Los Angeles Times - Friday July 10, 1992
Thomas H. Maugh II; Times Science Writer

Preliminary results with the technique show that it can protect bone-marrow transplant patients against infections by cytomegalovirus, which can cause lethal pneumonia.

Additional trials will begin this summer to test the technique on AIDS patients with lymphoma, said Dr. Stanley Riddell, an immunologist at the Fred Hutchinson Cancer Research Center in Seattle.

Riddell and his colleagues report today in the journal Science that they have perfected techniques to isolate specialized white blood cells from donors, grow large numbers in the laboratory and safely inject them into patients.

In the AIDS-lymphoma patients, who will also receive bone marrow transplants, they hope that the white blood cells will prevent the AIDS virus from infecting the transplanted marrow cells.

Their work is "clearly one of the very important advances in the field of human immunotherapy over the last 30 years," said Dr. Drew Pardoll, an immunologist at the Johns Hopkins University School of Medicine. He said the work holds the potential of protection not only against a broad variety of viral infections, but also against cancer.

"It's a very new and different approach in the human arena," Pardoll added. "The more approaches that you have, the better the chance that a combination of approaches will yield results that are clinically significant."

The approach adopted by Riddell, Dr. Phillip D. Greenberg, an immunologist at the University of Washington, and their colleagues, has been studied for 10 years in mice and shown to be very effective. In the animal studies, the researchers isolated from healthy animals white blood cells--called killer T cells or CD8 cells--that were targeted against cytomegalovirus (CMV) and other viruses. When these cells were propagated in the laboratory and infused into animals with a defective immune system, the cells protected the animals when they were exposed to the viruses.

But the problem was that human CD8 cells directed against a specific virus are hard to grow in the laboratory. Moreover, they have a strong tendency to lose their ability to recognize the target virus or be inactive when they are injected into animals.

But Hutchinson molecular biologist Kathe S. Watanabe developed techniques for growing the cells that overcame both problems.

The Washington group has treated five patients who received bone marrow transplants as a treatment for leukemia. Typically, about half of such patients become infected with CMV, which can cause a variety of complications.

For each patient, the team extracted CD8 cells from a compatible donor and grew large quantities in the laboratory over a period of six to 12 weeks. The patients received large doses of the cells in each of the first four weeks after their transplants.

Blood tests then showed that the patients had a strong immune response against CMV that persisted for weeks after the infusion--long enough to allow the implanted bone marrow to begin functioning as an effective immune system. None of the patients developed CMV infections.

The team plans to treat several more patients to determine if the technique provides protection against infection. Riddell cautioned that the technique is too complicated to be widely used.

Meanwhile, they are growing anti-HIV CD8 cells to treat an AIDS patient who will undergo a bone marrow transplant as therapy for lymphoma. Typically, the HIV infection spreads after such a transplant because the immune system is impaired. The Washington team hopes that the CD8 cells will keep the virus in check until the bone marrow begins functioning.

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