التفاصيل البيبلوغرافية
| العنوان: |
NKG2D-CAR-transduced natural killer cells efficiently target multiple myeloma. |
| 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 Jr., Daniel J., Río, Paula, Martínez-López, Joaquín |
| المصدر: |
Blood Cancer Journal; Aug2021, Vol. 11 Issue 8, p1-11, 11p |
| مصطلحات موضوعية: |
KILLER cells, MULTIPLE myeloma, ANTINEOPLASTIC agents, T cells, CELLULAR therapy |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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