First, the team selected a protein that bonds with one of the receptors. Using it as a molecular "scaffold" they affixed, or substituted, a new section that could bond with the second receptor, all without altering the original function or the physical structure of the larger scaffold protein. They succeeded; their new protein blocks both receptors.
When delivered in a nutrient-rich matrix and implanted in mice, the Stanford protein showed dramatic ability to halt the creation of new capillaries. "Samples treated with our dual-action protein have minimal blood vessel formation, similar to a sample in which angiogenic factors are absent," Cochran said. "Importantly, this engineered protein more strongly inhibits angiogenic processes compared to single-receptor blockers."
Some researchers have suggested that the same result might be accomplished more easily with a cocktail of drugs, each targeting a specific receptor. Cochran acknowledged the feasibility of such approaches, but pointed out that each drug in the cocktail would require clinical trials and the approval of the U.S. Food and Drug Administration. The new protein could be the basis for one drug.
"This is a major advantage of two-in-one molecules," said Cochran. "A single FDA-approval process could possibly shave years off the development process, and there are obvious cost benefits to manufacturing only one drug instead of several. In addition, using state-of-the-art protein engineering methods that have been developed within the past decade or so, such molecules could be engineered for optimal therapeutic benefit while reducing unwanted side effects"
Beyond cancer, Cochran noted, the prevention of angiogenesis could prove help
|Contact: Andrew Myers|
Stanford School of Engineering