Molecule developed that can seek out and destroy cancer cells
By Randolph E. Schmid, Associated Press, 10/01/01
WASHINGTON -- Scientists have developed a molecule that
appears to make cancer its own worst enemy.
In laboratory tests on mice, the molecule -- called icon -- killed
tumors by destroying the blood vessels that feed them. It also
caused the cancers to produce copies of icon, which spread
through the body and attacked other cancers.
The process eliminated human melanoma and prostate cancers
in the tested mice. The first trials in people are planned for next
year.
Drugs that inhibit the growth of the blood vessels that feed
cancer have received wide attention in recent years, though
early results reported last spring showed less promise than
had been hoped for.
The new therapy, developed by researchers Alan Garen and
Zhiwei Hu at Yale University, takes a different approach,
attacking the cells lining the blood vessels in tumors rather
than trying to prevent the growth of new blood vessels.
Their 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
launch next spring once approval is obtained from the Food
and Drug Administration.
He also cautioned against jumping to conclusions about
possible new cancer therapy. "There are differences between
animals and human beings."
But, Deisseroth added, "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.
The first trial will focus on people with melanoma -- a type of
skin cancer -- that has spread throughout the body, he said.
While the animal tests have worked on prostate cancer and
melanoma, in theory the therapy should work on any solid
cancer, Deisseroth said.
Garen said that cells lining the blood vessels in tumors have a
receptor on their surface called TF (tissue factor), 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 in a harmless virus that
was injected directly into a tumor. Once infected, the tumor
cells produce more icon and secrete it into the blood, where it
circulates. 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.
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 Folkmans
hypotheses 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 anti-cancer molecule "is brilliant
and deserves praise," Grant said. |
