neuroendocrine tumors - possible new treatment

[john]

Indium-111 may be a treatment for neuroendocrine tumors.

Infinitely sticky antibodies deliver cancer treatment

Using antibodies as "smart bombs" to carry doses of radiation straight to tumor cells is the aim of research by University of California, Davis, chemistry professor Claude Meares. The team has developed a new method to permanently bind radioactivity to antibodies.

Antibodies are proteins made by the immune system that fight disease by sticking to bacteria, viruses and cancerous cells. They are highly specific to one target. In theory, an antibody directed against a tumor cell could carry a toxin or a dose of radiation straight to the tumor.

Some clinical trials of these treatments are beginning, for example in ovarian cancer, said Meares.

To make these smart-bomb antibodies more effective, Meare's lab looked for ways to get tighter binding between the antibody and the radioactive element indium-111, contained in a small carrier molecule. In the experimental treatments currently in trials, antibodies are tagged with radioactivity using two natural molecules, biotin and streptavidin, that stick together but can pull apart again.

Instead, graduate student Albert Chmura, research assistant Molly Orton and Meares made an antibody that recognized and stuck to the radioactive carrier. Then they engineered the binding region of the antibody protein, so that when it meets the carrier molecule it not only binds to it, but forms a permanent chemical bond. It's rather like replacing Velcro with welding.

To treat cancer with this approach, you would need a double-headed antibody. One end would recognize the tumor, and the other would grab the radioactive carrier. The antibody would go into the body first and find it's way to the tumor. Then the radioactive carrier would be injected. Because this is a small molecule, it would reach the tumor quickly and stick to the antibody, delivering the maximum amount of radiation to the tumor cell while avoiding healthy tissues.

The research on permanent binding of antibodies and radioactive carriers is described in a paper by Chmura, Orton and Meares in the July 10 issue of Proceedings of the National Academy of Sciences of the U.S.A. Meares has licensed the patented discovery from the University of California, and has founded a company, Lexrite Labs of Dixon, Calif., to commercialize the invention.

Media contacts: Claude Meares, Chemistry, 530-752-0936, cfmeares@ucdavis.edu; Andy Fell, 530-752-4533, ahfell@ucdavis.edu.