NK92 cells stably transfected with CD16 are efficient against multiple myeloma cells ex vivo and in vivo, especially if combined with daratumumab
Giraldos, David ; Galano-Frutos, Evelyn (Universidad de Zaragoza) ; Cambronero-Arregui, Laura (Universidad de Zaragoza) ; Beltrán Visiedo, Manuel (Universidad de Zaragoza) ; Romanos, Eduardo ; Reina-Ortiz, Chantal ; Azaceta, Gemma (Universidad de Zaragoza) ; Martínez-Lázaro, Beatriz ; Menéndez-Jándula, Bárbara (Universidad de Zaragoza) ; García-Romero, Alejandro (Universidad de Zaragoza) ; Jiménez-Albericio, Francisco Javier (Universidad de Zaragoza) ; Marzo, Isabel (Universidad de Zaragoza) ; Naval, Javier (Universidad de Zaragoza) ; Anel, Alberto (Universidad de Zaragoza)
Resumen: Adoptive 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.
Idioma: Inglés
DOI: 10.1080/2162402X.2025.2559782
Año: 2025
Publicado en: OncoImmunology 14, 1 (2025), 17
ISSN: 2162-4011
Financiación: info:eu-repo/grantAgreement/ES/DGA/B31-20R
Financiación: info:eu-repo/grantAgreement/ES/DGA/B23-20R
Financiación: info:eu-repo/grantAgreement/ES/MCIU/FPU17-02586
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2019-105128RB-I00
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2022-136799OB-I00
Tipo y forma: Article (Published version)
Área (Departamento): Área Radiol. y Medicina Física (Dpto. Microb.Ped.Radio.Sal.Pú.)
Área (Departamento): Area Medicina (Dpto. Medicina, Psiqu. y Derm.)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)
Área (Departamento): Área Física Atóm.Molec.y Nucl. (Dpto. Física Teórica)
Área (Departamento): Área Biología Celular (Dpto. Bioq.Biolog.Mol. Celular)
You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not use the material for commercial purposes.
Exportado de SIDERAL (2025-10-24-16:55:52)
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Idioma: Inglés
DOI: 10.1080/2162402X.2025.2559782
Año: 2025
Publicado en: OncoImmunology 14, 1 (2025), 17
ISSN: 2162-4011
Financiación: info:eu-repo/grantAgreement/ES/DGA/B31-20R
Financiación: info:eu-repo/grantAgreement/ES/DGA/B23-20R
Financiación: info:eu-repo/grantAgreement/ES/MCIU/FPU17-02586
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2019-105128RB-I00
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2022-136799OB-I00
Tipo y forma: Article (Published version)
Área (Departamento): Área Radiol. y Medicina Física (Dpto. Microb.Ped.Radio.Sal.Pú.)
Área (Departamento): Area Medicina (Dpto. Medicina, Psiqu. y Derm.)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)
Área (Departamento): Área Física Atóm.Molec.y Nucl. (Dpto. Física Teórica)
Área (Departamento): Área Biología Celular (Dpto. Bioq.Biolog.Mol. Celular)
You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. You may not use the material for commercial purposes. Exportado de SIDERAL (2025-10-24-16:55:52)
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Este artículo se encuentra en las siguientes colecciones:
Articles > Artículos por área > Física Atómica, Molecular y Nuclear
Articles > Artículos por área > Bioquímica y Biología Molecular
Articles > Artículos por área > Radiología y Medicina Física
Articles > Artículos por área > biologia_celular
Articles > Artículos por área > Medicina
Record created 2025-10-24, last modified 2025-10-24