Researchers at the University of Pennsylvania Medical Center today were awarded patent number 5,824,311 for a new technology that has shown the potential in laboratory studies to cure breast and other major cancers linked to certain abnormal genes.
Broadly viewed, the approach targets cancer-causing receptor molecules found on the surface of tumor cells with two different antibodies that bind to the molecules, fatally disabling the receptor's activity and leading to the cancer cell's death.
The specific application of the concept detailed in the patent employs a pair of antibodies against a receptor protein called p185. The p185 protein assembles into a two-protein receptor complex thought to be involved in stimulating the uncontrolled growth of a number of dangerous cancers, including those of the breast and the pancreas. Instructions for producing the p185 protein in the cell are encoded by a gene known as neu.
The recently approved anti-breast-cancer drug Herceptin also acts on the receptor produced by the neu gene but brings only one antibody to bear on it. Experiments in rodent models, however, showed that a two-antibody strategy was significantly more powerful.
"In our two-antibody studies, we were able to achieve cures of tumors as opposed to simply reducing tumor growth," says Mark I. Greene, MD, PhD, a professor of pathology and laboratory medicine in whose laboratory the work was conducted. "In our experience, a single antibody against the receptor only diminishes the growth of tumor cells, whereas two antibodies disable the receptor so effectively that the cells perish."
Receptor proteins are convoluted structures with many sites -- called epitopes -- to which a wide array of antibodies can bind. It is possible for some of these sites not to be involved in the activity of the protein. Also, antibodies that bind in different ways to the same site can limit each other's effectiveness. Significantly, the antibodies used in Greene's studies bind to separate, functionally important epitopes.
"By combining antibodies to two distinct epitopes on nonoverlapping domains of the receptor complex, one achieves a much more effective disabling result than would otherwise be the case," Greene says.
The University of Pennsylvania Medical Center's sponsored research and training ranks third in the United States based on grant support from the National Institutes of Health, the primary funder of biomedical research and training in the nation -- $175 million in federal fiscal year 1997. In addition, for the third consecutive year, the institution posted the highest annual growth in these areas -- 17.6 percent -- of the top ten U.S. academic medical centers.
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