RT Journal Article
T1 Daratumumab in combination with urelumab to potentiate anti-myeloma activity in lymphocyte-deficient mice reconstituted with human NK cells.
A1 Ochoa, Maria C
A1 Perez-Ruiz, Elisabeth
A1 Minute, Luna
A1 Oñate, Carmen
A1 Perez, Guiomar
A1 Rodriguez, Inmaculada
A1 Zabaleta, Aintzane
A1 Alignani, Diego
A1 Fernandez-Sendin, Myriam
A1 Lopez, Ascension
A1 Muntasell, Aura
A1 Sanmamed, Miguel F
A1 Paiva, Bruno
A1 Lopez-Botet, Miguel
A1 Berraondo, Pedro
A1 Melero, Ignacio
K1 ADCC
K1 CD137
K1 NK cells
K1 daratumumab
K1 multiple myeloma
AB Daratumumab 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.
SN 2162-4011
YR 2019
FD 2019-04-13
LK https://hdl.handle.net/10668/26683
UL https://hdl.handle.net/10668/26683
LA en
DS RISalud
RD Apr 12, 2025