Fused cells hold promise of cancer vaccines.

What a shocking development. With small pulses of electricity, scientists have merged human-tumor and immune cells to create personalized vaccines against a deadly cancer.

In the first trial of this strategy in people, 7 of 17 patients with kidney cancer that had spread to other tissues developed tumor-specific immune responses after several vaccinations with the fused cells. Indeed, while conventional therapy keeps alive fewer than 10 percent of patients with advanced-kidney-cancer, four people in the vaccine trial experienced a complete remission, Alexander Kugler of the University of Gottingen and his German colleagues report in the March NATURE MEDICINE.

"This is very impressive," says Donald W. Kufe of the Dana-Farber Cancer Institute in Boston, who first showed that such hybrid-cell vaccines could trigger an immune attack on cancers in animals.

While researchers must do further work with more patients to confirm the vaccine strategy, the results bring renewed attention to specialized immune sentinels called dendritic cells. These cells patrol the human body, normally displaying bits of invading viruses or bacteria and ordering other immune cells to seek and destroy microbes bearing those fragments.

In the early 1990s, scientists seeking to unleash the immune system on cancer cells learned to grow human dendritic cells in the laboratory. That led to the first dendritic-cell vaccines, created by exposing the immune cells to a tumor antigen, a protein on the surface of cancer cells.

In initial trials, people with lymphoma, melanoma, or prostate cancer who received dendritic cells primed with a known tumor antigen showed strong anticancer immune responses (SN: 1/13/96, p. 23; 6/13/98, p. 380).

Hoping to create individualized vaccines without requiring that the tumor have a known antigen, Kufe's team in 1997 fused whole cancer cells with dendritic cells. They theorized that the dendritic cells would then alert the body to multiple tumor antigens, including those that researchers had not yet isolated.

"One of the advantages of this approach is that they're delivering not a particular antigen ... but the whole antigenic content of a tumor cell," says Eli Gilboa of the Duke University Medical Center in Durham, N.C.

After Kufe's animal testing proved promising, Kugler's group rushed to try similar vaccines in kidney cancer, which has no recognized tumor antigen. The investigators fused tumor cells from each patient with dendritic cells from another person, a hybrid they hoped would arouse the immune system even more than one made from the patient's own dendritic cells.

Before injecting the hybrid cells into people, the scientists irradiate the cells so that they can't grow out of control and create a new cancer threat.

The biggest concern investigators have about the vaccine strategy, says Kufe, is that it may also trigger a person's immune system to attack healthy tissues. After all, a cancer cell is largely a normal cell.

Yet neither the animals receiving the hybrid cancer vaccines nor the people in the German trial revealed such autoimmune side effects. "Autoimmunity is clearly a possibility, but it hasn't been seen. No one knows why, but that's the good news," says Kufe, who has begun testing a hybrid vaccine on breast cancer.

A research group in Berlin is working with a melanoma hybrid vaccine, and about 40 percent of patients in that trial are responding, notes Kugler. His group plans to directly compare the kidney cancer vaccine, which had a similar immune-response rate, with the current treatment standard of chemotherapy and immune-stimulating chemicals such as interferon.

Kufe predicts that scientists will find ways to make a larger percentage of cancer patients respond to the vaccines. "There are a number of strategies to make this [approach] even more potent," he says.