Lysis, cell complement-mediated

Complement Fixation. Complement is a component of the immune system capable of binding to an antibody after the antibody has reacted with an antigen. If that antigen is part of a whole cell, complement mediates a series of events which results in the lysis of the cell (11). 

Muronomab-CD3 (OKT-3) is a murine monoclonal antibody that targets the CD3 receptor. The CD3 receptor is only found on activated T cells and medullary thymocytes.10,11,14 After binding with the CD3 receptor, complement-mediated T cell lysis occurs rapidly. This agent is dosed at 5 mg/day. This dose is given daily for 10 to 14 days. Lower doses have been used successfully in liver transplant recipients.14... 

Golay J, Zaffaroni L, Vaccari T et al. Biologic response of B lymphoma cells to anti-CD20 monoclonal antibody rituximab in vitro CD55 and CD59 regulate complement-mediated cell lysis. Blood 2000 95 3900-3908. 

Another effector function/mode of action of mAbs is the so-called complement-dependent cytotoxicity or complement-mediated cell death . Activation of the complement system can lead to lysis of the antigen-presenting cell, or can induce inflammation reactions aimed at eliminating these cells efficiently. The successive steps of the complement activation can be summarized in a simplified way [9] ... 

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). 

Paroxysmal nocturnal hemoglobinuria is a very rare acquired disorder in which hemopoietic stem cells become peculiarly sensitive to complement-mediated lysis. Venous and possibly arterial thrombosis occurs in the brain and elsewhere. Patients are nearly always anemic at... 

Clayton, A., Harris, C.L., Court, J., Mason, M.D. and Morgan, B.P. (2003) Antigen-presenting cell exosomes are protected from complement-mediated lysis by expression of CD55 and CD59. Eur. J. Immunol. 33, 522-531. 

Optimal conditions for both antibody and complement dilutions have to be determined empirically, by a cytotoxicity test (see below). The complement-mediated lysis reaction proceeds between antibody-saturated target cells as one reactant, and complement as a second reactant. Therefore, when target cell surface antigens are saturated with the corresponding antibody, lysis will not increase with increasing antibody concentration. On the other hand, antibody aggregates, which can form at high concentrations (usu-... 

Monoclonal antibodies may be used as passive immunotherapy to treat malignancies. They react with specific antigens present on the surface of tumor cells and result in cell destruction. Rituximab was the first MoAb approved in the United States for the treatment of cancer. It is a chimeric MoAb directed against cluster differentiation 20 (CD20) markers, which are expressed on over 90% of B-cell NHL tumors. Rituximab is thought to result in B-cell depletion by a number of mechanisms, including complement-mediated and antibody-dependent cell lysis and induction of apoptosis. 

Jenski LJ, Sturdevant LK, Ehringer WD, Stillwell W. Omega-3 fatty acid modification of membrane structure and function 1. Dietary manipulation of tumor cell susceptibility to cell and complement-mediated lysis. Nutr Cancer 1993 19 135-146. 

CD59 renders blood cells susceptible to complement-mediated lysis. Patients with PNH are at risk of developing venous thrombosis, leukemia and aplastic anemia. 

Harris SL. Frank I, Yee A, Cohen GH, Eisenberg RJ. Friedman HM (1990) Glycoprotein C of herpes simplex virus type 1 prevents complement-mediated cell lysis and virus neutralization. J Infect Dis 162 331-337... 

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