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  1. AU="Huberty, Fanny"
  2. AU="Ju, Beomsoo"
  3. AU="Yu, Jessica"
  4. AU="Yamada, Hiroyuki"
  5. AU="Uruski, Pawel"
  6. AU="Laranjeiro, Ricardo"
  7. AU="Ahmadi, Reza"
  8. AU="Hoet, Peter H.M."
  9. AU=Sengupta Sohini AU=Sengupta Sohini
  10. AU="Conlon, Dara"
  11. AU=Endeman Henrik AU=Endeman Henrik
  12. AU="New, Sophie E.P"

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  1. Artikel: Efficient shRNA-based knockdown of multiple target genes for cell therapy using a chimeric miRNA cluster platform.

    Rossi, Matteo / Steklov, Mikhail / Huberty, Fanny / Nguyen, Thuy / Marijsse, Jérôme / Jacques-Hespel, Céline / Najm, Paul / Lonez, Caroline / Breman, Eytan

    Molecular therapy. Nucleic acids

    2023  Band 34, Seite(n) 102038

    Abstract: Genome engineering technologies are powerful tools in cell-based immunotherapy to optimize or fine-tune cell functionalities. However, their use for multiple gene edits poses relevant biological and technical challenges. Short hairpin RNA (shRNA)-based ... ...

    Abstract Genome engineering technologies are powerful tools in cell-based immunotherapy to optimize or fine-tune cell functionalities. However, their use for multiple gene edits poses relevant biological and technical challenges. Short hairpin RNA (shRNA)-based cell engineering bypasses these criticalities and represents a valid alternative to CRISPR-based gene editing. Here, we describe a microRNA (miRNA)-based multiplex shRNA platform obtained by combining highly efficient miRNA scaffolds into a chimeric cluster, to deliver up to four shRNA-like sequences. Thanks to its limited size, our cassette could be deployed in a one-step process along with all the CAR components, streamlining the generation of engineered CAR T cells. The plug-and-play design of the shRNA platform allowed us to swap each shRNA-derived guide sequence without affecting the system performance. Appropriately choosing the target sequences, we were able to either achieve a functional KO, or fine-tune the expression levels of the target genes, all without the need for gene editing. Through our strategy we achieved easy, safe, efficient, and tunable modulation of multiple target genes simultaneously. This approach allows for the effective introduction of multiple functionally relevant tweaks in the transcriptome of the engineered cells, which may lead to increased performance in challenging environments, e.g., solid tumors.
    Sprache Englisch
    Erscheinungsdatum 2023-09-20
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2662631-7
    ISSN 2162-2531
    ISSN 2162-2531
    DOI 10.1016/j.omtn.2023.102038
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Overcoming Target Driven Fratricide for T Cell Therapy.

    Breman, Eytan / Demoulin, Benjamin / Agaugué, Sophie / Mauën, Sebastien / Michaux, Alexandre / Springuel, Lorraine / Houssa, Julien / Huberty, Fanny / Jacques-Hespel, Céline / Marchand, Céline / Marijsse, Jérôme / Nguyen, Thuy / Ramelot, Nancy / Violle, Benjamin / Daro, Dorothée / De Waele, Peter / Gilham, David E / Steenwinckel, Valérie

    Frontiers in immunology

    2018  Band 9, Seite(n) 2940

    Abstract: Chimeric Antigen Receptor (CAR) T cells expressing the fusion of the NKG2D protein with CD3ζ (NKG2D-CAR T Cells) acquire a specificity for stress-induced ligands expressed on hematological and solid cancers. However, these stress ligands are also ... ...

    Abstract Chimeric Antigen Receptor (CAR) T cells expressing the fusion of the NKG2D protein with CD3ζ (NKG2D-CAR T Cells) acquire a specificity for stress-induced ligands expressed on hematological and solid cancers. However, these stress ligands are also transiently expressed by activated T cells implying that NKG2D-based T cells may undergo self-killing (fratricide) during cell manufacturing or during the freeze thaw cycle prior to infusion in patients. To avoid target-driven fratricide and enable the production of NKG2D-CAR T cells for clinical application, two distinct approaches were investigated. The first focused upon the inclusion of a Phosphoinositol-3-Kinase inhibitor (LY294002) into the production process. A second strategy involved the inclusion of antibody blockade of NKG2D itself. Both processes impacted T cell fratricide, albeit at different levels with the antibody process being the most effective in terms of cell yield. While both approaches generated comparable NKG2D-CAR T cells, there were subtle differences, for example in differentiation status, that were fine-tuned through the phasing of the inhibitor and antibody during culture in order to generate a highly potent NKG2D-CAR T cell product. By means of targeted inhibition of NKG2D expression or generic inhibition of enzyme function, target-driven CAR T fratricide can be overcome. These strategies have been incorporated into on-going clinical trials to enable a highly efficient and reproducible manufacturing process for NKG2D-CAR T cells.
    Mesh-Begriff(e) Antibodies, Blocking/immunology ; Antibodies, Blocking/pharmacology ; Cell Line, Tumor ; Cell Survival/drug effects ; Cells, Cultured ; Chromones/pharmacology ; Cytotoxicity, Immunologic/drug effects ; Cytotoxicity, Immunologic/immunology ; Enzyme Inhibitors/pharmacology ; Humans ; Immunotherapy, Adoptive/methods ; K562 Cells ; Ligands ; Morpholines/pharmacology ; NK Cell Lectin-Like Receptor Subfamily K/antagonists & inhibitors ; NK Cell Lectin-Like Receptor Subfamily K/immunology ; NK Cell Lectin-Like Receptor Subfamily K/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphoinositide-3 Kinase Inhibitors ; Receptors, Antigen, T-Cell/immunology ; Receptors, Antigen, T-Cell/metabolism ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism
    Chemische Substanzen Antibodies, Blocking ; Chromones ; Enzyme Inhibitors ; KLRK1 protein, human ; Ligands ; Morpholines ; NK Cell Lectin-Like Receptor Subfamily K ; Phosphoinositide-3 Kinase Inhibitors ; Receptors, Antigen, T-Cell ; 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (31M2U1DVID)
    Sprache Englisch
    Erscheinungsdatum 2018-12-12
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2018.02940
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.

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