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Lombardi research: Monoclonal antibodies primed to become potent immune weapons against cancer
Date:3/20/2009

r (Erbitux, Avastin), lung cancer (Avastin), and blood cancers (Rituxan, Campath), but they have appeared to primarily work by forcing tumor related receptors to shut down pro-growth signals, Weiner says.

"For years it has been presumed that the ability of antibodies to interfere with malignant cell-related signaling is the dominant mechanism of anticancer activity, but we have also known that the normal job of an antibody is to deliver an antigen to the body's immune system which then destroys the target," Weiner says.

Recent research by Weiner and others, however, now shows that antibodies can inhibit function not only as signaling manipulators but also as initiators of immune responses that leads to control of cancer, the authors say.

"We believe that Herceptin and Rituxan, as examples, work in part by immunizing people against cancer, but at this point, the magnitude of that response is variable and is frequently very small," Weiner says.

Scientists now believe that it will be possible to alter the antibodies so that they induce both kinds of human immunity the innate immune response that is short-lasting and which directly kills tumor cells, and a long-lasting "memory" response that comes from the adaptive immune response. "We have long thought that monoclonal antibodies are capable of stimulating the innate immune system, but we now have evidence that the therapy can prime an adaptive response as well. Such responses would make the treatment much more powerful, capable of keeping cancer under control," he says.

"For the first time we are using technology that can measure the immune response that is occurring in monoclonal antibody treatment, and which will help us build better antibodies that amplify and shape that immune response to become more powerful," Weiner says.

And in the future, it may be possible to build antibodies that are targeted to existing targets on a patient's tumor, as well as to tar
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Contact: Karen Mallet
km463@georgetown.edu
215-514-9751
Georgetown University Medical Center
Source:Eurekalert

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