دورية أكاديمية
NKG2D-CAR-transduced natural killer cells efficiently target multiple myeloma
| العنوان: | NKG2D-CAR-transduced natural killer cells efficiently target multiple myeloma |
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| المؤلفون: | Leivas, Alejandra, Valeri, Antonio, Córdoba, Laura, García-Ortiz, Almudena, Ortiz, Alejandra, Sánchez-Vega, Laura, Graña-Castro, Osvaldo, Fernández, Lucía, Carreño-Tarragona, Gonzalo, Pérez, Manuel, Megías, Diego, Paciello, María Liz, Sánchez-Pina, Jose, Pérez Martínez, Antonio, Lee, Dean A., Powell, Daniel J., Río, Paula, Martínez-López, Joaquín |
| المساهمون: | UAM. Departamento de Pediatría |
| بيانات النشر: | Springer Nature |
| سنة النشر: | 2022 |
| المجموعة: | Universidad Autónoma de Madrid (UAM): Biblos-e Archivo |
| مصطلحات موضوعية: | Cell Line, Tumor, Killer Cells, Natural, Mice, Inbred NOD, Multiple Myeloma, NK Cell Lectin-Like Receptor Subfamily K, Medicina |
| الوصف: | CAR-T-cell therapy against MM currently shows promising results, but usually with serious toxicities. CAR-NK cells may exert less toxicity when redirected against resistant myeloma cells. CARs can be designed through the use of receptors, such as NKG2D, which recognizes a wide range of ligands to provide broad target specificity. Here, we test this approach by analyzing the antitumor activity of activated and expanded NK cells (NKAE) and CD45RA− T cells from MM patients that were engineered to express an NKG2D-based CAR. NKAE cells were cultured with irradiated Clone9.mbIL21 cells. Then, cells were transduced with an NKG2D-4-1BB-CD3z-CAR. CAR-NKAE cells exhibited no evidence of genetic abnormalities. Although memory T cells were more stably transduced, CAR-NKAE cells exhibited greater in vitro cytotoxicity against MM cells, while showing minimal activity against healthy cells. In vivo, CAR-NKAE cells mediated highly efficient abrogation of MM growth, and 25% of the treated mice remained disease free. Overall, these results demonstrate that it is feasible to modify autologous NKAE cells from MM patients to safely express a NKG2D-CAR. Additionally, autologous CAR-NKAE cells display enhanced antimyeloma activity demonstrating that they could be an effective strategy against MM supporting the development of NKG2D-CAR-NK-cell therapy for MM. ; This study was supported by a grant from the Spanish Society for Hematology and Hemotherapy to Alejandra Leivas, the CRIS Foundation to Beat Cancer and the Instituto de Salud Carlos III (PI18/01519). |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2044-5385 |
| العلاقة: | Blood Cancer Journal; Gobierno de España. PI18/01519; Blood Cancer Journal 11.8 (2021): 146; http://hdl.handle.net/10486/704997Test; 146-1; 146-11; 11 |
| DOI: | 10.1038/s41408-021-00537-w |
| الإتاحة: | https://doi.org/10.1038/s41408-021-00537-wTest http://hdl.handle.net/10486/704997Test |
| حقوق: | © The Author(s) 2021 ; Reconocimiento ; openAccess |
| رقم الانضمام: | edsbas.D3696D7B |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20445385 |
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| DOI: | 10.1038/s41408-021-00537-w |