RESEARCHERS DEVELOP CANCER-FIGHTING PROCESS\Technique could boost immune reaction.

Byline: Lawrence K. Altman The New York Times

Scientists at Stanford University say they have developed a novel way to generate a powerful immune response targeted specifically against non-Hodgkins lymphoma, a cancer of the lymph system.

Preliminary results among four patients were promising, the research team reported Friday in the journal Nature Medicine.

The new, highly experimental technique is a different form of immunotherapy that researchers are trying to develop against several kinds of cancer.

The Stanford researchers start the multistep process by removing two kinds of tissue from a lymphoma patient. One tissue is a dendritic cell, which is important in stimulating immune reactions in humans. The cells are obtained from the blood. The second tissue is the lymphoma, which is removed by a biopsy and from which researchers isolate a protein from the surface of the cancerous cells. The protein is specific for each patient's cancer.

Then the protein is incubated in a laboratory with the patient's dendritic cells, a process that takes six months. Finally, the processed tissue is given back to the patient in a series of injections.

Because the therapy must be tailored to each patient, widespread testing to evaluate the effectiveness of the new therapy is impractical, said Dr. Ronald Levy, the head of the Stanford team.

"Basically the technique needs confirmation by other groups and additional testing before we decide to go further" on a large scale, Levy said in an interview.

In developing the lymphoma therapy, Levy's team adapted a technique developed by Dr. Ralph M. Steinman's group at Rockefeller University in New York. It allows scientists to grow an individual's dendritic cells in a laboratory.

Dendritic cells are so named because they have long spindles that give them a star-like appearance. Dendritic cells trap antigens like the cancer-associated protein and deliver them to T cells, specialized cells in the immune system that can destroy designated cells.

In the Stanford study, injection of the combined preparation generated a more robust immune response than possible from injection of just the cancer-associated protein.

Levy said his new approach to non-Hodgkins lymphoma is based on a similar immunotherapy that Dr. Kristian Thielemans developed and tested in mice at the Free University in Brussels.

In advancing to human tests, Levy's team conducted a pilot study that was primarily intended to monitor immune responses in four patients and to determine the therapy's safety.

No patient experienced a significant side effect. All four produced a strong immune response to the cancer-associated protein, though the response waned with time. Significant regression of the lymphoma occurred in three patients. One patient had complete remission that has lasted for 21 months.

However, non-Hodgkins lymphoma can recur unpredictably many years after regression following standard therapy. So the pilot study could not determine whether the novel immunotherapy is more effective than standard therapies. Nor could the pilot study determine how often the immunotherapy injections would be needed if the technique became standard.

To prove that the experimental therapy is more effective than standard therapies, the researchers need to show not only that it made the cancers shrink or go away, but also prevented their return.

"The easiest way to make that determination would be to use the therapy, see what results you get, and then compare them to what you would expect from past experience," Levy said.

Such experience is known as a historical control. A favorable result does not offer definitive proof. However, it can offer convincing evidence if the results are clear cut. When the findings are not so obvious, scientists test such therapies in controlled trials in which one group of patients receives the experimental therapy and a second group does not. Volunteers for such studies allow the choice to be made by lot.

Levy said he plans to test a few more patients "without a control group to get a bigger database to decide whether the therapy is worth pursuing."

If additional experiments show benefit for the immunotherapy, then Levy is hoping to improve the laboratory techniques.