Therapeutic antibodies are now the major class of successful protein drugs with many more in development to target a variety of major diseases. An important and desirable biological activity of most antibody drugs, especially for oncology targets, is antibody-dependent cell-mediated cytotoxicity (ADCC).
In ADCC, circulating natural killer (NK) cells perform lytic killing of antigen-bearing target cells through specific antibody cross-linking of the two cell types. Several signaling pathways are activated in the NK effector cells as a result of multiple FcγRIIIa receptors being engaged by the target cell-bound antibodies. These lead to lysis of target cells and induction of specific cytokines (e.g., through NFAT, or nuclear factor activator of T-cells) in the effector cells.
It is important to quantify the biological activity of any therapeutic antibody in a bioassay during drug development and manufacture. The potency of a manufactured lot is quantified relative to a reference preparation in a lot-release potency bioassay, and this bioassay must be both precise and accurate.