Antibody-dependent cellular cytotoxicity

Antibody-dependent cellular cytotoxicity (ADCC) is the destruction of antibody-coated target cells by immune effector cells, especially natural killer cells, that recognize antibody Fc regions.

Immunoglobulin G: Immunoglobulin G is the most abundant antibody class in blood and extracellular fluid. Its Fc region commonly coats targets and engages natural killer cell receptors.
Rituximab: Rituximab is a monoclonal antibody targeting CD20 on B cells, used to treat several cancers and autoimmune diseases. Its antitumor activity can include natural killer cell-mediated ADCC against CD20-positive cells.
Complement-dependent cytotoxicity: Complement-dependent cytotoxicity is target-cell damage caused by activation of the complement cascade, often ending in membrane attack complex formation. It can follow antibody binding too, but uses complement proteins rather than Fc-recruited effector cells.
Natural killer cell exhaustion: Natural killer cell exhaustion is a state of impaired NK-cell function associated with persistent stimulation and suppressive environments. Reduced effector function can weaken ADCC within chronically inflamed or tumor tissues.
Fc gamma receptor IIIA: Fc gamma receptor IIIA, or CD16a, is an activating receptor on natural killer cells and some myeloid cells. CD16a binds IgG Fc and initiates the principal natural killer cell route to ADCC.
Trastuzumab: Trastuzumab is a monoclonal antibody that binds HER2 and treats HER2-positive cancers. Its Fc-mediated recruitment of natural killer cells contributes to killing HER2-positive tumor cells.
Cell-mediated cytotoxicity: Cell-mediated cytotoxicity is the destruction of target cells by immune cells through direct contact and cytotoxic mechanisms. ADCC is a form distinguished by antibody-guided recognition of the target.
Tumor microenvironment: The tumor microenvironment is the collection of noncancerous cells, molecules, and physical conditions surrounding a tumor. Its suppressive signals and limited immune access can constrain ADCC in solid tumors.
Natural killer cell: A natural killer cell is a lymphocyte that can kill infected, stressed, or malignant cells without prior antigen-specific priming. It is the main effector cell in classic antibody-dependent cellular cytotoxicity.
Antibody glycoengineering: Antibody glycoengineering modifies antibody sugar structures to alter properties such as receptor binding and immune activity. Removing core fucose can strengthen Fc binding to CD16a and increase ADCC in some therapeutic antibodies.

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