In situ programming of leukaemia-specific T cells using synthetic DNA nanocarriers
Autor: | Smitha P. S. Pillai, Diana Reiman, Weihang Ji, Laura E. McKnight, Howell F. Moffett, Tyrel T. Smith, Martin E. Wohlfahrt, Matthias Stephan, Sirkka B. Stephan, Emmy Bonagofski |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Computer science T-Lymphocytes Biomedical Engineering Bioengineering Nanotechnology 02 engineering and technology Computational biology Mice 03 medical and health sciences Synthetic DNA Cell Line Tumor On demand medicine Animals Nanobiotechnology General Materials Science Electrical and Electronic Engineering Drug Carriers Immunity Cellular Leukemia Receptors Chimeric Antigen Gene Transfer Techniques Cancer DNA 021001 nanoscience & nanotechnology Condensed Matter Physics medicine.disease Atomic and Molecular Physics and Optics Chimeric antigen receptor 030104 developmental biology Cell culture Disease remission Nanoparticles Nanocarriers 0210 nano-technology |
Zdroj: | Nature Nanotechnology. 12:813-820 |
ISSN: | 1748-3395 1748-3387 |
DOI: | 10.1038/nnano.2017.57 |
Popis: | An emerging approach for treating cancer involves programming patient-derived T cells with genes encoding disease-specific chimeric antigen receptors (CARs), so that they can combat tumour cells once they are reinfused. Although trials of this therapy have produced impressive results, the in vitro methods they require to generate large numbers of tumour-specific T cells are too elaborate for widespread application to treat cancer patients. Here, we describe a method to quickly program circulating T cells with tumour-recognizing capabilities, thus avoiding these complications. Specifically, we demonstrate that DNA-carrying nanoparticles can efficiently introduce leukaemia-targeting CAR genes into T-cell nuclei, thereby bringing about long-term disease remission. These polymer nanoparticles are easy to manufacture in a stable form, which simplifies storage and reduces cost. Our technology may therefore provide a practical, broadly applicable treatment that can generate anti-tumour immunity 'on demand' for oncologists in a variety of settings. |
Databáze: | OpenAIRE |
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