NKG2D-CAR-transduced natural killer cells efficiently target multiple myeloma
Author
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, JoaquínEntity
UAM. Departamento de PediatríaPublisher
Springer NatureDate
2021-08-14Citation
10.1038/s41408-021-00537-w
Blood Cancer Journal 11.8 (2021): 146
ISSN
2044-5385DOI
10.1038/s41408-021-00537-wFunded by
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).Project
Gobierno de España. PI18/01519Subjects
Cell Line, Tumor; Killer Cells, Natural; Mice, Inbred NOD; Multiple Myeloma; NK Cell Lectin-Like Receptor Subfamily K; MedicinaRights
© The Author(s) 2021Abstract
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.
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Google Scholar:Leivas, Alejandra
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Valeri, Antonio
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Córdoba, Laura
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García-Ortiz, Almudena
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Ortiz, Alejandra
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Sánchez-Vega, Laura
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Graña-Castro, Osvaldo
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Fernández, Lucía
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Carreño-Tarragona, Gonzalo
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Pérez, Manuel
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Megías, Diego
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Paciello, María Liz
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Sánchez-Pina, Jose
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Pérez Martínez, Antonio
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Lee, Dean A.
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Powell, Daniel J.
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Río, Paula
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Martínez-López, Joaquín
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