Nonfucosylated rituximab potentiates human neutrophil phagocytosis through its high binding for FcgammaRIIIb and MHC class II expression on the phagocytotic neutrophils.

OBJECTIVE: Antibody-dependent cellular cytotoxicity mediated by natural killer cells via leukocyte receptor IIIa (FcgammaRIIIa) is greatly enhanced by the absence of the core fucose of Fc oligosaccharides, and is closely related to the clinical efficacy of anticancer processes in humans in vivo. Here, we focused on the physiological functions of nonfucosylated anti-CD20 IgG1 rituximab, in particular those functions mediated by human neutrophils, which highly express FcgammaRIIIb, a highly homologous FcgammaR to FcgammaRIIIa.
MATERIALS AND METHODS: After treatment with anti-CD20, the response of neutrophils to fluorescently labeled CD20(+) B-cell lymphoma in human whole blood was quantitatively analyzed by measuring their activities of antibody-dependent phagocytosis and major histocompatibility complex (MHC) class II expression on the phagocytotic neutrophils using flow cytometry.
RESULTS: In human whole blood, most of the added CD20(+) B-cell lymphoma died shortly, within 4 hours, irrespective of the presence or absence of anti-CD20. Neutrophils were not directly concerned in the death because depletion of neutrophils from human whole blood did not affect the phenomenon. However, neutrophils aggressively phagocytosed newly dead lymphoma cells, and the nonfucosylated anti-CD20 effectively enhanced neutrophil phagocytosis solely by enhancing binding for the phagocytosis coreceptor FcgammaRIIIb. Noteworthy, more increased expression of MHC class II was also observed on the phagocytotic neutrophils than those observed on spontaneous and fucosylated anti-CD20 stimulated phagocytotic neutrophils.
CONCLUSIONS: Our data showed that antibody therapy composed of nonfucosylated rituximab can activate human neutrophil functions involving phagocytosis and MHC class II expression, which may favorably potentiate the adaptive immune response in cancer patients.