X-Message-Number: 17837
From: "Gary Tripp" <>
Subject: targeting tumor blood vessels
Date: Sat, 3 Nov 2001 00:56:22 -0500

Researchers at Yale have developed a new molecule they call "icon" that
targets blood vessels in tumors for destruction by the immune system without
harming vessels in normal tissues.
"Our study resulted in the eradication of injected tumors and also of other
tumors in mice that had not been injected," said principal investigator Alan
Garen, professor of molecular biophysics and biochemistry at Yale
University. "This serves as a model of metastatic cancer. None of the normal
tissues in the mouse appeared to be harmed by our procedure."

Published in the October 9 issue of Proceedings of the National Academy of
Sciences, the study was conducted with human melanoma and prostate tumors
growing in mice. The gene for the icon was inserted into an adenovirus
vector that was injected into a tumor, resulting in the infection of tumor
cells that act within the mice as factories for producing the icon and
secreting it into the blood.

Garen said that in order to target tumor blood vessels without harming the
normal blood vessels, a molecule that is expressed specifically on the inner
surface of the tumor is needed. The molecule used for this study is called
tissue factor, whose normal function is to initiate blood clotting.

Blood clotting occurs when another molecule called factor VII, which
circulates constantly in the blood, binds to tissue factor. The binding of
factor VII to tissue factor is one of the strongest and most specific
interactions known in biology. Garen and Yale research scientist Zhiwei Hu,
constructed the icon, which is modeled after a camel's version of an
antibody. The icon is composed of two parts. One part targets the icon to
tissue factor by using factor VII as the targeting domain. The other part of
the icon is the region of a natural antibody that activates an attack by the
immune system against cells that bind to the icon.

"The result is that the tumor blood vessels are destroyed by the immune
system and consequently the tumor cells die because they lack a blood
supply," said Garen. "The normal blood vessels survive because they do not
express tissue factor and therefore do not bind the icon."

"This icon should work against all types of tumors that contain blood
vessels," said Garen. "The icon that will be used in a clinical trial is
derived entirely from human components and therefore should not be
significantly immunogenic, which is an advantage over antibodies used in
this kind of study."

Garen said the procedure could also be effective against other diseases that
require growing blood vessels, such as macular degeneration, the major cause
of blindness in older people.

A clinical trial is being arranged by Albert Deisseroth, M.D., formerly of
Yale, and currently President of the Sidney Kimmel Cancer Center in San

The study was funded in part by the National Institutes of Health and by
gifts from private donors.

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