Complement-dependent cytotoxicity CDC

It has been proposed that rituximab also functions through the complement-dependent cytotoxicity (CDC) pathway, specifically the classical pathway, which requires... 

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]. 

Antibodies represent a class of flexible molecular adaptors that play a vital role in the adaptive immune systems of vertebrates [1]. First discovered by von Behring and Kitasato in 1890 [2], it was not before 1960 that their basic structure was determined by Porter and Edehnaim [3]. With their inherent diversity and heterogeneity, antibodies mediate humoral and cellular immune responses, and directly execute biochemical mechanisms such as antigen recognition, complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) [4]. In most higher mammals, antibodies exist in five distinct classes (IgG, IgA, IgM, IgD, and IgE) that... 

IgM and IgG reactivities by flow cytometry and complement-dependent cytotoxicity (CDC) assays, evaluated using Tn(c) positive LS-C and Tn(c) negative LS-B colon cancer cells. A phase I clinical trial in prostate cancer patients showed that all patients immunized with Tn(c)-MBS-KLH/QS-21 developed high-titer antibody responses against Tn(c), confirming the tmmunogenicity of this Tn(c) vaccine. In addition, the levels of PSA observed in the treated patients either stabilized or dechned, of which the clinical impact and relevance remains to be validated. ... 

The anti-CD20 Mab had been purposely engineered with human constant regions (IgGl kappa isotype) to ensure that it would effectively bind complement and, through Fc receptors, effector cells so that it could effect complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) [5, 6] (Fig. 1). This was confirmed in vitro. Additionally, in vivo experiments in monkeys revealed immediate, profound, and specific B-cell depletion with recovery within 100 days. The effects of the antibody on the human immune system were unknown. It was expected to produce B-cell depletion and... 

This conjugate 45 is a particularly efficient two-component vaccine. It induced a strong IgG-type immune response in wild-type mice and elicited antibodies which strongly bind to MCF-7 breast tumour cells and also activate the complement dependent cytotoxicity (CDC) complex to... 

The second mechanism of cell death is the complement-dependent cytotoxicity (CDC), where a mAb or a molecule with a similar structure binds to its specific receptors on the target cells and the Fc portion of the antibody binds the complement proteins. Complement binding results in the activation of a complement cascade leading to formation of pores in the cell membrane compromising membrane integrity. 

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