Antibody‐dependent Cellular Cytotoxicity (ADCC)

Abstract

Antibody‐dependent cell‐mediated cytotoxicity (ADCC) is the killing of an antibody‐coated target cell by a cytotoxic effector cell through a nonphagocytic process, characterised by the release of the content of cytotoxic granules or by the expression of cell death‐inducing molecules. ADCC is triggered through interaction of target‐bound antibodies (belonging to IgG or IgA or IgE classes) with certain Fc receptors (FcRs), glycoproteins present on the effector cell surface that bind the Fc region of immunoglobulins (Ig). Effector cells that mediate ADCC include natural killer (NK) cells, monocytes, macrophages, neutrophils, eosinophils and dendritic cells. ADCC is a rapid effector mechanism whose efficacy is dependent on a number of parameters (density and stability of the antigen on the surface of the target cell; antibody affinity and FcR‐binding affinity). ADCC involving human IgG1, the most used IgG subclass for therapeutic antibodies, is highly dependent on the glycosylation profile of its Fc portion and on the polymorphism of Fcγ receptors. Key Concepts: Antibodies bound to target cells (virus‐infected or tumour cells) and Fc receptors expressed by cytotoxic cells are the major actors of ADCC. IgG and IgA can trigger ADCC by binding specifically to FcγR and FcαR, respectively. ADCC mechanisms that lead to target cell death vary depending on effector cells that are recruited by antibodies. FcγRIIa and FcγRIIIa polymorphism impact ADCC efficacy by IgG1 antibodies. Engineering FcIgG either by introducing point mutations or by modifying the glycosylation profile allows to optimise IgG1 antibodies for enhanced ADCC. Bispecific antibodies that bind activating molecules expressed by cytotoxic cells and tumour cells can mimic classical ADCC.

Large Extracellular Loop of Tetraspanin as a Potential Vaccine Candidate for Filariasis

“…IgG antibodies can bind to FcγRI and FcγRII receptors expressed on several inflammatory cells such as macrophages, neutrophils, eosinophils and participate in an ADCC mechanism [40]. Therefore, in this study we evaluated if anti-TSP LEL antibodies in the sera of EN subjects and immunized mice can participate in the killing of B. malayi L3 in vitro in an ADCC assay.…”

Enhancing antibody-dependent cell-mediated cytotoxicity: a strategy for improving antibody-based immunotherapy

“…Antibodies can bind to their specific antigens on the target cell surface via their antigen-binding fragment (Fab) portions and interact with effector cells via their fragment crystallizable region (Fc) portions thereby acting as bridges that link the effector to a target. While several classes of human antibodies can mediate ADCC, including IgG, IgA, and IgE, IgG1 is the most used subclass for cancer therapeutic antibodies [5]. In order for an effector cell to carry out ADCC it must express Fc receptors (FcR) that will bind the antibody [6].…”

Autoantibodies and their potential roles in diseases of the nervous system

“…The term ADCC originally was used to refer to killing mediated by natural killer (NK) cells, after recognition of bound IgG1 or IgG3 by FcγRIII (CD16) on the NK cell surface. However, it is now recognized that macrophages and polymorphonuclear cells can also initiate ADCC . Cross‐linking of the FcR by the antibody triggers degranulation of the NK cells (or release of toxic mediators from other cells) into a lytic synapse, and the cells to which the antibody is bound die by apoptosis.…”