ADCC Function

Mechanism of ADCC

The steps of ADCC are divided into four steps: antibody recognition of binding antigens, recruitment of binding effector cells, activation of effector cells, and killing target cells, and the mechanism of action of ADCC is mainly summarized into three pathways：

1. After the antibody binds to the target cells and activates the effector cells, the activated NK cells produce granzyme and perforin. Perforin is a cytotoxic substance stored in the cytoplasm of effector cells. In the presence of calcium ions, perforin forms polyperforin channels on the target cell membrane, so that water and electrolytes quickly enter the cell, resulting in cell disintegration and destruction; The essence of granzyme is a serine protease, which can enter the cell through the pores formed by perforin on the target cell membrane, activate the apoptosis-related enzyme system, and make the target cell apoptosis.
2. When NK cells are activated, FasL cytokines are expressed on the cell surface, bind to Fas receptors on the surface of target cells, and form Fas trimers on the surface of target cells. This trimeric protein binds to the intracellular Fas-associated with death domain protein (FADD) to recruit and activate the intracellular caspase-8 protein (cysteine-containing aspartate proteolytic enzyme), and hydrolyzes the intracellular protein through the caspase cascade, resulting in the disintegration and death of target cells.
3. The α tumor necrosis factor (TNF-α) expressed on the surface of NK cells can specifically bind to the tumor necrosis factor receptor (TNF-R1) expressed on the surface of target cells, so that TNF-R1 forms a trimer on the target cell membrane and binds to FADD to activate caspase8, similar to the second pathway, resulting in apoptosis of target cells.

Fig.1 Mechanism of ADCC.

Effectors of ADCC

The cells that mediate the ADCC effect are mainly leukocytes:

Creative Biolabs offers a range of ADCC effector cells, click on ADCC Cell Line to view!

Reference

1. Zahavi, D.; et al. Enhancing antibody-dependent cell-mediated cytotoxicity: a strategy for improving antibody-based immunotherapy. Antibody therapeutics. 2018, 1(1): 7–12.