dc.contributor.author | Leivas, Alejandra | |
dc.contributor.author | Valeri, Antonio | |
dc.contributor.author | Córdoba, Laura | |
dc.contributor.author | García-Ortiz, Almudena | |
dc.contributor.author | Ortiz, Alejandra | |
dc.contributor.author | Sánchez-Vega, Laura | |
dc.contributor.author | Graña-Castro, Osvaldo | |
dc.contributor.author | Fernández, Lucía | |
dc.contributor.author | Carreño-Tarragona, Gonzalo | |
dc.contributor.author | Pérez, Manuel | |
dc.contributor.author | Megías, Diego | |
dc.contributor.author | Paciello, María Liz | |
dc.contributor.author | Sánchez-Pina, Jose | |
dc.contributor.author | Pérez Martínez, Antonio | |
dc.contributor.author | Lee, Dean A. | |
dc.contributor.author | Powell, Daniel J. | |
dc.contributor.author | Río, Paula | |
dc.contributor.author | Martínez-López, Joaquín | |
dc.contributor.other | UAM. Departamento de Pediatría | es_ES |
dc.date.accessioned | 2022-11-04T12:50:52Z | |
dc.date.available | 2022-11-04T12:50:52Z | |
dc.date.issued | 2021-08-14 | |
dc.identifier.citation | Blood Cancer Journal 11.8 (2021): 146 | en_US |
dc.identifier.issn | 2044-5385 | es_ES |
dc.identifier.uri | http://hdl.handle.net/10486/704997 | |
dc.description.abstract | 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. | en_US |
dc.description.sponsorship | 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). | en_US |
dc.format.extent | 11 pag. | es_ES |
dc.format.mimetype | application/pdf | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Springer Nature | en_US |
dc.relation.ispartof | Blood Cancer Journal | en_US |
dc.rights | © The Author(s) 2021 | en_US |
dc.subject.other | Cell Line, Tumor | en_US |
dc.subject.other | Killer Cells, Natural | en_US |
dc.subject.other | Mice, Inbred NOD | en_US |
dc.subject.other | Multiple Myeloma | en_US |
dc.subject.other | NK Cell Lectin-Like Receptor Subfamily K | en_US |
dc.title | NKG2D-CAR-transduced natural killer cells efficiently target multiple myeloma | en_US |
dc.type | article | en_US |
dc.subject.eciencia | Medicina | es_ES |
dc.identifier.doi | 10.1038/s41408-021-00537-w | es_ES |
dc.identifier.publicationfirstpage | 146-1 | es_ES |
dc.identifier.publicationissue | 8 | es_ES |
dc.identifier.publicationlastpage | 146-11 | es_ES |
dc.identifier.publicationvolume | 11 | es_ES |
dc.relation.projectID | Gobierno de España. PI18/01519 | es_ES |
dc.type.version | info:eu-repo/semantics/publishedVersion | en_US |
dc.rights.cc | Reconocimiento | es_ES |
dc.rights.accessRights | openAccess | en_US |
dc.facultadUAM | Facultad de Medicina | es_ES |
dc.institutoUAM | Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD) | es_ES |