Monoclonal Magic Bullets

March 16, 1991

The search for "magic bullets" capable of hunting down a cancer in the human body, attacking a disease virus or repairing a defective organ has gone on for years.

For a time, monoclonal antibodies, disease-recognizing molecules made by hybrid mouse blood cells, seemed the answer.

There was success, to be sure. Antibodies cloned in the laboratories showed strengthened abilities to zero in on disease agents, especially cancers, that had eluded traditional medical or surgical attack. After much experimentation, however, doctors found they hadn't anticipated all the problems.

Allergic reactions proved a major hurdle. Because the antibody came from a mouse and not a human, patients' immune systems recognized it as alien, stimulating reactions. Moreover, the relatively large antibody molecule couldn't penetrate tissues to get at disease-causing organisms or the interior of tumors. Antibodies work best in tissue areas with good blood flow. Finally, the cell-splitting and combining process is time-consuming and tricky. So far, only two cloned antibodies have received federal approval for human use, with a couple more likely soon.

The relentless progress of biochemical science, however, keeps bringing new tools to the search. Researchers in Great Britain and the United States appear close to solving the allergic-reaction problem. It turns out that the long, stable part of an antibody molecule is what set off immune-system alarms and not the smaller, disease-antigen-binding part. Slicing off ever-smaller pieces of the mouse-produced antibodies and combining them with human antibody parts appears to avoid allergenic trouble.

Researchers are trying to use computer modeling to design antibodies that closely match disease organisms. That could take two to five years. Others have watched advances in molecular biology and learned how to force bacteria to produce antibody clones. From human white blood cells, they isolate genetic coding for an antibody, then insert it into a virus that infects bacteria, which then produce the antibody in quantity. That allows rapid, cheaper investigation of promising antibodies.

Still others have isolated antibody "recognition units" -- the molecular parts which bind to disease antigens -- and learned to make artificial ones. These, unlike whole antibodies, can penetrate tissues with limited blood supply. Combining recognition units with cancer-killing chemicals or substances to help X-rays identify blood clots, tumors or damaged tissue opens up new approach.

Maybe that magic bullet isn't so far off in the realm of dreams after all.

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