Antibody-dependent cell-mediated cytotoxicity

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Under ADCC (engl. Short for antibody-dependent cell-mediated cytotoxicity , dt .:, antibody-dependent cell mediated toxicity ') refers to an immunological mechanism in which an antibody-loaded target cell is destroyed by an effector cell of the immune system. The role of the effector cell is mainly taken over by NK cells , but also by macrophages , dendritic cells , as well as neutrophils and eosinophilic granulocytes . The ADCC thus represents a connection between the innate and the adaptive immune system.

Chemotaxis of granulocytes, explanations in the picture description

This mechanism assumes that specific antibodies have already been formed and that these are bound to the target cell. In order to be able to bind these antibodies, human NK cells express so-called Fcγ receptors , such as CD16 or CD32 , which are able to recognize the Fc domains of immunoglobulins. As soon as the contact between the NK cell and the complex of antibody and target cell is established, the effector cell releases interferon-γ as well as cytotoxic proteins. These include primarily two different but synergistic classes of protein: First, the perforins , which penetrate the cell membrane of the target cell and form a pore there; secondly, the granzyme that penetrate through these pores in the cell and there as serine proteases which apoptosis can trigger.

The ADCC is immunologically opposed to the CDC (short for complement dependent cytotoxicity , dt .: ' complement dependent toxicity'). The main difference is that with the latter, the target cell is destroyed without the help of an effector cell and the complement system is activated instead . Both processes are linked at the protein level and can influence each other. However, it is still unclear whether this mutual influence is mainly inhibiting or reinforcing.

Both mechanisms are used in the therapy of tumors with monoclonal antibodies , such as rituximab - an anti- CD20 antibody that is used in the treatment of non-Hodgkin lymphomas .

Individual evidence

  1. ^ Wei Wang, Amy K. Erbe, Jacquelyn A. Hank, Zachary S. Morris, Paul M. Sondel: NK Cell-Mediated Antibody-Dependent Cellular Cytotoxicity in Cancer Immunotherapy . In: Frontiers in Immunology . tape 6 , January 1, 2015, ISSN  1664-3224 , p. 368 , PMID 26284063 , PMC 4515552 (free full text).
  2. ↑ Laura M. Rogers, Suresh Veeramani, George J. Weiner: Complement in monoclonal antibody therapy of cancer . In: Immunologic Research . tape 59 , no. 1-3 , August 1, 2014, ISSN  1559-0755 , p. 203-210 , PMID 24906530 , PMC 4381956 (free full text).