Inhibitors spebrutinib (CC-292) and acalabrutinib (ACP-196) on macrophages´s phenotype and functions

FERNANDEZ GRECCO, HORACIO; GIORDANO, MIRTA N.; CABREJO, MARÍA; BLEJER, JORGELINA; CORDINI, GREGORIO; RISNIK, DENISE ; COLADO, ANA; BALBOA, LUCIANA; JANCIC. CAROLINA C.; GAMBERALE, ROMINA; MARÍN FRANCO, JOSÉ LUIS; SASIAIN, MARÍA DEL CARMEN; GENOULA, MELANIE; BEZARES, FERNANDO R.; ELÍAS, ESTEBAN ENRIQUE; GRASSI BASSINO, ALEJANDRA; VERGARA RUBIO, MARICEF; BORGE, MERCEDES

Mar del Plata

Congreso; 66 Reunión Anual de la Sociedad Argentina de Inmunología; 2018

SAI - SAIC

Ibrutinib is a first-in-class Btk inhibitor used in the treatment of Chronic Lymphocytic Leukemia (CLL). Besides its effects on leukemic B-cells, ibrutinib also affects functions on T cells, NK cells, and macrophages. Second generation Btk-inhibitors with higher selectivity have been developed and are being evaluated in clinical trials. Here we aimed to evaluate the effect of second-generation Btk inhibitors, spebrutinib, and acalabrutinib, on macrophages´ phenotype and functions.Macrophages were differentiated by culturing human monocytes with M-CSF. For M1 polarization GM-CSF+IFN-ɣ was used. Phagocytosis of CFSE labeled rituximab-coated CLL cells and M1/M2-associated markers were evaluated by flow cytometry. Glucose and lactate concentration in culture supernatants was determined using commercial kits and TNF-α secretion by ELISA. Statistical significance was determined using the Friedman test and the Dunn?s post-test.While we confirmed that ibrutinib reduces rituximab-coated CLL cells phagocytosis, we found that spebrutinib and acalabrutinib did not (n=7, p