About: The development of chimeric antigen receptors for the immunotherapy of lymphoma.     Goto   Sponge   NotDistinct   Permalink

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Description
  • T cells will be obtained from the blood of patients with B-NHL and will be stimulated with anti-CD3/CD28 antibodies and transduced with CD20 CAR lentivirus. We will work out procedures for large-scale T cell cultivation under GMP quality settings and we will prepare Standard Operating Procedures for manipulation with genetically modified cells. After expansion in vitro we will test the T cells to eliminate autologous tumor cells in vitro and also in vivo using the immunodeficient mice transplanted with autologous patient-derived malignant B cells. We will characterize transduced T cells and we will carry out safety tests in vitro and in vivo according the requirements of SUKL. In the second part of the proposed project, we will perform detailed phenotypic analysis of B-NHL cells with a goal to select additional suitable surface antigens which could be targeted by CAR. We will prepare novel CAR's to these antigens and we will test them in vitro and in vivo using immunodeficient mice. (en)
  • T lymfocyty budou získány od pacientů s diagnózou B-NHL odběrem krve, stimulovány in vitro pomocí anti-CD3 a anti-CD28 protilátek a transdukovány lentivirem exprimujícím CD20 CAR. Vypracujeme postupy pro velkoobjemovou kultivaci T lymfocytů za podmínek Správné výrobní praxe a vypracujeme Standartní operační postupy pro manipulaci s geneticky modifikovanými buňkymi. Po expanzi in vitro bude testována schopnost transdukovaných T lymfocytů zabít autologní nádorové buňky in vitro nebo in vivo v imunodeficitních myších, které přihojily autologní maligní buňky B-NHL získané od pacientů. Provedeme charakterizaci transdukovaných T lymfocytů a nezbytné testy bezpečnosti in vitro a in vivo dle požadavků SÚKL. Dále, provedeme analýzu buněk B-NHL s cílem vytipovat další vhodné povrchové antigeny, které by mohly být cíleny pomocí CAR. Proti těmto antigenům připravíme nové CAR a otestujeme je in vitro a in vivo v imunodeficitních myších.
Title
  • The development of chimeric antigen receptors for the immunotherapy of lymphoma. (en)
  • Vývoj chimerických antigenních receptorů pro imunoterapii lymfomů.
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  • NT14030
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  • Cancer Immnutherapy; Cellular Therapy; Genetically Modified T cells; Chimeric Antigen Receptor; Lymphoma (en)
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  • Cellular Therapy
  • Chimeric Antigen Receptor
  • Genetically Modified T cells
  • Cancer Immnutherapy
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