Molecule May Kill Cancer Cells

Tuesday, October 2nd 2001, 12:00 am

By: News On 6

WASHINGTON (AP) _ Researchers are planning human trials next year on a newly developed molecule that not only attacks cancer but forces it to produce more of the cancer-fighting molecules to join in the attack.

A pair of Yale University researchers developed the molecule, called icon.

In tests on mice that had human forms of prostate cancer and melanoma, icon eliminated the disease by destroying the blood vessels that fed the tumors.

In recent years drugs that inhibit growth of the blood vessels in tumors have received wide attention, though early results reported last spring showed less promise than had been hoped for.

The new therapy, developed by Alan Garen and Zhiwei Hu, takes a different approach. Instead of seeking to limit growth of these blood vessels, it directly attacks the cells lining the blood vessels.

The findings are reported in Tuesday's issue of Proceedings of the National Academy of Sciences.

``We're excited about it,'' Garen said. But he cautioned, ``From mice to men, that is a big jump. Until the trial is done with patients, you can't be sure.''

Dr. Albert Deisseroth of the Sidney Kimmel Cancer Center in San Diego is arranging clinical trials, which he hopes to begin next spring after the Food and Drug Administration approves the tests.

He also cautioned against jumping to conclusions about a possible new cancer therapy. ``There are differences between animals and human beings,'' Deisseroth said.

He added, however: ``When studies in animals are so reproducible and encouraging ... then you feel justified to invite individuals who are not responding to other forms of therapy to participate'' in trials.

Derrick Grant, a blood-vessel expert at Thomas Jefferson University in Philadelphia, called the findings ``very exciting.''

The paper ``puts a new and important spin on Judah Folkman's hypothesis that destroying the tumor vasculature can stop tumor growth,'' he said. Folkman, of Boston Children's Hospital, is a pioneer in efforts to battle cancer by attacking its blood supply.

Transferring the molecule into a tumor in a virus that forces the tumor to make more of the anticancer molecule ``is brilliant and deserves praise,'' Grant said.

Deisseroth said the first trial will focus on people with melanoma, a type of skin cancer, that has spread throughout the body.

While the animal tests have worked on prostate cancer and melanoma, in theory the therapy should work on any solid cancer, he said.

Garen said that cells lining the blood vessels in tumors have a receptor on their surface called TF which is not present on the cells lining blood vessels in other parts of the body.

His team found that a molecule circulating in the blood called fVII bonds strongly to TF.

The researchers created their new molecule by attaching an fVII molecule to a portion of a human antibody called Fc. Fc causes the breakdown of cells it binds to and activates the body's immune system to attack those cells.

The new icon molecule was inserted into a harmless virus that was injected directly into a tumor. Once infected, tumor cells produced more icon and secreted it into the blood, where it began circulating. When it encounters a tumor, it binds to the TF in its blood vessels, destroying them.

In mice with human melanoma or prostate cancer that received the molecule, both the injected tumor and others that were not directly injected disappeared.

``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 researchers reported.

Control mice with similar cancers that did not receive the molecule died within 63 days.