Optimal Chimeric Antigen Receptor (CAR)-mRNA for Transient CAR T Cell Generation.

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Tác giả: Christian Bär, Ulrich Blache, Stephan Fricke, Reni Kitte, Ulrike Köhl, Selina Schrader, Claudius Seitz, Robert Serfling, U Sandy Tretbar

Ngôn ngữ: eng

Ký hiệu phân loại: 641.576 Dining car cooking

Thông tin xuất bản: Switzerland : International journal of molecular sciences , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 69435

Genetically modified T lymphocytes expressing chimeric antigen receptors (CARs) are becoming increasingly important in the treatment of hematologic malignancies and are also intensively being investigated for other diseases such as autoimmune disorders and HIV. Current CAR T cell therapies predominantly use viral transduction methods which, despite their efficacy, raise safety concerns related to genomic integration and potentially associated malignancies as well as labor- and cost-intensive manufacturing. Therefore, non-viral gene transfer methods, especially mRNA-based approaches, have attracted research interest due to their transient modification and enhanced safety profile. In this study, the optimization of CAR-mRNA for T cell applications is investigated, focusing on the impact of mRNA modifications, in vitro transcription protocols, and purification techniques on the translation efficiency and immunogenicity of mRNA. Furthermore, the refined CAR-mRNA was used to generate transient CAR T cells from acute myeloid leukemia patient samples, demonstrating efficacy in vitro and proof-of-concept for clinically relevant settings. These results highlight the potential of optimized mRNA to produce transient and safe CAR T cells.
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