Alerting the Immune System to Tumors

Tumors go mostly unmolested by the body's natural defenses, partly because cancer cells are descendents of normal body cells. Now researchers have achieved success in human patients with a ruse that turns the immune system against these growths. In a preliminary trial of an unconventional vaccine, several patients rid themselves of kidney cancer, a kind of cancer that is particularly hard to cure.

Although the immune system doesn't recognize them as alarming, cancer cells have surface features, called antigens, that apparently distinguish them from healthy cells. Researchers have looked for ways to awaken immune cells to these antigens' presence. Normally, an immune sentinel known as a dendritic cell would seize an antigen from an invader and present it to another immune cell called a T cell. These and other immune infantry would then seek and destroy cells carrying the same antigens. But chemicals that tumors release make these dendritic cells unwilling to grasp these antigens.

A team led by urologist Alexander Kugler of the University of Göttingen, Germany, and colleagues tried a new twist to an approach that has been explored in recent years. They removed tumor cells from patients with metastatic kidney cancer and zapped them with a jolt of electricity to fuse them with dendritic cells. In contrast to what other teams had tried, the dendritic cells were not the individuals' own--which might have stimulated the patients' immune systems to react. The researchers vaccinated 17 patients with the hybridized cells. After 3 to 21 months, the results were mixed: In four patients, the tumors and all metastases disappeared completely. Two others saw their growths shrink by 50%, and one lost a tumor while retaining a metastasis. The remaining 10 patients showed no response, the researchers report in the March Nature Medicine.

"This is a pretty significant advance if the numbers hold up" in larger trials, says cancer immunologist Brian Czerniecki of the University of Pennsylvania in Philadelphia. He points out that less than 10% of kidney cancers respond at all to conventional treatments.