Daratumumab in combination with urelumab to potentiate anti-myeloma activity in lymphocyte-deficient mice reconstituted with human NK cells.

No Thumbnail Available

Date

2019-04-13

Authors

Ochoa, Maria C
Perez-Ruiz, Elisabeth
Minute, Luna
Oñate, Carmen
Perez, Guiomar
Rodriguez, Inmaculada
Zabaleta, Aintzane
Alignani, Diego
Fernandez-Sendin, Myriam
Lopez, Ascension

Advisors

Journal Title

Journal ISSN

Volume Title

Publisher

Metrics
Google Scholar
Export

Research Projects

Organizational Units

Journal Issue

Abstract

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.

Description

MeSH Terms

DeCS Terms

CIE Terms

Keywords

ADCC, CD137, NK cells, daratumumab, multiple myeloma

Citation