Blood: immune tolerance for macrophage low-phagocytosis mediated mAb-induced cell removal

Macrophage antibody-dependent phytopharyapharyaphal action (ADCP) is the main cytotoxic mechanism of therapeutic monoclonal antibodies (mAb, such as rituximatod) and antibody-induced hemolytic anemia andimmunityplatelet reductionrecently published an article in Blood, Pinney et alstudied the mechanisms for regulating the rate and ability of macrophages to perform ADCP in high-target-effect cell ratios, such as circulatory tumor loads in leukemia patientsby quantitatively imaging the macrophages in primary human patients and mice, the researchers found that after initial stimulation of mAb-conditioning lymphocytes, macrophages experiencea a brief rapid phagocytosis outbreak (1 hour) followed by a sharp decline in phage activity that lasts for several daysThis previously ambiguous period of ADCP, or "hypophagia", is present in all macrophages/mAb/target cells in vitro testing conditions and has also been observed in the body Kupffer cells in mice that have been removed by continuous alpha CD20 mAb-dependent circulating B cellsimportant, hypophagia has no effect on antibody-dependent phagocy and does not alter the viability of macrophagesIn the mechanism study, the study found that the rapid loss of the surface-activated Fc receptors of macrophage and subsequent protein degradation were the main mechanisms of loss of ADCP activity in phagiathese studies show that hypophagia is a key limiting step in macrophage-dependent cell removal through ADCP, and understanding that such limits on the cytotoxicity of inherent immune cells can help develop mAb therapy, or further optimize ADCP and improve patient prognosis