Myeloid cells as effector cells for monoclonal antibody therapy of cancer

Abstract

Monoclonal antibodies (mAbs) have become an important addition to chemo- and/or radiotherapy for the treatment of cancer. They have multiple effector functions that can lead to eradication of tumor, including induction of apoptosis, growth inhibition, and initiation of complement-dependent lysis. Furthermore, mAbs can recruit immune effector cells. Traditionally, natural killer cells have been considered as the main effector cell population in mAb-mediated tumor killing. Myeloid cells have potent cytotoxic ability, as well. Monocytes and macrophages have been shown to induce antibody-dependent cytotoxicity and phagocytosis of tumor cells in the presence of IgG anti-tumor mAb. Furthermore, neutrophils are the most abundant population of circulating white blood cells, and as such may constitute a formidable source of effector cells. However, when targeting neutrophils for tumor therapy, antibodies of the IgA subclass may be more effective. This article focuses on enlisting myeloid effector cells for mAb-based immunotherapy of cancer. Additionally, methods to study mAb-dependent phagocytosis of tumor cells by macrophages are compared.

Keywords: ADCC; ADPh; BsAb; CDC; CEA; CR3; CTL; DC; E:T; EGFR; Ep-CAM; FcαR; FcγR; G-CSF; GM-CSF; Granulocyte-colony stimulating factor; Her-2; IFN-γ; Ig; IgA Fc receptor; IgG Fc receptor; Interferon-γ; LTB4; M-CSF; Macrophage; Monoclonal antibody; NET; NK cell; Neutrophil; PRR; Phagocytosis; ROS; SCID; SIRPα; Severe combined immunodeficiency; T helper 17 cell; TAM; TLR; Th17; Tumor cell; VEGF; antibody dependent cellular cytotoxicity; antibody dependent phagocytosis; bispecific antibody; carcinoembryonic antigen; complement dependent cytotoxicity; complement receptor 3; cytotoxic T-lymphocyte; dendritic cell; effector to target ratio; epithelial cell adhesion molecule; epithelial growth factor receptor; granulocyte macrophage-colony stimulating factor; human epidermal growth factor receptor 2; immunoglobulin; leukotriene B4; mAb; macrophage-colony stimulating factor; monoclonal antibody; natural killer cell; neutrophil extracellular trap; pattern recognition receptor; reactive oxygen species; signal regulatory protein α; toll like receptor; tumor associated macrophage; vascular endothelial growth factor.