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Rockefeller University researchers discover immune-cell mechanism that boosts therapeutic antibody potency

Researchers at The Rockefeller University, in collaboration with Genentech, Inc., have made a surprising discovery about the mechanism by which two currently used clinical antibodies fight tumors. The finding, reported in the April issue of Nature Medicine, has immediate implications for increasing the potency of an entire class of cancer drugs now on the market and for developing more effective drugs in the future.

"This should have a significant impact on immunotherapy for cancer," says senior author Jeffrey V. Ravetch, M.D., Ph.D., Theresa and Eugene M. Lang Professor and head of the Leonard Wagner Laboratory of Molecular Genetics and Immunology at Rockefeller. "There are more than 20 other antibodies now being developed that are in various stages of clinical trials, and this finding shows a way to make them much more effective."

The scientists discovered that two anti-tumor antibodies, Herceptin and Rituxan, operate by harnessing the immune system and directing it to kill tumor cells. The antibodies connect to the immune system by engaging receptor pairs on the surface of certain immune cells. One of these receptors acts as an "on" switch to initiate an immune response, while the other acts as an "off" switch to hold the immune system in check and prevent it from attacking the body.

As effective as Herceptin and Rituxan are, the researchers found that removing or disabling the "off" switch could make an antibody many times more potent than before. Ravetch says the technology to do so is within reach.

"It's startling to learn that these antibodies do not work the way everyone has assumed," Ravetch says. "Now that we recognize this in vivo mechanism, we should be able to manipulate it to great effectiveness."

Antibodies are natures own defense against foreign intruders. Antibody molecules comprise two main segments: a variable region, which is highly specific in order to recognize any foreign shapeor pathogenit may encounter; and the Fc do
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Contact: Jim Stallard
stallaj@rockvax.rockefeller.edu
212-327-8977
Rockefeller University
27-Mar-2000


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