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Antibody-dependent cellular cytotoxicity (ADCC)

Signaling events upon antibody-dependent cellular cytotoxicity
Signaling events upon antibody-dependent cellular cytotoxicity

Antibody-dependent cellular cytotoxicity (ADCC) is one major mode of action of therapeutic monoclonal Abs (mAbs). This immune reaction relies on mAb dual activity: the variable region ensures the specific recognition of an antigen expressed by a target cell, and the “crystallizable fragment” Fc in the constant region binds to Fc receptors (FcRs) at the surface of effector cells. Depending on the Ab isotype, the Fc region displays different binding affinity for activatory FcRs [1].

ADCC is mediated by Natural Killer (NK) cells which express FcγRIIIA (CD16A), activatory receptors for IgGs. FcγRIIIA cross-linking at the surface of NK cells leads to downstream signaling, including increase in intracellular calcium concentration, calicneurin/calmodulin-mediated dephosphorylation of NFAT (nuclear factor of activated T cells), allowing its nuclear translocation and binding to promoter regions of ADCC relevant genes. Ultimately, the effector cells release cytotoxic granules which kill the target cells [1].

To assess the functionalities of your mAbs, InvivoGen offers an alternative to laborious classical ADCC assays mainly relying on NK cells or peripheral blood monocytes by using:

 

Review View our product flyer on Clinically-relevant monoclonal antibodies

 

References:

1. Quast I. et al. 2017. Regulation of antibody effector functions through IgG fc N-glycosylation. Cell. Mol. Life. Sci. 74(5):837.

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