Too many cures for too many diseases

Oxford University is maintaining its position as a world leader in research with two new ventures. Martin Ince visits its new therapeutic antibody centre

The University of Oxford's new Therapeutic Antibody Centre has one big problem: it has too many possible cures for far too many debilitating diseases on its books. Geoff Hale, research director of the centre, explains that antibodies designed to relieve disease are simple to dream up. "Look at the medical and scientific literature," he says, "and you will see many of them every week."

Antibodies are chemicals produced by the immune systems of people and animals in response to threats. Their molecules have active sites that vary according to the threat being dealt with. Many diseases cause antibodies to be produced, and the first use of concentrated antibodies to attack disease took place a century ago.

In 1975, Georges Kohler and Cesar Milstein in Cambridge found a way of producing indefinitely large numbers of identical antibodies from a single cell, called monoclonal antibodies, making it possible to produce pure antibodies in medically interesting amounts. This has meant a new generation of antibody drugs to add to those purified from human blood, including antibodies against anything from chickenpox to snakebite.

Dr Hale says that the centre in Oxford, established late last year at the Churchill Hospital, aims to get around the problem of antibody testing by a number of strategies. Because antibodies are so specific, animal testing is usually of no value in testing them. At the same time, bringing a new drug into use can cost Pounds 100 million. The centre aims to get new drugs into use faster and more cheaply, and at the same time to obtain insights into how antibodies work.

The key, Dr Hale says, is the fact that under British law, doctors and dentists can use any drug they like on patients, even if it has yet to complete the full approvals process. Instead, the proposed use has to satisfy the local ethics committee. Since the patients on whom the test is carried out are usually very ill, this approval tends to be available. Because Dr Hale came from Cambridge, most of the tests in which he is involved have been in that area and he now hopes to expand testing in Oxford.

However, the centre can test only five to ten new drugs per year. This means decisions have to be taken about which to test, which means making a judgement based on the severity and frequency of the disease, and on the likely success of an antibody therapy.

So far, the most favoured category of diseases is ailments of the immune system, the third biggest killer in Britain after cancer and heart disease. An example is diabetes, in which the immune system destroys the islets of langeshans in the pancreas, that produce insulin in the healthy body. Other such diseases include arthritis, in which the joints are attacked, multiple sclerosis, and vasulitis, a disease in which the immune system attacks the walls of blood vessels and causes bleeding. Other intriguing prospects include the possibility of antibodies to reduce the harmful effects of strokes. Strokes do damage by cutting off oxygen to part of the brain because of inflammation caused by the response of white blood cells to a clot in the bloodstream.

An antibody to reduce the white blood cell attack could cut the inflammation. One problem is that a large study would be needed to see whether any treatment for strokes was effective. Dr Hale says that a stroke antibody called CD18 is now in test use little over a year after its discovery. New drugs for inflammatory bowel disease are being tested on a similar timescale.

The centre is also pioneering a set of commercial relationships. It was set up with five-year funding from the Medical Research Council and LeukoSite, a firm based in Cambridge, Massachusetts, United States. In return, LeukoSite has first refusal on products researched at the centre and can suggest lines of research, although the centre is also allowed to form commercial links with other companies.