The Human CD38 Monoclonal Antibody Daratumumab Shows Antitumor Activity and Hampers Leukemia-Microenvironment Interactions in Chronic Lymphocytic Leukemia.

ABSTRACT: Purpose: To establish a proof-of-concept for the efficacy of the anti-CD38 antibody daratumumab in the poor prognosis CD38⁺ chronic lymphocytic leukemia (CLL) subtype.Experimental Design: The mechanism of action of daratumumab was assessed in CLL primary cells and cell lines using peripheral blood mononuclear cells to analyze antibody-dependent cell cytotoxicity (ADCC), murine and human macrophages to study antibody-dependent cell phagocytosis (ADCP), or human serum to analyze complement-dependent cytotoxicity (CDC). The effect of daratumumab on CLL cell migration and adhesion to extracellular matrix was characterized. Daratumumab activity was validated in two in vivo models.Results: Daratumumab demonstrated efficient lysis of patient-derived CLL cell

SUBMITTER: Matas-Cespedes A 

PROVIDER: S-EPMC5354986 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature