<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Non-viral nS/MAR DNA Vector-Based Genetic Modification of T Cells: Revolutionizing Adoptive Cell Therapies"^^ . "Adoptive cell therapies (ACT) employing Chimeric Antigen Receptors (CARs) or T cell receptors (TCRs), either personalized or off-the-shelf, have demonstrated promising results in cancer treatment. However, the current T cell engineering methods utilizing viral vectors face significant challenges due to their immunogenicity and potential for insertional mutagenesis. Furthermore, large-scale manufacturing of viral vectors is time-consuming and costly, posing obstacles for the application of CAR or TCR-transgenic T cells in personalized cancer immunotherapy with limited therapeutic windows.\r\nThis thesis uses an alternative non-viral genetic engineering approach of T cells with nano Scaffold/Matrix attachment region (nS/MAR) Vector technology, which holds potential for enhancing T cell-based therapies. These S/MAR DNA nanovectors, existing episomally and independent of antibiotic selection, offer numerous advantages over viral vectors. These benefits include cost-effectiveness, simplified manufacturing processes, reduced regulatory requirements, and the ability to modify T cells without the associated risk of mutagenesis while ensuring genetic transmission to daughter cells across unlimited cell divisions. Moreover, these vectors have no size limitations, facilitating the incorporation of larger transgenes, multiple expression cassettes, as well as desired gene regulatory and enhancer elements.\r\nMy work demonstrates the universal applicability of nS/MAR vectors for genetically modifying T cells in the field of ACT with broad applicability for CARs and TCRs transgenic receptors. nS/MAR vectors enable persistent reporter gene expression, such as GFP, in both cell lines and primary human T cells, without random integration or electroporation-induced cell toxicity. Furthermore, nS/MAR CAR-T cells exhibit comparable or superior anti-tumor efficacy to viral and other non-viral systems in several tumor models. Additionally, the versatility and efficacy of this technology in generating both off-the-shelf and patient-specific TCR-T cells were demonstrated in vitro. The platform also demonstrates potential in developing constructs with multiple expression cassettes, such as T cells redirected for antigen-unrestricted cytokine-initiated killing (TRUCKs), which enhance T cells with inducible cytokines, promising an improved therapeutic outcome in patients with brain tumor.\r\nFurthermore, this thesis investigates the potential translation of the nS/MAR technology into clinical applications. The developed streamlined manufacturing process reduces regulatory requirements, time and costs, as well as enhances safety, making personalized T cell therapies more accessible to patients with limited treatment windows, such as those with brain tumors.\r\nOverall, this platform represents an opportunity to improve patient outcomes and expand the application of non-viral CAR and TCR therapy in clinical practice."^^ . "2025" . . . . . . . "Alice"^^ . "De Roia"^^ . "Alice De Roia"^^ . . . . . . "Non-viral nS/MAR DNA Vector-Based Genetic Modification of T Cells: Revolutionizing Adoptive Cell Therapies (PDF)"^^ . . . "Non-viral nS/MAR DNA Vector-Based Genetic Modification of T Cells: Revolutionizing Adoptive Cell Therapies (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Non-viral nS/MAR DNA Vector-Based Genetic Modification of T Cells: Revolutionizing Adoptive Cell Therapies (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Non-viral nS/MAR DNA Vector-Based Genetic Modification of T Cells: Revolutionizing Adoptive Cell Therapies (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Non-viral nS/MAR DNA Vector-Based Genetic Modification of T Cells: Revolutionizing Adoptive Cell Therapies (Other)"^^ . . . . . . "small.jpg"^^ . . . "Non-viral nS/MAR DNA Vector-Based Genetic Modification of T Cells: Revolutionizing Adoptive Cell Therapies (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #34462 \n\nNon-viral nS/MAR DNA Vector-Based Genetic Modification of T Cells: Revolutionizing Adoptive Cell Therapies\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .