New Cancer Treatment Wipes Out Tumors

By STEVE MITCHELL, UPI Medical Correspondent

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WASHINGTON, Sep 19, 2002 (United Press International via COMTEX) -- An experimental treatment has eliminated deadly skin cancers in six patients whose tumors previously had resisted conventional therapies, a scientist at the National Cancer Institute reported Thursday.

The technique, which replaces a patient's ineffective immune system with cancer-fighting cells, also might prove useful against other cancers and help fight viral infections such as AIDS, Steven Rosenberg, chief of surgery at the NCI, said at a meeting sponsored by the American Medical Association.

Rosenberg's team used the therapy to treat 13 patients with a deadly version of skin cancer known as metastatic melanoma, which in many of the patients had spread to many areas of the body. Six had tumors shrink by at least 50 percent, with some losing nearly all of their melanomas. Four other patients experienced some tumor shrinkage while the remaining three did not respond to the treatment.

The first patient treated with the therapy was a 16 year old boy who had developed a melanoma on his knee. By the time he was enrolled in the study, the cancer had spread all over his body, leaving him with a a volleyball-sized tumor on his chest and a large tumor on his pelvis that caused him considerable pain, Rosenberg said.

The boy had failed on both conventional and other experimental therapies and probably had only a few months to live, Rosenberg said. But after receiving the therapy, "all of his cancer went away" and the boy has been cancer-free for two years, he said.

"The remarkable thing is that we could convert 90 percent of the person's immune system to fight cancer," Rosenberg told United Press International. "Now we need a deeper understanding of why it happened."

The body's immune system can generate defenders called T-cells that attack and kill cancerous cells. Often, however, these cells are too few in number to stave off aggressive cancers.

Over the past 20 years, Rosenberg and colleagues have tried to boost the level of T-cells by taking some from the patients' tumors, growing them in large numbers in lab dishes and injecting them back into the patients' bodies.

"The problem is that fewer than 1 percent of the cells injected back were able to survive," Rosenberg said. "Whenever we transferred cells in the previous studies, they were generally gone in a week. It's very hard to get enough cells to fight cancer."

The transferred cells might be unable to stick around because the immune system can accommodate only so many of them, Rosenberg explained. To "make room" for transferred cells, Rosenberg's team suppressed the patients' immune systems with a week's worth of chemotherapy prior to the T-cell transplant.

"We raised 10 to 100 billion of these T-cells with each treatment, which took about a month to grow," Rosenberg said.

The transferred cells, which were injected along with a T-cell growth-stimulating protein known as interleukin-2, remained in "numbers that have never been approached before," Rosenberg said. "We're not getting 1 percent of cells persisting but are getting up to 90 percent." The cancer-fighting cells persisted at high levels for as long as they looked, which so far has been for five months, he said. Suppressing the previously ineffective immune system also may have removed anything responsible for inhibiting T-cell growth in the first place, he added.

Over time, the patients' immune systems recovered, restoring their ability to fight infections. One patient developed pneumonia due to his hindered immune system but all of the patients survived the treatment. Other side effects included mild disorders where patients' immune systems attacked healthy tissue. While this resulted in vitiligo, a skin disorder that produces white patches of skin, and uveitis, an iris inflammation treatable with steroid drops, "it's a small price to pay for getting rid of your cancer," Rosenberg said.

Rosenberg and his colleagues now are trying to determine exactly what made the therapy so successful in some and less so in others. Because T-cells also are responsible for attacking virally infected cells, he said, this approach may prove useful against such diseases as well.

"It's just the first step, but it's an exciting first step," said Bernie Fox, chief of molecular and tumor immunology laboratories at the Earl A. Chiles Research Institute in Portland, Ore. "We have a study based on the same principle in prostate cancer next year ourselves," Fox told UPI. "I think this work will help bolster people still struggling doing this relatively expensive therapy to do it."

Martin A. Weinstock, professor of dermatology at Brown University and chair of the American Cancer Society's skin cancer advisory group, said the new therapy "is very promising and I hope it will pan out."

Weinstock told UPI, "It seems to work better than the older innovations but the data is very early and we can't say much for certain."

Rosenberg urged tempered enthusiasm because the therapy is still experimental and it has only been used to treat one type of cancer in a relatively small number of patients. His team is continuing to treat patients and plans to begin trials in patients with other cancers in the next several months.

The research is published in the Sept. 19 online version of the journal Science.