, optionally in combination with depletion columns, enabling capture of highly specific cell subsets. Moreover, synergy with other Streptamer-based technologies allows novel uses beyond cell isolation including integrated and automated on-column target cell activation. In conclusion, ATC technology is an innovative as well as versatile platform to select, stimulate and modify cells for clinical manufacturing and downstream therapies.
    MeSH term(s) Animals ; Cell Separation/methods ; Chromatography ; Humans ; Mice
    Language English
    Publishing date 2022-04-21
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-10320-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: eQTL mapping of transposon silencing reveals a position-dependent stable escape from epigenetic silencing and transposition of AtMu1 in the Arabidopsis lineage.

    Kabelitz, Tina / Kappel, Christian / Henneberger, Kirstin / Benke, Eileen / Nöh, Christiane / Bäurle, Isabel

    The Plant cell

    2014  Volume 26, Issue 8, Page(s) 3261–3271

    Abstract: Transposons are massively abundant in all eukaryotic genomes and are suppressed by epigenetic silencing. Transposon activity contributes to the evolution of species; however, it is unclear how much transposition-induced variation exists at a smaller ... ...

    Abstract Transposons are massively abundant in all eukaryotic genomes and are suppressed by epigenetic silencing. Transposon activity contributes to the evolution of species; however, it is unclear how much transposition-induced variation exists at a smaller scale and how transposons are targeted for silencing. Here, we exploited differential silencing of the AtMu1c transposon in the Arabidopsis thaliana accessions Columbia (Col) and Landsberg erecta (Ler). The difference persisted in hybrids and recombinant inbred lines and was mapped to a single expression quantitative trait locus within a 20-kb interval. In Ler only, this interval contained a previously unidentified copy of AtMu1c, which was inserted at the 3' end of a protein-coding gene and showed features of expressed genes. By contrast, AtMu1c(Col) was intergenic and associated with heterochromatic features. Furthermore, we identified widespread natural AtMu1c transposition from the analysis of over 200 accessions, which was not evident from alignments to the reference genome. AtMu1c expression was highest for insertions within 3' untranslated regions, suggesting that this location provides protection from silencing. Taken together, our results provide a species-wide view of the activity of one transposable element at unprecedented resolution, showing that AtMu1c transposed in the Arabidopsis lineage and that transposons can escape epigenetic silencing by inserting into specific genomic locations, such as the 3' end of genes.
    MeSH term(s) Arabidopsis/genetics ; Arabidopsis/metabolism ; Chromosome Mapping ; DNA Transposable Elements/physiology ; Epigenesis, Genetic ; Gene Expression Regulation, Plant ; Gene Silencing ; Quantitative Trait Loci
    Chemical Substances DNA Transposable Elements
    Language English
    Publishing date 2014-08-05
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 623171-8
    ISSN 1532-298X ; 1040-4651
    ISSN (online) 1532-298X
    ISSN 1040-4651
    DOI 10.1105/tpc.114.128512
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Bonn / Germany

    Z 4952: Show issues

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  5. Article ; Online: eQTL mapping of transposon silencing reveals a position-dependent stable escape from epigenetic silencing and transposition of AtMu1 in the Arabidopsis lineage

    Kabelitz, Tina / Kappel, Christian / Henneberger, Kristin / Benke, Eileen / Nöh, Christiane / Bäurle, Isabel

    2014  

    Abstract: Transposons are massively abundant in all eukaryotic genomes and are suppressed by epigenetic silencing. Transposon activity contributes to the evolution of species; however, it is unclear how much transposition-induced variation exists at a smaller ... ...

    Abstract Transposons are massively abundant in all eukaryotic genomes and are suppressed by epigenetic silencing. Transposon activity contributes to the evolution of species; however, it is unclear how much transposition-induced variation exists at a smaller scale and how transposons are targeted for silencing. Here, we exploited differential silencing of the AtMu1c transposon in the Arabidopsis thaliana accessions Columbia (Col) and Landsberg erecta (Ler). The difference persisted in hybrids and recombinant inbred lines and was mapped to a single expression quantitative trait locus within a 20-kb interval. In Ler only, this interval contained a previously unidentified copy of AtMu1c, which was inserted at the 3′ end of a protein-coding gene and showed features of expressed genes. By contrast, AtMu1c(Col) was intergenic and associated with heterochromatic features. Furthermore, we identified widespread natural AtMu1c transposition from the analysis of over 200 accessions, which was not evident from alignments to the reference genome. AtMu1c expression was highest for insertions within 3′ untranslated regions, suggesting that this location provides protection from silencing. Taken together, our results provide a species-wide view of the activity of one transposable element at unprecedented resolution, showing that AtMu1c transposed in the Arabidopsis lineage and that transposons can escape epigenetic silencing by inserting into specific genomic locations, such as the 3′ end of genes.
    Keywords ddc:630
    Subject code 572
    Language English
    Publishing date 2014-08-05
    Publishing country de
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: eQTL mapping of transposon silencing reveals a position-dependent stable escape from epigenetic silencing and transposition of AtMu1 in the Arabidopsis lineage

    Kabelitz, Tina / Kappel, Christian / Henneberger, Kristin / Benke, Eileen / Nöh, Christiane / Bäurle, Isabel

    2014  

    Abstract: Transposons are massively abundant in all eukaryotic genomes and are suppressed by epigenetic silencing. Transposon activity contributes to the evolution of species; however, it is unclear how much transposition-induced variation exists at a smaller ... ...

