Antibody dependent cell-mediated cytotoxicity

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Synonym(s)

ADCC; (e) antibody-dependent cell-mediated cytotoxicity

Definition
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Antibody-dependent cell-mediated cytotoxicity (ADCC) refers to an immune mechanism in which Fc receptor-carrying (CD16) effector cells recognize and specifically kill antibody-coated target cells. Effector cells are mainly NK cells (natural killer cells), but also macrophages, dendritic cells, neutrophils and eosinophils (Wei Wang et al. 2015). ADCC represents a link between the innate and the adaptive immune system.

General information
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Four stages and mechanisms leading to antibody-dependent effector-mediated killing of the target cell can be defined as follows:

  • recognition of the target cell and the Fc receptor; cross-linking on the surface of the effector cell
  • Phosphorylation of activation motifs (ITAMs) on the basis of immune receptor tyrosine by cellular src kinases within the effector cell
  • Triggering of three "main downstream signaling pathways" in the effector cell, resulting in polarization and release of the cytotoxic granules
  • Killing of the target cell via the perforin / granzyme apoptosis pathway. Perforins penetrate the cell membrane of the target cell and form a pore there. Granzymes are serine proteases that penetrate through these pores into the target cell to hydrolytically cleave intracellular proteins and thereby drive them into apoptosis.

Note(s)
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Various laboratory methods exist for determining ADCC (Miller AS et al. 2014). The classical method is the chromium-51 [ 51 Cr] release test. The cytotoxicity of NK cells can be determined by means of a flow cytometry-based cytotoxicity test, among others. In this procedure, the monoclonal antibody trastuzumab, which binds specifically to HER2-positive malignant cells, is used to trigger a defined ADCC (van der Haar Àvila I et al. 2019).

Literature
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  1. Miller AS et al (2014) Methods for measuring antibody-dependent cell-mediated cytotoxicity in vitro. Methods Mol Biol 1134:59-65
  2. Wei Wang et al (2015) NK Cell-Mediated Antibody-Dependent Cellular Cytotoxicity in Cancer Immunotherapy. Frontiers in Immunology 6: 368
  3. Rogers LM et al (2014) Complement in monoclonal antibody therapy of cancer. Immunologic Research 59: 203-210
  4. van der Haar Àvila I et al (2019) Evaluating Antibody-Dependent Cell-Mediated Cytotoxicity by Flow Cytometry. Methods Mol Biol 1913:181-194.

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Last updated on: 29.10.2020