Medical Missiles: Homing in on Disease

Medical Missiles: Homing in on Disease

By Mr Ghaz, November 17, 2009

Medical Missiles: Homing in on Disease

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Medical has often been something of a hit-or-miss affair. Such lifesaving drugs as penicillin were discovered by accident, and no one knew at first how or why they worked.

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But today this ignorance may, for the most part, be a thing of the past. With increased knowledge of how the body fights disease, scientists are able to design drugs that work in ways similar to those of the body’s natural defenses. These “target drugs” home in on invading organisms and destroy them.

Target Drugs

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The key to the body’s defense against disease lies in the antibodies of the immune system. These components recognize antigens – substances foreign to the body that live on the surface of invading viruses and bacteria – by their particular chemical characteristics. The antibodies then chemically “lock on” to the antigens and make them inactive – and the viruses and bacteria on which they exist as well.

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In 1975 two scientists, César Milstein and Georges Köhler of Cambridge University, England, developed antibodies in the laboratory as effective as those the human body itself produces. They reasoned that if a powerful toxin were attached to these artificial antibodies, then the antigen could be killed without affecting other cells. In addition, the two scientists observed that certain cancer cells also had particular chemical characteristics that could be targeted for destruction the same way.

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The scientists called the new wonder drugs monoclonal antibodies, and the idea seemed very promising. Milstein and Köhler received the 1984 Nobel Prize in medicine for their pioneering work.

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However, during clinical trials the two scientists ran into problems. The monoclonal antibodies were nowhere near as effective as the team had hoped: a patient’s immune system would identify the drugs, manufactured from mouse cells, as invaders themselves. Therefore, the immune system was producing anti-antibodies in response, and the monoclonal antibodies were being destroyed before reaching their targets.

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To overcome the problem, Milstein and Köhler turned to the Trojan-horse technique. The idea was to disguise the monoclonal antibodies so that they could enter the body unnoticed by the immune system. Genetics of the mouse cells had identified the small fragment of the gene that was responsible for manufacturing the active part of the monoclonal antibody. It was removed and spliced into the equivalent place in the human gene where the code for producing human antibodies is carried. In theory the immune system would then not “see” the foreign invader, and the active parts of the monoclonal antibody would reach its target.

Toward An All-In-One Drug

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Trials are not yet advanced enough to determine if the Trojan-horse technique will succeed, and further modifications to the drug may be necessary. But Milstein and Köhler are confidently advancing this line of research. One idea involves finding a way to link different monoclonal antibodies together to form an all-in-one strike force to combat an array of diseases. The elements of this compound drug would attack individual viruses and tumor cells as each is encountered.

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Unforeseen problems may lie ahead, but research on monoclonal antibodies may be laying the foundations for the one-shot wonder drug that both doctors and patients have dreamed about.