Toward medicines that recruit the body’s natural disease-fighting proteins

Like recruiters pitching military service to a throng of people, scientists are developing drugs to recruit disease-fighting proteins present naturally in everyone's blood in medicine's war on infections, cancer and a range of other diseases. They reported on the latest advances in this new approach here today at the 244th National Meeting & Exposition of the American Chemical Society, the world's largest scientific society.

David Spiegel, MD, PhD, who heads one of the major research teams developing ''antibody-recruiting molecules'' (or ARMs), said that the approach is a response to the old and seemingly impossible dream of identifying ''magic bullets'' for wide-ranging diseases. Antibodies are components of the immune defense system that latch onto microbes and other foreign material in the body and mark them for destruction.

''Antibodies have been wonderful drugs for autoimmune diseases and cancer,'' Spiegel explained. ''But, like other protein-based drugs, they cannot be given in a pill, and must be injected. They can also cause life-threatening allergic or immune reactions. We are developing a work-around ? antibody-recruiting medicines that can be taken orally and induce a patient's own antibodies to fight disease. They would be less expensive and easier to make. We hope it's the starting point toward entirely new approaches for treating a wide range of diseases.''

Everyone has numerous antibodies circulating in the blood, each programmed by the immune system to latch onto and mark for destruction specific bacteria, viruses, allergens (like plant pollen) and other material ? termed antigens ? that the body recognises as foreign. The body makes these antibodies as people are exposed to microbes and allergens in the environment.

However, researchers don't know why people have antibodies against some structures, like the 2,4-dinitrophenyl (DNP) epitope, which is similar to ingredients found in certain pesticides and agricultural chemicals. It could be due to environmental exposures, but researchers also think the body could have made these antibodies when exposed to some other substance that resembles DNP.

Antibodies against DNP are what Spiegel's team at Yale University is using in one strategy to make the immune system target various cancers and HIV, the virus that causes AIDS.