Dec. 2, 1997 When the immune system responds to disease it produces many different antibodies against different viral or bacterial proteins (antigens). One of the most exciting discoveries for medical science was how to produce, in the lab, many antibodies responding to a single antigen. These so-called monoclonal antibodies have found many uses in modern medicine, including the diagnosis of cancer. At the British Society for Immunology Annual Congress in Brighton this week Dr Martin Glennie, from the Tenovus Research Laboratory, Southampton, UK, will explain how he thinks monoclonal antibodies (mAbs) could be used in the treatment of cancer too.
There has been some interest in using antibodies with drugs or irradiation attached to target therapy at the site of a tumour. However, Dr Glennie and colleagues are using unmodified antibodies alone - these are often referred to as "naked mAbs". What interests the Southampton researchers is why some naked mAbs are highly effective in killing cancer cells whilst others are not.
The traditional thinking on how mAbs exert their effect is that they alert the body to danger and recruit immune cells to the site of the tumour. However, Dr Glennie now has evidence which suggests that the successful mAbs are the ones which can trigger a change in the cancer cells themselves. These mAbs tell the cancer cells to stop growing or even to commit suicide (a process known as programmed cell death). Thus the mAbs are restoring the very control mechanism thought to have gone wrong in cancer.
Dr Glennie and Professor George Stevenson (also at Southampton) have developed a mAb which recognises a molecule (CD20) found on the surface of B cells. They are using this in trials with patients with a type of cancer called transplant lymphoma. This cancer affects approximately 3% of patients who have had an organ transplant as a side-effect of the immunosuppressive drugs they need to take.
So far the mAb has been given to nine patients and Dr Glennie describes the results as "very impressive". The antibodies destroy all the patient's B cells, both cancerous and healthy. However healthy B cells return when all the mAb has gone from the patient's body, approximately 6 months after treatment. Surprisingly the patients seem to manage very well without their normal B cells!
Advances in antibody engineering and production means that the cost of making mAbs is falling rapidly, so that large-scale application is now economically viable. The prospects look good for a therapy that should be without the unpleasant side-effects of current cancer treatments.
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