Antibody-dependent cellular cytotoxicity effector function (ADCC)

Antibody-dependent cellular cytotoxicity (ADCC), also known as antibody-dependent cell-mediated cytotoxicity, is not a single molecule or receptor, but rather an immune effector mechanism. In this process, immune cells such as natural killer (NK) cells recognize and kill target cells that have been coated with specific antibodies. The key molecular interaction involves the binding of the Fc portion of these antibodies—most commonly IgG—to Fc gamma receptors (FcγRs), especially CD16/FcγRIIIa on NK cells. Upon engagement, NK cells release perforin and granzymes that induce apoptosis in the targeted cell. Other innate immune effectors capable of mediating ADCC include macrophages, neutrophils, eosinophils, monocytes, and dendritic cells; each expresses different types of Fc receptors suited for various antibody classes such as IgA or IgE in addition to IgG[1][3][5]. Therapeutic monoclonal antibodies used in oncology often rely on inducing ADCC against tumor-associated antigens. The efficiency of this process can be influenced by factors such as antigen density on targets, glycosylation patterns on therapeutic antibodies' Fc regions (e.g., afucosylated mAbs show enhanced activity), and genetic polymorphisms affecting patient Fc receptor expression. Because ADCC is an immunological process—not a discrete protein/gene/receptor—it should not be considered a canonical druggable “target” like enzymes or membrane proteins. Instead it is best described as an important functional outcome exploited by certain immunotherapies.[1][2][3][4]

Other names

Antibody-dependent cell-mediated cytotoxicityAntibody-dependent cellular cytotoxicityADCC

Drugs leveraging ADCC typically act by binding to antigens on target cells via their Fab region and engaging Fc gamma receptors (FcγR) on immune effector cells via their Fc region. This triggers the release of cytotoxic granules from the effector cell, leading to lysis of the antibody-coated target cell[1][3][5][8].