Macrophages are required for anti-CD19 mAb mediated B cell depletion in mice (50.16)

Abstract

Abstract Anti-CD20 mediated B cell depletion is an effective treatment for rheumatoid arthritis. An anti-CD19 mAb is under investigation as a new B cell depleting reagent. Studies have demonstrated that the interaction between the mAb Fc and Fc? receptors on effector cells is important for efficient target cell depletion. To enhance effector function, the anti-CD19 mAb was engineered with BioWa's Potelligent® technology to remove fucose from the Fc portion. The fucose-free mAb has increased affinity to human FCγRIIIa and mouse FCγRIV as well as improved cytotoxicity. The fucose-free anti-CD19 antibody (anti-CD19-aFuc) depleted >90% of murine B cells in human CD19 Transgenic mice. Further studies were carried out to investigate the mechanisms of action of anti-CD19-aFuc. B cell depletion was not affected in mice which were treated with to deplete NK cells or neutrophils. Similarly, depletion of B cells was not impaired in mice in which complement activation was blocked. In contrast, B cell depletion by anti-CD19-aFuc was significantly inhibited in mice in which macrophages were eliminated. Furthermore, anti-CD19-aFuc showed robust activity in an antibody dependent cellular phagocytosis assay with freshly isolate mouse macrophages as effector cells. These results suggest that anti-CD19-aFuc depletes B cells in mice through a macrophage dependent mechanism. This study is funded by MedImmune, LLC.