The impact of Fc receptors
on the development of autoimmune diseases.
IgG antibodies (with the exception of IgG3) are known to bind to neonatal Fc receptors
(FcRn) in the endosomes of endothelial cells following internalization, where they are protected from catabolism and recycled so that their half-lives are significantly longer than the half-lives of other antibodies (38).
Investigation of the interaction between the class I MHC-related Fc receptor
and its immunoglobulin G ligand.
To overcome the variability resulting from both cell donor sources and Fc receptors
, laboratories have developed modified cell lines that either enhance the NK ADCC response by down regulating NK cell inhibitory signals (J Immunol.
Unlike IgG, IgY antibodies do not bind to bacterial Fc receptors
, such as staphylococcal protein A or streptococcal protein G (JENSENIUS et al., 1981).
van Egmond, "Inefficient antigen presentation via the IgA Fc receptor
(FcaRI) on dendritic cells," Immunobiology, vol.
The most potent chemicals were DEX (both doses) and TCDD (high dose), up-regulating genes in the [CD8.sup.+] and [CD4.sup.+] arms of the antigen presentation pathway, major histocompatibility (MHC) I (B2m) and MHC II (CD74, HLA-DMA, HLA-DMB, HLA-DQA1, HLA-DQB1, HLA-DRA, HLA-DRB1) molecules, and three Fc receptors
. At the high dose, all four chemicals also altered a related pathway, crosstalk between dendritic and NK cells, and general function categories related to quantity and chemotaxis of antigen-presenting cells (APCs); and DEX altered additional APC functions.
(8) In addition, however, based on this tragic event, an increased emphasis on preclinical consideration of Fc receptor
interactions is likely to be required by regulatory agencies.
The patent, EP2801583, issued by the European Patent Office, "Genetically Modified Human Natural Killer Cell," includes a key composition claim directed to NantKwest's proprietary haNK cells that have been engineered to express a high affinity Fc receptor
, also described as CD16, in combination with an antibody that specifically binds to an antigen expressed by a cancer or infected cell.
The transaction adds to the company's increasing range with the addition of clinical-stage SYNT001, a humanised monoclonal antibody that inhibits the interaction of neonatal Fc receptor
(FcRn) with Immunoglobulin G (IgG) and IgG immune complexes with the potential to treat a number of rare IgG-mediated diseases.
For example, the toxicity profile of the mAbs has been illustrated in the case of trastuzumab (anti-HER2/neu), in which CARs carrying the IgG1-derived CH2CH3 domain as extracellular spacer may interact with the Fc receptor
expressed on innate immune cells (e.g., macrophages and NK cells), leading to antigen-independent activation .