In a new study, published in Proceedings of the National Academy of Sciences, scientists from the Scripps Research Institute were able to significantly enhance the treatment of metastatic breast cancer in animal models. The study showed a new hybrid compound remained in circulation for a week. In comparison, a small molecule drug was cleared in a matter of minutes.

In the study, the scientists created what is known as a "chemically programmed antibody" by using small cell-targeting molecules and a non-targeting catalytic monoclonal aldolase antibody in a novel self-assembly strategy. Antibodies are proteins produced by immune cells that are designed to recognize foreign pathogens harmful to the body; monoclonal antibodies are produced in the laboratory from a single cloned B-cell, the immune system cell that makes antibodies.

The therapeutic use of monoclonal antibodies has expanded rapidly over the last several years precisely because of their long half-life, combined with their overall lack of toxicity and the fact that they can be easily designed and produced. For cancer treatment, the ability of antibodies to direct immune system responses to specific tumor types is one of the factors that have led to their increased use.

Until recently, it had been widely accepted that while antibodies possess a number of therapeutically advantageous traits, treatment with monoclonals required a different antibody for each specific target. However, the paper's authors have been showing that scientists can use different small molecule targeting agents – called programming agents or adapters – to selectively direct the same antibody to different sites for different uses so that only a single antibody is required for multiple tasks.

"Although the study focused specifically on breast cancer, these new findings could have broad application in the treatment of a number of other cancers, potentially increasing the efficacy of a number of existing or undeveloped small molecule therapies," said Subhash C. Sinha, Ph.D., associate professor in the Scripps Research Department of Molecular Biology and the Skaggs Institute for Chemical Biology, who led the research.

SOURCES:
Proceedings of the National Academy of Sciences, online edition, July 5, 2006
Scripps Research Institute (http://www.scripps.org)