Fc receptor-mediated antibody-dependent cell-mediated phagocytosis (ADCP) is an important mechanism of action (MOA) of therapeutic antibodies designed to recognize and mediate the elimination of virus-infected or diseased (e.g., tumor) cells. Unlike antibody-dependent cell-mediated cytotoxicity (ADCC), which is mediated primarily through FcγRIIIa expressed on NK cells, ADCP can be mediated by monocytes, macrophages, neutrophils and dendritic cells via FcγRIIa, FcγRIIIa and FcγRI. All three receptors can participate in antibody recognition, receptor clustering and signaling events that result in ADCP.
Current methods used to measure ADCP rely on the isolation of primary human monocytes, ex vivo differentiation into macrophages and measurement of target cell engulfment. These assays are laborious and highly variable due to complex assay protocols and unqualified assay reagents. As a result, these current methods are difficult to establish in quality-controlled, drug development settings.
The FcγRI ADCP Bioassay is a bioluminescent cell-based assay for measuring the potency and stability of antibodies and other biologics with Fc domains that bind and activate FcγRI. The assay consists of a genetically engineered Jurkat T cell line that expresses the high-affinity human FcγRI and a luciferase reporter. The bioassay workflow is simple, robust, consistent and overcomes many of the limitations of traditional methods.