WASHINGTON—The human body has strong immune defenses against cells of foreign species. For example, cells that produce a sugar known as galactose-alpha(1,3)galactose, found in many mammalian species but not in humans, trigger a hyperacute response in humans that destroys the great majority of the interloper cells. Cancer cells, however, which also contain many molecules not found in normal cells, nonetheless often elude the immune system’s defenses.
A single enzyme—alpha(1,3)galacto-syltransferase or alpha-GT—creates the foreign sugar. Now, researchers at the Stoddard Cancer Research Institute, Methodist & Lutheran Health System, Des Moines, are trying to exploit the natural immunity of the human to the nonhuman enzyme and turn the immune system that attacks foreign species cells against human breast cancer cells.
Charles J. Link, Jr., MD, director of the Institute, reported the work at the Susan G. Komen Breast Cancer Foundation 5th Annual Conference on Innovations in Quality Care.
Getting that foreign enzyme into human breast cancer tissues would produce the sugar, causing the immune system to perceive the breast cancer cells as foreign and destroy them, Dr. Link explained.
In effect, breast cancer cells infected with the foreign enzyme and introduced into a patient would act as a vaccine against the individual’s own breast cancer cells.
Tests on a mouse model have thus far proved the theoretical principle, Dr. Link said, and data are being gathered with an eye toward undertaking human trials. To that end, the alpha-GT gene has been cloned into an artificial herpesvirus that has a high propensity for infecting breast cells.
In the animal studies, breast cancer was induced both in knockout mice lacking alpha-GT and in normal mice. The gene was then inserted into the knockout mice.The virus-borne alpha-GT infection afforded the knockout mice "complete protection" from breast cancer cells, Dr. Link said, whereas every one of the normal controls had died of the cancer within 17 days.
