Ochoa, Maria CPerez-Ruiz, ElisabethMinute, LunaOñate, CarmenPerez, GuiomarRodriguez, InmaculadaZabaleta, AintzaneAlignani, DiegoFernandez-Sendin, MyriamLopez, AscensionMuntasell, AuraSanmamed, Miguel FPaiva, BrunoLopez-Botet, MiguelBerraondo, PedroMelero, Ignacio2025-01-072025-01-072019-04-132162-4011https://hdl.handle.net/10668/26683Daratumumab is an anti-CD38 fully human IgG1 mAb approved for multiple myeloma treatment. One of the proposed mechanisms of action is the induction of antibody-dependent cellular cytotoxicity (ADCC) mediated by NK cells. NK cells acquire surface CD137 expression in the presence of solid-phase-attached daratumumab and when encountering a daratumumab-coated CD38+ tumor cell line. In this setting, addition of the agonist anti-CD137 mAb urelumab enhances NK-cell activation increasing CD25 expression and IFNɣ production. However, in vitro ADCC is not increased by the addition of urelumab both in 4h or 24h lasting experiments. To study urelumab-increased daratumumab-mediated ADCC activity in vivo, we set up a mouse model based on the intravenous administration of a luciferase-transfected multiple myeloma cell line of human origin, human NK cells and daratumumab to immuno-deficient NSG mice. In this model, intravenous administration of urelumab 24h after daratumumab delayed tumor growth and prolonged mice survival.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/ADCCCD137NK cellsdaratumumabmultiple myelomaresearch article31143521open access10.1080/2162402X.2019.1599636PMC6527281https://www.tandfonline.com/doi/pdf/10.1080/2162402X.2019.1599636?needAccess=truehttps://pmc.ncbi.nlm.nih.gov/articles/PMC6527281/pdf