000163255 001__ 163255
000163255 005__ 20251024172258.0
000163255 0247_ $$2doi$$a10.1080/2162402X.2025.2559782
000163255 0248_ $$2sideral$$a145772
000163255 037__ $$aART-2025-145772
000163255 041__ $$aeng
000163255 100__ $$aGiraldos, David
000163255 245__ $$aNK92 cells stably transfected with CD16 are efficient against multiple myeloma cells ex vivo and in vivo, especially if combined with daratumumab
000163255 260__ $$c2025
000163255 5060_ $$aAccess copy available to the general public$$fUnrestricted
000163255 5203_ $$aAdoptive cell therapy and the use of monoclonal antibodies are two therapeutic modalities implemented in the treatment of multiple myeloma (MM). In this study, we combined the anti-CD38 therapeutic mAb daratumumab with different types of NK cells, leveraging the antibody-dependent cell-mediated cytotoxicity (ADCC) performed by these immune cells. Daratumumab was initially combined with activated and expanded NK cells (eNK), resulting in significant cytotoxic activity against human MM cell lines. As an alternative model to minimize the variability among donors of NK cells, the NK92 cell line was used, which showed greater cytotoxic activity than eNK cells against MM cell lines. However, since NK92 cells lacked CD16 receptor expression, they could not be used in combination with mAbs. To circumvent this, we performed a CD16 transfection on NK92 cells, generating the stable NK92-CD16 cell line. These cells were tested in combination with daratumumab against human MM cell lines with excellent results under various conditions, such as 2D and 3D cultures, even at very low effector-to-target ratios. NK92-CD16 cells were then tested in the presence of daratumumab against plasma cells from MM patients, with anti-myeloma activity even against cells from relapsed patients. In vivo experiments using MM xenografts or intravenous injection of MM cells in NGS mice, followed by treatment with NK92-CD16 cells in the presence or absence of daratumumab showed tumor regressions, especially in the second model, with nearly complete elimination of the MM cells when NK92-CD16 cells were combined with daratumumab.
000163255 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B31-20R$$9info:eu-repo/grantAgreement/ES/DGA/B23-20R$$9info:eu-repo/grantAgreement/ES/MCIU/FPU17-02586$$9info:eu-repo/grantAgreement/ES/MICINN/PID2019-105128RB-I00$$9info:eu-repo/grantAgreement/ES/MICINN/PID2022-136799OB-I00
000163255 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc$$uhttps://creativecommons.org/licenses/by-nc/4.0/deed.es
000163255 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000163255 700__ $$aGalano-Frutos, Evelyn$$uUniversidad de Zaragoza
000163255 700__ $$aCambronero-Arregui, Laura$$uUniversidad de Zaragoza
000163255 700__ $$aBeltrán Visiedo, Manuel$$uUniversidad de Zaragoza
000163255 700__ $$aRomanos, Eduardo
000163255 700__ $$0(orcid)0000-0003-2683-0814$$aReina-Ortiz, Chantal
000163255 700__ $$0(orcid)0000-0001-5068-7355$$aAzaceta, Gemma$$uUniversidad de Zaragoza
000163255 700__ $$aMartínez-Lázaro, Beatriz
000163255 700__ $$aMenéndez-Jándula, Bárbara$$uUniversidad de Zaragoza
000163255 700__ $$aGarcía-Romero, Alejandro$$uUniversidad de Zaragoza
000163255 700__ $$aJiménez-Albericio, Francisco Javier$$uUniversidad de Zaragoza
000163255 700__ $$0(orcid)0000-0002-2315-9079$$aMarzo, Isabel$$uUniversidad de Zaragoza
000163255 700__ $$0(orcid)0000-0003-2156-8378$$aNaval, Javier$$uUniversidad de Zaragoza
000163255 700__ $$0(orcid)0000-0002-5175-8394$$aAnel, Alberto$$uUniversidad de Zaragoza
000163255 7102_ $$11011$$2770$$aUniversidad de Zaragoza$$bDpto. Microb.Ped.Radio.Sal.Pú.$$cÁrea Radiol. y Medicina Física
000163255 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000163255 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000163255 7102_ $$12004$$2390$$aUniversidad de Zaragoza$$bDpto. Física Teórica$$cÁrea Física Atóm.Molec.y Nucl.
000163255 7102_ $$11002$$2050$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Biología Celular
000163255 773__ $$g14, 1 (2025), 17$$pOncoimmunology$$tOncoImmunology$$x2162-4011
000163255 8564_ $$s4051399$$uhttps://zaguan.unizar.es/record/163255/files/texto_completo.pdf$$yVersión publicada
000163255 8564_ $$s1540913$$uhttps://zaguan.unizar.es/record/163255/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000163255 909CO $$ooai:zaguan.unizar.es:163255$$particulos$$pdriver
000163255 951__ $$a2025-10-24-16:55:52
000163255 980__ $$aARTICLE