Rituximab-IgG2 is a phagocytic enhancer in antibody-based immunotherapy of B-cell lymphoma by altering CD47 expression.

Antibody-dependent cellular phagocytosis (ADCP) by monocytes and macrophages contributes significantly to the efficacy of many therapeutic monoclonal antibodies (mAbs), including anti-CD20 rituximab (RTX) targeting CD20 B-cell non-Hodgkin lymphomas (NHL). However, ADCP is constrained by various immune checkpoints, notably the anti-phagocytic CD47 molecule, necessitating strategies to overcome this resistance. We have previously shown that the IgG2 isotype of RTX induces CD20-mediated apoptosis in B-cell lymphoma cells and, when combined with RTX-IgG1 or RTX-IgG3 mAbs, can significantly enhance Fc receptor-mediated phagocytosis.

Impact of Fc receptors and host characteristics on myeloid phagocytic response to rituximab-treated 3D-cultured B-cell lymphoma.

Antibody-based immunotherapy is successful in treating cancer, but its effectiveness varies among patients. Therefore, understanding myeloid phagocytic responses to therapeutic antibodies is critical. Immunoglobulin Fc receptors and host characteristics were evaluated in phagocytosis of 3D-cultured CD20 B-cell lymphoma (spheroids) treated with different anti-CD20 rituximab (RTX) monoclonal antibody isotypes.

Exploring complement-dependent cytotoxicity by rituximab isotypes in 2D and 3D-cultured B-cell lymphoma.

Background: The therapeutic IgG1 anti-CD20 antibody, rituximab (RTX), has greatly improved prognosis of many B-cell malignancies. Despite its success, resistance has been reported and detailed knowledge of RTX mechanisms are lacking. Complement-dependent cytotoxicity (CDC) is one important mode of action of RTX.

The Human Monocyte-A Circulating Sensor of Infection and a Potent and Rapid Inducer of Inflammation.

Monocytes were previously thought to be the precursors of all tissue macrophages but have recently been found to represent a unique population of cells, distinct from the majority of tissue macrophages. Monocytes and intestinal macrophages seem now to be the only monocyte/macrophage populations that originate primarily from adult bone marrow. To obtain a better view of the biological function of monocytes and how they differ from tissue macrophages, we have performed a quantitative analysis of its transcriptome in vivo and after in vitro stimulation with LPS.

Quantitative In-Depth Transcriptome Analysis Implicates Peritoneal Macrophages as Important Players in the Complement and Coagulation Systems.

To obtain a more detailed picture of macrophage (MΦ) biology, in the current study, we analyzed the transcriptome of mouse peritoneal MΦs by RNA-seq and PCR-based transcriptomics. The results show that peritoneal MΦs, based on mRNA content, under non-inflammatory conditions produce large amounts of a number of antimicrobial proteins such as lysozyme and several complement components. They were also found to be potent producers of several chemokines, including platelet factor 4 (PF4), Ccl6, Ccl9, Cxcl13, and Ccl24, and to express high levels of both TGF-β1 and TGF-β2.