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Immune therapy could treat leukemias, autoimmune diseases, transplant rejection

effects on B cell depletion. A CD20 mAb is now marketed as Rituximab.

Importantly, the researchers found that the CD19 mAb treatment dramatically depleted growth of malignant B cell tumors in the animals. In ten mice transplanted with malignant B cell lymphomas, the CD19 mAb treatment prevented the appearance of circulating and tissue tumor cells for up to seven weeks in all the animals. In contrast, all untreated mice died from their tumors by three weeks.

"We were actually quite shocked at how effectively CD19 mAb-treatments prevented malignant B cell expansion," said Tedder. "Treatment of such tumors in mouse models is extraordinarily difficult."

Finally, when the researchers measured the effects of CD19 mAb treatment on blood levels of antibodies produced by B cells, they found a significant reduction in circulating antibody levels as well as B cell mediated "humoral immune responses" in the animals, including reductions in autoantibodies of the type produced in autoimmune diseases and transplant rejection.

According to Tedder, the results of the CD19 mAb animal studies warrant rapid advance to clinical trials for treatment of B cell leukemias and other malignancies that derive from early B cell precursors and perhaps antibody-producing B cells.

The CD19 mAbs may show broader effectiveness than Rituximab, he said, because CD20 is expressed only by mature B cells, in contrast to CD19, which is expressed by both mature and immature B cells and by antibody-producing cells.

Tedder noted that in general such immunotherapies are likely to produce far fewer side effects than current chemotherapies -- which can produce secondary malignancies, sterility and growth retardation in children who take them for leukemias.

In particular, the researchers' finding that the treatment greatly depletes B cells in the peritoneum -- a major source of autoantibody-producing cells in mice -- could make it an effective treatment for
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Contact: Dennis Meredith
dennis.meredith@duke.edu
919-681-8054
Duke University Medical Center
11-Oct-2005


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