Very promising results.
Vaccine Shrinks Tumors In Kidney Cancer Study
By Susan Okie
Washington Post Staff Writer
Tuesday, February 29, 2000; Page A02
An experimental cancer vaccine, made by fusing a patient's tumor cells with specialized cells of the immune system, has produced dramatic shrinkage of tumors in a small study of patients with advanced kidney cancer, researchers reported yesterday.
Although the results need to be confirmed in larger studies, they are encouraging enough that doctors in several countries are launching experiments using the same approach to treat other malignancies, including skin cancer, breast cancer and ovarian cancer.
The effort to enlist the immune system to fight cancer is a booming research field, but most trials of cancer vaccines in human patients have had no more than modest success, and no vaccine has been approved by the Food and Drug Administration. The results of the new study, in which more than one-third of patients responded favorably to the vaccine, are among the most promising to date, researchers said.
"Showing immunotherapy can work is an important step forward," said Jay A. Berzofsky, chief of the molecular immunogenetics and vaccine research section at the National Cancer Institute.
In five of the first 23 patients treated with the vaccine, cancers disappeared completely and have not recurred during at least eleven months of followup, said Alexander Kugler, a urologist at the University of Gottingen, Germany, who led the study. In three additional patients, tumors shrank by more than 50 percent, he said. All patients had kidney cancer that had spread to other organs, a situation in which five-year survival with current treatments is less than 10 percent.
In people who reacted favorably, "responses occur in all the different organs to which [kidney] cancer spreads," including lungs, bones and brain, said Donald W. Kufe of Boston's Dana Farber Cancer Institute, who wrote an editorial accompanying the study in the March issue of the journal Nature Medicine. On X-rays and scans, he said, "you can see [the tumors] go away."
But immunotherapy is a field in which dramatic early results have often been hard to replicate, warned H. Kim Lyerly, a professor of surgery, pathology and immunology at Duke University School of Medicine. "I was encouraged, but I think my enthusiasm is for them to continue to study [the treatment] on a larger scale," he said.
The treatment--administered as an injection under the skin of the groin, with a booster six weeks later--produced mild fever in some patients but no other significant side effects.
Each patient's vaccine was custom-made, using cancer cells from the patient's tumor as well as immune-system cells called dendritic cells, obtained from the blood of a donor. Dendritic cells are a type of white blood cells that have the job of "presenting" foreign proteins to other immune system cells, thereby identifying targets to be attacked.
"I would call the dendritic cell the conductor of the immune system," Kufe said.
Researchers mixed tumor cells with dendritic cells and then pulsed them with electric current, which induced a small percentage of the cells to fuse, Kugler said. The fused dendritic/tumor cells, called heterokaryons, were then injected into the patient as a vaccine.
The idea is that the newly created "fusion cells" have the same proteins as the tumor cells as well as "all the machinery that the dendritic cell uses to stimulate the immune system," said Kufe. In theory, these hybrid cells may then direct the immune system to mount an attack against multiple proteins on the patient's tumor cells.
The German researchers deliberately used dendritic cells from a non-matched donor to make each patient's vaccine, hoping to produce a more vigorous immune response against the tumor, Kugler said.
Patients were evaluated with CT scans (cross-sectional X-rays) three months after the first injection. If the scans showed significant tumor shrinkage, patients continued to receive boosters every three months.
In the results published in the journal, four of 17 patients treated with the vaccine responded with complete disappearance of cancer, and two showed a partial response, with more than 50 percent shrinkage of tumors. One additional patient had a "mixed response," with shrinkage of a soft-tissue tumor but progression of cancer in the bones. An additional six patients have since been treated. One of those patients experienced a complete response and one had a partial response.
After vaccination, 11 of 17 patients tested positive on a skin test against their tumor cells, indicating that their immune system had been primed to attack the tumor. Other tests suggested the vaccine activated T cells, white blood cells important in fighting infections and cancer.
Kidney cancer strikes about 31,200 Americans each year and kills about 11,900. The most common type, renal cell carcinoma, accounts for about 85 percent of kidney tumors and was the cancer treated in the study. The overall five-year survival for renal cell carcinoma is about 60 percent, according to the American Cancer Society. For patients whose tumors have spread to distant organs, five-year survival is less than 10 percent.
A research team in Berlin is testing a similar vaccine against malignant melanoma, a frequently fatal skin cancer, Kugler said. Additional trials are planned in Europe for ovarian cancer, multiple myeloma and liver cancer.
A trial of a similar vaccine for breast cancer has begun at Dana Farber, and other trials are in the works there for malignant melanoma and kidney cancer, Kufe said. The concept of a vaccine based on fused dendritic and tumor cells was developed at Dana Farber Cancer Institute, which has applied for a patent, he said, adding that he has no financial interest in such vaccines. |