    Abstract Transposons are massively abundant in all eukaryotic genomes and are suppressed by epigenetic silencing. Transposon activity contributes to the evolution of species; however, it is unclear how much transposition-induced variation exists at a smaller scale and how transposons are targeted for silencing. Here, we exploited differential silencing of the AtMu1c transposon in the Arabidopsis thaliana accessions Columbia (Col) and Landsberg erecta (Ler). The difference persisted in hybrids and recombinant inbred lines and was mapped to a single expression quantitative trait locus within a 20-kb interval. In Ler only, this interval contained a previously unidentified copy of AtMu1c, which was inserted at the 3′ end of a protein-coding gene and showed features of expressed genes. By contrast, AtMu1c(Col) was intergenic and associated with heterochromatic features. Furthermore, we identified widespread natural AtMu1c transposition from the analysis of over 200 accessions, which was not evident from alignments to the reference genome. AtMu1c expression was highest for insertions within 3′ untranslated regions, suggesting that this location provides protection from silencing. Taken together, our results provide a species-wide view of the activity of one transposable element at unprecedented resolution, showing that AtMu1c transposed in the Arabidopsis lineage and that transposons can escape epigenetic silencing by inserting into specific genomic locations, such as the 3′ end of genes.
    Keywords Text ; ddc:630
    Subject code 572
    Language English
    Publishing date 2014-08-05
    Publishing country de
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Arabidopsis

    Brzezinka, Krzysztof / Altmann, Simone / Czesnick, Hjördis / Nicolas, Philippe / Gorka, Michal / Benke, Eileen / Kabelitz, Tina / Jähne, Felix / Graf, Alexander / Kappel, Christian / Bäurle, Isabel

    eLife

    2016  Volume 5

    Abstract: Plants as sessile organisms can adapt to environmental stress to mitigate its adverse effects. As part of such adaptation they maintain an active memory of heat stress for several days that promotes a more efficient response to recurring stress. We show ... ...

    Abstract Plants as sessile organisms can adapt to environmental stress to mitigate its adverse effects. As part of such adaptation they maintain an active memory of heat stress for several days that promotes a more efficient response to recurring stress. We show that this heat stress memory requires the activity of the
    Language English
    Publishing date 2016-09-28
    Publishing country England
    Document type Journal Article
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.17061
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Distinct signal transduction pathways downstream of the (P)RR revealed by microarray and ChIP-chip analyses.

    Zaade, Daniela / Schmitz, Jennifer / Benke, Eileen / Klare, Sabrina / Seidel, Kerstin / Kirsch, Sebastian / Goldin-Lang, Petra / Zollmann, Frank S / Unger, Thomas / Funke-Kaiser, Heiko

    PloS one

    2013  Volume 8, Issue 3, Page(s) e57674

    Abstract: The (pro)renin receptor ((P)RR) signaling is involved in different pathophysiologies ranging from cardiorenal end-organ damage via diabetic retinopathy to tumorigenesis. We have previously shown that the transcription factor promyelocytic leukemia zinc ... ...

    Abstract The (pro)renin receptor ((P)RR) signaling is involved in different pathophysiologies ranging from cardiorenal end-organ damage via diabetic retinopathy to tumorigenesis. We have previously shown that the transcription factor promyelocytic leukemia zinc finger (PLZF) is an adaptor protein of the (P)RR. Furthermore, recent publications suggest that major functions of the (P)RR are mediated ligand-independently by its transmembrane and intracellular part, which acts as an accessory protein of V-ATPases. The transcriptome and recruitmentome downstream of the V-ATPase function and PLZF in the context of the (P)RR are currently unknown. Therefore, we performed a set of microarray and chromatin-immunoprecipitation (ChIP)-chip experiments using siRNA against the (P)RR, stable overexpression of PLZF, the PLZF translocation inhibitor genistein and the specific V-ATPase inhibitor bafilomycin to dissect transcriptional pathways downstream of the (P)RR. We were able to identify distinct and overlapping genetic signatures as well as novel real-time PCR-validated target genes of the different molecular functions of the (P)RR. Moreover, bioinformatic analyses of our data confirm the role of (P)RŔs signal transduction pathways in cardiovascular disease and tumorigenesis.
    MeSH term(s) Cardiovascular Diseases/genetics ; Cardiovascular Diseases/metabolism ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/metabolism ; Chromatin Immunoprecipitation ; Gene Expression Regulation/drug effects ; Genistein/pharmacology ; HEK293 Cells ; Humans ; Kruppel-Like Transcription Factors/antagonists & inhibitors ; Kruppel-Like Transcription Factors/genetics ; Kruppel-Like Transcription Factors/metabolism ; Macrolides/pharmacology ; Oligonucleotide Array Sequence Analysis ; Promyelocytic Leukemia Zinc Finger Protein ; Protein Kinase Inhibitors/pharmacology ; RNA, Small Interfering/genetics ; Receptors, Cell Surface/antagonists & inhibitors ; Receptors, Cell Surface/genetics ; Receptors, Cell Surface/metabolism ; Signal Transduction/drug effects ; Transcriptome ; Vacuolar Proton-Translocating ATPases/antagonists & inhibitors ; Vacuolar Proton-Translocating ATPases/genetics ; Vacuolar Proton-Translocating ATPases/metabolism
    Chemical Substances Kruppel-Like Transcription Factors ; Macrolides ; Promyelocytic Leukemia Zinc Finger Protein ; Protein Kinase Inhibitors ; RNA, Small Interfering ; Receptors, Cell Surface ; prorenin receptor ; ZBTB16 protein, human (147855-37-6) ; bafilomycin A1 (88899-55-2) ; Genistein (DH2M523P0H) ; Vacuolar Proton-Translocating ATPases (EC 3.6.1.-)
    Language English
    Publishing date 2013-03-04
    Publishing country United States
    Document type Journal Article
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0057674
    Database MEDical Literature Analysis and Retrieval System OnLINE

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