Molecule to eradicate cancer

Researchers at Yale have developed a molecule they call icon, that targets blood vessels in tumours for destruction by the immune system without harming vessels in normal tissues.

"Our study resulted in the eradication of injected tumours and also of other tumours 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."

The study was conducted with human melanoma and prostate tumours growing in mice. The gene for the icon was inserted into an adenovirus vector that was injected into a tumour, resulting in the infection of tumour 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 tumour blood vessels without harming the normal blood vessels, a molecule that is expressed specifically on the inner surface of the tumour 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 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 tumour blood vessels are destroyed by the immune system and consequently, the tumour 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."