Mouse shows how Rituximab removes human B cells
The monoclonal antibody Rituximab has been approved for the treatment of non-Hodgkin's lymphoma since 1997, but how Rituximab disposes of the cancerous (and normal) B cells is unknown. Research in a new mouse model reported in The Journal of Experimental Medicine suggests that the drug works by triggering the removal of B lymphocytes by scavenger cells.
Antibodies like Rituximab can remove cells in a variety of ways, including killing cells directly, inducing cell suicide, or triggering killing by other immune cells and molecules. Rituximab binds to CD20, a protein found on the surface of all B lymphocytes. In humans it is difficult to analyze how this leads to the elimination of B lymphocytes as only small numbers of cells can be sampled from the blood.
To mimic the clinical situation, Thomas Tedder and colleagues treated mice with a panel of antibodies specific for mouse CD20 (Rituximab is an antibody that binds to human but not mouse B cells). The antibodies that were effective in removing B cells did so by allowing B cell recognition by specialized 'scavenger' immune cells known as macrophages, which carry antibody receptors on their surface.
Less than half of patients with lymphoma respond to anti-CD20 therapy, so drugs that increase the number of macrophages or levels of antibody receptors might improve the response to Rituximab.
The new insight into how CD20 antibodies remove B cells should allow the design of better therapies not only for lymphoma, but also autoimmune diseases caused by rogue self-reactive B cells (as in rheumatoid arthritis), in which CD20 antibody trials are already underway.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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