October 17, 2013 | by Tami Dennis
“Identification and grafting of a unique peptide-binding site in the Fab framework of monoclonal antibodies.” That’s the title of a study published online recently ahead of print in Proceedings of the National Academy of Sciences. Researchers will understand the implications; the average person may not. The key word, however, is the one most understandable to the lay reader or cancer patient: unique.
In short, researchers at City of Hope have hit upon a revolutionary avenue to combat cancer – and potentially many other diseases.
“This discovery provides a new way to aim cancer treatments to avoid side effects. Like the laser target designator that guides a smart bomb, this technology can be used to ensure that medicines make their way specifically to cancers,” said study co-author Joshua M. Donaldson. “The pretargeting can be applied to any antibody, and the cargo (bomb) is anything that can be attached to the guidance system.”
Monoclonal antibodies are proteins that the body produces to fight invaders. Researchers have long wanted to use these proteins to fight cancer efficiently and effectively, but with limited success. Genetic engineering is less than practical, and chemically attaching cancer drugs to the proteins leads to reduced efficacy and increased side effects.
But “efficiently and effectively” now appears possible.
The City of Hope team, led by John Williams, found that monoclonal antibodies have a hole in the middle, one in which a specific peptide (a kind of molecule) fits neatly. Think of a lock and key or, as Williams describes it, a tractor and trailer.
“With this specific hitch, you can take any tractor and hook up any trailer, effectively allowing you to mix-and-match the appropriate equipment for a specific job,” Williams said.
However you describe the connection, it now has a name: a meditope. And perhaps the most obvious use of the meditope is to fight cancer.
“The next steps are to determine the specific antibody and chemotherapy (cancer medicine) combinations to direct against various cancers,” Donaldson said. “We hope to improve on the gains that have been made in moving from nondirected toxic drugs to more cancer-specific drugs. This allows patients to receive cancer treatments without debilitating side effects like low blood counts, infections and dehydration.”
The possibilities are so extraordinary that the team was recently awarded a $1 million grant from the W.M. Keck Foundation, a well-known – and extremely prestigious – name in scientific circles.
So remember the term “meditope.” You’ll be hearing it again.
The research reported in this article was supported by, among others, the National Cancer Institute of the National Institutes of Health under grant number P30 CA033572 and R21 CA135216. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.