Rituximab complement-dependent cytotoxicity

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

Rituximab is a chimeric monoclonal antibody that targets CD20 lymphocytes (see Chapter 55). This depletion takes place through cell-mediated and complement-dependent cytotoxicity and stimulation of cell apoptosis. Depletion of lymphocytes reduces inflammation by decreasing the presentation of antigens to T lymphocytes and inhibiting the secretion of proinflammatory cytokines. Rituximab rapidly depletes peripheral cells although this depletion neither correlates with efficacy nor with toxicity. 

For complement-dependent cytotoxicity, a complex cascade of protein binding and cleavage occurs that culminates in final complement mediated effector functions of phagocytosis, recruitment and activation of leukocytes, and osmotic lysis. It has been reported that Rituximab (anti-CD20) utilizes a complement-dependent mechanism for tumor cell destruction [14], If the desired effect of a therapeutic antibody is complement-dependent activity, the isotype subgroup chosen should be one that binds to complement proteins (IgGl or IgG3). 

Tositumomab and iodine I-tositumomab is a monoclonal antibody that blocks (complement-dependent cytotoxicity) CD20 antigen, which is found on the surface of normal and malignant B lymphocytes. Cell death is associated with ionizing radiation from the radioisotope. It is indicated in the treatment of patients with CD20-positive, follicular, non-Hodgkinr s lymphoma, with and without transformation, whose disease is refractory to rituximab and has relapsed following chemotherapy. 

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). 

Anti-CD20 MoAB linked to radioactive yttrium (Y ) murine version of the rituximab antibody monoclonal antibody to CD20 (a B-lymphocyte surface antigen)-positive cells binds complement and increases antibody dependent cellular cytotoxicity radioactive linkage delivers radiation dose directly to tumor cells to decrease damage to normal cells... 

The monoclonal antibody rituximab, which binds to CD20, has been approved by FDA for the treatment of non-Hodgkin lymphoma and rheumatoid arthritis. After binding to CD20-positive cells, the exposed distal Fc part of the antibody leads to subsequent complement activation, antibody-dependent cell-mediated cytotoxicity, activation of natural killer cells, and finally cell lysis... 

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