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 Article of Interest - Cancer

Immune Cells Used to Stop Severe Cancer
New Approach Brings Success to an Old Idea

By David Brown, Washington Post, September 20, 2002,

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A research team at the National Cancer Institute has successfully treated several cases of advanced and usually fatal cancer with immune system cells taken from the patients, grown in large numbers and given back to them.


The treatment is one of many strategies scientists are using to try to harness the human immune system's capacity to produce rare cells capable of hunting down and attacking tumors.


The research also marks the first success in a decade for a once-highly touted strategy conceived by Steven A. Rosenberg, a cancer institute surgeon and one of the founders of "immunotherapy." His experiments in the late 1980s, first with mice and then with humans, were viewed by some as the path to the elusive "cure for cancer." Their clinical results, however, were disappointing in almost all cases.


The new strategy worked only half the time and has been tried only in the skin cancer known as melanoma, but the results suggest it may be applicable to other malignancies.


"As a proof of principle, he's hit a home run," Robert A. Figlin, an oncologist and immunotherapist at the University of California at Los Angeles School of Medicine, said of Rosenberg's findings. They are reported today in Science Express, the online site for the journal Science.Most of the steps of the therapy had been tried before, but "what's new here is putting all the pieces together to get a more successful outcome," said Richard Childs, a physician at the National Heart, Lung and Blood Institute who has tried immunotherapy, with some success, in kidney cancer patients.


The treatment produced several dramatic recoveries, Rosenberg reported yesterday at a meeting of science writers organized by the American Medical Association. One teenage boy had a "volley-ball-size tumor" in his pelvic cavity that caused so much pain he required around-the-clock treatment with narcotic painkillers. It disappeared with immunotherapy, Rosenberg said.


Melanoma, which is a cancer of the skin's pigment-producing cells, can be cured by surgery, but not chemotherapy. Once it has spread to distant organs, few, if any, people survive for a long time.


The National Cancer Institute team treated 13 patients with advanced forms of the cancer. They had exhausted all other therapies, including at least one designed to stimulate their immune systems. After the new treatment, six responded with what appears to be total disappearance of the tumors. Four had partial responses that are not expected to last (although one patient's disease has been stable for a year). Three had no response and have died.


Rosenberg's strategy has always been to exploit the existence of immune system cells that can be found buried deep in cancerous tumors fighting a valiant, but almost always futile, battle against the rapidly dividing cells.


In the 1980s, he and his colleagues isolated these "tumor-infiltrating lymphocytes" (TIL), grew them up in culture dishes outside the body and reinfused them into the bloodstream. Although they appeared to retain their anti-cancer properties, they didn't survive in the body long enough to make a practical difference.


In their most recent strategy, the researchers isolated TIL from multiple samples of each patient's tumor and grew them in the laboratory. As many as 50 different samples from each patient were tested against the person's cancer cells. The samples that killed the most cancer cells were selected for reinfusion into the bloodstream.

Before that was done, the patients underwent chemotherapy to temporarily wipe out their immune systems and "make room" for the incoming TIL. After the reinfusion, each person also received numerous doses of interleukin 2, an immune system hormone previously shown to stimulate anti-tumor activity.


Unlike in previous experiments, large quantities of TIL were found in the bloodstreams of several of the patients. It was clear that in some patients, the cells not only survived, but proliferated.


For example, in one patient whose tumor disappeared, 97 percent of bloodstream lymphocytes were anti-cancer a week after the infusion. In another, 63 percent were anti-cancer. In those two patients, tumor-infiltrating lymphocytes were still detectable four months later.


A main reason for the greater success of this treatment, several experts said, is that a mixture of lymphocytes -- helper and killer cells -- were used. Previously, many researchers, including Rosenberg, had used only killer cells. This meant the new infusions were a melange of cells with different characteristics and extremely complicated relationships with each other.


In four patients, the TIL attackers were so active they killed some normal pigment-producing cells, creating white areas of skin, a condition called vitiligo. This suggested that side effects could pose a problem in treatment of other cancers.


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