Antibody dependent cellular cytotoxicity

Antibody-dependent Cellular Cytotoxicity (ADCC) Anticancer Dtugs... 

Ab2 S Anti-idiotype antibody which binds to the antigen binding region Ab3 Anti-anti-idiotype antibody Abcc Antibody dependent cellular cytotoxicity... 

Rituximab is a monoclonal antibody to the CD20 receptor expressed on the surface of B lymphocytes the presence of the antibody is determined during flow cytometry of the tumor cells. Cell death results from antibody-dependent cellular cytotoxicity. The pharmacokinetics of rituximab are best described by a two-compartment model, with a terminal half-life of 76 hours after the first infusion and a terminal half-life of 205 hours after the fourth dose.36 Rituximab has shown clinical activity in the treatment of B-cell lymphomas that are CD20+. Side effects include hypersensitivity reactions, hypotension, fevers, chills, rash, headache, and mild nausea and vomiting. 

Niwa R, Shoji-Hosaka E, Sakurada M, et al. Defucosylated chimeric anti-CC chemokine receptor 4 IgGl with enhanced antibody-dependent cellular cytotoxicity shows potent therapeutic activity to T-cell leukemia and lymphoma. Cancer Res 2004 64 2127-2133. 

ADCC ADP AM ara-C ATP BAPTA antibody-dependent cellular cytotoxicity adenosine diphosphate acetoxymethyl ester cytosine arabinoside adenosine triphosphate bis- (o-aminophenoxy)-ethane-N,N,N, N -tetraacetic acid... 

An alternative mechanism is based on non-complement dependent cytotoxicity, e.g., food allergen stimulation of mechanisms of antibody dependent cellular cytotoxicity (ADCC), cytotoxicity of natural killer cells or macrophages. The contribution of ADCC in gastroenteropathy of children induced by cow s milk allergens was demonstrated by Owen et al. (1993). 

Nechansky A, Schuster M, Jost W, Siegl P, Wiederkum S, Gorr G Kircheis R. (2007) Compensation of endogenous IgG mediated inhibition of antibody-dependent cellular cytotoxicity by glycoengineering of therapeutic antibodies. Mol Immunol 44 1826-1828. 

The precise mechanism of rituximab, as well as other monoclonal antibodies, is still incompletely understood despite extensive investigations. To our current knowledge, the mechanism of rituximab activity includes antibody-dependent cellular cytotoxicity (ADCC), complement dependent C5Totoxicity (CDC). and a direct pro-apoptotic effect (3,4). 

Niwa R, Hatanaka S, Shoji-Hosaka E et al. Enhancement of the antibody-dependent cellular cytotoxicity of low-fucose IgGl Is independent of FcgammaRIIIa functional polymorphism. Clin Cancer Res 2004 10 6248-6255. 

Yamane-Ohnuki N, Kinoshita S, Inoue-Urakubo M, Kusunoki M, Lida S, Nakano R, Wakitani M, Niwa R, Sakurada M, Uchida K, Shitara K, Satoh M. Establishment of FUT knockout Chinese Hamster Ovary cells an ideal host cell line for producing completely defucosylated antibodies with enhanced antibody-dependent cellular cytotoxicity. Biotech Bioeng 2004 87 614—622. 

Shinkawa T, Nakamura K, Yamane N, shoji-Hosaka E, Kanda Y, Sakurada M, Uchida K, Anazawa H, Satoh M, Yamasaki M, Hanai N, Shitara K. The absence of fucose but not the presence of galactose or Bisecting A-Acetylglucosamine of human IgGl complex-type oligosaccharides shows the critical role of enhancing the antibody-dependent cellular cytotoxicity. J Biol Chem 2003 278 3466-3473. 

Type II Drugs often modify host proteins, thereby eliciting antibody responses to the modified protein. These allergic responses involve IgG or IgM in which the antibody becomes fixed to a host cell, which is then subject to complement-dependent lysis or to antibody-dependent cellular cytotoxicity. 

Figure 22.2 Cellular activation by CpG DNA. CpG DNA directly activates dendritic cells (DCs), monocytes and macrophages, to express increased levels of co-stimu-latory molecules, to increase antigen presentation, and to secrete high levels of chemokines and cytokines, such as interleukin 12 (IL-12), interferon-a(IFN-a), and tumor necrosis factor-a (TNF-a), and monocytes and macro-phages have increased antibody-dependent cellular cytotoxicity (ADCC) activity. NK cells are induced to express IFN-7 by these cytokines acting in concert with CpG, and have increased lytic activity. B cells rapidly produce IL-b and IL-10 and express increased levels of costimulatory molecules. B cells rapidly enter the cell cycle and become resistant to some forms of activation-induced cell death. T cells are not directly activated by CpG, but because of the T helper 1 (Thl)-like cytokine environment, and the increased antigen presenting cell (APC) activity, antigen-specific Thl cells and cytotoxic T lymphocytes (CTL) are generated.

In mouse spleen, enhanced antibody-dependent cellular cytotoxicity response 407... 

Antibody-dependent cellular cytotoxicity by natural killer (NK) cells. 

Engineered IgG antibodies have been constructed with altered affinity to human Fey receptors and altered potency in vitro and in animal models [14, 31-33]. Mutations of critical residues in the Fc region (CH2 domain or the hinge region joining CH1 and CH2) have enhanced or decreased antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) [33-37]. In addition, alterations in residues located at the CH2 domain of I gC, i involved in binding with Clq protein, a component of the complement activation cascade, resulted in a significant increase in CDC activity [34, 35]. 

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