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A single protein helps the body keep watch over the Epstein-Barr virus
Date:2/17/2012

elbrck Center for Molecular Medicine in Germany, "but we had never been able to get the mice in our models to actually produce any mature B cells. The immune response against the LMP1-producing B cells was so robust that the cells were eliminated very early on."

Their breakthrough came when Zhang and colleagues reengineered the model to lack T cells. "The mice were initially fine, but succumbed within two to three months to aggressive B cell lymphomas," Rajewsky said. "The profile mimicked very closely what we see in immunosuppressed lymphoma patients." In additional experiments with Rajewsky's original model, the team eliminated the mice's T cells before activating the viral protein in B cells, sparking a similar but even more rapid fatal disease.

The team also made several observations with possible clinical application. First, they noted that in the mouse model the LMP1 producing B cells were being attacked by a specific kind of T cell called a CD4+ T cell. "Transplant patients who develop B cell lymphomas because they are immunosuppressed by their anti-rejection drugs are often treated with T cells that carry the CD8 marker," Rajewsky noted. "These results would argue for also considering CD4+ T cells for treatment."

Second, they found that tumors in the LMP1 producing mice often displayed targets recognized by another kind of immune cell called a natural killer (NK) cell. Seeing an opportunity, Rajewsky worked with cancer immunologist Glenn Dranoff, MD and colleagues at Dana-Farber Cancer Institute, to test a potential therapeutic agent that uses a portion of the NK cell activating receptor called NKG2D, fused to the stimulatory Fc portion of an antibody, a combination capable of activating and directing immune attack against tumor cells. In a transplantation model of LMP1-fueled lymphomas, the NKG2D-Fc fusion proved quite capable of reducing tumor growth and prolonging survival of the recipients.

"These preclinical results
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Contact: Erin Tornatore
erin.tornatore@childrens.harvard.edu
617-919-3110
Children's Hospital Boston
Source:Eurekalert

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