Yale researchers develop new cancer treatment

BY ZANDER DRYER

Two Yale scientists are prepared to announce a major new discovery in the ongoing battle against cancer. Alan Garen, a professor of molecular biophysics and biochemistry, and research assistant Zhiwei Hu have developed a new molecule—dubbed "icon"—that is injected into tumors as part of a harmless virus that kills cancer cells by targeting their blood vessels for destruction by the immune system. Before the cancer cells die, however, they produce new copies of the virus containing icon. The virus then spreads to target other cancer sites.

GETTY IMAGES After a new cancer-fighting molecule proved successful in laboratory mice trials, scientists are hopeful that the molecule--developed by two Yale researchers--will also work in humans.

In an article to be published in the Tues., Oct. 9 issue of Proceedings of the National Academy of Sciences, Garen and Hu describe a successful trial of icon therapy in laboratory mice injected with human melanoma and prostate cancers.

"Virtually all of the viable tumor cells were eliminated, and the mice appeared to be free of the disease and in good health at the end of the experiments, which lasted up to 194 days," the pair wrote. Control mice, however—which were not given icon—died within 63 days.

Fighting cancer cells by attacking their blood vessels has drawn considerable attention recently. But results released last spring disappointed many scientists, as the technique appeared to be less successful than they had initially hoped. Garen and Hu's icon therapy takes a different tack from earlier efforts, however. Rather than stopping the growth of new blood vessels, icon turns the immune system against existing blood vessels. Icon binds to tissue factor cells, which line the blood vessels that feed cancer cells—but not other blood vessels found elsewhere in the body. "The result is that the tumor blood vessels are destroyed by the immune system and consequently the tumor cells [themselves] die because they lack a blood supply," Garen told the Associated Press. "The normal blood vessels survive because they do not express tissue factor and therefore do not bind the icon."

Garen is guardedly optimistic about his work. "We're excited about it," he admitted. But as he considers human trials, Garen is more cautious. "From mice to men, that is a big jump," he told the AP. "Until the trial is done with patients, you can't be sure."

Dr. Albert Deisseroth, who worked at Yale before assuming his current position as president of the Sidney Kimmel Cancer Center in San Diego, is preparing a clinical trial of icon therapy for people with melanoma.

The trial is slated to begin next spring, contingent on FDA approval. Deisseroth joined Garen in urging cautious optimism. "There are differences between animals and human beings," he told the AP. But "when studies in animals are so reproducible and encouraging," he added, "you feel justified to invite individuals who are not responding to other forms of therapy to participate [in a clinical trial]."

If humans do respond to icon treatment, Garen and Hu's discovery will have wide-ranging implications. "This icon should work against all types of tumors that contain blood vessels," Garen said.

He added that icon therapy could stop other diseases that rely on blood vessels, such as macular degeneration, which is the leading cause of blindness in the elderly.

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